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Principal Investigators Association | www.principalinvestigators.org
2
NIH R01 Grant Application Mentor: An Educational How-to Manual — 4th Edition
“NIH R01 Grant Application Mentor: An Educational How-to Manual, 4th Edition” is published by Scientific
Researchers Resources, Inc., 9990 Coconut Road, Suite 316, Bonita Springs, FL 34135 USA.
Telephone: (800) 303-0129 ~ Fax: (239) 676-0146 ~ Email: [email protected] ~
Website: www.principalinvestigators.org
This report is endorsed as a valuable tool for continuing professional development by Principal
Investigators Association.
Retired Founder: Leslie C. Norins, MD, PhD
© 2014 Principal Investigators Association. The entire contents of this publication are protected by
Copyright, worldwide. All rights reserved. Reproduction or further distribution by any means, beyond the
paid customer, is strictly forbidden without written consent of Principal Investigators Association, including
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Economical rates for bulk or electronic purchases are available upon request; institutional inquiries welcome.
Principal Investigators Association — as well as this educational manual — is completely independent
and not controlled by any government agency, organization or society, consultancy, contractor, or
vendor. It is not endorsed by, nor does it have any official connection with, the National Institutes of
Health. Opinions expressed by private authors are their own, and not official government opinions.
Although the publisher believes the presented information is accurate, grant writing is part science,
part art, and interpretations and strategies differ, even among experts. Also, individual circumstances
vary. Therefore, no warranty is made that the information will apply in any particular case, or that a
grant application will result in an award.
3
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NIH R01 Grant Application Mentor: An Educational How-to Manual — 4th Edition
Table of Contents
Table of Contents
Introduction....................................................................................................6
Chapter 1: Starting the Grant Application Process........................................8
Qualifying for an NIH Grant......................................................................9
Map Out Your Plan................................................................................18
Choose Your Project..............................................................................21
Define Your Project................................................................................23
Create a Writing Schedule.....................................................................29
Conclusion.............................................................................................31
Chapter 2: Outlining Your Project and Individual Qualifications..................32
Formulating Your Project Summary/Abstract.........................................34
Keep Your Project Narrative Brief..........................................................48
Use All the Parts of the Biographical Sketch.........................................51
Conclusion.............................................................................................78
Chapter 3: Showing Your Institution’s Resources and Commitment...........80
Detail Your Facilities and Other Resources...........................................81
List Your Available Equipment...............................................................89
Sharing Plans Address Specific Research Resources..........................91
Conclusion...........................................................................................109
Chapter 4: Proving Your Research Topic’s Significance...........................110
Specific Aims Nail Down the Steps......................................................112
Research Strategy Has 3 Parts...........................................................120
Overall Impact Brings Everything Together.........................................147
Cite Your Bibliography and References...............................................153
Conclusion...........................................................................................155
Chapter 5: Special Considerations............................................................156
Complete the Inclusion Enrollment Report..........................................157
Informing Reviewers About Human Subjects......................................168
Informing Reviewers About Vertebrate Animal Test Subjects.............191
Informing Reviewers About “Select Agents”........................................197
Conclusion...........................................................................................204
Chapter 6: Budgeting Your Research.......................................................206
Strategy for Planning Your Budget......................................................208
Create Your Budget.............................................................................213
Modular Budgets Have a Limit.............................................................215
Form a Detailed Budget.......................................................................224
Conclusion...........................................................................................235
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NIH R01 Grant Application Mentor: An Educational How-to Manual — 4th Edition
Table of Contents
Chapter 7: Submitting Your Application....................................................236
Ensure All Additions Are Attached and Comply With Guidelines.........240
Create a Cover Letter..........................................................................245
Review Your Proposal for Content.......................................................248
Review Your Proposal for Writing Quality............................................254
11 Simple Mistakes That Can Derail Your Grant Application..............257
Make These Final Checks...................................................................259
Submitting the Application...................................................................261
Should You Withdraw the Application? ...............................................262
Chapter 8: The NIH Application Review Process......................................264
NIH Review Process: A Brief Overview...............................................265
NIH Checks Your Application...............................................................266
Your Application Gets an NIH ID Number............................................267
Your Application Is Assigned to an IRG, SRG and Institute/Center.....268
Submitting Additional Information........................................................270
Initial Peer Review ..............................................................................272
Basic Layout of Initial Peer Review......................................................275
How Reviewers Score Applications.....................................................277
Additional Review Criteria....................................................................283
Summary Statements..........................................................................286
Second Level of Review: Institute/Center Advisory Council or Board.288
When You Can Expect to Hear Back ..................................................289
Just-in-Time Information......................................................................291
Resubmission......................................................................................293
Appendix A: R01 Checklist........................................................................300
Appendix B: Index.....................................................................................305
Color Key:
Throughout this report, we have used highlighted text to indicate the following:
— original text by authors of this report
(no color)
(pink)
— directly quoted NIH information
— paraphrased NIH information
(yellow)
— directly quoted information from successful NIH grant applications
(blue)
5
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NIH R01 Grant Application Mentor: An Educational How-to Manual — 4th Edition
Introduction
Introduction
Applying for a National Institutes of Health (NIH) R01 grant is an involved
process with many facets to consider and extensive guidelines to follow. This
manual will guide you through the steps involved and help you submit the best
proposal possible.
Of course, all research begins with an idea, and you must determine if yours
should be funded by an R01 grant. Your research must meet NIH’s priorities, but it
is just as essential that the grant is the appropriate mechanism for your project.
Once you’ve verified that an R01 is right for you, you’ll need to work out
the specifics. Think about when to apply, what to title your proposal, and how to
articulate your hypothesis. But before you actually begin, consider creating a writing
schedule. Chapter 1 includes a sample timetable that will help you move through the
steps of the application process more easily and manage your time effectively.
As you begin writing your proposal, remember the message you are trying to
convey. You should explain your project thoroughly so readers will understand all
aspects of it. But you also want to tell a compelling story and entice reviewers to
approve your research.
Several chapters of this manual help guide you through the writing process.
They offer advice for developing your Project Summary/Abstract, Biographical
Sketch, Environment section and Research Plan. They also help you ensure your
Research Strategy addresses your project’s Innovation, Significance, Approach and
Overall Impact.
When considering your project costs, refer to our chapter on creating a budget.
You may also need to consult the section detailing considerations for special agents
and human and animal subjects. Each chapter includes checks to ensure you’re
following NIH guidelines every step along the way.
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NIH R01 Grant Application Mentor: An Educational How-to Manual — 4th Edition
Introduction
Before you submit your application, take time to review it. Make certain you’ve
included all the necessary components and adhered to all rules. You’ll also need to
correct any errors and remedy weaknesses before sending your proposal to NIH.
Once you’ve submitted your application, it goes through a comprehensive
review. The final chapter of this manual delineates that process. It also explains
what NIH scores mean and what steps you can take after you receive them.
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NIH R01 Grant Application Mentor: An Educational How-to Manual — 4th Edition
Chapter 1: Starting the Grant Application Process
Chapter 1:
Starting the Grant Application Process
Before you can begin filling in your National Institutes of Health (NIH) grant
application, there are several steps you must take first. For instance, you have to
define the research project idea for which you are seeking funding. This may seem
rather obvious, but the process for doing so is anything but simple.
You will also have to determine whether your research project will even qualify
for an NIH grant, and several factors influence that determination.
Then — before you write a single word of your application — you should map
out a strategy for it, which can include the following:
• Determining if the R01 grant mechanism is right for you.
• Picking a research project that you feel passionate about, yet which meets
NIH funding priorities at the same time.
• Choosing people with expertise and experience who can advise you as you
work on your application.
Next, you will need to more clearly define your proposed research project.
NIH has specific criteria for investigators it will support, and there are explicit
concepts every grant application must include to be considered. For instance, how
you formulate your project title and hypothesis can significantly influence your
research’s fundability.
Finally, you should develop a writing schedule to ensure that your grant
application meets NIH’s submission deadlines. There are several possible tactics
that you may use to help you.
Now, let’s walk through each of the steps.
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NIH R01 Grant Application Mentor: An Educational How-to Manual — 4th Edition
Chapter 1: Starting the Grant Application Process
QUALIFYING FOR AN NIH GRANT
You may have an amazing research idea that will shake the very roots of the
scientific world, but if it does not meet the requirements set out by the NIH and
its Institutes, Centers and Offices (ICOs), your application will not get past the
initial review.
First, every application topic must be consistent with the NIH mission statement:
“NIH’s mission is to seek fundamental knowledge about the nature and
behavior of living systems and the application of that knowledge to enhance health,
lengthen life, and reduce the burdens of illness and disability.”
The goals of the agency are:
• to foster fundamental creative discoveries, innovative research strategies, and
their applications as a basis for ultimately protecting and improving health;
• to develop, maintain, and renew scientific human and physical resources that
will ensure the Nation's capability to prevent disease;
• to expand the knowledge base in medical and associated sciences in order to
enhance the Nation's economic well-being and ensure a continued high return
on the public investment in research; and
• to exemplify and promote the highest level of scientific integrity, public
accountability, and social responsibility in the conduct of science.
In realizing these goals, the NIH provides leadership and direction to programs
designed to improve the health of the Nation by conducting and supporting research:
• in the causes, diagnosis, prevention, and cure of human diseases;
• in the processes of human growth and development;
• in the biological effects of environmental contaminants;
• in the understanding of mental, addictive and physical disorders; and
• in directing programs for the collection, dissemination, and exchange of
information in medicine and health, including the development and support
of medical libraries and the training of medical librarians and other health
information specialists.
9
Principal Investigators Association | www.principalinvestigators.org
NIH R01 Grant Application Mentor: An Educational How-to Manual — 4th Edition
Chapter 1: Starting the Grant Application Process
What this means:
The agency states that its goals include the following:
• Foster fundamental creative discoveries, innovative research strategies and
their applications as a basis for ultimately protecting and improving health;
• Develop, maintain, and review scientific human and physical resources that
will ensure the nation’s capability to prevent disease;
• Expand the knowledge base in medical and associated sciences to enhance
the nation’s economic well-being and ensure a continued high return on the
public investment in research; and
• Exemplify and promote the highest level of scientific integrity, public
accountability and social responsibility in the conduct of science.
As a result, NIH indicates that it will conduct and support research in the
following areas:
• Causes, diagnosis, prevention and cure of human diseases;
• Processes of human growth and development;
• Biological effects of environmental contaminants;
• Understanding of mental, addictive and physical disorders; and
• Directing programs for the collection, dissemination and exchange of
information in medicine and health, including development and support
of medical libraries and the training of medical librarians and other health
information specialists.
On the other hand, the agency would not fund projects like the following:
• Devising strategies to conserve water resources;
• Projects related to environmental pollution but unrelated to human health,
such as floating plastic debris in the ocean or carbon dioxide absorption by
concrete; and
TIP:
Review NIH’s
qualifying elements
and compare them
to your proposed
research idea to
make sure they
match up before
you move forward
with your grant
application.
• Research regarding dynamic water processes as they affect climate and
environmental change.
Consequently, your initial step must be to review the above qualifying elements
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NIH R01 Grant Application Mentor: An Educational How-to Manual — 4th Edition
Chapter 1: Starting the Grant Application Process
and compare them to your proposed research idea. If there is a good match, then you
should move forward with your grant application.
If your proposed research does not meet NIH mission or other requirements,
however, you should consider seeking a grant award from another source, such as
the National Science Foundation (NSF). For example, NIH might fund computermodeling research that seeks to predict the structure of cellular proteins and the
spread or containment of infectious diseases, such as avian flu. Whereas NSFsponsored research in math and computer modeling more likely would be used to
design a concert hall, simulate weather patterns and assemble an investment portfolio
that reduces risk and maximizes reward.
Institutes, Centers and Offices (ICOs) Also Weigh in
Next, you must consider that NIH is made up of 27 semiautonomous ICOs. And
each of these has its own defined research focus.
The NIH’s Center for Scientific Review (CSR) staff performs the initial review
of your grant application before assigning it to one of its review panels called Study
Sections, which are organized around specific scientific subject matter. Nonetheless,
you can suggest that a specific Study Section review your application, even though
the CSR has the final decision.
Of the 27 ICOs, the following accept R01 grant applications for investigatorinitiated research proposals:
National Cancer Institute (NCI, www.cancer.gov) — Through basic and
clinical biomedical research and training, the NCI conducts and supports
research regarding cancer prevention and/or manageability, early-stage
identification, innovative treatment development.
National Eye Institute (NEI, www.nei.nih.gov) — NEI conducts and supports
research that seeks to prevent and treat eye diseases and other vision disorders,
including sight-saving treatments, visual impairment and blindness reduction,
and quality-of-life improvements.
11 Principal Investigators Association | www.principalinvestigators.org
NIH R01 Grant Application Mentor: An Educational How-to Manual — 4th Edition
Chapter 1: Starting the Grant Application Process
National Heart, Lung and Blood Institute (NHLBI, www.nhlbi.nih.gov) —
NHLBI backs grants centered on treating diseases of the heart, blood vessels,
lungs and blood; blood resources; and sleep disorders.
National Human Genome Research Institute (NHGRI, www.genome.gov)
— Devoted to advancing health through genome research, the NHGRI supports
research aimed at expanding understanding of human biology and improving
human health.
National Institute on Aging (NIA, www.nia.nih.gov) — The NIA leads a
national research program regarding the biomedical, social and behavioral
aspects of the aging process; age-related disease and disability prevention; and
a better quality of life for older Americans.
National Institute on Alcohol Abuse and Alcoholism (NIAAA,
www.niaaa.nih.gov) — NIAAA focuses on research to improve the treatment
and prevention of alcoholism and alcohol-related problems.
National Institute of Allergy and Infectious Diseases (NIAID,
www.niaid.nih.gov) — NIAID’s research centers on understanding, treating,
and preventing infectious, immunologic, and allergic diseases.
National Institute of Arthritis and Musculoskeletal and Skin Diseases
(NIAMS, www.niams.nih.gov) — NIAMS supports research into the causes,
treatment, and prevention of arthritis and musculoskeletal and skin diseases; as
well as basic and clinical scientist training to carry out this research.
National Institute of Biomedical Imaging and Bioengineering (NIBIB,
www.nibib.nih.gov) — NIBIB promotes fundamental discoveries, design,
and development, and translation and assessment of technological capabilities
in biomedical imaging and bioengineering, enabled by relevant areas of
information science, physics, chemistry, mathematics, materials science and
computer sciences
Eunice Kennedy Shriver National Institute of Child Health and Human
Development (NICHD, www.nichd.nih.gov) — The NICHD supports child-
Principal Investigators Association | www.principalinvestigators.org
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NIH R01 Grant Application Mentor: An Educational How-to Manual — 4th Edition
Chapter 1: Starting the Grant Application Process
centered research regarding fertility, pregnancy, growth, development and
medical rehabilitation.
National Institute on Deafness and Other Communication Diseases (NIDCD,
www.nidcd.nih.gov) — The NIDCD conducts and supports biomedical research
and research training on normal mechanisms as well as diseases and disorders of
hearing, balance, smell, taste, voice, speech and language.
National Institute of Dental and Craniofacial Research (NIDCR, www.
nidcr.nih.gov) — NIDCR leads national research to understand, treat, and
prevent infectious and inherited craniofacial-oral-dental diseases and disorders.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK,
www2.niddk.nih.gov) — NIDDK conducts and supports basic and applied
research regarding diabetes, endocrinology and metabolic diseases; digestive
diseases and nutrition; and kidney, urologic and hematologic diseases.
National Institute on Drug Abuse (NIDA, www.nida.nih.gov) — NIDA’s
funding efforts focus on research across several disciplines to improve drug
abuse and addiction prevention, treatment and policy.
National Institute of Environmental Health Sciences (NIEHS,
www.niehs.nih.gov) — NIEHS seeks to define how environmental exposures,
genetic susceptibility and age interact to affect an individual’s health.
National Institute of General Medical Sciences (NIGMS, www.nigms.nih.
gov) — The NIGMS supports basic biomedical research that is not targeted to
specific diseases. NIGMS funds studies on genes, proteins and cells, as well
as on fundamental processes like communication with and between cells, how
our bodies use energy and how we respond to medicines. NIGMS also supports
research training programs for biomedical scientists and has special programs to
encourage underrepresented minorities to pursue biomedical research careers.
National Institute of Mental Health (NIMH, www.nimh.nih.gov) — NIMH
is dedicated to understanding, treating and preventing mental illnesses through
basic research on the brain and behavior, and through clinical, epidemiological
and services research.
13 Principal Investigators Association | www.principalinvestigators.org
NIH R01 Grant Application Mentor: An Educational How-to Manual — 4th Edition
Chapter 1: Starting the Grant Application Process
National Institute on Minority Health and Health Disparities (NIMHD,
www.nimhd.nih.gov) — NIMHD mission is to lead scientific research to
improve minority health and eliminate health disparities by evaluating all
minority health and health disparities research and activities of the NIH while
supporting research in minority health and health disparities.
National Institute of Neurological Disorders and Stroke (NINDS, www.
ninds.nih.gov) — NINDS’s mission is to support and conduct research,
both basic and clinical, on the normal and diseased nervous system, foster
investigators’ training in the basic and clinical neurosciences, and seek better
understanding, diagnosis, treatment and prevention of neurological disorders.
National Institute on Nursing Research (NINR, www.ninr.nih.gov) — NINR
awards grants for clinical and basic research to establish a scientific basis
for individual patient care, including patient management during illness and
recovery; risk reduction for disease and disability; promoting healthy lifestyles
and quality of life for those with chronic illness; and caring for those at the end
of life. This research may also include families within a community context,
and may focus on the special needs of at-risk and underserved populations,
emphasizing health disparities.
National Library of Medicine (NLM, www.nlm.nih.gov) — NLM conducts
and supports research in biomedical communications and provides grant
for training, medical library resources, and biomedical informatics and
communications research.
National Center for Complementary and Alternative Medicine (NCCAM,
www.nccam.nih.gov) — The NCCAM explores complementary and alternative
medicine (CAM) practices in the context of rigorous science and trains CAM
researchers.
Now, let’s look at how your particular research idea might fit into one of these
ICO’s coverage areas.
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NIH R01 Grant Application Mentor: An Educational How-to Manual — 4th Edition
Chapter 1: Starting the Grant Application Process
For example, if your proposal involves a potential new treatment for uterine
cancer, you would not look to the NINDS or NIDDK for funding opportunities.
Instead, a logical first step would be to examine possible grants sponsored by the NCI.
STRATEGY:
You can specifically
request in your
cover letter that
your application
be forwarded to a
particular ICO for
consideration. And
you can contact institutional program
officers at each
ICO for direction.
And if you are submitting a request for an R01 grant, you can specifically request in
your cover letter that your application be forwarded to the NCI for consideration.
Alternatively, if your research centers on asthma triggers in older adults, you
would likely request that NIAID review your grant application.
One tactic for selecting which ICO(s) might be the best fit is to contact specific
institutional program officers — frequently called POs — to assess their level of
enthusiasm for your research and how it might fit into any initiatives that group
might be considering. If you feel your proposal could fall under more than one
ICO, you can contact POs at each institute for direction.
How do you find a relevant PO for your proposal? Once you have selected the
ICO(s) that best fit with your proposed research, go to that group’s Web site. Once
there, you can review the staff directory to locate the appropriate PO. For example,
on the NAIAD site you can click on “Grants” under “Funding,” and there you will
find a link for “Grant Application.” Once there, you can clink on the “Contact Staff
for Help” link.
When you speak with the PO you have identified, you can request details
regarding possible topics for investigator-initiated research, such as the following:
• New scientific directions and opportunities, including published concepts (for
example, NIAID posts its Concepts: Potential Opportunities on its Web site,
www.niaid.nih.gov).
• Unpublished high-priority topics.
One way to approach this conversation is to schedule it beforehand and write
a brief, one-page or less lay explanation of your research and submit it to the PO.
This will prevent you from wasting meeting time trying to explain the finer points
of your proposal. This meeting is also a great time to make a friend of your PO,
making sure to consider any offered advice seriously.
15 Principal Investigators Association | www.principalinvestigators.org
NIH R01 Grant Application Mentor: An Educational How-to Manual — 4th Edition
Chapter 1: Starting the Grant Application Process
Your Institution Must Qualify for NIH Support as Well
In addition to your research qualifying for NIH support, your host institution
must also qualify.
In fact, NIH actually awards most grant types — including R01 grants — to the
institution rather than to the individual applying for the grant. Universities, small and
large businesses, and foreign institutions are among those that qualify for R01 grants.
On the other hand, NIH limits the eligibility for other types of grants. For
instance, foreign institutions may not apply for small business awards such as an
SBIR grant. Similarly, most federal organizations may receive NIH grants, but
those in the Public Health Services may get NIH funds only under exceptional
circumstances.
Keep in mind that although NIH grants primarily go to domestic institutions,
REMEMBER:
NIH actually
awards most grant
types — including
R01 grants — to
the institution
rather than to the
individual applying
for the grant.
you do not need U.S. citizenship or affiliation to become a principal investigator
for most grant types, including R01. You, however, must have U.S. citizenship for
a small business award, and you must be a U.S. citizen or a permanent resident —
that is, have an Alien Registration Card — for fellowships, career development
awards (with one minor exception) and training grants.
NIH also outlines the following requirements for foreign principal investigators
working on NIH-funded grants:
• If you are not a U.S. citizen but working at a U.S. institution, you must
remain there long enough to finish your project.
- If you do not have a permanent visa, state in your application that your visa
will allow you to remain in the United States long enough to be productive
on the project.
- Your institution must ensure that you have an appropriate visa.
• Persons from countries listed as State Sponsors of Terrorism cannot work
with any agent covered by the USA Patriot Act.
Additionally, when a foreign institution submits an application, NIH requires
additional steps to register for electronic application.
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Qualifying for an R01 NIH Grant
NIH supports scientists at various stages in their careers, from pre-doctoral
fellowships to investigators with extensive experience who run large research
centers. Nonetheless, the agency — as well as some of its ICOs — does have
minimal eligibility requirements for most research grants, including the R01.
Here are NIH’s criteria if you are seeking an independent research grant, such as
an R01:
• Hold an advanced degree appropriate to the research (in most fields, you
likely would need a Ph.D. or M.D.)
• Within your institution, hold a position or rank that allows you to apply for
such grants (often assistant professor or higher).
• Have a publication or patent record or a history of high-level research
supervision in the field in which you are applying.
• Work in a research institution that has the resources — meaning equipment
and lab space — you will need.
You must show the NIH peer reviewers that you can handle leading a major
research project. That means your grant application must clearly demonstrate
your expert qualifications, your institute’s commitment to you and your project,
and the independent space you will have by the time NIH or one of its ICOs
makes the award.
If you find that you do not meet NIH’s R01 qualifications, the agency offers
other funding mechanisms that might be more appropriate and prepare you
substantially for your first R01 opportunity. These can take the form of a Pathway
to Independence Award or New Innovator Award.
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MAP OUT YOUR PLAN
Understand that from the start that the grant application process takes a good
deal of time. Generally, experts recommend that you should plan to spend roughly
two months or longer preparing your R01 application. And if your research will
TIP:
require human or animal subjects, the preparation time could increase as much as
Experts
recommend that
you plan to spend
roughly two
months or longer
preparing your R01
application.
six months.
Even if your application flies through the review process on the first try and is
approved for funding, you likely will not see a penny of the award for another six
to 18 months.
Reviewers, however, may not approve an application on its first pass through
the process. And even with approval, you may not receive funding for your
proposal, depending on the amount of money available for approved applications.
And because NIH funds approximately 17 percent of the R01 and R01
equivalent applications it receives, and most applicants must revise and resubmit
their proposals. This means your award might not be forthcoming for as long as
28 months from the time you initially apply until you potentially receive funding
based on your resubmission.
Therefore, having a game plan for your application is a must.
Nail Down Your Strategy
The average NIH grant lasts three to five years. Consequently, one grant will
not fund your life’s work as a researcher.
As a result, you should look further down the road in your career. One option
is to plan your research goals for a longer period — for instance, the next 10 years.
Then you can divide your goals into segments that you can accomplish in three to
five years.
Suppose, for example, you choose to study methicillin-resistant Staphylococcus
aureus (MRSA). This is a broad topic, so you break your research into three grant
topics, each covering three years:
1. The contribution of gene regulation to DNA mutation, insertion, deletion
and rearrangement in MRSA.
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Chapter 1: Starting the Grant Application Process
2. The transfer of genes between Staphylococcus aureus strains that allow
them to become methicillin-resistant.
3. How to determine the specific genetic requirements that allow
Staphylococcus aureus to become methicillin-resistant.
This particular approach has three advantages:
• It keeps your research projects small and manageable. When applying for
a grant, you should propose an amount of work that you can do within the
time and resources you request. New investigators, in particular, frequently
propose too much in one application, and reviewers may reject their proposals
merely because there is an unreasonable amount of work involved.
• It forces you to consider your research in terms of maintaining your career,
which helps you to avoid the common pitfall of failing to get a renewal for
your project.
• This type of big-picture planning helps to keep you focused on your main
idea, as well as how you will pursue it for several years of funding.
Make Sure the R01 Is the Right Mechanism for You
As part of your grant application strategy, you must determine whether the R01
grant mechanism is right for your proposed area of research. As a first step, you
should speak with your identified PO and with experienced investigators in your
institution for their guidance. Another resource likely will be your institution’s
sponsored research office.
NIH offers hundreds of specialized award types with varying characteristics,
so if this is your first application, you should seek guidance in choosing your grant
mechanism. In addition, there are other issues that only add to the complexity:
• Not all ICOs participate in all the grant activity codes. For instance, most
ICOs use R01s, but there are several — such as the National Cancer Institute
— that do not use R03s (for small research programs).
• Different ICOs or initiatives may have different requirements even for
the same activity code. For example, AIDS-related R01 applications have
different deadlines than other R01s.
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• ICOs might use a certain grant type for only certain areas of science. For
instance, if your research involves platform development for drug discovery,
you might be required to use the R41 mechanism, which assists researchers in
commercializing innovative technologies, rather than an R01.
One strategy is to speak with a relevant PO at NIH who may help you focus
down on the grant mechanism that is right for your proposed research.
Specifically when requesting an R01 award, you should remember that these
provide three to five years of support to researchers who have preliminary data.
If you lack this, consider an exploratory/developmental research grant (R21) or a
small grant (R03) that will fund such efforts. The data you thereby obtain will then
support a later R01 application.
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STRATEGY:
Speak with a
relevant NIH PO
who may help you
focus down on the
grant mechanism
that is right for your
proposed research.
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Chapter 1: Starting the Grant Application Process
CHOOSE YOUR PROJECT
There are seven points you should consider when choosing your R01 research area:
1. Pick a research topic that will allow you to make a large impact on a
focused area. Your peer reviewers will examine your grant application to determine
how your research will advance the scientific field. In fact, this, along with your
project’s feasibility, likely will be the determining factors regarding your research’s
fundability. The more focused your project, the less likely it will overlap with another
application. Consider the following questions when selecting your topic:
• Can the research make a difference? For instance, will it open a new area of
discovery or develop a new approach to a significant problem?
• Will reviewers consider your research area to have the same priority that you
do? Get an unbiased opinion from a mentor or other trusted colleague.
• How will your idea stack up against NIH review criteria? We will examine
these criteria in later sections of this manual.
2. Define the current gaps and opportunities in your field. Carve out your own
research niche. Avoid crowded areas because making a difference will be more difficult
when you have more competitors. At the same time, find an interesting challenge that
you likely will be able to solve. Read the scientific literature so you understand the
current state of the problem(s) you want to address and what research to avoid because
it has already been accomplished. Also, brainstorm ideas with colleagues.
3. Be an expert. Perhaps obviously, you should choose a research topic within
TIP:
your area of expertise. Although you can recruit collaborators to fill experience
Write a single
sentence that
demonstrates
how your project
is well-focused,
makes an impact
and has a testable
hypothesis.
gaps, you should have first-hand knowledge of the science and most of the methods
related to your grant application. Reviewers expect you to be the expert in your
proposed investigational area, and this must be supported in your application.
Assess your strengths and how they match the requirements of potential projects.
4. Examine potential research areas at NIH. The R01 grant mechanism is
for investigator-initiated research, which allows you to select the topic. But you
should also review the priorities at the various ICOs to determine if your proposal
fits among their stated internally or forecasted research needs.
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5. Make sure your project is doable. Consider writing a single sentence that
demonstrates how your project is well-focused, makes an impact and has a testable
hypothesis. By limiting yourself to this format, this will help you determine if
you can truly accomplish your research goals within your award period and using
the level of resources that you might request. Also make sure that your science
relates to the cause, diagnosis, prevention or cure of human disease — which ties it
squarely to the NIH mission statement.
6. Get advice on your project’s merits. Obtain the NIH PO’s opinion
regarding your research idea. Speak with experts at your institution and other
colleagues to get their perspective concerning your proposed research’s impact.
Based on this input, rate the impact of your topic. If it scores poorly, refine your
idea or find another topic.
7. Look at your proposed topic through a reviewer’s eyes. Find the Study
Sections that likely would review your area of science, and identify three or more
members who would likely serve as your reviewers. Although these may not turn
out to be your actual reviewers, they likely will have similar expertise to those who
are. Review their published writings, and keep them in mind as you construct and
review your application. This will give you an idea of the how they might assess
your proposal.
Once you have worked through all seven of these points, you should be able
to distill your research topic into a sufficiently focused idea that will allow you to
develop your grant application more readily.
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Chapter 1: Starting the Grant Application Process
DEFINE YOUR PROJECT
When determining what your research project will entail, follow these steps to
help you stay on track:
TIP:
• Create a solid, testable hypothesis
Think of your
hypothesis as the
glue that holds
your application
together, and never
force a hypothesis
on experiments
that are not truly
hypothesis-driven.
• Write a provisional title
• Decide when to apply
Creating Your Hypothesis
Most successful grant applications start with a focused, testable hypothesis, and
your research design should be able to prove — or disprove — your hypothesis.
In fact, your application should ask questions that test your hypothesis rather than
indicate you are searching for a problem or simply collecting information.
Think of your hypothesis as the glue that holds your application together. The
results of your experiments and research will ultimately determine whether your
hypothesis is good science.
Also keep in mind that you should never force a hypothesis on experiments
that are not truly hypothesis-driven. A statement such as, “We hypothesize that a
comprehensive analysis of plasma protein in blood from patients with colon cancer
will reveal the presence of unique biomarkers,” is obvious and does not add to
your proposal. A better approach would be: “We hypothesize that by extending the
sensitivity of mass spectrometry-based proteomics to routine detection of proteins at
pg/ml concentrations with CVs less than 10 percent, we will enable the detection of
low-abundance proteins that are more likely to display specificity for colon cancer.”
In addition, you should explicitly state your specific, falsifiable hypothesis.
Regardless of whether you have a general, overarching one that covers the entire
proposal or a specific one for each research aim, there should be a hypothesis in
your application.
A vague statement such as, “We hypothesize that tumor tissues and normal
tissues from the same organ will have different patterns of gene expression,” is
useless. Instead, you should be more specific — for example, “We hypothesize
that tumor tissue will display a gene expression profile showing elevated
inflammatory responses.”
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Some experts even suggest keeping your research proposal so tightly focused that
you have only one hypothesis.
Research that tests a hypothesis is likely to give meaningful results, regardless
of whether the data support or refute the hypothesis. NIH generally prefers grant
proposals that have an impact on future research, and a testable, significant
hypothesis can provide that impact.
Write a Provisional Title
The next step is writing an initial or working title to further focus your research
idea and guide preparation.
Direct from NIH: The NIH Application Guide states:
Descriptive Title of Applicant’s Project
Enter a brief descriptive title of the project. This field is required (Part I:
Instructions for Preparing and Submitting an Application I-47PHS SF424 (R&R)
Adobe Forms Version C Application Guide).
A “new” application must have a different title from any other PHS project
submitted for the same application due date with the same PD/PI. A “resubmission”
or “renewal” application should normally have the same title as the previous grant
or application. If the specific aims of the project have significantly changed, choose
a new title.
A “revision” application must have the same title as the currently funded grant.
NIH and other PHS agencies limit title character length to 200 characters,
including the spaces between words and punctuation.
What this means:
You will finalize your title after completing your application. All reviewers
will read it, so it must be informative. It may even color perception of your entire
submission. At the same time, the NIH grant application limits your title to 200
characters, including letters, numbers, spaces and any punctuation.
REMEMBER:
NIH limits your title
to 200 characters,
including letters,
numbers,
spaces and any
punctuation.
The title is your first chance to win over reviewers with an innovative, creative
idea that they will want to champion for funding. Consequently, a title that stands
out from others and virtually compels reviewers to read your application gives you
one more advantage.
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By the way, keep in mind that — far from the niches of science — companies
struggle to condense powerful advertising messages into terse phrases. For
example, “Coke is it” or “A diamond is forever.” Even newspaper headline writers
grapple with this challenge.
Therefore, your title is a significant piece of information that must be a
unique, relevant and intriguing description of your research plan that conveys the
following:
• What you will do
• How you will do it
• What the results will be
Because NIH wants to fund work that can seriously impact society and advance
science, you should point to the outcome of your research in the title.
Keeping all this in mind, here are 13 tips for creating successful titles:
1. Be original and relevant. Make sure your title differs from those of already
submitted applications or from funded research. NIH wants fresh, innovative
projects. You can review databases of existing applications and awards at www.
projectreporter.nih.gov and contact the appropriate NIH scientific review officer to
ensure that your title is not redundant or closely similar to another.
2. Be accurate and use agency-friendly keywords that help officials direct
your proposal to the appropriate study section. For example, using “epidemiology
of” in the title will help the reviewer route the application to an epidemiology
study section, such as the Neurological, Aging and Musculoskeletal Epidemiology
(NAME) Study Section.
3. Find out which themes are mission-relevant, priority areas for
research, or emerging as future priorities. Decision-makers at NIH seek advice
from many sources when setting research priorities, including the scientific
community at-large, federal advisory councils, individual researchers, professional
societies, patient organizations, and voluntary health associations. Areas which
continue to receive attention include cancer, HIV/AIDS, pediatric and adult obesity,
and aging related topics. Recent emphasis across the NIH has been the Brain
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Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative,
as evidenced by their announcement of its first wave of investments totaling $46
million in fiscal year 2014 funds (http://www.nih.gov/news/health/sep2014/od-30.
htm). Since each individual IC sets its own priorities based on the input it receives,
it is best to check each one for their most current areas of emphasis.
4. Use results-driven words instead of those that describe your process. For
example, from funded R01 applications:
• Age Related Change in Mitochondrial Angiotensin System and Mitochondrial
Decline
• Microfluidic Immunoprofiling for Biomarker Discovery in Rheumatoid
Arthritis
• Preclinical Analyses of Advanced Prostate Cancer in Genetically-Engineered
Mice
You will notice that all of these titles conform to the previous descriptive title
character limit of 81 characters. The new 200 character limit will be reflected in
R01 submissions beginning in October 2014.
5. Be authoritative. That means that you should let reviewers know that
you know what you are talking about. For instance, if your research focuses
on developing nuclear magnetic resonance methods to visualize sequence and
damage-specific DNA flexibility at the atomic scale in the presence and absence of
supercoiling, your grant title could be “Dynamics of Normal and Damaged DNA
Under Relaxed and Supercoiled Conditions.”
6. Keep NIH criteria in mind, including significance, innovation,
investigators, approach and environment. For instance, “DNA Replication Control
and Its Application to Selective Killing of Cancer Cells,” can show significance,
approach and innovation.
7. Use plain language. Consider the simple, direct and economical use
of the words that make up this successful grant proposal title: “Public Health
Preparedness and Response for Bioterrorism.” Alternatively, a wordy, awkward and
dramatic way of saying the same thing might be “Will Public Health Authorities Be
Ready When and If the Horrors of Bioterrorism Unfold in Their Cities?”
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8. Follow the rules. As stated earlier, the NIH application limits title length
to 200 characters. If yours is longer, it will be cut off at the 201st character, which
could strip away the meaning and impact carried by the deleted words.
9. Use active, forward-thinking verbs, such as “defining,” “improving”
or “development,” that tell readers your project points to results. For example,
consider the following from awarded R01 apllications::
• Defining Mechanisms and Targets in WNT Addicted Human Malignancies
(PQ22)
• Improving Network Analysis and Visualization for Infectious Disease Control
• Development of Goggle System for Fluorescence Image-Guided Surgery
10.View your title as a work in progress. Your final title may differ from
your initial one because a proposal’s specifics typically change during the writing
process. Finalize your provisional title when you have completed the application.
11.Get input from peer scientists and individuals outside your field,
preferably an English professor or an editor for proofreading and language use.
Colleagues with grant-writing experience can be especially helpful.
12.If you are resubmitting, keep your proposal’s original title so that
agency officials easily recognize it and look for the changes that you have made.
13.Proofread your title before you hit the “send” button. Do not rely on your
spell-checking program. Instead, use a dictionary because terminology must be
spelled correctly. A seemingly insignificant error could destroy your chances of
winning funding.
Finally, remember that NIH uses your title — as well as your abstract — to
assign your application to a study section and institute for review. The agency
also uses it to report your research dollars to Congress. So your title plays a vital
role not only in the review process, but also throughout the life of your research
and grant.
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NIH R01 Grant Application Mentor: An Educational How-to Manual — 4th Edition
Chapter 1: Starting the Grant Application Process
Deciding When to Apply
NIH has three annual deadlines for submitting applications for new R01
grants: Feb. 5, June 5 and Oct. 5. For renewal R01 applications, these dates shift
to March 5, July 5 and Nov. 5. And if you are submitting an AIDS or AIDS-related
R01 application, there are different deadlines: Jan. 7, May 7 and Sept. 7. At the
same time, if your proposal is a response to an ICO’s special request for a specific
research topic, the ICO can choose a special deadline at its discretion, which you
can find on the ICO’s Web site.
R01 Type
Grant Cycle 1 Deadline Grant Cycle 2 Deadline Grant Cycle 3 Deadline
New Grant Application
Feb. 5
June 5
Oct. 5
Renewal Grant Application
March 5
July 5
Nov. 5
AIDS/AIDS-related
May 7
Sept. 7
Jan. 7
Grant Application
REMEMBER:
NIH uses your
title and abstract to
report your
research dollars to
Congress.
Tactically, many researchers wonder if they should target a particular deadline
because the competition might not be as great at that time of year.
Officially, NIH maintains that you should submit your grant application based
upon the quality of the science rather than perceived differences in funding success
rates during the various grant cycles. An outstanding proposal will always attract
strong consideration regardless of what time of year you submit it.
Therefore, you should submit your application as soon as your ideas are fully
developed, capable of being clearly presented and well supported by convincing
preliminary data.
That said, if your grant proposal scores near the percentile cutoff point for
funding, timing can make a difference. But this situation does not represent a
substantially better success rate.
Note: The deadlines above are accurate as of October 2014. Changes may
occur, however, and you should reconfirm your various deadlines for the grant
cycles relevant to your application.
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Chapter 1: Starting the Grant Application Process
CREATE A WRITING SCHEDULE
Now that you have developed a provisional title and hypothesis, you can
establish a writing schedule to ensure that your application is ready to submit
before one of the grant cycle deadlines.
There is a great deal of information to accumulate, digest and then integrate
into your application, and this will take time. The last thing you want is to submit
a grant proposal that is incomplete, sloppy or shortsighted because you ran out
of time. As part of your writing schedule, consider other responsibilities that you
currently have, such as teaching, lab duties, personal obligations, etc.
NIH suggests allowing at least two months for planning and writing your grant
application, at least one month to get feedback on it, and then two weeks for final
STRATEGY:
reviewing and proofreading before submitting it. Of course, the more complex your
Allow at least two
months for planning and writing
your grant application, at least
one month to get
feedback on it, and
then two weeks for
final reviewing and
proofreading before
submitting it.
proposed research, the longer each stage of the process will take. Some experts even
caution that preparing and writing your application can take as long as six months.
Consequently, you should set up a timetable for getting each section of the
application completed and ready for review. For example:
Task
Research field of interest to narrow research topic to manageable subject for application
Review NIH Institutes and Centers for potential matching research focus
Formulate hypothesis
Create provisional title for grant proposal
Submit hypothesis and title to colleagues for review and feedback
Prepare Significance statement for Research Strategy section
Prepare Innovation statement for Research Strategy section
Outline Specific Aims section
Etc.
Due Date
Once you have outlined your writing schedule, your last few tasks should
involve assembling your application materials, having the packet reviewed by
trusted colleagues (including a proofreader as well as those familiar with the
science) and final submission before the deadline.
As you go through each task, do not attempt to make each section perfect on
your first pass. Think of this stage as a work in progress. Once you have all the
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Chapter 1: Starting the Grant Application Process
application sections completed in this rough-draft format, you can review the
entire package as a whole, editing and rewriting to make sure that the sections
flow more coherently. Then submit it in final form.
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Chapter 1: Starting the Grant Application Process
CONCLUSION
Once you have worked through the planning stages to clearly define your
research project, choose your team, formulate your title and hypothesis, and
develop your writing schedule, you will have laid the groundwork for writing a
potentially successful R01 grant application. Moving forward, you will know your
deadline to ensure your application arrives at NIH on time, as well as all the steps
that must occur in the interim.
The more time and effort you put into your planning process, the more effective
it will be and the more smoothly your proposal writing will be. Every grant
application requires a great deal of information, work and time, and planning ahead
only helps you to stay focus on your goals. n
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NIH R01 Grant Application Mentor: An Educational How-to Manual — 4th Edition
Chapter 2: Outlining Your Project and Individual Qualifications
Chapter 2:
Outlining Your Project and
Individual Qualifications
There are specific sections of the National Institutes of Health’s (NIH’s) R01
grant application that allow you to outline your research topic and direction.
As you approach these areas, think of yourself as a storyteller. You are trying
to get the reviewers emotionally involved to the point that they champion your
proposal. All good stories have a resolution. Yours will be how your research will
advance the scientific field and enable future investigations.
Your story begins with a Project Summary/Abstract, which is a brief yet detailed account of your proposed research. This section is important because initial
NIH reviewers will use it to determine the study section that reviews your application. In addition, the Project Summary is the only section of your proposal that every reviewer reads. Most of them will scan the rest of your application, but they all
read your Abstract in its entirety.
This chapter tells you what to include and what to leave out of your Project
Summary. It also details NIH guidelines pertaining to Abstracts — such as the
maximum number of pages — and gives you examples that illustrate what NIH
wants to see.
We also examine the Biographical Sketch section, which is more than a simple
biography of the principal investigator (PI). There are ways you can creatively use
this area to increase your chances of successfully obtaining funding.
The Biographical Sketch section must include a personal statement, an account
of the PI’s positions and honors, a list of peer-reviewed publications or manuscripts
in press, and research support. This chapter describes each of these elements and
how to effectively include them in your Biographical Sketch.
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Chapter 2: Outlining Your Project and Individual Qualifications
In addition, we explore the requirements for proposals with multiple PIs. You
must provide a rationale for using this approach and a description of your plans for
making it work. This chapter includes examples of appropriate documentation for
applications with multiple PIs.
The chapter also explains how letters of support can help new investigators
applying for an R01 grant. It offers suggestions for the type of individual to provide
a letter of support, clarifies why you should write the first draft of the letter for
these individuals, and includes tips for crafting effective support letters.
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Chapter 2: Outlining Your Project and Individual Qualifications
FORMULATING YOUR PROJECT SUMMARY/ABSTRACT
Direct from NIH: The NIH Application Guides states:
Project Summary
The Project Summary must contain a summary of the proposed activity suitable
for dissemination to the public. It should be a self-contained description of the project
and should contain a statement of objectives and methods to be employed. It should
be informative to other persons working in the same or related fields and insofar
as possible understandable to a scientifically or technically literate lay reader. This
Summary must not include any proprietary/confidential information.
The Project Summary is meant to serve as a succinct and accurate description of
the proposed work when separated from the application. State the application’s broad,
long-term objectives and specific aims, making reference to the health relatedness
of the project (i.e., relevance to the mission of the agency). Describe concisely the
research design and methods for achieving the stated goals. This section should
be informative to other persons working in the same or related fields and insofar
as possible understandable to a scientifically or technically literate reader. Avoid
describing past accomplishments and the use of the first person. Finally, please make
every effort to be succinct. This section must be no longer than 30 lines of text, and
follow the required font and margin specifications. An abstract which exceeds this
allowable length may be flagged as an error by the agency upon submission. This
would require a corrective action before the application will be accepted.
As noted above, do not include proprietary, confidential information or trade
secrets in the description section. If the application is funded, the Project Description
will be entered into an NIH database and made available on the NIH Research
Portfolio Online Reporting Tool (RePORT, available at http://report.nih.gov) and will
become public information.
The attachment must be in PDF format. (See Section 2.6 for additional
information on preparing attachments.)
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What this means:
NIH states that your Project Summary/Abstract should be “a succinct and
accurate description of the proposed work when separated from the application.”
Further, “it should be a self-contained description of the project and should contain
a statement of objectives and methods to be employed.” It should also outline your
application’s broader, long-term goals and specific aims, as well as reference how
your proposed research relates to human health, NIH says.
The agency also indicates that your intended audience for this section includes
those “working in the same or related fields and insofar as possible [this section]
should be understandable to a scientifically or technically literate lay reader.” You
can expect all of the peer reviewers to read this portion of your grant application.
At the same time, NIH warns that you should not include any proprietary or
confidential information or trade secrets in the Project Summary. If you proposal
receives funding, the summary becomes part of the public record.
Format Note: The Project Summary can be no longer than 30 lines of text.
You must use the Arial, Helvetica, Palatino Linotype or Georgia font in black
at 11 point size or larger. You may use a symbol font to insert Greek letters or
special characters, but the font size requirement still applies. In addition, there
can be no more than 15 characters — including characters and spaces — per
inch. And there can be no more than six lines of text per inch, using at least halfinch margins on all sides of the 8½” x 11” page.
Keep in mind that initial reviewers in the Center for Scientific Research (CSR)
likely will use the Project Summary/Abstract to assign your application to a
particular Scientific Review Group (SRG) or study section, as well as to the peer
reviewers who will examine it. Therefore, it should contain certain keywords so
that SRG staff can readily assign your application and NIH computer systems can
retrieve your grant properly. And SRG members who are not primary reviewers
probably will rely heavily on your summary to understand your proposal during the
group’s general meeting to discuss application fundability.
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Many grant-writing experts suggest that you write your Project Summary/
Abstract last as you construct your application materials. They maintain that this
allows you to gain a more comprehensive understanding of your research proposal.
If you choose to write your Summary/Abstract early, you should consider it
provisional and revisit it after you finish writing the rest of your application —
especially the research plan — to make sure it is a true reflection of your proposal.
One rationale for writing a provisional Summary/Abstract early is to make sure
that your proposal’s main ideas are clear and concise in your mind. Once you have
written the rest of your application materials, go through them with a highlighter
(or the electronic equivalent), and mark all of the key terms that are important to
understanding your research. Then revisit your provisional Abstract to make sure
every keyword that you highlighted appears in a faithful context.
What to Include
STRATEGY:
Many grant-writing
experts suggest
that you write your
Project Summary/
Abstract last as
you construct
your application
materials.
Each of NIH’s Institutes, Centers and Offices (ICOs) appears to have a slightly
different idea regarding what you should include in this relatively brief description
of your proposed research.
For example, the National Cancer Institute (NCI) indicates that your Project
Summary should incorporate the following:
•A brief background of the project;
•Specific aims, objectives or hypotheses;
•Significance of the proposed research and relevance to public health;
•Unique features and innovation of the project;
•Methodology (action steps) to be used;
•Expected results; and
•Description of how your results will affect other research areas.
In addition, NCI indicates that the Abstract should succinctly describe every
major aspect of the project except the budget. And it should have a distinct section
that describes its relevance to public health.
NCI also offers the following suggestions regarding your Project Summary/
Abstract:
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•Be complete, but brief.
•Use all of the space allowed (30 lines of text).
•Avoid describing past accomplishments and using the first person.
•Write the abstract last so that it reflects the entire proposal.
•Remember that NCI and NIH will use the abstract for purposes other than
the review, such as to provide a brief grant description in annual reports,
presentations and public dissemination.
The National Institute for Allergy and Infectious Diseases (NIAID), on the
other hand, offers different —and quite specific — instructions along with a few
similarities:
•In the first sentence, describe the significance of your research to your field
and relevance to NIAID’s mission: to better understand, treat, and prevent
infectious, immunologic, and allergic diseases.
•Next, state your hypothesis and your research’s innovative potential.
•Describe your Specific Aims and long-term objectives.
•Don’t include graphs or images.
So be sure to examine your potential reviewing institutes’ Project Summary
requirements before you finalize this portion of your grant application.
Use Storytelling Tactics to Engage Reviewers
Most reviewers make up their minds regarding your proposal’s merit as they
read the first page of your application, according to principal investigators who
have served in such roles. And they read the rest of your application looking to
support their original impression.
Consequently, the quicker you grab their attention, the more likely you will
engage them to support your proposal.
Your Project Summary/Abstract should present the opening chapter of your
story, offering a short description of what the reader will find in the narrative.
Therefore, the Summary should be a faithful, although condensed, replica of
the narrative. NIH reviewers indicate that applicants often submit Abstracts that
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contain ideas found nowhere in the application’s body, or Summaries that fail to
include important ideas that do appear in the main sections.
As stated earlier, reviewers use the Project Summary/Abstract to prepare
themselves to intelligently read the application as a whole. Therefore, if the
Abstract is an unfaithful map, they are like drivers heading into one state while
holding a map of another.
A good place to begin your abstract is to get your reviewers’ attention answer
four questions:
1.What is the problem or need that your proposal will address?
2.Why is it so important that it must be resolved? In other words, what is the
REMEMBER:
The Summary
should be a
faithful, although
condensed, replica
of the narrative.
significance?
3.Why are you the only person or group, or best-suited one, who can resolve
the problem or need?
4.What is your proposed solution to address the problem?
Look to Project Summary/Abstract Examples
Example 1: NIAID offers the following outstanding example from an actual
grant application broken down by the elements NIAID indicates are important for
its applications:
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Proposal Title: Mechanisms of Integrin-Mediated Costimulation in T Cells
NIAID-
Abstract
Significant
Topics
Significance of
The integrin 1421 (VLA-4) contributes to the etiology
the proposed
of common autoimmune disorders, including multiple
research
sclerosis, inflammatory bowel disease, and systemic lupus
erythematosus. Although VLA-4 is widely viewed as
contributing to T cell function by directing cell trafficking
and by enhancing cell adhesion, VLA-4 potently costimulates
T cell activation.
The mechanisms underlying this costimulation are not well
understood and may play a significant role in the etiology of
human immune disorders.
Our long-range goal is to understand how to manipulate the
costimulatory functions of VLA-4 in order to regulate T cell
activation in vivo. Our immediate objective is to determine
how VLA-4 modulates T cell responses to antigen.
Here, we present preliminary data characterizing a previously
unknown effect of VLA-4 ligation on the movement of
signaling complexes induced by the TCR. Our specific
hypothesis is that structures containing SLP-76 and ADAP
are required for the transmission of tension-dependent
Innovation and
costimulatory signals initiated upon VLA-4 ligation.
The rationale for the proposed work is that it will provide an
unique features of enhanced understanding of the fundamental mechanisms that
the proposal
enable the integration of the signaling pathways downstream
of the TCR and VLA-4.
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NIH R01 Grant Application Mentor: An Educational How-to Manual — 4th Edition
Chapter 2: Outlining Your Project and Individual Qualifications
Methodology or
Three aims will examine how ADAP contributes to T cell
specific aims
costimulation and how cytoskeletal tension contributes to
VLA-4 dependent costimulatory signals:
1. How does ADAP contribute to the assembly and
translocation of SLP-76 microclusters?
2. How does costimulation depend on the VLA-4dependent immobilization of microclusters?
3. How does cytoskeletal tension contribute to T cell
Re-emphasis of
costimulation by VLA-4?
These studies explore a novel effect of VLA-4 ligation, the
the proposal’s
lateral immobilization of TCR-induced complexes, and use it
innovation
as a tool to dissect the pathways involved in costimulation by
VLA-4. We expect these studies to define the mechanisms by
which VLA-4 ligation costimulates T cell activation.
This will have a positive impact on our understanding of
autoimmune disease, and will assist in the identification of
unique intracellular targets for drug development. This work
will also generate insights into the systems linking cell shape
to cell growth and proliferation, providing useful insights into
cancer.
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Chapter 2: Outlining Your Project and Individual Qualifications
Example 2: NIAID again breaks down the Abstract by the elements it indicates
are important:
Proposal Title: T Cell Epitope Mimicry for Autoimmune Responses in SLE
NIAID-Significant Abstract
Topics
Significance of the
Systemic lupus erythematosus (SLE) is a complex,
proposed research
autoimmune disorder predominantly affecting young
females. Despite being multigenic, the HLA complex
in general and HLA-DR in particular remains the most
Innovation and
dominant genetic risk factor for disease susceptibility.
A striking feature is the strong association of autoantibody
unique features of
specificities with some HLA haplotypes. This application
the proposal
addresses the mechanisms for this close association.
In this application we will test the hypotheses that in lupus
patients, molecular mimicry with microbial peptides is
responsible for the selective enrichment of T cells reactive
with lupus-associated autoantigens.
Depending on microbial exposure, the HLA dictates the
nature of cross-reactive peptides it binds and thereby the
autoantigen selection. This process leads to activation of
self-reactive T cells, autoantibody production, epitope
spreading and end organ damage.
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Chapter 2: Outlining Your Project and Individual Qualifications
Methodology or
Using Ro60 as the candidate autoantigen and HLA-DR and
specific aims
-DQ transgenic mice, following specific aims are proposed
to seek evidence for our hypothesis:
1. To identify the molecular mimics of T cell epitopes
on Ro60.
2. To demonstrate that multiple exposures to peptide
mimics of Ro60 T cell epitopes influences the Ro60
reactive T cell repertoire.
3. To determine the pathogenic potential of anti-Ro60
initiated autoimmune responses in lupus-prone
NZM2328 mice transgenic for HLA-DR3 and -DQ2.
The findings from this application will clearly demonstrate
that T cell responses to lupus-associated antigens can
Re-emphasis of
initiate autoimmune responses in SLE.
This will shift the current paradigm that SLE is
the proposal’s
predominantly a B cell mediated disease to a more rational
innovation
model in which both T and B cells have their unique roles
in disease manifestation. This will provide a theoretical
framework from which rational therapeutic approach can
be devised.
Based upon NIAID’s examples, we reviewed NCI’s Project Summary/Abstract
requirements and compared them to actual award-winning grant applications. The
following examples are the result of that evaluation.
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Example 3: This one correlates NCI’s key elements to the actual Abstract
language:
Proposal Title: Molecular Interactions and Restoration Strategies of PTEN and
P53 in Gliomas
NCI-Significant
Abstract
Topics
Brief background
PTEN and p53 are the most frequently mutated tumor
suppressors in human cancer, including gliomas. Recent
evidence shows that wild-type PTEN and wild-type
p53 (wt-p53) enhance each other’s tumor suppressive
functions. Wt-p53 induces PTEN gene transcription and
wt-PTEN protects wt-p53 protein from degradation.
We recently found, for the first time, that PTEN has
unexpected tumor promoting properties in some glioma
cells and tumor xenografts. We have preliminary
evidence that PTEN acquires these unexpected tumor
promoting properties by enhancing the half-life and
oncogenic effects of gain-of-function p53 mutants
Specific aims,
(mut-p53).
Based on these findings, we formulate the following
objectives, or
novel hypothesis: PTEN tumor suppressor can exhibit
hypotheses
tumor promoting properties in the setting of gain-of-
Significance of the
function mut-p53.
Therefore, therapeutic strategies that aim at restoring
proposed research and PTEN expression or function could lead to varying
relevance to public
effects that depend on the mutational status of p53.
health
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Methodology
Chapter 2: Outlining Your Project and Individual Qualifications
To test this hypothesis and its prognostic, mechanistic,
functional and therapeutic implications, we propose the
following studies:
• In aim #1, we will use a large number of banked
human glioblastoma specimens to determine the
association between the combined PTEN/p53
mutational status and clinical outcome.
• In aim #2, we will investigate the mechanism
through which PTEN regulates mut-p53 protein
levels and function.
• In aim #3, we will assess the in vivo effects of
restoring PTEN to glioma tumors with varying
p53 mutational status.
• In aim #4, we will determine if small molecule
modulators of p53 can reverse the tumor
promoting effects of PTEN in mut-p53 cells and
tumors.
The results from all aims will be assessed for their
consistency with the hypothesis.
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Expected results
Chapter 2: Outlining Your Project and Individual Qualifications
Successful completion of the studies proposed in this
application would:
1. establish the combined PTEN/p53 status as a
prognostic parameter (aim 1),
2. uncover previously unknown mechanistic and
functional interactions between PTEN and
mut-p53 (aim 2),
3. determine conditions and strategies for a
successful therapeutic restoration of PTEN (aim
3), and
4. have important clinical implications for the use of
small molecule modulators of p53 by identifying
a subset of tumors that are more sensitive to
these drugs and providing a rationale for their
45 How results will
combination with PTEN restoration (aim 4).
The findings will have important implications on
affect other research
determining patient prognosis and developing new
areas
therapies against human cancers.
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NIH R01 Grant Application Mentor: An Educational How-to Manual — 4th Edition
Chapter 2: Outlining Your Project and Individual Qualifications
Example 4: Here, you can see how the Principal Investigator clearly connected
the NCI’s key elements to her actual Abstract language:
Proposal Title: HER3 Signaling in Development and Cancer of the Breast
NCI-Significant
Abstract
Topics
Brief background
The ErbB family of receptor tyrosine kinases includes
EGFR, ErbB2/HER2, ErbB3/HER3 and ErbB4/HER4.
Abundant evidence supports the causal role of HER2
overexpression in up to 25% of all breast cancers. While
HER3 lacks intrinsic kinase activity, HER3 is often
overexpressed in breast cancers that overexpress HER2.
Heterodimerization of HER2 with HER3 increases
proliferation, survival, and transformation of breast cells.
Tyrosine-phosphorylated HER3 potently engages the
phosphatidylinositol-3 kinase (PI3K)/Akt pathway, which
increases tumor cell proliferation and survival.
Inhibitors of HER2 such as the monoclonal antibody
trastuzumab and the dual EGFR/HER2 tyrosine kinase
inhibitor (TKI) lapatinib are currently approved for
treatment of HER2-overexpressing metastatic breast
cancer. However, many breast cancers with HER2 gene
amplification do not respond and/or eventually escape
Specific aims,
trastuzumab and lapatinib.
It is our hypothesis that 1) signaling by HER2:HER3
objectives, or
heterodimers is essential for mammary tumorigenesis,
hypotheses
and 2) HER3 expression enhances tumor cell survival,
Significance of the
rendering tumors resistant to therapies that target HER2.
According to these hypotheses, HER2-positive breast
proposed research
tumors would be less frequent and less malignant in the
and relevance to
absence of HER3, and therapeutic antibodies targeting
public health
HER3 may prevent or reverse trastuzumab or lapatinib
resistance.
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Unique features and
These results would support the development of
innovation of the
treatments targeting HER3 and its downstream effectors
project
as alternative or adjuvant therapy for patients with HER2-
Methodology
positive breast cancers.
We have designed experiments testing this hypothesis,
using a novel genetic approach to conditionally eliminate
ErbB3 (endogenous mouse HER3) expression specifically
in the mammary epithelial cells (MECs) of mice.
•In Aim 1, we will determine if HER3/ErbB3 is required
for development of the mammary epithelium. We will
use mice harboring MEC-specific loss of ErbB3 to
examine mammary glands at each stage of post-natal
mammary gland development. These studies will reveal
the role of HER3/ErbB3 in untransformed MECs that
may ultimately contribute to transformation.
•Experiments in Aim 2 will determine if HER3/ErbB3
is required for mammary tumorigenesis in vivo. We
will use genetically engineered mouse models of
HER2-driven and HER2-independent breast cancers to
determine if ErbB3 is required for their formation and
malignant progression.
•Aim 3 will determine if HER3 inhibition (genetic and
pharmacologically) sensitizes HER2 overexpressing
breast cancer cells to anti-HER2 therapies. Mice
bearing HER2-overexpressing breast cancers will be
treated with monoclonal antibodies targeting HER3 in
Expected results
combination with lapatinib and trastuzumab.
In summary, the experiments outlined in this proposal
will provide the necessary knowledge with which to
determine if selective targeting of ErbB3 might be an
alternative choice for advanced therapy tailored to HER2overexpressing breast cancers, as well as those that do not
overexpress HER2.
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Chapter 2: Outlining Your Project and Individual Qualifications
KEEP YOUR PROJECT NARRATIVE BRIEF
Direct from NIH: The NIH Application Guides states:
Project Narrative
Provide Project Narrative in accordance with the announcement and/or agencyspecific instructions. Please click the Add Attachment button to the right of this
field to complete this entry.
For NIH and other PHS agencies applications, using no more than two or
three sentences, describe the relevance of this research to public health. In this
section, be succinct and use plain language that can be understood by a general, lay
audience.
If the application is funded, this public health relevance statement will be
combined with the project summary (above) and will become public information.
A separate Research Plan form is required for NIH and other PHS agencies
applications. Refer to Section 5.5, Research Plan Form, for separate file uploads
and instructions.
What this means:
Where the Project Summary/Abstract is 30 lines of text targeted toward
scientists in the same field, the Project Narrative is much shorter and serves a
completely different purpose, NIH maintains.
The agency states the Project Narrative should be no more than two or three
sentences describing your proposed research’s relevance to the public health
arena. In addition, “in this section, be succinct and use plain language that can be
understood by a general, lay audience.”
The NIH RePORTER online grant award reporting tool often refers to the
Project Narrative as the “Public Health Relevance Statement.” It appears below —
and frequently as part of — the Project Summary/Abstract in the RePORTER tool.
As such, the Project Narrative will be part of the public record.
NIAID makes the following suggestions for constructing your Project
Narrative:
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•In lay language, describe your project’s potential to improve public health in
two or three sentences.
•Don’t include graphs or other images.
Also, like the Project Summary/Abstract, many grant-writing experts suggest
TIP:
Use lay language
in your Project
Narrative to
describe your
project’s potential
to improve public
health in two or
three sentences.
writing the Project Narrative after you have completed the bulk of your application.
They reason that — at that point — you will have a clearer picture of your
proposal’s scope and how it impacts public health.
Look at These Examples
With all this in mind, use the following examples of Project Narratives taken
from successful NIH grant applications:
Example 1:
Proposal Title: p90RSK: A Flow Responsive Mediator of Inflammation
Project Narrative: The role of inflammation in cardiovascular disease and
diabetes has become increasingly evident. At the basic science level understanding
the specific signaling events involved in these mechanisms is a key issue that will
be addressed here by biochemistry, cell biology, and in vivo transgenic mice. These
studies should provide insight into mechanisms by which disturbed flow promotes
vascular inflammation and facilitate development of new therapeutic approaches to
limit atherosclerosis, especially in DM.
Example 2:
Project Title: Capsid-Targeting HIV-1 Antivirals
Project Narrative: Effective treatment of HIV/AIDS requires the development
of novel antiviral compounds that can complement the existing drug arsenal. This
research project will define the mechanism of antiviral compounds acting on a
novel HIV-1 target — the capsid. The studies proposed herein will facilitate the
development of novel therapies and help elucidate the stage of HIV-1 infection
termed uncoating.
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Chapter 2: Outlining Your Project and Individual Qualifications
Example 3:
Project Title: Signaling Mechanisms in Regulation of Tumor Angiogenesis
Project Narrative: Cancer is currently one of the most prevalent causes
of death in the U.S.A., and current therapeutic options aim only to slow the
progression of cancer. Therefore, a renewed effort must be made to identify
nontoxic endogenous circulating anticancer molecules which could be exploited as
therapeutic targets. My laboratory has cloned and expressed one such circulating
molecule, and is presently testing it in a cell culture system and in live mice having
tumors. The data being developed from these proposed studies have potential
applications to cure solid tumor growth (cancers) in which angiogenesis contributes
to the disease phase.
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USE ALL THE PARTS OF THE BIOGRAPHICAL SKETCH
Direct from NIH: The NIH Application Guides states:
Provide a biographical sketch for the senior/key person. Recommended
information includes: Education and Training, Research and Professional
Experience, Collaborators and Affiliations (for conflicts of interest), Publications
and Synergistic Activities. Save the information in a single file and attach here.
This is required information. The Guide then further states:
Use the sample format on the Biographical Sketch Format Page to prepare this
section for all (modular and other) grant applications. The Biographical Sketch
may not exceed four pages per person. This 4-page limit includes the table at the
top of the first page. See the sample of a completed Biographical Sketch.
What this means:
NIH limits the Biographical Sketch — also known as the Biosketch — to
no more than four pages per person and provides a form for presenting this
information. Your application must include a complete Biosketch for all Senior/
Key Personnel and Other Significant Contributors.
NIH defines Senior/Key Personnel as the Project Director (PD)/Principal
REMEMBER:
The Biosketch is
your opportunity
to detail your
knowledge, skills
and ability to
perform your
proposed research.
Investigator (PI) “and other individuals who contribute to the scientific
development or execution of the project in a substantive, measureable way,
whether or not salaries or compensation are requested under the grant.” Usually,
these Senior/Key Personnel have doctoral or other professional degrees, NIH says,
adding that you should also include those with master’s and baccalaureate degrees
if their involvement meets the above definition.
You will also need a Biosketch for any Other Significant Contributors, those
persons who commit to contribute to the project’s scientific development or
execution, NIH states. They are usually listed as presenting “effort of zero
person months” or “as needed” on your application. Consultants likely will be in
this category.
The Biosketch is your opportunity to detail your knowledge, skills and ability
to perform your proposed research. Demonstrate that you are the individual most
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qualified to do it. Reviewers scrutinize this section to ensure that you and other
investigators and proposed staff have the proper experience with the proposed
techniques.
Although NIH limits the Biosketch to four pages per person, the form for
this portion is only the first page and provides space only for the key personnel’s
education. You then add up to three additional pages to complete the individual’s
Biographical Sketch. NIH additionally instructs you to complete this information
“beginning with baccalaureate or other initial professional education, such as
for More Info
on This Form residency training
nursing, and include postdoctoral training, Click
separately
referencing
Program Director/Principal Investigator (Last, First, Middle):
when applicable.”
BIOGRAPHICAL SKETCH
Provide the following information for the Senior/key personnel and other significant contributors in the order listed on Form Page 2.
Follow this format for each person. DO NOT EXCEED FOUR PAGES.
NAME
POSITION TITLE
eRA COMMONS USER NAME (credential, e.g., agency login)
EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, include postdoctoral training and
residency training if applicable.)
DEGREE
INSTITUTION AND LOCATION
MM/YY
FIELD OF STUDY
(if applicable)
Please refer to the application instructions in order to complete sections A, B, C, and D of the Biographical
Sketch.
What Your Biosketch Should Include
Direct from NIH: The NIH Application Guides states:
Following the educational block, complete sections A, B, C, and D as described
below.
A. Personal Statement. Briefly describe why your experience and qualifications
make you particularly well-suited for your role (e.g., PD/PI, mentor, participating
faculty) in the project that is the subject of the application. Within this section you
may, if you choose, briefly describe factors such as family care responsibilities,
illness, disability, and active duty military service that may have affected your
scientific advancement or productivity.
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B. Positions and Honors. List in chronological order previous positions,
concluding with your present position. List any honors. Include present
membership on any Federal Government public advisory committee.
C. Selected Peer-reviewed Publication and Patent Citations. NIH encourages
applicants to limit the list of selected peer-reviewed publications, manuscripts in
press, and patent citations to no more than 15. Do not include manuscripts submitted
or in preparation. The individual may choose to include selected publications based
on recency, importance to the field, and/or relevance to the proposed research.
When citing articles that fall under the Public Access Policy, were authored or coauthored by the applicant and arose from NIH support, provide the NIH Manuscript
Submission reference number (e.g., NIHMS97531) or the PubMed Central (PMC)
reference number (e.g., PMCID234567) for each article. If the PMCID is not yet
available because the Journal submits articles directly to PMC on behalf of their
authors, indicate “PMC Journal – In Process.” A list of these journals is posted at:
http://publicaccess.nih.gov/submit_process_journals.htm. Citations that are not
covered by the Public Access Policy, but are publicly available in a free, online
format may include URLs or publications are not acceptable as appendix material).
D. Research Support. List both selected ongoing and completed (during the
last three years) research projects (Federal or non-Federal support). Begin with
the projects that are most relevant to the research proposed in this application.
Briefly indicate the overall goals of the projects and responsibilities of the senior/
key person identified on the Biographical Sketch. Do not include number of person
months or direct costs.
Don’t confuse “Research Support” with “Other Support.” Though they sound
similar, these parts of the application are very different. As part of the biosketch
section of the application, “Research Support” highlights your accomplishments,
and those of your colleagues, as scientists. This information will be used by the
reviewers in the assessment of each individual’s qualifications for a specific role in
the proposed project, as well as to evaluate the overall qualifications of the research
team. In contrast, “Other Support” information is required for all applications that
are selected to receive grant awards. NIH staff will request complete and up-to-date
“other support” information from you after peer review. This information will be
used to check that the proposed research has not already been Federally-funded.
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What this means:
The Biosketch must include the following sections, but keep in mind that it
cannot exceed four pages:
•Personal Statement — Here, you should briefly describe why your
experience and qualifications make you particularly well-suited for your role
(such as Principal Investigator, mentor, etc.).
•Positions and Honors — List your previous positions in chronological order,
concluding with your present one. Also, list any honors and include any
memberships on federal government public advisory committees.
•Peer-Reviewed Publications and Manuscripts in Press (in chronological
order) — NIH suggests that you limit the list of selected peer-reviewed
publications or manuscripts in press, and patent citations, to no more than
15 — but has not strictly enforced this to date. The agency indicates that
you should not include manuscripts submitted or in preparation, but you
may choose to include selected publications based upon recency, importance
in the field and/or relevance to the proposed research. Additionally, if the
article falls under the Public Access Policy, was authored or co-authored by
the applicant and arose from NIH support, you need to provide only the NIH
Manuscript Submission reference number or the PubMed Central (PMC)
reference number.
•Research Support — For this section, list both selected ongoing and
completed (during the last three years) research projects. Begin with the most
relevant to your current proposal, and briefly state the project’s overall goals
and the responsibilities of the Senior/Key Personnel. Keep in mind that this is
not the place for the number of person months or direct costs.
Now, let’s look at the Biosketch parts one at a time to show how they will affect
your application.
Personal Statement
The Personal Statement is a relatively new Biosketch component added in
January 2010. It should detail why you are the best individual for a role in the
project.
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Reviewers now consider the information you include here when they examine
your qualifications. These may include your pedigree, your research experience
or your track record of resolving challenges in new areas. You need to point
out specifically why you think you are the most qualified person to lead your
proposed project.
At the same time, you should avoid sounding as if you are boasting. Instead,
reference specific objectives and criteria in your background, grants you have
already been awarded and publications that resulted from those grants.
Point to presentations you gave, address changing fields of study, and if you are
a new investigator — but not an early-stage one — you can detail your experience
working in a national laboratory.
If you have been in the research field for years but never had an NIH grant,
the Personal Statement is where you can clearly note that, although you are new
to this funding source, you are not an early-stage investigator. That is an important
distinction reviewers need to know.
NIH instructs reviewers to be less stringent when judging preliminary data
STRATEGY:
In your Personal
Statement,
reference
specific objectives
and criteria in your
background, grants
you have already
been awarded and
publications that
resulted from those
grants
from early-stage investigators because they have not had the resources to perform
preliminary research. Reviewers would rather judge you on your track record as a
postdoctoral researcher than as a graduate student.
New Investigator Case Study
A Principal Investigator (PI) returns to academia from a successful career as
an executive in the biotechnology and pharmaceutical industries, having managed
annual budgets up to $100 million. Prior to that, the PI was in the NIH Intramural
Program for 10 years and was awarded NIH tenure decades ago. The PI is also a
member of the Institute of Medicine. On the other hand, the PI has never received
an NIH grant because funding always came from other sources. In that sense, the
PI is a new investigator.
The best way to leverage this PI’s unusual background to obtain NIH grant
funds is by making it explicitly clear in the Personal Statement. By referencing
such items as IOM membership, tenure in a very competitive environment, and
responsibility for $100-million projects, the PI in this example demonstrates her
competence, experience and track record to NIH reviewers who are predominantly
from academia.
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This PI would qualify for the new investigator category, but would not receive
any breaks because of “lack of experience.” At the same time, she may be given
some leeway in terms of presentation because reviewers would recognize that she
was not used to following the NIH format. The PI would be judged as the senior
investigator that she is.
Early Investigators Stress Independence
Early investigators, obviously, should take a different tack. In particular,
they should stress their independence from others at their institutions if they will
perform their research in that setting and want the NIH to fund it.
As a result, reviewers suggest that the early investigator’s Personal Statement
should include such language as the following:
•“Although I did my postdoctoral training here, I have moved on to
independent status with my own lab space.”
•“I have been the intellectual behind the project for the last year.”
•“I wrote the grant proposals.”
•“My former mentor is going in a different direction.”
In addition, including a letter from the former mentor would help reinforce that
the early investigator is independent and delineate the differences between what he
is doing now and what the mentor is continuing to do.
TIP:
Early investigators should stress
their independence
from others at their
institutions if they
will perform their
research in that
setting and want
NIH to fund it.
Another key issue for early investigators is the degree of institutional
commitment in the form of lab and other work space and position within the
organization. The stronger you can indicate your institution’s backing for your
research proposal, the better your application will fare.
Get Creative
The Personal Statement also offers you the opportunity to clarify who does
what — and who pays for what — in a series of experiments involving multiple
personnel and funding sources.
Case Study 1: A junior investigator has a K01 grant — for which you, as the
Principal Investigator on a renewal R01 grant, are the sole mentor — that has
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overlapping aims with your renewal R01. The K01 mainly supports salary and not
the entire support infrastructure. The R01 has many more aims, but some overlap
with the K01. In this case, the question becomes: Should you list the K01 recipient
as Senior/Key Personnel or Other Significant Contributor on your R01 if you are
not going to use any funding for your proposal as salary for this individual?
For this case, because the K01 is a training or transition grant, you would
simply need to explain the relationship between the K01 grant and the parent R01
in your Personal Statement and possibly in the Environment statement because the
K01 recipient is a positive feature of the environment. The K01 recipient should
complete a Personal Statement for the R01 application as an Other Significant
Contributor and use it to explain the relationship between the two grants. You
should also explain the salary support issue in the Budget Justification section of
the R01 application.
Case Study 2: You have a K award for a small randomized controlled trial on
a treatment you developed and will soon submit an R01 application that builds on
the data you have collected as part of it. In this case, the questions regarding your
Personal Statement become:
•Should you emphasize your status as an early-career and new investigator?
•Should you emphasize how the pilot data were collected as part of the K
award?
Here, you should discuss your background, which should clearly reflect your
status as both an early-stage and a new investigator. You have already succeeded in
the competitive grants environment by receiving a K award and then successfully
used that K award to generate experimental results that will lead directly to a
larger project of increased scope. Be sure to clearly indicate how your prior work
is directly related to and effectively supports the work you propose in the R01.
Highlight your ability to think strategically to consider the next question to be
answered and how that impacts your proposal.
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Personal Statement Example
NIH does not specify whether to write the personal statement on the biosketch
in first or third person. As such, they provide examples to illustrate both
(http://nihgrants.blogspot.com/2011/06/nih-biosketch-personal-statement-first.html):
First Person:
Personal Statement
The goal of the proposed research is to investigate the interaction between
drug abuse and normal aging processes. Specifically, we plan to measure
changes in cognitive ability and mental and physical health across a five-year
period in a group of older drug users and matched controls. I have the expertise,
leadership, and motivation necessary to successfully carry out the prosed work.
I have a broad background in psychology, with specific training and expertise
in key research areas for this application. As a postdoctoral fellow at Berkeley,
I carried out ethnographic and survey research and secondary data analysis on
psychological aspects of drug addiction. At the Division of Intramural Research at
the National Institutes on Drug Abuse (NIDA), I expanded my research to include
neuropsychological changes associated with addiction. As PI or co-Investigator
on several previous university- and NIH-funded grants, I laid the groundwork for
the proposed research by developing effective measures of disability, depression,
and other psychosocial factors relevant in the aging substance abuser, and by
establishing strong ties with community providers that will make it possible to
recruit and track participants over time. In addition, I successfully administered
the projects (e.g., staffing, research protections, budget), collaborated with other
researchers, and produced several peer-reviewed publications from each project.
As a result of these previous experiences, I am aware of the importance of frequent
communication among project members and of constructing a realistic research
plan, timeline, and budget. The current application builds logically on my prior
work, and I have chosen co-investigators (Drs. Gryczynski and Newlin) who
provide additional expertise in cognition, gerontology, and geriatrics. In summary,
I have a demonstrated record of successful and productive research projects in an
area of high relevance for our aging population, and my expertise and experience
have prepared me to lead the proposed project.
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Third Person:
Personal Statement
The goal of the proposed research is to investigate the interaction between drug
abuse and normal aging processes. Specifically, the research team plans to measure
changes in cognitive ability and mental and physical health across a five-year
period in a group of older drug users and matched controls. Dr. PI has the expertise,
leadership and motivation necessary to successfully carry out the proposed work.
She has a broad background in psychology, with specific training and expertise in
key research areas for this application. As a postdoctoral fellow at Berkeley, Dr.
PI carried out ethnographic and survey research and secondary data analysis on
psychological aspects of drug addiction. At the Division of Intramural Research at
the National Institute on Drug Abuse (NIDA), she expanded her research to include
neuropsychological changes associated with addiction. As PI or co-Investigator
on several university- and NIH-funded grants, she laid the groundwork for the
proposed research by developing effective measures of disability, depression,
and other psychosocial factors relevant to the aging substance abuser, and by
establishing strong ties with community providers that will make it possible
to recruit and track participants over time. In addition, Dr. PI successfully
administered the projects (e.g. staffing, research protections, budget), collaborated
with other researchers, and produced several peer-reviewed publications from each
project. As a result of these previous experiences, Dr. PI is aware of the importance
of frequent communication among project members and of constructing a realistic
research plan, timeline, and budget. The current application builds logically on
her prior work, and she has chosen co-investigators (Drs. Gryczynski and Newlin)
who provide additional expertise in cognition, gerontology and geriatrics. During
2005-2006, Dr. PI’s career was disrupted due to family obligations. However,
upon returning to the field, she immediately resumed her research projects and
collaborations and successfully competed for NIH support. In summary, Dr. PI has
a demonstrated record of accomplished and productive research projects in an area
of high relevance for our aging population, and her expertise and experience have
prepared her to lead the proposed project.
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Positions and Honors
This section of the Biographical Sketch is rather straightforward. Here, you
should list your employment history — that is, dates, places and the nature of the
positions. In addition, include any honors and memberships on any federal public
advisory committees.
NIH provides the following example:
Positions and Honors
Positions and Employment
1998-2000
Fellow, Division of Intramural Research, National Institute of Drug
Abuse, Bethesda, MD
2000-2002
Lecturer, Department of Psychology, Middlebury College,
Middlebury, VT
2001-
Consultant, Coastal Psychological Services, San Francisco, CA
2002-2005
Assistant Professor, Department of Psychology, Washington
University, St. Louis, MO
2005-
Associate Professor, Department of Psychology, Washington
University, St. Louis, MO
Other Experience and Professional Memberships
1995-
Member, American Psychological Association
1998-
Member, Gerontological Society of America
1998-
Member, American Geriatrics Society
2000-
Associate Editor, Psychology and Aging
2003-
Board of Advisors, Senior Services of Eastern Missouri
2003-2004
NIH Peer Review Committee: Psychobiology of Aging, ad hoc reviewer
2005-2009
NIH Risk, Adult Addictions Study Section, member
Honors
2003
Outstanding Young Faculty Award, Washington University, St. Louis,
MO
2005
Excellence in Teaching, Washington University, St. Louis, MO
2008
Award for Best in Interdisciplinary Ethnography, International
Ethnographic Society
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Peer-Reviewed Publications and Manuscripts in Press
NIH officially “encourages” applicants to list no more than 15 selected peerreviewed publications, manuscripts in press or patent citations. And do not include
any manuscripts that you have submitted but are not published or which are
currently in preparation.
Many applicants struggle to choose their top 15 publications to support their
experience and ability. In response, NIH reviewers suggest that you select them
as follows:
STRATEGY:
NIH reviewers
suggest that, if you
have numerous
publications to
your credit, you
should select your
15 publications
“permitted” as
follows: the 5 most
recent, the 5 most
important to your
field, and the 5
most relevant to
your proposed
research.
1.Five most recent,
2.Five most important to your field, and
3.Five most relevant to your proposed research.
Some applicants, however, may have 50, 100 or more published papers they
wish to cite.
If that is your challenge, remember that reviewers will always be interested in
what you have done lately. They want to see what you have done during the last
five years, regardless of whether that includes five papers or 10.
If what you have done recently is directly related to your proposal, your 15
most recent publications cover all three categories. On the other hand, if you
think your 15 most recent do not demonstrate your strength as an investigator,
you should go back to older publications and use the five or six that demonstrate
the following:
•That you have previously worked in the field;
•That you have a successful track record in several different fields; and
•That you have made an impact in your field.
The publication limitation guidelines have sparked many questions, such as
whether including more than 15 publications will upset reviewers and whether
applicants should include all the PubMed Central Identification (PMCID)
information for each. Applicants also are unsure whether they should include an
appendix for those publications that are “in press” or whether they should add
already-published papers so they are readily available to reviewers.
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To answer these concerns, consider the following:
•Few applicants have limited their publication list to 15, and reviewers
apparently have not reacted negatively to this. But reviewers stress that you
should identify those publications you think are most relevant — even if you
exceed the 15. Reviewers do get irritated when they have to scan through a
list of 56 publications to find the three that actually relate to the application.
Note: If citations become too numerous, the NIH could more strictly enforce
the nominal limit, or reviewers could become less tolerant of overage. So stay
alert for such shifts.
•As for adding the PMCID codes, it is the law. NIH could “withdraw you
administratively,” using government funding agency language, if you fail to
include this information.
•Regarding publications in your appendix materials, regulations state that you
should include only those that are not publicly accessible on the Internet.
Therefore, include only those that are “in press” and not yet published online.
List More Than 15 if …
Another way to approach the publication limit is to list more than 15
publications — as long as this does not take your Biosketch to more than four
pages. In this case, you have to weigh how reviewers will respond if you or your
co-investigator(s)/key personnel have extensive research experience, a strong
history of federal grant awards and a long list of related publications.
If you have a strong track record, you should set aside the 15 most relevant,
impactful and recent articles to spare reviewers the necessity of wading through a
very long list. You can afford to omit the rest of your references and simply state,
for example, “15 of the most relevant of 225 published over the last 20 years.” If
you think you have 20 or 30 references highly relevant to the proposal, then you
should probably include them, even knowing you are technically exceeding the
official ceiling. The key is to be selective.
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Illustrate Your Track Record
The publications list also allows you to demonstrate that you have a track
record as a successful researcher. R01 grant applications are limited to 12 pages so
STRATEGY:
If you have a strong
track record, you
should set aside
the 15 most
relevant, impactful
and recent articles
to spare reviewers
the necessity of
wading through a
very long list.
you do not have much space to provide the background or experimental details or
to present 35 figures of preliminary data.
The Biographical Sketch(s) does not count toward the 12-page limit. So you
should reference your published papers that demonstrate feasibility and your
track record, and then use your application to present only those figures that
have not been published and demonstrate key points. This would include the key
scientific points that establish your hypothesis’ validity or key technical points that
demonstrate your approach’s feasibility.
The publication list is also an ideal place to show previous collaboration with
any co-investigator(s) you will be working with under the new proposal. In fact,
NIH reviewers indicate that showing you have a history of working with the
collaborators is “very important,” and the publication list is “one of the cheapest
places to demonstrate that.”
In fact, you may be better served to sacrifice some of your more impactful
publications to include a few that indicate you have worked with the proposed
collaborators. You can then add a sentence that says, “This team includes
collaborators who have worked together in the past and published X number of
TIP:
You may be better
served to sacrifice
some of your more
impactful publications to include a
few that indicate
you have worked
with your proposed
collaborators.
63 papers, as demonstrated below.”
Reviewers generally have reduced enthusiasm for many collaborative proposals
because of insufficient evidence that the researchers have previously worked
together. For example, if one collaborating researcher is in Philadelphia and the
other is in Washington, D.C., the reviewer will want to know that you have already
discovered ways to bridge the geographical distance. Co-authored publications are
one tool to convince reviewers that you make a successful team.
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Learn From This Example
NIH provides the following example of the Peer-Reviewed Publications or
Manuscripts in Press portion of the Biosketch. Note that in this case, the applicant
has broken her 15 publications into just two groups:
•Most relevant to the current application
•Additional recent publications of importance to the field
She also has noted that she chose the 15 listed publications from a larger group
of 42 to demonstrate that she has additional experience.
C. Peer-Reviewed Publications or Manuscripts in Press (Selected from 42 peerreviewed publications)
Most relevant to the current application
1.Merryle, R.J. & Hunt, V.L. (2004). Independent living, physical disability
and substance abuse among the elderly. Psychology and Aging, 23(4), 10-22.
2.Hunt, V.L., Jensen, J.L. & Crenshaw, W. (2007). Substance abuse and mental
health among community-dwelling elderly. International Journal of Geriatric
Psychiatry, 24(9), 1124-1135.
3.Hunt, V.L., Wiechelt, S.A. & Merryle, R. (2008). Predicting the substanceabuse treatment needs of an aging population. American Journal of Public
Health, 45(2), 236-245. PMCID: PMC9162292
4.Hunt, V.L., Newlin, D.B. & Fishbein, D. (2009). Brain imaging in
methamphetamine abusers across the life-span. Gerontology, 46(3), 122-145.
5.Hunt, V.L. & Sher, K.A. (2009). Successful intervention models for older
drug-abusers: Research across the life-span. American Psychologist, in press.
NIHMSID: NIHMS99135
Additional recent publications of importance to the field (in chronological
order)
1.Gryczynski, J., Shaft, B.M., Merryle, R. & Hunt, V.L. (2002). Community
based participatory research with late-life addicts. American Journal of
Alcohol and Drug Abuse, 15(3), 222-238.
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2.Shaft, B.M., Hunt, V.L., Merryle, R. & Venturi, R. (2003). Policy
implications of genetic transmission of alcohol and drug abuse in female
nonusers. International Journal of Drug Policy, 30(5), 46-58.
3.Hunt, V.L., Marks, A.E., Shaft, B.M., Meryle, R. & Jensen, J.L. (2004).
Early-life family and community characteristics and late-life substance
abuse. Journal of Applied Gerontology, 28(2), 26-37.
4.Hunt, V.L., Merryle, R. & Jensen, J.L. (2005). The effect of social support
networks on morbidity among elderly substance abusers. Journal of the
American Geriatrics Society, 57(4), 15-23.
5.Hunt, V.L., Pour, B., Marks, A.E., Merryle, R. & Jensen, J.L. (2005). Aging
out of methadone treatment. American Journal of Alcohol and Drug Abuse,
15(6), 134-149.
6.Hunt, V.L., Marks, A.E., Venturi, R., Crenshaw, W. & Ratonian, A. (2006).
Community-based intervention strategies for reducing alcohol and drug
abuse in the elderly. Addition, 104(9), 1436-1606. PMCID: PMC9000292
7.Merryle, R. & Hunt, V.L. (2006). Randomized clinical trial of cotinine in
older nicotine addicts. Age and Ageing, 38(2), 9-23. PMCID: PMC9002364
8.Hunt, V.L., Jensen, J.L. & Merryle, R. (2008). The aging addict:
ethnographic profiles of the elderly drug user. NY, NY: W.W. Norton &
Company.
9.Hunt, V.L. (2009). Contrasting ethnicity with race in the older alcoholic.
The Journals of Gerontology Series B: Psychological Sciences and Social
Sciences, in press. PMCID: PMC Journal — In Process.
10.Hunt, V.L. (2009). Intervening successfully with the older methadone
patient. Journal of Applied Gerontology, 13(4), 67-79.
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Upcoming Changes to the Biosketch Format
NIH’s plan to modify the current biosketch format is scheduled to roll
out for all grant applications received for FY 2016 funding and beyond
(http://grants.nih.gov/grants/guide/notice-files/NOT-OD-14-091.html). In practice,
this means that applications submitted in early 2015 will use this new format
which is described on the SF424 (R&R) Applications and Electronic Submission
Page (http://grants.nih.gov/grants/funding/424/index.htm). Until this time,
read any RFAs you plan to apply for very carefully, since they may be part of the
pilot phase of the implementation that requires use of the new biosketch format. In
summary, these changes include:
• Increasing the total biosketch length to five pages, instead of two or four.
• There is a new Section C - Contributions to Science. This section will
succeed the Selected Peer-Reviewed Publications section. In this new
section C, applicants will briefly describe up to five of their most significant
contributions to science. Each description should be no longer than one half
page, including figures and citations. For each contribution, the applicant
will reference up to four peer-reviewed publications relevant to that specific
contribution. Be sure to provide a URL to a full list of your published work
as found in a publicly available digital database such as PubMed or My
Bibliography.
OMB No. 0925-0046 (Approved Through 5/31/2016)
BIOGRAPHICAL SKETCH—Pilot Format (To Be Used for Specific FOAs only)
Provide the following information for the Senior/key personnel and other significant contributors.
Follow this format for each person. DO NOT EXCEED FIVE PAGES.
NAME
POSITION TITLE
eRA COMMONS USER NAME (credential, e.g., agency login)
EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, include postdoctoral training and
residency training if applicable.)
DEGREE
INSTITUTION AND LOCATION
MM/YY
FIELD OF STUDY
(if applicable)
NOTE: The Biographical Sketch may not exceed five pages. Follow the formats and instructions below.
A. Personal Statement
Briefly describe why you are well-suited for your role in the project described in this application. The relevant
Principal factors
Investigators
| www.principalinvestigators.org
mayAssociation
include aspects
of your training; your previous experimental work on this specific topic or related
topics; your technical expertise; your collaborators or scientific environment; and your past performance in this
or related fields (you may mention specific contributions to science that are not included in Section C). Also,
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Why change the format?
The purpose of these changes has best been summarized by Dr. Sally Rockey,
NIH’s Deputy Director for Extramural Research. Her complete web posting on this
subject may be found at http://nexus.od.nih.gov/all/2014/05/22/changes-to-thebiosketch/:
The primary focus of the new NIH biosketch will be the magnitude and
significance of the scientific advances associated with a researcher’s discoveries
and the specific role the researcher played in those findings. This change will
help reviewers evaluate you not by where you’ve published or how many times,
but instead by what you’ve accomplished. Hopefully, this change will redirect
the focus of reviewers and the scientific community more generally from widely
questioned metrics, like the number of published papers, the number of citations
received by those papers, or one of several statistical approaches used to normalize
citations.
We strongly believe that allowing a researcher to generate an account of his
or her own work will provide a clearer picture of each individual’s contributions
and capabilities. But one might question whether this new biosketch will have a
negative impact on younger investigators whose body of work may not be as robust
as more established investigators. I believe the contrary is true; this new format
will give early career investigators a platform for describing and framing the
significance of their contributions, which should help reviewers better understand
their accomplishments without having to rely simply on a list of publications.
The NIH provides the following example of the new Section C:
C. Contributions to Science
1. My early publications directly addressed the fact that substance abuse is
often overlooked in older adults. However, because many older adults were
raised during an era of increased drug and alcohol use, there are reasons to
believe that this will become an increasing issue as the population ages. These
publications found that older adults appear in a variety of primary care settings
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or seek mental health providers to deal with emerging addiction problems.
These publications document this emerging problem but guide primary care
providers and geriatric mental health providers to recognize symptoms, assess
the nature of the problem and apply the necessary interventions. By providing
evidence and simple clinical approaches, this body of work has changed
the standards of care for addicted older adults and will continue to provide
assistance in relevant medical settings well into the future. I served as the
primary investigator or co-investigator in all of these studies.
a. Gryczynski, J., Shaft, B.M., Merryle, R., & Hunt, M.C. (2002).
Community based participatory research with late-life addicts.
American Journal of Alcohol and Drug Abuse, 15(3), 222-238.
b. Shaft, B.M., Hunt, M.C., Merryle, R., & Venturi, R. (2003). Policy
implications of genetic transmission of alcohol and drug abuse in
female nonusers. International Journal of Drug Policy, 30(5), 46-58.
c. Hunt, M.C., Marks, A.E., Shaft, B.M., Merryle, R., & Jensen, J.L.
(2004). Early-life family and community characteristics and late-life
substance abuse. Journal of Applied Gerontology, 28(2),26-37.
d. Hunt, M.C., Marks, A.E., Venturi, R., Crenshaw, W. & Ratonian, A.
(2007). Community-based intervention strategies for reducing alcohol
and drug abuse in the elderly. Addiction, 104(9), 1436-1606. PMCID:
PMC9000292
2. In addition to the contributions described above, with a team of collaborators,
I directly documented the effectiveness of various intervention models for older
substance abusers and demonstrated the importance of social support networks.
These studies emphasized contextual factors in the etiology and maintenance
of addictive disorders and the disruptive potential of networks in substance
abuse treatment. This body of work also discusses the prevalence of alcohol,
amphetamine, and opioid abuse in older adults and how networking approaches
can be used to mitigate the effects of these disorders.
a. Hunt, M.C., Merryle, R. & Jensen, J.L. (2005). The effect of social
support networks on morbidity among elderly substance abusers.
Journal of the American Geriatrics Society, 57(4), 15-23.
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b Hunt, M.C., Pour, B., Marks, A.E., Merryle, R. & Jensen, J.L. (2005).
Aging out of methadone treatment. American Journal of Alcohol and
Drug Abuse, 15(6), 134-149.
c. Merryle, R. & Hunt, M.C. (2007). Randomized clinical trial of
cotinine in older nicotine addicts. Age and Ageing, 38(2), 9-23. PMCID:
PMC9002364.
3. Methadone maintenance has been used to treat narcotics addicts for many years
but I led research that has shown that over the long-term, those in methadone
treatment view themselves negatively and they gradually begin to view
treatment as an intrusion into normal life. Elderly narcotics users were shown
in carefully constructed ethnographic studies to be especially responsive
to tailored social support networks that allow them to eventually reduce their
maintenance doses and move into other forms of therapy. These studies also
demonstrate the policy and commercial implications associated with these
findings.
a. Hunt, M.C. & Jensen, J.L. (2003). Morbidity among elderly substance
abusers. Journal of the Geriatrics, 60(4), 45-61.
b. Hunt, M.C. & Pour, B. (2004). Methadone treatment and personal
assessment. Journal Drug Abuse, 45(5), 15-26.
c. Merryle, R. & Hunt, M.C. (2005). The use of various nicotine delivery
systems by older nicotine addicts. Journal of Ageing, 54(1), 24-41.
PMCID: PMC9112304
d. Hunt, M.C., Jensen, J.L. & Merryle, R. (2008). The aging addict:
ethnographic profiles of the elderly drug user. NY, NY: W. W. Norton &
Company.
Complete List of Published Work in My Bibliography: http://www.ncbi.nlm.nih.
gov/sites/myncbi/collections/public/1PgT7IEFIAJBtGMRDdWFmjWAO/?sort=dat
e&direction=ascending
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When writing this section, keep the following in mind:
• What do you consider your most significant contributions to science? This can
be contributions to science in general, to a specific scientific discipline, or a
combination.
• The background for the scientific question or problem you are highlighting in
each contribution
• A recap of the critical findings for each
• How these findings were used to guide future progress in addressing healthrelated problems or advancing technology
• What was your specific role in the described work?
Sections A, B, and D, (Personal Statement, Positions and Honors, and Research
Support, respectively) have remained the same.
Research Support
In the Biosketch’s Research Support section, you should list both ongoing and
completed projects, including those with both federal and non-federal funding. Start
with the projects most relevant to the current application and briefly indicate their
overall goals and responsibilities of the Senior/Key Personnel involved in the current
proposal. This, however, is not the place to detail the number of person months and
direct costs.
Be sure not to confuse “Research Support” with “Other Support.” Although they
may sound similar, these parts of the application are quite different. The Biosketch’s
Research Support section highlights your scientific accomplishments and your role
in selected grants. Reviewers will use this information to assess each individual’s
qualifications for a specific role in the project, as well as their roles on the research
team.
The Other Support section, on the other hand, includes information required for
all applications that are selected to receive awards. NIH staff will request complete
and up-to-date Other Support information from awarded researchers after peer review
and then check this information to ensure that the proposed research has not already
been federally funded.
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NIH provides the following example of the Research Support portion of the
Biosketch:
2. Research Support Ongoing Research Support
R01 DA942367-03
Hunt (PI)
09/01/07-08/31/12
Health trajectories and behavioral interventions among older substance abusers
The goal of this study is to compare the effects of two substance abuse
interventions on health outcomes in an urban population of older opiate addicts.
Role: PI
R01 MH922731-05
Merryle (PI)
07/15/05-06/30/10
Physical disability, depression and substance abuse in the elderly
The goal of this study is to identify disability and depression trajectories and
demographic factors associated with substance abuse in an independently-living
elderly population.
Role: Co-Investigator
Faculty Resources Grant, Washington University
08/15/09-08/14/11
Opiate Addiction Database
The goal of this project is to create an integrated database of demographic, social
and biomedical information for homeless opiate abusers in two urban Missouri
locations, using a number of state and local data sources.
Completed Research Support
K02 AG442898
Hunt (PI)
09/01/06-08/31/09
Drug Abuse in the Elderly
Independent Science Award: to develop a drug addiction research program with a
focus on substance abuse among the elderly.
Role: PI
R21 AA992075
Hunt (PI)
01/01/04-12/31/06
Community-based intervention for alcohol abuse
The goal of this project was to assess a community-based strategy for reducing
alcohol abuse among older individuals.
Role: PI
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Letters of Support Can Help New Investigators
Direct from NIH: The NIH Application Guides states:
Attach all appropriate letters of support, including any letters necessary to
demonstrate the support of consortium participants and collaborators such as
Senior/Key Personnel and Other Significant Contributors included in the grant
application. Letters are not required for personnel (such as research assistants)
not contributing in a substantive, measurable way to the scientific development or
execution of the project. Letters should stipulate expectations for co-authorship,
and whether cell lines, samples or other resources promised in the letter are freely
available to other investigators in the scientific community or will be provided to
the particular investigators only. For consultants, letters should include rate/charge
for consulting services and level of effort/number of hours per year anticipated.
In addition, letters ensuring access to core facilities and resources should stipulate
whether access will be provided as a fee-for-service. Do not place these letters
in the Appendix. Consultant biographical sketches should be in the Biographical
Sketch section.
What this means:
If you are a young investigator, you can use letters of support from your
department chair, collaborator(s) and contractor(s) to fill in any gaps in the
capabilities outlined in your Biographical Sketch. The letters can even be from
colleagues with whom you have worked. These letters do not fall within the NIH’s
application page limit, so you can include as many as you feel are necessary.
For standard R01 applications, NIH reviewers will weigh the importance of
letters of support based on whether there is a significant gap in your capabilities
that must be filled by a collaborator. In these cases, simply naming a consultant
will not be sufficient. You will need a strong, specific letter of support from that
individual stating exactly what he will provide to the project and demonstrating
REMEMBER:
Letters of support
do not fall within
the NIH’s application page limit, so
you can include as
many as you feel
are necessary.
enthusiasm for it.
Although technically not required for collaborators who are co-investigators
with Biosketches in the proposal, a letter of support may still prove valuable if you
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have a history of working with the individual.
Also, if you are entering a new field, having a letter of support from an
established expert in that field is beneficial. For example, if you have always been a
basic bench person but now wish to study a specific disease, getting a clinician with
expertise in that disease to write a supporting letter helps to establish your credibility.
The letter should specify what support the person is offering, and it must be
plausible. You can write a desired draft for the person to review and sign, but do
not make all of your supporting letters look the same. Take the time to determine
what aspects of your proposal would be most interesting and relevant to each of
your collaborators.
Here are four reasons you should craft the initial draft of your letters of support:
TIP:
You can write a
desired draft of a
letter of support for
the person to review and sign, but
do not make all of
your supporting
letters look the
same.
•Congruence. You know your grant application strategy best, so your
self-written draft letter of support becomes part of that overall strategy.
Communicating to others exactly what you need and what to cover — and
then asking them to prepare it — can be difficult and time-consuming. If
you do it for them, you establish momentum and eliminate any breakdown
in communication.
•Expectations. Initial conversations with contractors and collaborators when
you request letters of support may leave both sides with faulty assumptions
regarding what to include. When they see your expectations in the letter you
construct for them, however, you avoid potential misunderstandings. This
ensures that everyone is “on the same page” from the beginning.
•Timeliness. Your grant application is a high priority for you, and you are
well aware of any deadlines. But your collaborators and contractors may not
have the same priorities, and your letter of support may drop lower on their
to-do list. When you offer to write the letter, you likely will receive a quicker
response that meets your deadlines.
•Facilitation. Allowing your contractors and collaborators to edit your
letters is easier for them than drafting the letters on their own. They can
read your letter and offer comments and clarifications without having to
start from scratch.
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Keys to Crafting Effective Letters of Support
When you write a letter of support, here are a few tips to keep in mind:
1.Clarify duties, roles and timelines. Offer specific details regarding what
you expect the collaborator or contractor to do, as well as the deadline. This
will avoid potential misunderstandings later. And when individuals other
than the applicant write their own letters of support, they are often more
vague than what the applicant needs. Therefore, make sure the letter draws
attention to what you, as the applicant, have done that is relevant to any NIH
requirements — or those of any ICOs that may potentially review it.
2.Write it from the contractor or collaborator’s point of view. Tailor each
letter to the collaborator or contractor’s specific duties, and write it as if they
wrote the letter. If you prepare more than one letter, make sure to use unique
language for each.
3.Display enthusiasm. The letter should convey the individual’s enthusiasm
for the project by outlining specifics, such as resource and time commitment
and interest in the project’s details.
4.Get the standard details correct. Address the letter according to the grant’s
guidelines. It will be going to either the applicant or NIH. Have the final,
agreed-upon version written on an institutional letterhead, and have it signed
by someone authorized to make the commitment.
In addition, many experts recommend that these letters should have a specific
structure, including the following three elements:
•Statement of support — Use one to three sentences to show enthusiasm and
identify the specific project by name.
•Supporting paragraphs — Explain how the individual’s research, expertise
and technical skills will support the applicant. Detail the individual’s relevant
experience and how it bears on the project, as well as his or her previous
track record on similar projects. And if you have worked with them before,
describe the project and the results. Finally, explain specific duties to perform,
and describe the use of any equipment or other resources.
•Cordial closing — The closing’s formality will depend on the relationship
between the applicant and the person who is supporting them. If the two
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have a previous productive working relationship, it can be less formal. If that
relationship is more limited, the closing should be more formal.
Multiple PIs Means Additional Documentation
If your proposal includes multiple Project Directors (PDs)/Principal
Investigators (PIs), you will have to complete and upload a separate Biographical
Sketch for each of the PDs/PIs. In addition, you will have to create and upload a
Multiple PD/PI Leadership Plan.
Direct from NIH: The NIH Application Guides states:
For applications designating multiple PD/PIs, a leadership plan must be
included. For applications designating multiple PD/PIs, all such individuals
must be assigned the PD/PI role on the Senior/Key Profile form, even those at
organizations other than the applicant organization. A rationale for choosing a
multiple PD/PI approach should be described. The governance and organizational
structure of the leadership team and the research project should be described,
including communication plans, process for making decisions on scientific
direction, and procedures for resolving conflicts. The roles and administrative,
technical, and scientific responsibilities for the project or program should be
delineated for the PD/PIs and other collaborators. Do not submit a leadership plan
if you are not submitting a Multiple PD/PI application.
If budget allocation is planned, the distribution of resources to specific parts of
the project or the individual PD/PIs should be delineated in the Leadership Plan. In
the event of an award, the requested allocations may be reflected in a footnote on
the Notice of Grant Award.
What this means:
NIH does not place a page limit on this document, stating only that it should
include the following:
A.The rationale for choosing a multiple PD/PI approach rather than having a
single PD/PI to lead the proposed research.
B.The governance and organization structure of the leadership team and the
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research project, including:
• Communication plans;
• Process for making decisions regarding scientific direction; and
• Procedures for resolving conflict.
C.The roles and administrative, technical and scientific responsibilities for the
project or program for each of the PDs/PIs and other collaborators.
In addition, if you have planned the budget allocation, your Leadership Plan
should detail resource distribution to specific project components or individual
PDs/PIs.
NIH offers the following examples of Leadership Plans (http://grants.nih.gov/
grants/multi_pi/sample_leadership_plans.pdf), noting that applications should
follow any special instructions offered by individual ICOs:
Example 1:
Principal Investigator 1 and Principal Investigator 2 will provide oversight of
the entire program and development and implementation of all policies, procedures,
and processes. In these roles, PI1 and PI2 will be responsible for the implementation
of the Scientific Agenda, the Leadership Plan, and the specific aims, and ensure
that systems are in place to guarantee institutional compliance with U.S. laws,
Department of Health and Human Services and National Institutes of Health policies
including biosafety, human and animal research, data and facilities.
Specifically, PI1 will oversee aim 1 and be responsible for all animal research
approvals. PI2 is responsible for aims 2, 3, and 4 including the implementation
of all human subjects research and approvals. PI1 will serve as contact PI
and will assume fiscal and administrative management including maintaining
communication among PIs and key personnel through monthly meetings. He will
be responsible for communication with NIH and submission of annual reports. The
responsibilities of the contact PI will be rotated to PI2 in even years of the grant
award. Publication authorship will be based on the relative scientific contributions
of the PIs and key personnel.
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Example 2:
Principal Investigator 1 at Institution A will be responsible for the oversight
and coordination of project management for aim 1 involving the molecular
design and production of vectors expressing tumor-specific antigens. Principal
Investigator 2 at Institution B will be responsible for aims 2 and 3 including the
in vivo and in vitro testing of vaccines. Each PI will be responsible for his own
fiscal and research administration.
The PIs will communicate weekly, either by phone, e-mail, or in person, to
discuss experimental design, data analysis, and all administrative responsibilities.
All PIs will share their respective research results with other PIs, key personnel,
and consultants. They will work together to discuss any changes in the direction of
the research projects and the reprogramming of funds, if necessary. A publication
policy will be established based on the relative scientific contributions of the PIs
and key personnel.
PI1 will serve as contact PI and be responsible for submission of progress
reports to NIH and all communication.
Intellectual Property: The Technology Transfer Offices at Institutions A and
B will be responsible for preparing and negotiating an agreement for the conduct of
the research, including any intellectual property. An Intellectual Property Committee
composed of representatives from each institution that is part of the grant award, will
be formed to work together to ensure the intellectual property developed by the PIs is
protected according to the policies established in the agreement.
Conflict Resolution: If a potential conflict develops, the PIs shall meet and
attempt to resolve the dispute. If they fail to resolve the dispute, the disagreement
shall be referred to an arbitration committee consisting of one impartial senior
executive from each PI’s institution and a third impartial senior executive mutually
agreed upon by both PIs. No members of the arbitration committee will be directly
involved in the research grant or disagreement.
Change in PI Location: If a PI moves to a new institution, attempts will be
made to transfer the relevant portion of the grant to the new institution. In the event
that a PI cannot carry out his/her duties, a new PI will be recruited as a replacement
at one of the participating institutions.
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CONCLUSION
After your Abstract, many reviewers turn to your Biographical Sketch as the
next stop in their assessment process. They want to make sure you have the skills,
background and general acumen to take on the research you are proposing.
And with each of these sections, you have only very limited space to present
the details that support your research, education and overall background to
demonstrate early in the application that you have a viable proposal worth funding.
And you want to grab the reviewers’ attention, get them emotionally involved and
turn them into champions for your project. n
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79 Chapter 2: Outlining Your Project and Individual Qualifications
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NIH R01 Grant Application Mentor: An Educational How-to Manual — 4th Edition
Chapter 3: Showing Your Institution’s Resources and Commitment
Chapter 3:
Showing Your Institution’s Resources
and Commitment
One of the core criteria National Institutes of Health (NIH) reviewers use to
score your grant application is the Environment in which you perform the research.
They want to ensure you will have the resources — meaning the institutional
support, equipment and physical items — you need to successfully complete your
proposed investigation. Additionally, they want to know of any unique features of
your scientific environment, subject populations or collaborative arrangements that
will benefit your project. You will detail these elements in the Facilities and Other
Resources and Equipment sections of the application.
Where you perform your research has not always been so important. In fact,
reviewers note that “environment is one of the review criteria that used to be
virtually meaningless. Almost nobody got a bad score for it.” As one characterized
it, “The only place that a reviewer could find information about [it] was the list of
centrifuges and computers, which is really not very helpful.”
Obviously, this is no longer the case.
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DETAIL YOUR FACILITIES AND OTHER RESOURCES
Direct from NIH: The NIH Application Guide states:
Facilities & Other Resources
This information is used to assess the capability of the organizational
resources available to perform the effort proposed. Identify the facilities to be used
(Laboratory, Animal, Computer, Office, Clinical and Other). If appropriate, indicate
their capacities, pertinent capabilities, relative proximity and extent of availability
to the project. Describe only those resources that are directly applicable to the
proposed work. Provide any information describing the Other Resources available
to the project (e.g., machine shop, electronic shop) and the extent to which they
would be available to the project.
No special form is required but this section must be completed and attached
for submissions to NIH and other PHS agencies unless otherwise noted in an
FOA. Describe how the scientific environment in which the research will be
done contributes to the probability of success (e.g., institutional support, physical
resources, and intellectual rapport). In describing the scientific environment in
which the work will be done, discuss ways in which the proposed studies will
benefit from unique features of the scientific environment or subject populations or
will employ useful collaborative arrangements.
For Early Stage Investigators (ESIs), describe institutional investment in the
success of the investigator, e.g., resources for classes, travel, training; collegial
support such as career enrichment programs, assistance and guidance in the
supervision of trainees involved with the ESI’s project, and availability of organized
peer groups; logistical support such as administrative management and oversight and
best practices training; and financial support such as protected time for research with
salary support. See http://grants.nih.gov/grants/new_investigators/.
If there are multiple performance sites, describe the resources available at each
site.
Describe any special facilities used for working with biohazards or other
potentially dangerous substances. Note: Information about select agents must be
described in the Research Plan, Section 11 (Select Agent Research).
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What this means:
As you construct the Facilities and Other Resources section, you should answer
the following questions:
1.What facilities will you use? Include the following subheadings and describe
the capacities (including square footage), pertinent capabilities, relative
proximity and extent of availability of each to your project:
•Laboratory
•Clinical
•Animal
•Computer
•Office
•Other, such as machine shop, electronic shop, etc.
2.How will the scientific environment in which you perform your research
contribute to your success? Include the following sections, and describe how
your studies benefit from unique features of the scientific environment or
subject populations and useful collaborative arrangement:
•Institutional support
•Physical resources
•Intellectual rapport
3.For early-stage investigators, describe the following:
•Institutional investment in your success — for instance, resources for
classes, travel and training
•Collegial support, such as career-enrichment programs, and availability of
organized peer groups
•Logistical support — for example, administrative management and
oversight and best-practices training, and financial support such as
protected time for research with salary support
4.If there are multiple sites where your research will be performed, describe
the resources available at each site.
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5.Detail any special facilities you will use for working with biohazards or
other potentially dangerous substances. If you are using anything classified
as a Select Agent, be sure to describe any special facilities used for working
with these substances.
For this section, you should list any distinctive features, which may include the
following:
•A unique set of technical capabilities
•Access to a special patient population
•The collaborative nature of interactions between you and your colleagues
•A particular emphasis in a special area, such as neurobiology
This not only informs reviewers how your institution supports your research,
but also underscores your qualifications as the best person to perform your
proposed research. For early-stage investigators in particular, reviewers look for
TIP:
For early-stage
investigators,
reviewers look for
evidence of how
your institution
values your
research and
its level of commitment to helping you
succeed.
evidence of how your institution values your research and its level of commitment
to helping you succeed.
In addition, first-time applicants often find succeeding with a proposal rather
challenging. They frequently need assistance with start-up funds, access to graduate
students, or departmental support for travel, training, or career-enrichment programs.
And if you are an early-stage investigator still working at the same institution
where you performed your postdoctoral work, NIH reviewers may be skeptical of
your application — especially if you are nearly in the same research area and your
postdoctoral mentor still has active grants. A reviewer likely will wonder if the funds
might indirectly benefit the mentor instead of funding you. You must demonstrate
that you are independent and that your proposed research is your project.
Reviewers may also be skeptical when you are a long-term postdoctoral
researcher and your institution offers to make you a research assistant professor —
if you get a grant. NIH wants to see that your institution has already made you a
research assistant professor, not that it is making its commitment to you contingent
upon you getting the grant.
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Remember that institutional support also addresses your research’s feasibility,
including your freedom to carry out your research, away from classrooms,
advising, committees and other day-to-day duties that compete for your time.
Reviewers want to be sure that you will have both time and facilities to tackle the
research that you describe.
At the same time, some may believe that NIH chooses reviewers only from
“distinguished” institutions, which may create a sense of bias. But the average
study section likely offers a geographically and scientifically diverse panel, and
many reviewers work at or certainly appreciate the constraints of working at
institutions that might lack unlimited resources.
Resources Support Independence
There is no limitation regarding this section’s length as long the information
you provide specifically relates to your available facilities and resources.
As you write this section, there are some key elements that you should include
— if they are applicable to your proposal:
•Support your “intellectual rapport” section by explaining any collaborations
REMEMBER:
Institutional support
addresses your
research’s
feasibility,
including your
freedom to carry
out your research,
away from classrooms, advising,
committees and
other day-to-day
duties that compete
for your time.
with same-institution-based colleagues who impact your proposed research.
•Highlight the unique population of your locality, noting such things as
underserved groups, high incidences of specific diseases or conditions, rural/
urban setting, etc.
•Stress your access to pertinent resources based upon geography — for
example, proximity to veterans’ centers, public health facilities, children’s
hospitals and states’ departments of health, among others.
•Underscore proof of institutional support such as mentoring availability,
university-based grants, institutional clinical research centers and library
support.
•Make sure the Facilities and Other Resources matches your proposal’s budget
request section.
•Take advantage of the correct adjectives when describing your resources —
“specially-constructed modules,” “state-of-the-art laboratory,” “cutting-edge
clinical operations,” “dynamic imaging” and “centralized data collection,” to
get you started.
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In addition, if your research will involve animals, you must document the
animal facilities in this section. If your institution has accreditation from the
Association for Assessment and Accreditation of Laboratory Animal Care
STRATEGY:
Support your
“intellectual
rapport” section
by explaining any
collaborations with
same-institutionbased colleagues
who impact your
proposed research.
International (AAALAC), according to the National Institute of Allergy and
Infectious Diseases (NIAID), you do not need to detail basic items such as the
number of animal cages. Instead, you only have to note AAALAC accreditation.
On the other hand, if your institution does not have this accreditation, then you
must spell everything out.
One option as you construct this application document is to use subheads that
reflect NIH’s requirements. Although the agency does not require a special form for
this document, you might consider the following outline based upon NIH-requested
information and suggested items from several university grant administration offices:
Facilities and Other Resources
XXX University/Institution
In this section, outline the general scientific environment in which you will
conduct your research and how it will contribute to your proposal’s successful
outcomes.
Research Population: If you have human test subjects, include this section and
use it to note ways in which your research will benefit from the subject populations
in your area.
Research Facilities: Here, indicate how your institution’s resources will
support your proposed research. Denote any specific elements that will be
available, such as a machine shop, electronic shop, etc., and the extent to which
they will be available. Also, mention any additional institution-specific facilities
that might impact your proposal — for instance, associated children’s healthcare
centers, public clinics, veterans’ hospitals, etc. And if there are multiple research
sites, describe the resources available at each.
Biohazard Facility: If your research calls for using biohazards or other
possibly dangerous substances, you must describe any special facilities for working
with them.
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Collaborative Arrangements/Intellectual Rapport: Detail any collaborative
relationships with your institutional colleagues — such as mentors and other
investigators, among others.
Departmental Resources: In addition to institutional resources, be sure to
indicate any within your department or division that may benefit your research.
Institutional Support: As stated earlier, indicating your institution’s support
for you and your research is key for reviewers, and you should use this section for
this purpose. This can include available mentors, administrative support and grantwriting education.
Laboratory: In this section, detail your laboratory space, including the
location(s), number of rooms, dimensions and available equipment.
Animal: If your proposal involves using animal test subjects, you should
use this section to note AAALAC accreditation or, if that is lacking, provide
information regarding animal care resources.
Computer: Here, you should indicate the computers, databases, servers and
other data storage/computing equipment available for your project.
Office: Will your institution provide you and your collaborators/staff with
office space? If so, you should note this, including location(s), number of office(s)
and square footage.
Clinical: Use this section to note clinical facilities that are available at your
institution.
If you are an early-stage investigator, you should include all of the above, and
you can add the following section for the Facilities and Other Resources document:
Early-Stage Investigator
Resources for Continuing Education: In this section, note any institutional
resources for classes and/or training and career enrichment programs.
Institutional Support: You can break this section into the following two areas:
Mentorship: Detail how your institution/department fosters your research
efforts through a mentorship program.
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Collaboration: If your institution offers organized peer groups, you can note
that here.
Logistical Support: Indicate any assistance with administrative management
and oversight, as well as training offered regarding best lab management practices
and other topics.
Financial Support: If your institution ensures protected time for research with
salary support, startup funds or institution-sponsored grants, you should detail that
in this section.
Here is an example of a Facilities and Other Resources section from a successful
grant application (Tumor Necrosis Superfamily Ligands and Lymphocytes Role in
Liver Regeneration, Principal Investigator: Robert A. Anders, MD):
Resources:
Laboratory: Dr. X has 400 square feet of laboratory space located on the 3rd floor
of the Cancer Research Building within the 4,000 square foot area encompassing
the Division of Gastrointestinal/Liver Pathology laboratory. His laboratory is well
equipped for molecular biology work. The laboratory within which Dr. X is situated
contains a microfuge (2), vortexers, power supplies, programmable thermal cyclers for
PCR, refrigerator/freezers (2 each), a -80 C freezer, environmental shakers, waterbaths
(2), fume and biologic safety hoods, gel electrophoresis and preparative balances. In
addition, Dr. X has access to 250 square feet of shared facilities on the 3rd floor of the
Cancer Research Building, which includes an autoclaving and dishwashing service,
a dark room with a film processing unit, cold rooms, a densitometer, and ultra-pure
water source, a Stargene Eagle Eye II get imaging system, a Wallac TriLux multiplate
scintillation/luminescence counter, and a cryostat. A dedicated area for cell culture
work (~250 square feet) is also located on the 3rd floor immediately adjacent to his
research lab in the Cancer Research Building for which space is allocated to Dr. X’s
lab and contains sterile hood for culture work, incubators (2), water bath, a microscope
(1) and a refrigerator/freezer for storing culture related materials.
Shared resources: Within the 4,000 square feet of the Division of
Gastrointestinal/Liver Pathology there are many shared resources, which include:
an ABI 7300 real-time PCR machine, a NanoDrop spectrophotometer, sequencing
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rigs (8), analytic balances, pH meter, a Packard microplate flourometer, fluorescent
microscope with attached computer and image analysis software.
Animal facilities: Dr. X has allocated animal space in the facilities Cancer
Research Building. This space consists of up to 250 cages, which is enough to house
mice used in this proposal over the 5-year time period. Shared animal facilities are also
available in the Broadway Research Building. All animal work related to this proposal
by Dr. X’s laboratories. All facilities are compliant with local and federal regulations
concerning animal work and include procedure rooms, hoods with fume extraction to
perform surgeries under anesthesia, euthanizing facilities and storage rooms.
Computers: Dr. X is equipped with two Dell Optiplex GX400 PC computers
with Intel Pentium III processor containing CD-ROM/CD-RW, Zip drive, 17” flat
screen monitors and networked to a Hewlett-Packard L4050 laser printer. Both
computers contain Microsoft Office 2000, Reference Manager version 10, Corel
Draw Graphics Suite 11 and GeneCodes Sequencer software as well as Internet
access. These computers are also networked to two additional Dell Pentium III
computers and a Hewlett-Packard L4500 color laser printer.
The Department of Pathology has provided Dr. X with a Dell Pentium 4 optilex
GX620 computer, which is connected to the university’s intranet and the Internet.
The computer contains software enabling electronic mailing, Medline literature
searches and searches of all major protein and nucleic acid databases. Software
programs in the computer include word processing, statistical analysis, spreadsheet
analysis, and graphics.
Office: Dr. X’s office has 100 square feet of space and is located on the 3rd floor
of the Cancer Research Building. His lab space is located a short distance down the
hall. Photocopiers, a fax machine and secretarial support are available.
Other: The university’s medical institutions have numerous core facilities readily
available for use. Dr. X is also a member of the cancer center at the university,
which provided access to core facilities at a reduced pricing. These include two
DNA sequencing facilities, an oligonucleotide synthesis facility, a laser capture
microdissection facility, a cell imaging facility, and the tissue microarray facility. The
library is on-campus and most journals are available on line through a campus-wide
network. PathPhoto, a full service multimedia facility, is easily accessible.
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LIST YOUR AVAILABLE EQUIPMENT
In addition to your institution’s resources, your application also must list the
equipment available for your research.
Direct from NIH: The NIH Application Guide states:
List major items of equipment already available for this project and, if
appropriate identify location and pertinent capabilities.
What this means:
The list includes “major items of equipment.” And be sure to indicate their
locations and capabilities. NIH defines “equipment” as “an article of tangible,
nonexpendable, personal property that has a useful life of more than one year and
an acquisition cost of $5,000 or more, or the capitalization threshold established by
the organization, whichever is less.”
If your institution receives little NIH funding, however, the agency maintains
that you should list even basic items.
Here is an example of an Equipment list:
The lab is newly renovated space consisting of four rooms:
One lab is equipped for molecular biology and contains gradient PCR machine
in specialized hood, western blotting gel apparatus, digital balances, pH meter, 2
microwaves, and 1 microfuge, refrigerator and 2 water baths. The cytocentrifuge
will also be located there.
The second room contains BSL2 space, with 4 biosafety hoods, 5 CO2
incubators, counting microscope and an inverted microscope, 2 tabletop centrifuges,
refrigerated and unrefrigerated and 2 waterbaths. The outer area of this room contains
a refrigerator and -80 freezer. The variomax from Miltenyi is located here.
The third room contains the analytical Gallos flow cytometer, the Elisa plate
reader with computer, 2 centrifuges, and microfuge. In addition, the third room has
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a refrigerator for cold supplies, 2 waterbaths, and the fume hood. The TQ prep for
blood preparation is located there. There is also a robosep instrument from Stem
sep, which we will use to separate the microparticles via magnetic beads.
The fourth room is equipped for an office for the postdocs and has computers
with printers and cubicles for each person.
Access to other equipment includes access to milliQ water, ultracentrifuges,
Real time PCR machines, Luminex access, access to a dark and cold room.
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SHARING PLANS ADDRESS SPECIFIC RESEARCH
RESOURCES
NIH wants to know you will appropriately share any resources developed
through its grants and requires you to complete three plans as part of your
application in certain circumstances:
1.Data-Sharing Plan
2.Sharing Model Organisms
3.Genome-Wide Association Studies (GWAS)
Direct from NIH: The NIH Application Guide states:
NIH considers the sharing of unique research resources developed through
NIH-sponsored research an important means to enhance the value and further the
advancement of the research. When resources have been developed with NIH funds
and the associated research findings published or provided to NIH, it is important
that they be made readily available for research purposes to qualified individuals
within the scientific community. See Supplemental Instructions Part III, 1.5 Sharing
Research Resources.
1. Data Sharing Plan: Investigators seeking $500,000 or more in direct
costs (exclusive of consortium F&A) in any year are expected to include a brief
1-paragraph description of how final research data will be shared, or explain why
data-sharing is not possible. Specific Funding Opportunity Announcements may
require that all applications include this information regardless of the dollar level.
Applicants are encouraged to read the specific opportunity carefully and discuss
their data-sharing plan with their program contact at the time they negotiate
an agreement with the Institute/Center (IC) staff to accept assignment of their
application. See Data-Sharing Policy or http://grants.nih.gov/grants/guide/noticefiles/NOT-OD-03-032.html.
2. Sharing Model Organisms: Regardless of the amount requested, all
applications where the development of model organisms is anticipated are expected
to include a description of a specific plan for sharing and distributing unique model
organisms or state why such sharing is restricted or not possible. See Sharing
Model Organisms Policy, and NIH Guide NOT-OD-04-042.
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3. Genome Wide Association Studies (GWAS): Applicants seeking funding for
a genome-wide association study are expected to provide a plan for submission
of GWAS data to the NIH-designated GWAS data repository, or an appropriate
explanation why submission to the repository is not possible. GWAS is defined as
any study of genetic variation across the entire genome that is designed to identify
genetic associations with observable traits (such as blood pressure or weight) or the
presence or absence of a disease or condition. For further information see Policy
for Sharing of Data Obtained in NIH Supported or Conducted Genome-Wide
Association Studies, NIH Guide NOT-OD-07-088, and http://gwas.nih.gov/.
What this means:
These are separate documents that you upload as part of your application, but
they do not count toward the application page limit.
Keep in mind that reviewers will comment on your resource sharing plans. If
you argue that your resources should not be shared — which is an option in specific
situations — they will scrutinize any rationale you propose as well.
Data-Sharing Plan
If your grant application requests $500,000 or more in direct costs in any year
of the proposed research, NIH expects you to include a data-sharing plan with
your proposal. Remember also that if your application is a response to a particular
Funding Opportunity Announcement, that announcement might require you to
submit this plan regardless of the funding level.
REMEMBER:
If you argue that
your resources
should not
be shared — which
is an option in
specific situations
— reviewers will
scrutinize any
rationale you
propose as well.
The data-sharing plan should consist of a brief, one-paragraph description
regarding how you will share your final research data. Alternatively, if you feel that
data-sharing is not possible, you should use this plan to explain why.
What to Include
The exact content of your data-sharing plan will depend on the data you collect
and how you plan to share it. For instance, your data-sharing plan might simply
describe the following:
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•Expected data-sharing schedule,
•Final dataset’s format,
•Documentation to be provided,
•Whether you will provide any analytic tools,
•If you will require a data sharing agreement, including a brief description of
the agreement, and
•Mode of data sharing.
Consider the following example from NIH:
This application requests support to collect public-use data from a survey of
more than 22,000 Americans over the age of 50 every 2 years. Data products from
this study will be made available without cost to researchers and analysts.
User registration is required in order to access or download files. As part of the
registration process, users must agree to the conditions of use governing access
to the public release data, including restrictions against attempting to identify
study participants, destruction of the data after analyses are completed, reporting
responsibilities, restrictions on redistribution of the data to third parties, and proper
acknowledgement of the data resource. Registered users will receive user support,
as well as information related to errors in the data, future releases, workshops, and
publication lists. The information provided to users will not be used for commercial
purposes, and will not be redistributed to third parties.
Some data-sharing plans, however, may be more elaborate. For instance, here is
an example from an actual grant application from the National Institute of Allergy and
Infectious Diseases (NIAID) — Note: Redacted material is indicated by brackets ([]):
Sharing of data generated by this project is an essential part of our proposed
activities and will be carried out in several different ways. We would wish to
make our results available both to the community of scientists interested in [this
disease] and the biology of [its causative agent] to avoid unintentional duplication
of research. Conversely, we would welcome collaboration with others who could
make use of the vaccine assessment protocols developed in [the project].
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Our plan includes the following:
Presentations at national scientific meetings. From the projects, it is expected
that approximately four presentations at national meetings would be appropriate.
There is an annual [Disease] Study Group meeting, of which the PI is secretary.
This one-day meeting of interested persons presents new information on a variety
of topics related to [the disease]. It is expected that the investigators from this
[project] will be active participants of this focused group.
Annual lectureship. A lectureship has brought to the University distinguished
scientists and clinicians whose areas of expertise were relevant to those interested
in [the disease]. Lecturers have been [list of names]. Visiting lecturers will be
scheduled to interact with the investigators of the project as appropriate with
their specific areas of expertise which will provide an opportunity for members to
present their work to the visitor.
Newsletter. The [disease interest group] publishes a newsletter which currently
has a circulation of [number]. The newsletter’s intent is to disseminate new
information regarding [the disease]. The activities and discoveries of [the project]
will be allocated 20% of the newsletter’s coverage.
Web site of the Interest Group. The [interest group] currently maintains
a Web site where information [about the disease] is posted. Summaries of the
scientific presentation from the [quarterly project] meetings will be posted on this
Web site, written primarily for a general audience. [Link to Web site.]
Annual [Disease] Awareness week. Beginning this fall during the week of
[date], the [interest group] will be sponsoring a [Disease] Awareness week. As part
of that program, there will be a research poster display with discussions. In future
years, [the project investigators] will be active participants in this program.
SAGE Library Data. [This project] will generate data from several SAGE
libraries. It is our explicit intention that these data will be placed in a readily
accessible public database. All efforts will be made to rapidly release data through
publication of results as quickly as it is possible to analyze the experiments. Data
used in publications will be released in a timely manner. SAGE data will be made
accessible through a public site that allows querying as has been set up for a similar
project. This site can be accessed at [link to Web site].
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Alternatively, if you need to justify why you will not share data or wish to
restrict it, NIH offers the following examples:
Example 1
The proposed research will involve a small sample (less than 20 subjects)
recruited from clinical facilities in the New York City area with Williams syndrome.
This rare craniofacial disorder is associated with distinguishing facial features, as
well as mental retardation. Even with the removal of all identifiers, we believe that
it would be difficult if not impossible to protect the identities of subjects given the
physical characteristics of subjects, the type of clinical data (including imaging) that
we will be collecting, and the relatively restricted area from which we are recruiting
subjects. Therefore, we are not planning to share the data.
Example 2
The proposed research will include data from approximately 500 subjects being
screened for three bacterial sexually transmitted diseases (STDs) at an inner city
STD clinic. The final dataset will include self-reported demographic and behavioral
data from interviews with the subjects and laboratory data from urine specimens
provided. Because the STDs being studied are reportable diseases, we will be
collecting identifying information. Even though the final dataset will be stripped of
identifiers prior to release for sharing, we believe that there remains the possibility
of deductive disclosure of subjects with unusual characteristics. Thus, we will
make the data and associated documentation available to users only under a datasharing agreement that provides for: (1) a commitment to using the data only for
research purposes and not to identify any individual participant; (2) a commitment
to securing the data using appropriate computer technology; and (3) a commitment
to destroying or returning the data after analyses are complete.
Further, if you submit a data-sharing plan, NIH expects you to enact that
plan. If you fail to comply — depending on the severity and duration of the
noncompliance — the agency can act to protect its interests. For example, NIH
may make data sharing an explicit term and condition of any subsequent awards
you receive.
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The NIH also offers the following as a template example plan for addressing
key elements for a data sharing plan under NIH extramural support:
Example Data Sharing Plan for FOA-XX-XXXX
What data that will be shared:
I will share phenotypic data associated with the collected samples by depositing
these data at ________________ which is an NIH-funded repository. Genotype
data will be shared by depositing these data at ________________. Additional
data documentation and de-identified data will be deposited for sharing along
with phenotypic data, which includes demographics, family history of XXXXXX
disease, and diagnosis, consistent with applicable laws and regulations. I will
comply with the NIH GWAS Policy and the funding IC’s existing policies on
sharing data on XXXXXX disease genetics to include secondary analysis of data
resulting from a genome wide association study through the repository. Metaanalysis data and associated phenotypic data, along with data content, format, and
organization, will be available at ____________. Submitted data will confirm with
relevant data and terminology standards.
Who will have access to the data:
I agree that data will be deposited and made available through
________________ which is an NIH-funded repository, and that these data
will be shared with investigators working under an institution with a Federal
Wide Assurance (FWA) and could be used for secondary study purposes such
as finding genes that contribute to process of XXXXXX. I agree that the names
and Institutions of persons either given or denied access to the data, and the bases
for such decisions, will be summarized in the annual progress report. Metaanalysis data and associated phenotypic data, along with data content, format, and
organization, will be made available to investigators through ____________.
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Where will the data be available:
I agree to deposit and maintain the phenotypic data, and secondary analysis of
data (if any) at ________________, which is an NIH-funded repository and that
the repository has data access policies and procedures consistent with NIH data
sharing policies.
When will the data be shared:
I agree to deposit genetic outcome data into ________________ repository as
soon as possible but no later than within one year of the completion of the funded
project period for the parent award or upon acceptance of the data for publication,
or public disclosure of a submitted patent application, whichever is earlier.
How will researchers locate and access the data:
I agree that I will identify where the data will be available and how to access
the data in any publications and presentations that I author or co-author about these
data, as well as acknowledge the repository and funding source in any publications
and presentations. As I will be using ________________, which is an NIH-funded
repository, this repository has policies and procedures in place that will provide
data access to qualified researchers, fully consistent with NIH data sharing policies
and applicable laws and regulations.
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Sharing Model Organisms
If your research anticipates developing model organisms, regardless of
your award amount, NIH requires you to include a specific plan for sharing and
distributing unique model organisms or indicate why such sharing is not possible
or restricted.
Direct from NIH: The NIH Application Guide and Web site (http://grants.nih.
gov/grants/policy/model_organism/model_organisms_faqs.htm) state:
All applications where the development of model organisms is anticipated are
expected to include a description of a specific plan for sharing and distributing
unique model organism research resources generated using NIH funding so that
other researchers can benefit from these resources, or state appropriate reasons
why such sharing is restricted or not possible. Model organisms include but are not
restricted to mammalian models, such as the mouse and rat; and non-mammalian
models, such as budding yeast, social amoebae, round worm, fruit fly, zebra
fish, and frog. Research resources to be shared include genetically modified or
mutant organisms, sperm, embryos, protocols for genetic and phenotypic screens,
mutagenesis protocols, and genetic and phenotypic data for all mutant strains.
This expectation is for all applications where the development of model
organisms is anticipated, regardless of funding amount.
The term “model organism” includes mammalian models, such as the mouse
and rat, and non-mammalian models, such as budding yeast, social amoebae,
roundworm, Arabidopsis, fruit fly, zebrafish, and frog. Examples of model
organisms for which a sharing plan is expected when new, genetically modified
organisms are developed is posted on the NIH Model Organism for Biomedical
Research Web site (http://www.nih.gov/science/models/). This list is updated
periodically. Although genetic variants of viruses, bacteria, and other prokaryotic
organisms should be made widely available pursuant to the NIH policy (see
FAQ4), at this time NIH is not expecting the submission of a sharing plan from
investigators who intend to develop non-eukaryotic organisms. Genetically
modified organisms are those in which mutations have been induced by chemicals,
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irradiation, transposons or transgenesis (e.g., knockouts and injection of DNA into
blastocysts), those in which spontaneous mutations have occurred, and congenic
or consomic strains. Depending on accepted practice, new, genetically modified
model organisms developed with NIH funding may be shared as mature organisms,
sperm, eggs, embryos, or even the vectors used to generate transgenic or knockout
organisms (refer to FAQ 17). The term “resources” includes materials and data
necessary for the production and understanding of model organisms, such as
vectors, non-human embryonic stem cells, established cell lines, protocols for
genetic and phenotypic screens, mutagenesis protocols, and genetic and phenotypic
data for all mutant strains.
What it means:
Unlike the data-sharing plan, there is no grant award threshold associated with
the model organism sharing plan.
Model organisms are new, genetically modified organisms developed for
research. Genetically modified organisms are those in which the mutations have
been induced by chemicals, irradiation, transposons or transgenesis (for example,
knockouts and injection of DNA into blastocysts), those in which spontaneous
mutations have occurred, and congenic or consomic strains. And these new model
organisms may be shared as mature organisms, sperm, eggs, embryos or vectors
used to generate transgenic or knockout organisms.
Further, model organisms include mammalian models, such as mice and rats,
and non-mammalian models, like budding yeast, social amoebae, roundworm,
Arabidopsis, fruit fly, zebrafish and frog. You can find examples of model
organisms on the NIH Model Organism for Biomedical Research Web site at
www.nih.gov/science/models.
The agency also notes that you should make genetic variants of viruses,
bacteria and other prokaryotic organisms available under the model organism
sharing policy. “At this time NIH is not expecting the submission of a sharing plan
from investigators who intend to develop non-eukaryotic organisms.”
When considering the resources that you must share as part of the model
organism sharing plan, NIH indicates that you should include “materials and data
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necessary for the production and understanding of model organisms,” including
vectors, non-human embryonic stem cells, established cell lines, protocols for
genetic and phenotypic screens, mutagenesis protocols, and genetic and phenotypic
data for all mutant strains.
NIH does not place a page limit on your model organism sharing plan and notes
that these can range from a simple paragraph to complex, multipage documents.
Here is an example of simple model organism sharing plan from NIH:
As for our plan to share materials and our management of intellectual
property, we will adhere to the NIH Grant Policy on Sharing of Unique Research
Resources including the Sharing of Biomedical Research Resources Principles
and Guidelines for Recipients of NIH Grants and Contracts issued in December,
1999. All model organisms generated by this project will be distributed freely
or deposited into a repository/stock center making them available to the broader
research community, either before or immediately after publication. Our lab has
demonstrated its commitment to sharing by providing … over the past X years. If
we assume responsibility for distributing the newly generated model organisms,
we fill requests in a timely fashion. In addition, we will provide relevant protocols
and published genetic and phenotypic data upon request. Material transfers will be
made with no more restrictive terms than in the Simple Letter Agreement (SLA)
or the Uniform Biological Materials Transfer Agreement (UBMTA) and without
reach-through requirements. Should any intellectual property arise which requires
a patent, we will ensure that the technology (materials and data) remains widely
available to the research community in accordance with the NIH Principles and
Guidelines document.
A moderately complicated model organism sharing plan is also possible, and
these frequently involve the use of mammalian models. NIH provides this model
organism plan example from an application involving mice:
Following the characterization and peer-reviewed publication of the transgenic
mouse strain generated, mice will be freely distributed to investigators at academic
institutions wanting mice for non-commercial research. Individual requests for
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shipment of mice generated by this program project funding to AAALAC (Association
for Assessment and Accreditation of Laboratory Animal Care International) accredited
institutions will be honored. The recipient investigators would provide written
assurance and evidence that the animals will be used solely in accord with their local
IACAC review; that animals will not be further distributed by the recipient without
consent of our Program; that animals will not be used for commercial purposes.
Requests for mice from for-profit corporations to use the mice commercially
will be negotiated by our institution’s technology transfer office. All licensing shall
be subjected to distribution pursuant to my institution’s policies and procedures on
royalty income. The technology transfer office will report any invention disclosure
submitted to them to the appropriate Federal Agency.
In addition, all of the transgenic mice generated will be deposited in at an NIHsupported mouse repository. NIH-supported repositories cryopreserve embryos or
sperm and distribute the frozen embryos or mice to biomedical researchers. For
the mice I generate I will use standard nomenclature and receive approval from
the Mouse Genome Informatic (MGI) nomenclature committee
(http://www.informatics.jax.org/mgihome/nomen/index.shtml).
To facilitate sharing and distribution of the transgenic/knockout mice and
associated resources developed under this grant, mice will be maintained in a specific
pathogen-free facility. This facility will maintain the mice free of the following
microorganisms and pathogens (e.g., pinworms, mouse hepatitis virus (MHV), Sendai
virus, mycoplasma, mites, etc.). Should the transgenic/knockout mice become infected
with any of these microorganisms, the mice will be rederived through embryo transfer.
“Other Research Resources” generated with funds from this grant will include
DNA constructs, etc. These resources, as available, would also be freely distributed
upon request to qualified academic investigators for non-commercial research.
My institution and I will adhere to the NIH Grants Policy on Sharing of Unique
Research Resources including the “Sharing of Biomedical Research Resources:
Principles and Guidelines for Recipients of NIH Grants and Contracts” issued
in December, 1999. Specifically, material transfers would be made with no
more restrictive terms than in the Simple Letter Agreement or the UBMTA and
without reach-through requirements. Should any intellectual property arise which
requires a patent, we would ensure that the technology remains widely available
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to the research community in accordance with the NIH Principles and Guidelines
document.
And finally, the model organism sharing plan can become quite complex.
Examine the following NIH-offered example:
Special Requirements Section of RFA-XX-OI-011
1. Plans to share research resources. All vectors for transgenic production and
mouse strains generated over the past several years have been distributed freely
to the broader academic community, either before or immediately on publication.
Indeed we have supplied over 250 requested laboratories with either vectors,
mice, or both. Requestees typically receive the desired reagents within two weeks
to two months of their request, depending on their chronological position in the
queue. The infrastructure for this rapid sharing of newly developed reagents (both
vectors and mice) continues to be in place in my lab and supported by the Office of
Technology and Licensing, Applicant Institution (see attached letter by XXXXX).
2. Intellectual property rights. Consistent with Applicant Institution’s policy
on intellectual property rights (see attached letter by XXX), my lab will make
available any and all strains of transgenic mice produced under this grant for
use at other academic or not-for-profit institutions at no cost except for standard
maintenance and transportation expenses. (Applicant Institution) will receive the
right to use these reagents for educational, research, or other nonbusiness purposes.
Applicant Institution may establish a non-exclusive commercial license granting
Applicant Institution’s rights to use such animals at specific for-profit entities; in
these cases, Applicant Institution will maintain the right to grant non-exclusive
licenses for use of these materials by academic or not-for-profit institutions.
Transfer of materials to not-for-profit entities will be implemented under terms
no more restrictive than the Uniform Biological Materials Transfer Agreement (see
example of the Applicant Institution simple letter MTA attached in the appendix).
Transfer of materials to for-profit entities will be mediated through the Applicant
Institution Office of Technology and Licensing, and typically involves a simple
license agreement with execution or annual fees as deemed appropriate, but in no
way prohibitive to the ready distribution of these reagents.
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Intellectual property rights as pertains to ABC-XYZ reagants.The Non-Profit
Institute holds a patent on the use of ABC in mammalian cells. They have made
clear that any reagents harboring ABC or XYZ sequences can be freely distributed
amongst academic, not-for-profit institutions. Such transfers would be done under
a joint Applicant Institution/Non-Profit Institute simple letter MTA (see attached
letter from Dr. XXX, Office of Technology and Licensing, Applicant Institution).
Should reagents be transferred to for-profit institutions, an inter-institutional license
(Applicant Institution/Non-Profit Institute) will be drafted with execution or annual
fees as deemed appropriate, but in no way prohibitive to the ready distribution of
these reagents. Those reagents generated in collaboration with Dr. SSSS would
require an inter-institutional MTA involving Applicant Institution/Non-Profit
Institute/Non-Profit Research Center. These simple agreements are already in place.
Intellectual property rights as pertains to @@@ reagents. For-Profit Company
holds a patent on the use of @@@ in @@@@. The memorandum of understanding
between For-Profit Company and PHS makes it clear that any and all @@@
containing reagents generated under this grant can be readily shared with the broader
academic community under a simple MTA, and do not infringe on the uses under
restriction (namely: @@@@, @@@ and @@@). Should our reagents be transferred
to for-profit institutions, an inter-institutional license (Applicant Institution/For-Profit
Company) will be drafted with execution or annual fees as deemed appropriate. Of
course, current For-Profit Company licensing issues as surrounds for-profit institutions
would have to be settled between that institution and For-Profit Company.
Intellectual property rights as pertains to the &&& locus. The Non-Profit
Research Center holds a license on use of &&& sequences. This license stipulates
free use for academic, not-for-profit institutions and involves a simple letter MTA.
Those reagents generated in collaboration with Dr. SSSS that incorporate &&&
sequences will require an inter-institutional MTA involving Applicant Institution
Medical School and Non-Profit Research Center. These simple agreements are
currently in place. Should reagents be transferred to for-profit institutions, an interinstitutional license (Applicant Institution Medical School/Non-Profit Research
Center) will be drafted with execution or annual fees as deemed appropriate, but in
no way prohibitive to the ready distribution of these reagents.
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Genome-Wide Association Studies (GWAS)
If your proposal includes GWAS, regardless of the amount of the award you
are requesting, you must include a plan for submitting GWAS data to the NIHdesignated data repository or provide a suitable explanation for why this is not
possible.
Direct from the NIH Web site (http://gwas.nih.gov/pdf/gwas_data_sharing_
plan.pdf):
In developing a data-sharing plan, the applicant should consider the following:
•Will the data be shared in accordance with the NIH GWAS Policy?
oState whether your IRB or Privacy Board has approved the data-sharing
aspects of your project, or the timeline for such approval.
oIf your application or proposal is being considered for funding and involves
human subjects research, IRB approval typically is required prior to grant
award (just-in-time) or finalization of a contract.
•When data are shared in accordance with NIH GWAS data repository:
oWhich data will be shared?

Describe the data elements, study populations, and study documents that
will be included in the data-sharing. The minimum expectation is that data
generated and used for funded analyses and documentation sufficient for
interpretation of data (e.g., study protocol and manuals, data collection
instruments) will be shared.
oWhose data will be shared?

Will data from all study participants that are included in the analyses be
shared?

If only a subset will be shared, provide the rationale (e.g., tiered consent
that addresses/addressed sharing).
oWhen will the data be shared?

Provide a timeline for data-sharing. The expectation is that data will be
shared once the data have been cleaned.
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oWill there be restrictions on use limitations for the shared data?

This should be determined in consultation with your institution. Your
institution will document appropriate uses of the data and data use
limitations as part of the institutional certification. Verification of the
appropriate uses of the data and data use limitations stated in your datasharing plan may be requested from your institution prior to award.

E.g., Use may be limited to studies of specific conditions or traits, or
certain types of uses or users (e.g., non-commercial use only).

Is additional consent needed for sharing data as described in the NIH
GWAS Policy? If a new consent process is necessary, the application may
include plans and budget for a new consent process.
•If the data will not be shared through the NIH GWAS data repository:
oWhat is the justification for not sharing?

E.g., For use of existing data/specimens, your institution may determine
that consent is not adequate for data-sharing as described in the NIH
GWAS Policy, and it may not be possible to obtain additional consent
(e.g., due to the age of the data/specimens).

Other issues may preclude sharing such as local laws and limitations,
concerns about harms to individuals or groups, or other cases where the
expectations of the data submission cannot be met.
oSpecify an alternative data-sharing plan, if another data-sharing mechanism
is acceptable.
What it means:
When writing your GWAS plan, you first must state whether you will share the
data according to NIH’s policy, including the following details:
•Whether your institutional review board (IRB) or privacy board has approved
your application’s data-sharing aspects, or the timeline for acquiring such
approval.
•If your proposal involves human subjects research, NIH typically requires
IRB approval prior to awarding a grant or finalizing a contact.
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Next, you would outline the following:
•Describe the data to be shared, including the data elements, study populations
and study documents. At a minimum, NIH expects you to share data
generated and used for funded analyses and documentation sufficient for data
interpretation — for example, study protocol and manuals and data collection
instruments.
•Detail whether you will include data from all study participants in shared
analyses. If you will share only a subset, provide a rationale for this decision,
such as tiered consent that addresses sharing.
•Provide a timeline regarding when you will share the data — remember that
NIH expects you to share the data once it has been cleaned.
•Outline any use limitations for the shared data. You should determine this by
consulting your institution, which will document appropriate uses of the data
and limitations as part of the institutional certification. And your institution
may request verification of the appropriate data use stated in the data-sharing
plan prior to award. For example, your institution may limit use to studies of
specific conditions or traits, or certain types of uses or users. Also note any
additional consent needed for data sharing in this section.
If you plan not to share data through the NIH GWAS data repository, you
should include the following information:
•Provide a justification for not sharing. For example, if you are using existing
data/specimens, your institution may determine consent is not adequate for
data-sharing as described by the NIH GWAS policy, and obtaining additional
consent may not be possible because of the age of data/specimens, for
instance.
•Specify an alternate data-sharing plan if there is a mechanism that is
acceptable.
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Now, review the following example GWAS data-sharing plans from NIH:
The university IRB has advised us that the genome-wide association data
produced through this award may be shared through the NIH GWAS data
repository, consistent with data-sharing under the NIH data-sharing policy for
genome-wide association studies. The IRB will review the data-sharing aspect of
this project at their March meeting. We have asked the IRB to verify that:
•The submission of data to the NIH GWAS data repository and subsequent
sharing for research purposes will be consistent with the informed consent
requested of study participants from whom the data and specimens will be
obtained;
•The investigator’s plan for de-identifying datasets is consistent with the
standards outlined in the NIH GWAS Policy;
•It has considered the risks to individuals, their families, and groups or
populations associated with data to be submitted to the NIH GWAS data
repository; and
•The genotype and phenotype data to be submitted will be collected in a
manner consistent with 45 C.F.R. Part 46.
We will share study documents, individual-level genotype and phenotype data,
and other study information described in the Policy, for the study population. We
will share the individual-level genome-wide genotyping data produced as part of
Specific Aim 1, and the individual-level phenotypic data included in the analyses
under Specific Aim 2. Genotyping data will include the genotypes as well as the
intensity files used to call the genotypes. Phenotype data will include the outcomes
and traits described in Table 2, and the additional analysis variables described
in Table 3. A number of these are derived variables, and we will provide the
underlying variables as well. The study will also collect a number of additional
variables which will be shared (Appendix 2). Data will be shared for all of the
study participants included in these analyses; participants who do not give consent
for sharing data will be excluded from the study (“Study population” section).
For study documentation, the study protocol and manual of operations, as well
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as questionnaire and data abstraction forms, will be provided. We will share the
genotype and phenotype data once the genotyping data have been cleaned; we
expect the cleaning to be complete no more than two months after genotyping is
finished. This is month 24 in the proposed study timeline. The draft consent form
provides for tiered consent, including data being used for any studies of genetics
and health, or data being used for any genetic studies of mood and factors that
affect mood. Data use limitations will be verified, and appropriate uses provided in
more detail, by the university IRB.
We also plan to release the data to qualified researchers who wish to collaborate
with the study investigators. The availability of data for collaborators will be
advertised on the study Web site. The data will be available through a secure FTP
site maintained by the university’s IT department, or sent on encrypted physical
media via trackable mail.
We acknowledge the intellectual property and scientific publication elements of
the NIH GWAS Policy.
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CONCLUSION
Environment is one of the core criteria that NIH reviewers will use to assess
your grant application. Therefore, you cannot afford to give your Facilities and
Other Resources section short shrift. And simply providing a list of lab equipment
and supplies that you will have access to will not suffice as well.
You will have to demonstrate that your institution is behind you and your
research. And this is particularly true for early-stage investigators.
Similarly, NIH requires you to indicate how you will share your data, model
organisms and GWAS. This is an effort by the agency to enhance the value of your
research and promote additional investigations in your field. The plans you propose
for sharing these materials — or refusing to do so — will be part of the materials
reviewers will scrutinize and use to assess your application. n
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Chapter 4: Proving Your Research Topic’s Significance
Chapter 4:
Proving Your Research Topic’s Significance
Probably the most important parts of your National Institutes of Health
(NIH) R01 application are those in which you describe your proposed research.
Specifically, these are the Specific Aims and Research Strategy sections. They
address your project’s Significance, Innovation and Approach, which are three of
the five core grant criteria that reviewers use to score your application.
At the same time, these sections will heavily influence your application’s
Overall Impact score. Unfortunately, there is no template for incorporating overall
impact into your application, and there is no section called “Overall Impact” —
or even an incentive to simply add a paragraph labeled as such. Instead, the NIH
Office of Extramural Research has stated that you should describe “impact” clearly
in the words you feel are relevant to your project.
Consequently, we will examine how you can use the Specific Aims and
Research Strategy to perform double-duty:
1. Fulfill the Significance, Innovation and Approach criteria
2. Support the Overall Impact of your research
As you address each of these sections, note that NIH limits your Specific Aims
to no longer than one page, and the Research Strategy cannot exceed 12 pages for
an R01 application.
Language Is Important
Also keep in mind that although terms like “aims,” “goals,” and “objectives”
may seem interchangeable, they have separate meanings within your application.
•Goals are strategic and high-level. For instance, “Our goal is to understand
signal transduction in breast cancer.”
•Objectives often are a restatement of your hypothesis in a way that can be
falsifiable. For example, if our hypothesis is that the EGF receptor axis is key
in mediating steroidal effects on proliferation, your objective would be to
determine the mechanism by which that occurs.
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•Aims are the outlines of your tactics or tasks to be performed. For instance,
“Aim 1 is to establish a culture system of primary breast epithelial cells,” or
“I have accomplished this aim.”
Or think of it using this analogy:
•Goals are the view from 30,000 feet
•Objectives are the view from 10,000 feet
•Specific Aims are the view from 1,000 feet
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SPECIFIC AIMS NAIL DOWN THE STEPS
Direct from NIH:
State concisely the goals of the proposed research and summarize the expected
outcome(s), including the impact that the results of the proposed research will exert
on the research field(s) involved.
List succinctly the specific objectives of the research proposed, e.g., to test a
stated hypothesis, create a novel design, solve a specific problem, challenge an
existing paradigm or clinical practice, address a critical barrier to progress in the
field, or develop new technology.
Follow the page limits for the Research Strategy in the Table of Page limits at
http://grants.nih.gov/grants/forms_page_limits.htm unless specified otherwise in
the FOA.
What this means:
In this section, NIH indicates that you should briefly list your research’s
specific objectives, which may include the following:
•Test your hypothesis
•Solve a specific challenge
•Challenge an existing paradigm or clinical practice
•Address a critical barrier to progress in the field
•Develop new technology.
Individual NIH Institutes, Centers or Offices (ICOs) may have additional
suggestions for crafting your Specific Aims. For instance, the National Cancer
Institute (NCI) indicates that your Specific Aims should cover the following:
•Broad, long-term goals;
•Specific objectives and hypotheses to be tested;
•Expected outcomes; and
•Impact on the research field.
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NCI further recommends that your Specific Aims should include the following
sections:
1.Brief narrative to describe the project’s long-term goals and the
hypothesis(es) to be tested, which you should adequately support with
citations and preliminary data. Explain how you will use the results to test
the hypothesis.
2.Numbered list of the aims. For clarity, each aim should consist of only one
sentence. Use a brief paragraph under each aim if you need to provide detail.
Most successful applications have two to four Specific Aims. And be sure
that all aims are related — but not necessarily dependent upon each other.
3.Brief statement regarding the overall impact of the research.
Specific Aims are almost always limited to a single page in length, unless
otherwise stated in the FOA.
Keep in mind that reviewers usually receive a small, focused project better than
a diffuse, multifaceted project.
Some reviewers have called the Specific Aims the most important page in your
entire application because it may be the only section unassigned reviewers read
TIP:
to understand your Approach, Innovation and Overall Impact. They may make up
Keep in mind that
reviewers usually
receive a small,
focused project
better that a diffuse,
multifaceted project.
their minds immediately whether your work should receive funding, and then read
the rest of your proposal searching for details to reinforce their initial opinions.
If they immediately determine that they like your project, they will look for
supportive points they can put in their review. On the other hand, if they decide
they do not like it, they probably will begin to search for faults.
The Specific Aims is a one-page document that you will upload in the Research
Plan Attachments area of the application.
Format Note: The Specific Aims section must follow the general application
formatting requirements. You must use one of the following fonts in 11 point size
or larger:
•Arial
•Helvetica
•Palatino Linotype or
•Georgia
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You may use a symbol font to insert Greek letters or special characters, but
the font size requirement still applies. In addition, there can be no more than 15
characters — including characters and spaces — per inch. And there can be no
more than six lines of text per inch, using at least half-inch margins on all sides of
the 8½” x 11” page.
Overcome Specific Aims Challenges
There are several common challenges that applicants face — and proven
ways to overcome them — that specifically apply to their Specific Aims,
including the following:
Challenge 1: If your reviewer reads your Specific Aims and finds them
interesting but remains unconvinced, she likely will read the rest of your application
to determine if your project is feasible. Therefore, be sure to end the page with a brief
paragraph that states your work’s impact — that is, how your project, if successful,
will change your field of research. Spelling this out for the reviewer allows them to
easily grasp your proposal’s strengths without having to work for it.
For example: “These two innovative methods, as well as the expertise of
the team assembled, will combine to examine whether microparticles can offer
important windows on the physiologic world of pregnancy and preeclampsia and
set the stage for further longitudinal studies that seek to predict preeclampsia to
allow for early treatment.”
Challenge 2: Reviewers often make the following comment on the summary
statement: “If the first specific aim doesn’t work, the whole proposal goes out the
window. If the researcher doesn’t get a positive result with it, he or she can’t do
aims 2 or 3, so we’re not going to fund this until we see the data that have basically
finished Aim 1.”
If the aims follow each other so that Aim 2 follows Aim 1 and Aim 3 follows Aim
2, you must tell the reviewers what you intend to do if you get an unexpected result
with Aim 1. Convince them that there is a future to your proposal nonetheless.
The best grant applications are those with interconnected — but not
STRATEGY:
If the aims follow
each other so that
Aim 2 follows Aim
1 and Aim 3 follows
Aim 2, you must
tell the reviewers
what you intend
to do if you get an
unexpected result
with Aim 1.
interdependent — aims. Reviewers look for those experiments where the results do
not particularly matter because the various outcomes are equally interesting.
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For example, interconnected Specific Aims might include the following:
Specific Aim 1: Test the hypothesis that plasma microparticles
detected in pregnant women will reveal physiologic events during
gestation and preeclampsia.
Specific Aim 2: Test the hypothesis that proteomics performed
on microparticles over gestation and on subsets of microparticles
from normal and preeclamptic women will reveal key differences in
protein expression patterns associated with preeclampsia.
Challenge 3: If you are submitting a competitive renewal and change the thrust
of your research from the original proposal, tell reviewers why you changed the
Specific Aims, and detail your new directions. The reviewer will see the summary
statement from the initial award and know your original award’s Specific Aims.
Some reviewers are very particular about that, wondering, “Did the Principal
Investigator succeed in the first five years?” If not, they likely will not give that
PI for a second chance. As a result, you must inform reviewers why you changed
directions, such as because something came up that was more interesting to pursue
or a new technology became available.
Crafting Your Specific Aims
TIP:
Three to four aims
support enough
hypothesis-testing
strategies and
description within
the application
and better support the number of
researchers under
the budget and
likely four-year
project duration.
115 The three or four Specific Aims that make up the body of your research plan are
the real engine that drives your application. Why is it usually three or four aims?
There is no rule regarding how many aims your proposal should have, but three or
four is the average for most NIH R01 applications.
An application with only one or two aims leaves the reviewer to weigh only
one or two strategies to test your hypothesis, which means it likely does not have a
broad enough scope to truly impact the field.
With more than four aims, space limitations will not allow you to sufficiently
describe your aims to convince reviewers you have fully developed them. Three
to four aims support enough hypothesis-testing strategies and description within
the application and better support the number of researchers under the budget and
likely four-year project duration.
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You might consider using a standard format for each of your aims using
separate sections. One reviewer recommends breaking your aims down into the
following:
•Rationale — This provides the strategic context, meaning what you are
trying to show and why. This is also the place where you defend the specific
approach you plan to use, consider alternatives and begin to describe your
logic in designing your experiments.
•Experimental Approach — Here, detail how the experiments will be
performed. Try to build reviewer confidence that you can perform them. For
established investigators, you can highlight key papers in your bibliography
that support your experience in the proposed techniques. New investigators
either must show preliminary data demonstrating such familiarity or recruit
collaborators with widely-acknowledged expertise in the method.
•Outcomes and Alternatives — Use this section to describe your
experiments’ potential results and their implications for your proposed
model(s).
You should also consider including an experimental flow chart that provides a
glimpse into the broader strategic thinking guiding your project. Such flow charts
can illustrate how your plan to prioritize between the different approaches, which
outcomes confirm — or undermine — your model, and available alternatives if an
experiment fails.
Rely on This Example
Here is a Specific Aims example from a successful NIH grant application
(Combining Anti-Invasive and Anti-Angiogenic Therapies for the Treatment of
GBM, Principal Investigator: Panagiotis Z. Anastadiadis, PhD). Keep in mind that
as originally submitted, this section takes up just over one page but here appears on
two pages because of our formatting changes:
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Instant angiogenesis is a hallmark feature of glioblastoma multiforme (GBM)
that contributes to the highly malignant nature of the tumor. Recent studies with the
humanized monoclonal antibody bevacizumab, which targets the pro-angiogenic
factor VEGF, have demonstrated significant therapeutic benefit in patients with
recurrent GBM. Unfortunately, bevacizumab therapy alters the natural history of
the disease, and tumor recurrence on anti-angiogenic therapy often is characterized
by an aggressive multi-focal disease progression associated with a rapid clinical
decline. Thus, with bevacizumab therapy rapidly becoming the standard of care
for recurrent GBM, there is an urgent need to understand how anti-angiogenic
therapies influence basic tumor biology and to develop novel strategies to
overcome the pro-invasive effects of bevacizumab therapy.
Both previous published reports and our preliminary data in an orthotopic
xenograft model demonstrate that bevacizumab therapy is associated with
increased infiltration of tumor cells at the invading edge and a multi-focal failure
pattern. Further, our data suggest that Src family kinase (FFK) activation represents
a key factor promoting the migration and invasiveness of GBM cells in culture
and in animal models, including bevacizumab-treated animals bearing glioma
xenografts. SFKs are crucial mediators of the pro-migratory and transforming
function of activated receptor tyrosine kinases, including EGFR, PDGFR and
c-Met, which are commonly amplified or activated in human GBM. Consistent
with this, dasatinib, a competitive kinase inhibitor that targets all members of the
Src family potently suppresses bevacizumab-induced invasion and multi-focal
disease. Based on these data, we have initiated a clinical trial within the North
Central Cancer Treatment Group (NCCTG) to evaluate the efficacy of combined
bevacizumab and dasatinib treatment in the recurrent GBM setting. Our overall
hypothesis is that inhibition of GBM invasion with dasatinib will significantly
increase the efficacy of bevacizumab therapy and suppress invasion and multifocal disease progression. In addition, our preliminary data argue that at least in
some cases, resistance to dasatinib treatment in vivo correlates with activation
of the phosphatidylinositol 3-kinase (PI3K) pathway. Consistent with this, SFK
and PI3K inhibitors can act synergistically to suppress the migration of dasatinibresistant GBM cells, suggesting that dual inhibition of these pathways in patient
tumors may further increase therapeutic benefit.
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The objectives of this project are to understand the intersection between SFK and
VEGF signaling pathways on GBM migration and invasiveness, to define genetic
and molecular characteristics that predict responsiveness to combined bevacizumab
and dasatinib treatment, and to identify signaling pathways associated with synergy
between SFKs and PI3K inhibition when combined with anti-angiogenic therapy. To
achieve these objectives we propose the following specific aims:
Specific Aim 1. Assess the combined effects of bevacizumab and dasatinib
on GBM invasion
Using a panel of human GBM intracranial mouse xenografts we will evaluate
the efficacy of dasatinib ± bevacizumab therapy on overall survival, invasion, and
multi-focal pattern of disease progression, and correlate a number of molecular
characteristics, including overall expression and activation status of SFKs,
activation of critical upstream or downstream SFK effectors, PI3K signaling, as
well as the expression of neo-angiogenesis and hypoxia markers with response
to treatment. Similar comparisons will also be performed in samples of recurrent
GBM patients treated with bevacizumab/dasatinib in the NCCTG clinical trial
N0872. Results will be further validated using samples of recurrent GBM patients
treated with single agent bevacizumab (Mayo Clinic) or dasatinib (RTOG 0627)
Specific Aim 2. Examine the role of individual SFKs and specific
downstream signaling effectors on bevacizumab-induced invasion
Individual GBM lines will be genetically and pharmacologically manipulated to
determine the role of individual SFKs on bevacizumab-induced invasion in vitro and
in vivo. The role of specific downstream SFK signaling effectors, including p120ctn,
p130cas, Vav2, and Rac1, on bevacizumab-induced invasion will also be tested.
Specific Aim 3. Examine the combined effect of SFK and PI3K inhibition
on GBM migration and invasiveness, and test the effects of dual inhibition on
bevacizumab responsiveness
We will examine the role of PI3K effectors, including AKT, GSK3b, mTOR
and Rac1, on the migration/invasion of GBM cells. We will also determine
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synergistic effects of dasatinib with inhibitors of known PI3K effectors, and
examine the efficacy of anti-SFK/PI3K/VEGF combination therapy in orthotopic
GBM xenografts.
The poor survival of patients with malignant gliomas underscores the need
for insights into the mechanisms involved in gliomagenesis and development of
resistance to treatment with subsequent identification of targets of therapy and
factors responsible for response and resistance. Inhibition of angiogenesis with
the monoclonal antibody bevacizumab represents a novel promising direction
in glioma treatment. Collectively, the studies in this project are designed to 1)
improve our understanding of the role of SFK inhibition with dasatinib in blocking
tumor progression on bevacizumab, 2) provide a scientific basis for identifying
patients who are most likely to benefit from dasatinib/bevacizumab combination
treatment, and 3) test novel combinatorial therapies to more effectively block tumor
invasion in bevacizumab treated patients.
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RESEARCH STRATEGY HAS 3 PARTS
Direct from NIH:
Organize the Research Strategy in the specified order and using the instructions
provided below, or as stated in the Funding Opportunity Announcement. Start each
section with the appropriate section heading – Significance, Innovation, Approach. Cite
published experimental details in the Research Strategy section and provide the full
reference in the Bibliography and References Cited section (Part I Section 4.4.9).
Follow the page limits for the Research Strategy in the Table of Page limits at
http://grants.nih.gov/grants/forms_page_limits.htm unless specified otherwise in the
FOA. Note that the page limit for this attachment will be validated as a single file.
(a) Significance
• Explain the importance of the problem or critical barrier to progress in the field
that the proposed project addresses.
• Explain how the proposed project will improve scientific knowledge, technical
capability, and/or clinical practice in one or more broad fields.
• Describe how the concepts, methods, technologies, treatments, services, or
preventative interventions that drive this field will be changed if the proposed
aims are achieved.
(b) Innovation
• Explain how the application challenges and seeks to shift current research or
clinical practice paradigms.
• Describe any novel theoretical concepts, approaches or methodologies,
instrumentation or interventions to be developed or used, and any advantage
over existing methodologies, instrumentation, or interventions.
• Explain any refinements, improvements, or new applications of theoretical
concepts, approaches or methodologies, instrumentation, or interventions.
(c) Approach
• Describe the overall strategy, methodology, and analyses to be used to
accomplish the specific aims of the project. Unless addressed separately in
the Resource Sharing Plan attachment below, include how the data will be
collected, analyzed, and interpreted.
• Discuss potential problems, alternative strategies, and benchmarks for success
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anticipated to achieve the aims.
• If the project is in the early stages of development, describe any strategy to
establish feasibility, and address the management of any high risk aspects of the
proposed work.
• Point out any procedures, situations, or materials that may be hazardous to
personnel and precautions to be exercised. A full discussion on the use of select
agents should appear in the Select Agent Research attachment, below.
If research on Human Embryonic Stem Cells (hESCs) is proposed but an
approved cell line from the NIH hESC Registry cannot be identified, provide a strong
justification for why an appropriate cell line cannot be chosen from the Registry at this
time.
If an applicant has multiple Specific Aims, then the applicant may address
Significance, Innovation and Approach for each Specific Aim individually, or may
address Significance, Innovation and Approach for all of the Specific Aims collectively.
What this means:
Your 12-page Research Strategy section will have three main parts:
1.Significance
2.Innovation
3.Approach
These correspond to three primary criteria NIH reviewers use to evaluate your
proposal, and you should begin each section with the corresponding subheading.
In addition, your Research Strategy will also include a Preliminary Studies
section (if it is a new application) or a Progress Report (for renewal and revision
applications). You can address these by including the appropriate subheading —
Preliminary Studies or Progress Report, depending on the type of application —
within one of the main sections listed above.
NIH also allows you to choose to present the Preliminary Studies/Progress
Report aim-by-aim or in a section by itself. Keep in mind, however, that veteran
reviewers likely will be most comfortable seeing it as a separate section because
that is the way they are used to seeing it before the application form changed in
January 2010. Consequently, this currently tends to be the more effective strategy.
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As you write your proposal, however, you may find that you are describing
an aim in the Specific Aims section, and you need to reveal a particular piece
of preliminary data to establish your aim’s feasibility. You could place the data
discussion within the specific aim, or you could include it within a large section
of Preliminary Data and reference the specific aim with a statement such as, “As
shown before, we have experience using the 454 sequencing system and have been
able to do parallel sequencing of all of the RLAs from leukocytes.”
Although NIH does not assign page limits for each section, it does suggest that
you break up the 12 pages as follows:
•Significance — 10-15 percent (1-2 pages)
•Innovation — 15-20 percent (2-2½ pages)
•Approach — 33-50 percent (4-6 pages)
•Preliminary Data/Progress Report — 25 percent (3 pages)
Keep in mind, however, that these are merely NIH’s recommendations.
You may find that you need more room for your Approach or Significance, and
must take the needed space from another section. For instance, one reviewer
recommends presenting a shorter Innovation and using that additional space to
better detail your Approach or to show additional data.
Section 1: Significance
Your Research Strategy’s Significance should indicate the following, according
to NIH:
• The importance of the problem or critical barrier to progress in the field that
your project addresses;
• How your proposal will improve scientific knowledge, technical capability
and/or clinical practice in one or more broad fields; and
• How your successful project will change the concepts, methods, technologies,
treatments, services or preventive interventions that drive this field.
In addition, the National Institute of Allergy and Infectious Diseases (NIAID)
suggests that you consider your proposal’s significance both in terms of your
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scientific field’s state and your long-term research goals. With this in mind, the
institute maintains you should include the following in your Significance section:
• How your research will advance your scientific field.
• What knowledge gaps your proposal will fill, demonstrating that you are
aware of these gaps as opportunities.
• The new and unique nature of your work.
• Your successes associated with related grants.
• How your work meets NIH’s mission to improve health through science.
Reviewers will ultimately judge your application on your research’s
likelihood to ultimately cure, treat or prevent disease.
Your strategy for this section will also depend upon your audience — meaning
your reviewers’ expertise in your field — NIAID notes, pointing to two scenarios:
• Scenario 1 — The study section is narrowly focused in your scientific area,
allowing you to write less regarding your research’s significance.
• Scenario 2 — The study section is more diverse, meaning you must include
more significance information.
Keep in mind also that NIH reviewers use this section to assign your
application to an institute for possible funding, and your description obviously will
affect that decision.
STRATEGY:
One tactic is to
complete your
Approach section
before tackling
the Significance
because you will
have a clearer
overall perspective
of your proposal.
One other tactic is to complete your Approach section before tackling the
Significance because you will have a clearer overall perspective of your proposal.
Further, the National Cancer Institute (NCI) weighs in with these additional
tactics for successfully writing this section:
• Carefully review published data in your field, and avoid outdated research.
Use citations not only as support for specific statements, but also to establish
familiarity with all of the relevant publications and points of view. Someone
working in your field may assess your application, and if you do not mention
their contributions, they may not favorably review your proposal.
• Highlight your awareness of potential barriers and alternate approaches.
• Point out how others can apply your research to your scientific field and/or
related areas.
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• Clearly state all public health considerations.
• Demonstrate that you can attain your objectives within your stated timeframe.
• Stress any experimental method innovations, such as new strategies, research
methods and/or proposed interventions.
Significance ≠ Impact
Many investigators are unsure regarding the difference between “significance” and
“impact.” NIH states that “significance” is how important your research would be if
everything worked perfectly, and “impact” is the likelihood that the project, as written,
will change the relevant scientific field and make a difference in human health.
In other words, “significance” is whether the project is worth doing, and
“impact” is what NIH gets for its money at the end of the project.
At the same time, your research cannot have impact if it is not worth doing, so
high scores for both Significance and Impact are important indicators for funding.
Nonetheless, if your research plan is seriously flawed or reviewers do not think
your team has the necessary experience and resources to complete the proposed
experiments, then your proposal likely will not have much impact, even if the topic
is highly significant.
For example, if your research involves the connection between obesity and
pneumococcal infection, your Significance section might detail how much obesity
exists and how much worse the problem of pneumococcal infection is in the obese
population. You can then support this statement with statistics to establish the
topic’s importance in the reader’s mind.
Remember, however, that this section should not look like a book report. You
should not perform an exhaustive review of related scientific literature. Although
you should do a literature review, you do not need to include every paper in your
REMEMBER:
Your research cannot have impact if it
is not worth doing,
so high scores for
both Significance
and Impact are
important indicators
for funding.
application’s Bibliography.
Continuing with the example above, the applicant believes the chronic level
of inflammation in obesity changes the way T cells respond to infection, which
influences the outcome of a pneumococcal infection. In the resulting Significance
section — which should take up one or two pages — the investigator would
explain how her proposal would expand the field, is new, etc., based upon NIH
guidelines noted above. Therefore, this section might outline how this research
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could lead to new treatments, vaccines and/or additional research to address
pneumococcal infection in the obese population.
In addition, NIH provides the following details to help clarify the difference
between significance and impact:
Significance
Significance is evaluated and scored
independently of the evaluation and
scoring of investigators, innovation,
approach, and environments
The evaluation of significance assumes
that the “aims of the project are
achieved” and/or will be “successfully
completed.”
• Moreover, reviewers should
evaluate the significance of the
project within the context of a
(research) field. For example,
autism is a significant field of study,
but not all studies (projects) of
autism are significant.
• Research fields may vary widely,
so it would be helpful if reviewers
identify in their reviews the research
fields within which the project
addresses an important problem or
critical barrier to progress.
• The research field may be focused
on a specific area (enzymology)
or a specific disease (e.g., autism),
or maybe more broadly defined to
cut across many health issues (e.g.,
language training, psychology).
125 Overall Impact
Overall Impact is not a sixth review criterion.
Overall Impact is not necessarily the
arithmetic mean of the scores for the scored
review criteria.
Overall Impact takes into consideration, but is
distinct from, the scored review criteria.
Overall Impact is the synthesis/integration of
the five core review criteria that are scored
individually and the additional review criteria
which are not scored individually.
To evaluate, the reviewers make an
assessment of the likelihood for the project
to exert a sustained, powerful influence on
the research fields involved, in consideration
of the scored review criteria and additional
review criteria (as applicable for the project
proposed).
• Likelihood (i.e., probability) is primarily
derived from the investigators’ approach
and environment criteria.
• Sustained, powerful influence is primarily
derived from the significance and
innovation criteria.
• Research fields may vary widely, so it
would be helpful if reviewers identify
in their reviews the research fields they
believe will be influenced by each project.
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Perhaps one of the biggest influences on your application’s Overall Impact
is the Significance section. Therefore, you must tell the reviewer why what you
propose is important.
For example, you might begin your Significance section by stating:
“Obesity is associated with increased complications of
pneumococcal infection, which is frequently fatal for this
population.”
Although this is factually correct, you should go on to explain how much
obesity exists and how much worse it is getting. In addition, note how dangerous
pneumococcal infection is for the obese population, and include some statistics to
support the topic’s importance and be very specific.
If your research will not affect a large group of people, you can make
a translation argument — meaning your results could lead to additional
developments. If your proposal involves basic science, this type of Significance
reasoning becomes critical.
Now, let’s look at sample Significance language, including where many firsttime applicants run into challenges:
“Obesity is a growing problem in the United States, with much
of the population overweight or obese. [Here, you should provide
additional specifics so that reviewers have a clearer picture
regarding just how many people are affected by this and could
potentially benefit from your research.] And estimates are that the
problem will get worse. [How much worse do you think it will get?
Be specific.] Obesity increases the risk for many problems. [Like
what? Explain that.] In poignant fact, what kills most obese patients
TIP:
If your research
will not affect a
large group of
people, you can
make a translation
argument —
meaning your
results could lead
to additional
developments.
is pneumococcal infection. [That’s a known fact, so you need to tell
the reviewer how many.]”
Constructing Your Significance
When writing your Significance section, you should be able to address all of
your main points within roughly four paragraphs using the following plan:
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• Paragraph 1: Introduce the problem you plan to solve.
Example: “The development of an HIV vaccine that generates broadlyneutralizing antibodies remains an elusive goal. Recombinant subunit glycoprotein
vaccines have generated antibody responses that neutralize laboratory-adapted
strains or neutralize only very neutralization-sensitive primary isolates of HIV.
Recent studies of HIV-infected populations, however, indicate that up to 20 percent
of individuals develop significant neutralization breadth. Our laboratory has
recently published results indicating that …”
• Paragraph 2: Additional background as needed: Here, cover the most
important points that support the first paragraph’s information.
Example: “The structure and variability of the HIV envelope protein (Env)
creates a significant challenge for generating an effective neutralizing antibodybased vaccine. Env is present on the virion surface as a trimer of heterodimeric
gp120(SU)/gp41 (TM) subunits. Gp120 variable loop glycosylation is extensive,
creating a barrier to access for antibodies knows as the ‘glycan shield’ (REF). The
extreme sequence variability of gp120’s exposed variable loops creates the need for
either targeting highly conserved regions.”
• Paragraph 3: Hit significance hard by describing the approach that will
overcome any difficult challenges.
Example: “In this application we describe an approach that will overcome the
difficult challenges described above. Using a polyvalent immunogen with a novel
combination of molecular adjuvants, we hypothesize that a broad neutralizing
antibody response against HIV primary isolates will be generated. Indeed,
preliminary data presented later in this application are strongly supportive that this
approach will be successful. Experiments described in this application will extend
these findings to the SIV/macaque model, providing sufficient proof-of-principle to
support the development of this regimen for human studies.”
• Paragraph 4: Emphasize the significance in a broader context.
Example: “Results from this study will be significant not only in advancing
the development of new generations of vaccines for HIV, but also will provide
fundamental new knowledge regarding the nature of B cell signaling pathways
and the adjuvants required to optimize affinity maturation in a vaccine context.
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Broad-based neutralizing responses may be of great benefit against a number of
pathogenic viruses, including …”
In addition, be sure to use plain language to mention the following:
1.Why the results stemming from your hypothesis and plan are important.
2.How your findings will change science or medicine.
3.If lives will be saved or if the quality of life will be improved and how.
4.What new rationales for treatment you will test and why.
Essentially, tell the reviewer what you are going to achieve that’s different.
Learn From This Example
You can refer to the following Significance example from a successful R01
application (Capsid-Targeting HIV-1 Antivirals, Principal Investigator: Christopher
R. Aiken, PhD) as you’re writing your own:
Significance
Formerly a veritable death sentence, HIV infection has become a manageable
disease that requires lifelong therapy. Various combinations of small molecule
drugs targeting the viral reverse transcriptase (RT) and protease (PR) enzymes are
tailored to inhibit replication to low or undetectable levels while minimizing the
emergence of drug-resistant viral mutants. These drugs are highly effective, yet
are expensive, exhibit significant side effects, and can engender viral resistance
via acquisition of mutations. Thus there is a need for continued development of
compounds directed against novel viral and cellular targets. By blocking multiple
viral functions essential for replication, the effectiveness of antiretroviral therapy
can be improved, with the ultimate hope that elimination of the virus from an
infected individual can someday be achieved.
HIV enters cells by fusion of viral with cellular membranes, releasing the viral
core into the cytoplasm of the target cell. The biochemistry of the fusion reaction
is relatively well understood, yet the ensuing early post-entry steps in infection
are obscure. The HIV-1 core consists of the genomic RNA and associated proteins
(NC, IN, RT) encased by the conical viral capsid. The capsid is a polymer of the CA
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protein arranged in a lattice of hexameric units (8, 26). The CA protein consists of
two domains connected by a flexible linker. The N-terminal domain (NTD) interacts
to form the hexameric ring, while the C-terminal domain (CTD) makes dimeric
contacts between the CA hexamers (26). The viral capsid is metastable; intact cores
containing a complete viral capsid can be purified at 4°C, and these cores shed the
CA protein spontaneously when incubated at 37°C. Disassembly of the viral capsid
in the target cell has recently emerged as a key step in infection, a conclusion that
is based on several lines of evidence. First, our group has shown that mutations in
the viral capsid protein (CA) that alter the stability of the viral capsid also lead to
reduced infection, owing to an impairment in reverse transcription in the target cell
(16). Second, cells express restrictive proteins that potently block retrovirus infection
at an early post-entry stage by targeting the capsid (3, 35, 40), likely perturbing
virus uncoating in target cells (41). The host protein cycophilin A (CypA) also play
an essential role in HIV-1 infection by associating with the viral capsid (5, 18, 44).
The CypA-CA interaction can be disrupted by treatment with cyclosporine A (CsA)
or mutations in CA, leading to impaired infection of target cells (21, 37). Third, we
describe herein a novel small molecule that inhibits HIV-1 infection by binding to
CA and destabilizing the viral capsid. Collectively these studies indicate that HIV1 infection is sensitive to changes in capsid stability and that the viral capsid is an
attractive target for therapeutic intervention.
There are currently no clinically approved therapies targeting the HIV-1 CA
protein, but two molecules targeting HIV-1 CA have been reported. CAP-1 is
a small molecule that binds to CA near the base of the N-terminal domain and
inhibits HIV-1 assembly in vitro (23, 42). CAP-1 has weak antiviral activity
in replication assays, and studies of resistance have not been performed,
perhaps because of weak potency of the inhibitor. Such studies are critical for
understanding the mechanism of action and specificity of antiviral compounds. A
second CA-targeting molecule, CA-I, is a peptide that was identified via phagedisplay technology (39). CA-I binds to HIV-1 CA and inhibits CA assembly in
vitro (43). Recently, a “stapled,” i.e., conformationally constrained, version of CA-I
was reported to inhibit HIV-1 infection (57). Antiviral peptides are useful for proofof-principle studies and have been used clinically, though there are significant
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problems associated with production and delivery of such inhibitors. Therefore,
small molecule inhibitors are generally preferable to peptides as therapies.
Compounds targeting viral capsids have been utilized extensively to study
the process of picornaviral uncoating. Specifically, compounds in the WIN series
of inhibitors, discovered at Sterling-Winthrop in the 80’s, bind to a cleft in the
poliovirus capsid and inhibit uncoating (11, 17, 56). Structural analysis of WIN
compound binding to virions has shown that only minor conformational changes in
the capsid are induced, suggesting that the compounds act by “locking down” the
capsid, thus preventing conformational changes required for capsid disassembly
(20). By selecting for poliovirus resistance to WIN 51711 in culture, two types
of resistance mutations were identified in each the four capsid proteins: one class
inhibited compound binding, and did not result in drug dependence, while mutations
of the other class did not abolish binding of the inhibitor but destabilized the viral
capsid (30). The latter mutations also render PV infection dependent on the inhibitor
(29). Thus, mutations in the viral capsid can lead to WIN compound resistance by
altering capsid stability, which reduces the fitness of the virus in the absence of the
inhibitor. Although the WIN compounds were not fully developed for clinical use, the
compounds proved very useful as probes for picornaviral capsid function.
In collaboration with Dr. X at [the company], we have recently initiated
studies to understand the mechanism of novel inhibitors that were identified by
[the company’s] drug discovery efforts. Several small tripeptide-like compounds
were found to inhibit HIV-1 replication by targeting the viral CA protein. The
compounds had no effect on RT or PR activity in vitro, and analysis of viral
mutants that were selected for resistance to one of the compounds revealed
that resistance is conferred by changes in CA. [The company] has no plans to
pursue development of these inhibitors, but has provided them to us for to pursue
basic studies of HIV-1 capsid function. In this R01 application, we propose a
comprehensive set of studies involving virology and structural biology to further
define the mechanism of action of this class of compounds. In addition to defining
a novel antiviral mechanism and potentially facilitating the development of new
antivirals, these studies will result in an improved understanding of HIV-1 capsid
function, thus elucidating the process of HIV-1 uncoating.
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Section 2: Innovation
You should use the Innovation section of your Research Strategy to explain the
following, according to NIH:
•How your proposal challenges and seeks to alter current research and clinical
practice standards.
•Any new theoretical concepts, approaches or methodologies; instrumentation
or interventions you plan to develop or use; and how these are better than
existing methodologies, instrumentation or interventions.
•Refinements, improvements or new applications of theoretical concepts,
approaches or methodologies, instrumentation or interventions.
In addition, NIAID advises applicants to be careful with this section.
Demonstrating how your work is new and unique and how it will add significantly
to what is known is sufficient evidence of innovation, the institute states in its
online Research Plan Tutorial and Flowchart. If your proposal involves highly
innovative approaches, on the other hand, you must build a strong case to challenge
current models and your reasons for doing so.
At the same time, NCI recommends that your Innovation section should be no
longer than a page and include the following:
•Why your proposal’s concepts and methodology are new to your research field.
•How your study design and outcomes are new.
•Any novel findings from preliminary data you will detail in the Approach section.
Therefore, to show your project’s pioneering nature, you should present it in the
context of what is already known regarding your field and what the challenges are.
You can accomplish this with a brief, concise background section. And then you
can clearly state what is new and groundbreaking about your proposal.
Do not make the reviewer guess where the novelty is, and do not be afraid to
use the word “innovative.” For example, consider the following:
“This work is innovative because it will characterize the
microparticles in plasma of pregnant women in a rigorous way that
will lead to new methods to diagnose abnormal pregnancies.”
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And although NIH presents three bullet points in its directions for the Innovation
section, you do not need to make each a subhead and address them individually in
your application, reviewers say. The bullet points are good guidelines, and if you
cover them all, you can be confident that you have a thorough Innovation section. But
do not organize your information by bullets or subheads. Rather, provide a narrative
that demonstrates you have thought about the pioneering nature of what you are
proposing and that you have considered how your approach is different from others.
In fact, some reviewers recommend that your Innovation section should be no longer
than a paragraph or two.
Be aware that some reviewers will focus their attention on the techniques
you use — to the virtual exclusion of other considerations. There is still a way
to emphasize the innovative components of your application if your work is
based upon applying established techniques in a groundbreaking way to solve an
important challenge. Namely, describe the endpoint of your experiments, if they
work as planned, and then explain what is new and novel about the information
you will have at the end of your project.
If you have been truly novel in applying established techniques, you will have
a unique set of data that addresses a previously unanswered question — and therein
lies your innovation.
At the same time, your proposal must be feasible, which means being too
creative can present challenges for reviewers because they are established
investigators. They have an eye for what they feel will not work, which makes
them somewhat skeptical if your research is too creative, some reviewers say.
There are essentially two ways to address this:
1.Data — The data you present in your Preliminary Data section can convince
reviewers. As part of that section, you should not only present the data, but
STRATEGY:
Describe the
endpoint of your
experiments, if they
work as planned,
and then explain
what is new and
novel about the
information you will
have at the end of
your project.
also explain what you feel it means.
2.Track record — Your personal history as a research scientist is also
vitally important to show that you know what you are doing regarding a
highly innovative approach within your research. Your published works,
employment history, education — essentially anything that allows you to
demonstrate that you can think outside the proverbial box.
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How your reviewers respond to your Innovation section typically involves how
deeply they have read in their own research fields, how broadly their knowledge
extends into other fields, and how much novelty and risk they are willing to
tolerate. Historically, however, reviewers are mostly conservative and often do
not support work at the earlier, potentially more pioneering stages. Consequently,
if your proposal involves decidedly groundbreaking work, you might consider an
R21 grant instead of an R01 so you can establish preliminary data (if it is currently
unavailable) before moving forward with an R01.
Review This Example
Here are a few examples of Innovation sections:
From Plasma Microparticles Reveal Physiology of Normal and Preeclamptic
Pregnancies (Principal Investigator: Dorothy E. Lewis, PhD):
Innovation
These studies are high risk, high reward, in that characterization of
microparticles over gestation and in preeclampsia has not been done. The
hypothesis that they are indicative of physiologic events in vivo is novel and
testable. We have considerable expertise in flow cytometric methods and a longterm interest in maternal health. These attributes make us the ideal group to
perform these studies. Coupled with the subset proteomics approaches, we will
greatly advance understanding of the physiology of pregnancy and the development
of biomarkers for preeclampsia.
From Engineering fibrin polymers for enhanced angiogenesis (Principal
Investigator: Thomas Harrison Barker, PhD):
In this project, we first propose to engineer “designer” peptides based on
fibrin knob sequences that enable exquisite control over both the association
(ka) and dissociation (kd) of the peptide to fibrin’s polymerization pockets. Then,
utilizing these engineered sequences, we will demonstrate the capacity to alter
the biochemical features of fibrin polymer systems by generating a recombinant
“plug-and-play” expression system that will enable the production and delivery
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of engineered integrin-specific fibronectin domains (as well as other potentially
therapeutic proteins) into fibrin polymer systems. Additionally, utilizing various
polyethylene glycol (PEG) configurations (e.g., monofunctional, bifunctional,
and multifunction-branched) coupled with our engineered synthetic fibrin knob
variants; we will demonstrate the ability to alter the polymer network ranging from
complete inhibition of polymerization (in the case of mPEG) to the potential blend
of fibrous and amorphous polymer (bPEG & mbPEG). Finally, the “designer” fibrin
will be optimized for endothelial cell invasion and angiogenesis using specifically
designed microfluidic chambers for in vitro angiogenesis assays and in vivo models
of angiogenesis, i.e., the chick chorioallantoic membrane (CAM) model and
subcutaneous wound chamber assays.
Section 3: Approach
The Approach section is the heart of your Research Strategy. This is where you
will provide the details of your research to convince reviewers that you understand
what the work entails and have the resources and expertise to conduct the research.
According to NIH, you should use this section to detail the following:
•Your overall strategy, methodology and analyses you plan to use to
accomplish your specific aims. And if you have not included a separate
resource-sharing plan, you should use this section to indicate how you will
collect, analyze and interpret data, as well as any resource-sharing plans as
appropriate.
•Potential challenges, alternative strategies and benchmarks for success that
you anticipate to achieve your aims.
•If your project is in the early development stages, note any strategies to
establish feasibility and how you plan to manage any high-risk aspects.
•Any hazardous procedures, situations or materials and precautions you will
use to address them.
NIAID further recommends that you follow these strategies for this section:
•Describe the first set of experiments for each Specific Aim.
•Define the potential next steps for the aims, but do not describe them in detail.
This may lend itself to a flowchart or decision tree where you can indicate
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that if you get result X, then you will follow plan X, but if you get result Y,
you will follow plan Y.
•Provide enough experimental detail to demonstrate to reviewers that you
understand what your proposal involves and can effectively conduct the
research.
oIf you are a more experienced investigator, cite relevant work to show your
expertise.
oIf you are a new investigator, indicate you can handle an experimental
method, and particularly point out if you have used it before. If you have,
cite it, and skip the description.
oIf you lack the expertise to accomplish the work, point out colleagues who
do. Their Biosketches should highlight experience that supports their roles
on your application.
oOutline your methods in less detail than you would in a publication. Provide
more detail for unique or new methods, and keep graphics simple because
they are clearer and can save space.
•Explain experiments to which you bring a unique ability.
oIf your first experiments are ordinary or contracted out, focus instead on
those that you bring something unique to and that are interesting.
oNext, describe your strategy, showing subsequent experiments based upon
the results.
oDraw connections between your personal statement and other Biosketch
information, highlighting what you are doing that’s different and what you
do well.
•Incorporate milestones and timelines, assessing whether they are appropriate
as you write.
•If you do not need the information to support your case, leave it out of the
Approach section. Reviewers will look for flaws and heavily penalize you for
them. So do not give them ammunition by including anything you feel you do
not need.
•Include a timetable showing how and when you will accomplish your
Specific Aims, noting any overlap of experiments and alternative paths.
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NCI also suggests that your Approach include the following additional details:
•For early-stage projects, your strategy to establish feasibility and address
high-risk aspect management
•New methodologies used and why you feel they are an improvement.
Further, NCI notes that you should number your Approach sections to
correspond to your Specific Aims numbers. And you may include the preliminary
data or progress report before the Specific Aims or integrate the data/report as part
of your methods description for each aim.
The institute also recommends that you avoid excessive experimental detail
by referring to publications that describe your methods. Keep in mind that any
publications you cite should be your own if possible. And indicate why you will
use one approach or method (if applicable) — and include the “how” and the
“why” — rather than others because this will demonstrate that you simply did not
overlook any alternatives. If you are using a complex technology for the first time,
be sure to demonstrate your familiarity with the experimental details and potential
challenges. If necessary, add a co-investigator or consultant who is familiar with
the technology.
If your application involves proposed collaborations and offers of materials
or reagents that have restricted availability, document this with letters from the
individuals involved, NCI says.
Finally, note that if you propose to use human embryonic stem cells (hESCs)
and wish to use a cell line that is not an approved cell line from the NIH hESC
Registry, you must “provide a strong justification for why an appropriate cell line
cannot be chosen at the time of application” in the Approach section.
Allow Enough Time
Because the Approach is so central to your Research Strategy section, you will
spend most of your proposal-writing time on it. And it is what reviewers will spend
most of their time evaluating. They will be especially careful to scrutinize it for
potential problems, alternative strategies and benchmarks for success.
REMEMBER:
Reviewers will be
especially careful
to scrutinize the
Approach for
potential problems,
alternative
strategies and
benchmarks for
success.
NIH’s Office of Extramural Research last year looked at the five key criteria
— Approach, Significance, Innovation, Investigators and Environment — and
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how well scores for each correlated statistically with an applicant’s Overall Impact
score. Based upon this analysis, the Approach score turned out to be the best
predictor of the final impact score, with a correlation coefficient of 0.82.
The Approach section is also where many new Principal Investigators make one
or more of the standard errors that are relatively easy to identify and describe. If this is
the case, your Summary Statement may include such stock critiques as the following:
•The applicant is overly ambitious
•One or more aims are unfocused or underdeveloped
•An aim is just a fishing expedition for a missing gene or interactions
•There is too little description of results analysis
•The applicant over-relies on a preferred hypothesis
•An aim is just too risky.
Reviewers may genuinely identify these flaws in a grant application, but they
occasionally invoke them as a cover when they lack enthusiasm for a proposal and
cannot precisely articulate why. Anticipating these critiques during your proposal
TIP:
Anticipating
critiques during
your proposal
writing is one of the
best defenses you
have, and knowing
that the Approach
score provides
the strongest
correlation to your
Overall Impact
score shows that
this section is
where you should
devote most of
grant preparation
time.
137 writing is one of the best defenses you have, and knowing that the Approach score
provides the strongest correlation to your Overall Impact score shows that this
section is where you should devote most of grant preparation time.
Keep in mind that reviewers do not want to see details like which restriction
enzymes you are going to use and which buffer goes with particular restriction
enzymes or the brand of mass spectrometer you are going to use. What they are
really interested in is your thought process regarding how you will accomplish each
aim, including the following:
•Have you carefully thought through the problem you are trying to solve?
•What is your initial plan of attack?
•How likely is that plan of attack to work?
•What are the possible things that could go wrong?
•What aspects of feasibility have you not yet demonstrated?
•What is your plan for dealing with those problems if the experiments do not
work?
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To address the stock critiques above, some reviewers suggest that you spend a
paragraph or two explaining the rationale of each aim, noting why you are doing it
and outlining the experiment related to each one. You should also choose figures,
tables or other visual data that allow reviewers to understand that you are the
expert, careful and will do what you say you will.
You will also want to tie the different areas of your application together to
better support your proposal. For instance, if you are demonstrating the feasibility
of recruiting a target sample size in a psychosocial treatment outcome study, you
will want to discuss your ability to recruit a specific number of participants in both
the Environment/Resources section and in your Approach. The ability to recruit
adequate patient population is that crucial to clinical studies. In this case, you
would use one sentence in the Approach to document annual patient accruals and/
or past successes in recruiting patients, and then use the Environment section to
provide slightly more detail regarding why your institution is such a good place to
do the clinical research with access to your target study population.
In addition, for research that involves nonstandard, nontrivial “data analysis”
needs, be sure to sufficiently describe those needs in your Approach because this
will inspire reviewer confidence in your project. With the Research Plan’s 12-page
limit, you should use approximately a half-page for this, or as much as a full page
if your data analysis is particularly complex and integral to your success. If your
project is a biomarker study or clinical trial, for example, remember that NIH will
assign statisticians to specifically evaluate the statistical design and power issues,
which you must discuss in your Approach.
You can also use your Approach section to provide details regarding novel
aspects of your work. For instance, you plan to use a better, more innovative
method of calculating sample size that reviewers likely will not recognize. Should
you stick with the more conventional sample-size calculations? Or put the more
sophisticated method in an appendix?
Neither. Instead, you should reference a publication that explains the new
method and provide a brief description of its advantages in your Approach. If you
feel you need a larger explicative discussion, seek your review officer’s permission
to submit it as supplemental material once you have your study section assignment.
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Example Proves Helpful
As an example, consider the following, which was taken from a successful grant
application (Tumor Necrosis Superfamily Ligands and Lymphocytes Role in Liver
Regeneration, Principal Investigator: Robert Anders, MD). It is not the full section,
which goes on for several pages, but it should give you an idea of structure and
content. In this case, the applicant has broken the section down so that he can address
each Specific Aim, and this example details only one section of the first aim.
Aim 1. Define the LTßR Dependent Cell Survival Program Controlled by
the c-JUN N-Terminal Kinase (JNK) Pathway. Cell survival or death following
JNK activation is cell context dependent. Cell fate after JNK activation depends
on interplay of cell type, duration of activation and induction of downstream
targets. Our preliminary data shows 1) hepatocyte death occurs following partial
hepatectomy in LTßR deficient mice, 2) partial hepatectomy fails to stimulate JNK
kinase in LTßR deficient mice, 3) stimulation of the LTßR increases JNK kinase
activity in the liver, 4) LTßR-/- hepatocytes are more sensitive in vitro to TNK
mediated apoptosis. We will investigate the LTßR dependent mechanisms that
control cell survival through JNK activation.
Aim 1.1. Are hepatocytes or non-hepatocytes required for LTßR dependent
JNK activation following partial hepatectomy? It is known that both hepatocytes
and non-hepatocytes (also referred to as non-parenchymal cells) participate in liver
regeneration. We know that liver regeneration is impaired in both LTßR-/- and
alb-LTßR-/- mice. The LTßR-/- mice have no expression of the LTßR in any of the
liver cell types, while alb-LTßR-/- specifically lacks the LTßR only on hepatocytes.
We will determine both in vivo and in vitro, if the absence of JNK activation seen
in LTßR-/- is specific to hepatocytes or also seen in non-hepatocytes.
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Aim 1.1
in vivo
LTßR-/- miceEm
ALB-LTßR-/- mice
+ control WT mice
}
in vitro
WT & -control LTbR-/- mice
Isolate primary
cultures
phxT
Hepatocytes
Non-hepatocytes
Treat with
LTßR agonists
- control TNFR-/- miceAt
JNK activity
IP kinase
In vivo approach. We will perform partial hepatectomies on wild type, LTßR-/-,
alb-LTßR and TNFRI-/- mice, with three surviving mice for each genotype. Liver
lysates will be harvested at 48 hours. JNK kinase activity toward a GST-C-Jun
substrate will be determined from liver homogenates, identical to what was done in
preliminary data figure 12. We anticipate JNK activity in the positive control WT
mice and diminished activity in the negative control TNFRI-/- mice. If hepatocyte
LTßR is necessary for JNK stimulation, both alb-LTßR-/- and LTßR-/- would lack
JNK activity. However, if JNK activity is from non-hepatocytes we expect altLTßR-/- to show more JNK activity than LTßR-/-. This basic first step will define
which population of LTßR expressing cells is responsible for JNK activity.
In vitro approach. It is possible hepatocytes and non-hepatocytes both stimulate
JNK kinase. To directly test if LTßR stimulation can elicit JNK activity we will
isolate both cell types for in vitro analysis. WT and LTßR-/- hepatocytes and nonhepatocytes will be isolated through our current primary hepatocyte isolation
procedure. Non-hepatocytes remain in the supernate after a low speed spin that
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pellets hepatocytes. We will plate hepatocytes and allow non-hepatocytes to remain
in suspension. Cell cultures will be treated separately with two LTßR agonists, antiLTßR agonist antibody ACH6 (a well characterized LTßR agonist antibody (17, 57,
58)) or the cytokine LIGHT (R&D systems #1974-LT). TNF treatment will serve
as a positive control known to elicit JNK activity. We will treat with doses of antiLTßR agonist ranging from 0-1 microgram/mL and LIGHT ranging from 0-500 ng/
ml. We will use the fusion protein LTßR-Ig (made in Dr. X’s lab) and an antibody
that specifically blocks LIGHT binding to the LTßR (see collaborative letter from
Dr. Y) in all of our in vitro work. These blocking agents reassure we are witnessing
a direct LIGHT/LTßR event. We will compare the JNK activity 24 hours after LTßR
stimulation in WT and LTßR-/-. If hepatocytes can elicit JNK activity we anticipate
stimulation of the LTßR in WT hepatocytes but not LTßR-/- hepatocytes to result in
JNK activity. If non-hepatocytes can elicit JNK activity we anticipate stimulation
of the WT derived non-hepatocytes but not those from LTßR-/- to result in JNK
activity. As a control we anticipate both WT and LTßR-/- mice to induce JNK activity
following TNF treatment. Additional controls using the alb-LTßR-/- mice will also be
performed if it appears hepatocytes are capable of responding to LTßR stimulation.
We expect alb-LTßR-/- non-hepatocytes capable of responding to LTßR stimulation,
but not alb-LTßR-/- hepatocytes …
Preliminary Data for New Applicants
Direct from NIH:
Preliminary Studies for New Applications: For new applications, include
information on Preliminary Studies. Discuss the PD/PI’s preliminary studies,
data, and or experience pertinent to this application. Except for Exploratory/
Developmental Grants (R21/R33), Small Research Grants (R03), and Academic
Research Enhancement Award (AREA) Grants (R15), preliminary data can be an
essential part of a research grant application and help to establish the likelihood of
success of the proposed project. Early Stage Investigators should include preliminary
data.
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What this means:
NIH introduced this section in January 2010 as part of its application overhaul,
and you should include this only if your application is new. And keep in mind that
this section is included as part of your 12-page Research Strategy.
Although reviewers will not place as much emphasis on Preliminary Data for
early-stage investigators as they do for more established researchers, every new
R01 application should include details regarding the project director(s)/principal
investigator(s)’s preliminary studies, data and/or experience related to the proposal.
In addition, NIAID indicates that this preliminary data shows that you are on
the right track with your research, and your Specific Aims should build on this
previous research as a foundation. “Reviewers use this section together with the
biographical sketches to assess the investigator peer review criterion, reflecting
your competence to do this work,” the institute states. Therefore, preliminary
data builds reviewer confidence that you can handle the technologies involved,
understand the methods and effectively interpret the research’s results.
NIAID suggests that you include the following details in your Preliminary
Studies section:
•Critically interpret preliminary results.
oProvide alternative meanings to the data to show you have thoroughly
considered the problem and can meet future challenges.
oIf you are not critical of your own results, you can be sure reviewers will be.
•Include sufficient information to show you know what you are talking about.
oThe more complex your proposal, the more data you will need.
oExplain how your early work has prepared you for this new project.
•Focus on your preliminary or unpublished data from your lab, although you
may include other people’s publications. If you present results from other
labs, be sure to clearly indicate which data are yours and which are not.
•Include previous experience that shows you can direct the proposed research
and achieve its aims.
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What to Include and What to Leave Out
The first purpose when presenting preliminary data is to demonstrate feasibility
and that you have the necessary expertise to carry out the procedures you propose
in the Research Methods. Consequently, some applicants wonder if they should
include contradictory data in their applications.
In response, reviewers point out that this section’s purpose focuses more on your
ability to successfully collect and analyze the data rather than on the results of that data.
Preliminary data supporting your hypothesis and research plan, however, are
potent evidence in your favor. They indicate that you are on the right track, and
reviewers weigh this heavily. At the same time, there are subtleties to reporting this
data, and possible variations involve the following:
1.Primacy of the outcomes,
2.Positive/negative results, and
3.Statistical power of your preliminary studies to detect effects.
And there are several possible outcomes and resulting implications for your
proposal based upon your preliminary data:
Positive/
Null/ Negative
Results
Positive
Null/Negative
Positive
Null/Negative
Statistical
Power
Implications
Reviewer may wonder why you need to conduct the
proposed study because you already have strong
support for your hypothesis
This result presents the biggest potential challenge for
your proposal because your preliminary data shows
Adequate
you failed to detect effects, although you had adequate
power to do so.
This is your most desirable potential outcome. Because
the statistical power was insufficient to detect effects,
your statistical test for this outcome presumably
Inadequate was not significant (if it is, you have to suspect
chance). Therefore, you are on the right track with
your preliminary studies, and your results bear the
replication you are proposing.
Although this situation presents a challenge, you can
address it by implying there was inadequate statistical
Inadequate
power to differentiate between the means as not to be
believed or is a product of chance.
Adequate
Courtesy: William Gerin, PhD
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Your main challenge with preliminary data is the null result as your primary
outcome. This is not necessarily fatal if your sample size was small and your
statistical power was inadequate. In this case, you would not necessarily have to
mention the data’s statistical power, and the reviewer will examine the sample size
and understand the limitations there.
When you do present contradictory data, be sure to then explain what you have
done to generate confirmatory data that supports your hypothesis.
Review This Example
Here is a partial example of a Preliminary Studies section from a successful
NIH application (Combining Anti-Invasive and Anti-Angiogenic Therapies for the
Treatment of GBM, Principal Investigator: Panagiotis Z. Anastasiadis, PhD):
Preliminary Data
C1. Serially transplantable xenograft model of human glioma. A number of
different animal models of human GBM have been created to date. Conventional
GBM cell lines grown in culture fail to maintain proper EGFR and PTEN signaling,
often losing both EGFR amplification and wild type PTEN function. As a result,
orthotopic xenograft models of these cell lines fail to accurately represent key
features of GBM biology and do not invade surrounding brain tissues. Induced
overexpression of oncogenes, i.e., mutant EGFR or v-src, in glioma cell lines also
fail to accurately recapitulate GBM biology since any oncogene changes in these
tumors are clonal, instead of heterogeneous at the cellular level (as is the case in the
majority of GBMs) and the degree of oncogene overexpression/activation is superphysiological. A panel of GBM xenograft lines that are established and maintained by
direct tumor implantation into the flank of nude mice is propagated in the laboratory
of our collaborator. Orthotopically transplanted tumors from these cell lines preserve
the histopathologic characteristics of the derivative primary human specimens, and
importantly, display a similar invasive potential to the original tumor [83]. Over 20
GBM xenograft lines have been generated to date, and eight of them, representing a
wide spectrum of genetic variability associated with human GBM, including EGFR/
PDGFR amplification, inactivation of PTEN, expression of mutant EGFRvIII,
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deletion of p16, and p53 mutation will be used in these studies. Based on the
preservation of both the genetic and histopathologic characteristics of human GBM,
we believe that this serially transplantable xenograft model system provides a unique
test-bed for the evaluation of novel therapeutic strategies directed against GBM.
C2. SFK activity in untreated GBM xenografts is associated with invasion.
SFKs modulate key signaling pathways implicated in driving tumor invasion in
GBM. As a preliminary test of whether SFKs might influence invasion in our
xenograft model, we evaluated the expression and activation levels of Src and the
downstream effector p120 catenin in a panel of our xenograft lines by western
blotting and compared these levels to the extent of tumor invasion based on an
evaluation of H&E tumor sections. As seen in Figure 2, there was a spectrum of
Src activation across the xenograft lines evaluated. Interestingly, the three tumor
lines (GBM6, GBM8, and GBM26) with the highest level of Y228 phosphorylation
of p120-catenin are the most invasive tumor lines. Of specific interest, GBM10
has modest levels of active Src, but low levels of Y228 p120 phosphorylation,
and untreated GBM10 tumors exhibit limited tumor invasiveness. These data
are consistent with previous studies suggesting that SFKs play a central role in
mediating glioma tumor invasion [43, 72-75, 79].
SFK-mediated signaling through the p120-catenin/Vav2 and the p130/
DOCK180 pathways modulates Rho family GTPases, which supervise
reorganization of the cytoskeleton to permit cell migration. To evaluate whether
these signaling pathways were active in GBM, we used immunohistochemistry
in orthotopic GBM xenografts to evaluate the activation status of these SFKdependent pathways within the non-invasive tumor core and at the invading tumor
edge. Consistent with the role of SFKs in driving tumor invasion, SFK activation
is dramatically higher at the leading/invading edges of xenografted GBM tumors.
Likewise, SFK-mediated phosphorylation of a number of direct SFK substrates,
including p120, p130cas and Vav2, was specifically observed at the invasive tumor
edge but not in the tumor core. SFKs directly affect the cytoskeleton, while p120
and p130cas-dependent pathways critically modulate Rho GTPases; consistent
with activation of these pathways, Rho GTPase-dependent phosphorylation (at
Ser3) of the actin severing enzyme cofilin [84] is also upregulated at the invasive
tumor fronts (data not shown). Moreover, consistent with these pathways being
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modulated by SFKs, treatment of mice with dasatinib significantly suppressed
SFK phosphorylation and downstream signaling events (not shown) in mice
with orthotopic GBM tumors. Furthermore, treatment of SF767 glioma cells
with dasatinib suppressed the phosphorylation of SFKs at Y416, p120 at Y228,
p120cas at Y410, and inhibited Rac1 activity in pull-down assays (data not shown).
Collectively, the data argue that increased SFK activity is associated with an
invasive phenotype in GBM xenografts and that dasatinib can block both SFK
activation and downstream signaling events in animal models of human GBM …
Progress Report for Renewal/Revision Applications
Direct from NIH:
Progress Report for Renewal and Revision Applications. For renewal/revision
applications, provide a Progress Report. Provide the beginning and ending dates for the
period covered since the last competitive review. Summarize the specific aims of the
previous project period and the importance of the findings, and emphasize the progress
made toward their achievement. Explain any significant changes to the specific aims
and any new directions including changes to the specific aims and any new directions
including changes resulting from significant budget reductions. A list of publications,
patents, and other printed materials should be included in the Progress Report
Publication List attachment; do not include that information here.
If you are submitting a renewal or revision application, you will provide a
progress report rather than preliminary studies information. This progress report
should contain the following information, according to NIAID:
•Your project period beginning and end dates.
•A summary of your findings’ importance as related to your Specific Aims.
•Published and unpublished results, highlighting your progress toward
achieving your Specific Aims.
When writing these reports, reviewers recommend that you indicate the dates
and restate the Specific Aims. Then you should include a narrative summary of the
progress you have made for each aim. At the same time, you will not have to relist
your publications because you will upload them as a separate document. Ideally,
your progress report should be roughly a page or two.
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OVERALL IMPACT BRINGS EVERYTHING TOGETHER
Direct from NIH (SF424 (R&R) Application Guide, Version C, for NIH
and Other PHS Agencies):
Overall Impact. Reviewers will provide an overall impact/priority score
to reflect their assessment of the likelihood for the project to exert a sustained,
powerful influence on the research field(s) involved, in consideration of the
following five core review criteria, and additional review criteria (as applicable for
the project proposed).
Overall Impact (From NOT-OD-09-025)
• Overall Impact is not a sixth review criterion.
• Reviewers will write a paragraph summarizing the factors that informed their
Overall Impact score.
• Overall Impact is not necessarily the arithmetic mean of the scores for the
scored review criteria.
• Overall Impact takes into consideration, but is distinct from, the scored
review criteria.
• Overall Impact is the synthesis/integration of the five core review criteria that
are scored individually and the additional review criteria which are not scored
individually.
• To evaluate, the reviewer(s) make an assessment of the likelihood for the
project to exert a sustained, powerful influence on the research field(s)
involved, in consideration of the scored review criteria, and additional review
criteria (as applicable for the project proposed).
oLikelihood (i.e., probability) is primarily derived from the investigator(s),
approach and environment criteria.
oSustained powerful influence is primarily derived from the significance and
innovation criteria.
oResearch field(s) may vary widely, so it would be helpful if reviewers
identify in their reviews the research field(s) they believe will be influenced
by each project.
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What this means:
Many applicants ask, “What is ‘impact,’ and how can I show it in my
proposal?” And as stated earlier, investigators frequently are confused by the
difference between “significance” and “impact.”
Essentially, NIH has instructed reviewers to evaluate significance by asking, “If
all of your experiments work, then how important will your results be?” The big
picture in reviewers’ minds is whether the research is worth doing.
Impact, on the other hand, includes the likelihood that the experiments will
succeed. If they do not work, then there will not be any impact, even if the research
is highly significant.
NIH has provided a few case studies to illustrate the difference between Overall
Impact and Significance:
Case Study 1: An application proposes to disrupt a well-known signal
transduction pathway in mice and see if it results in an increased incidence of a
particular type of breast cancer in mice.
Significance: Breast cancer is an important disease in women. However, that
alone is not sufficient to say that this project has high significance. The reviewers
should evaluate whether this proposed project addresses an important problem in
breast cancer or a critical barrier to progress in breast cancer research. For example,
will research on this signal transduction pathway in mice advance the concepts,
methods, technologies, etc., related to studies of human breast cancer?
•Although breast cancer is a very important disease, the reviewers need to
address whether the proposed signaling pathway and the work in mice will be
important for understanding, treating, or preventing human breast cancer.
•If the signaling pathway under study is also important in another disease,
such as colon cancer, the Significance might be higher, since the results of the
project will be more broadly applicable.
•A project that addresses a slow growing type of breast cancer that responds
well to existing therapies/treatments would be of lower significance because
it is less likely to change clinical practice.
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Overall Impact: What is the likelihood that this project conducted by these
investigators in their environment, with this level of innovation and the proposed
approaches, will have a sustained powerful influence on the field?
•If the proposed work in mice will strongly predict what is happening in
humans, the investigators are highly qualified, the environment is strong,
the approach to disrupting the pathway is innovative, and the approach is
flawless, the project may be likely to have high Overall Impact.
•Even if the pathway and the mouse model are very significant for breast
cancer in humans, the investigators are very experienced and in a great
environment, and the approaches are sound, if the proposed work is not
innovative or is confirmatory and duplicates many other published reports,
the Overall Impact of the project on breast cancer research might be only
moderate to low.
•Even if the topic is very significant for breast cancer in humans, the
investigators are very experienced and in a great environment, and the project
is innovative, the approach may be flawed, reducing the chance of generating
useful data, which would reduce the likely Overall Impact on breast cancer
research.
•Even if this project is very innovative, well conceived, and likely to have
high overall impact, a subsequent project to clone and characterize receptor
subtypes for this family of signal transduction molecules may be viewed as
having less Overall Impact, since it might not be as innovative. Conversely,
such a project might be viewed as having a greater Overall Impact, since the
work is essential to develop a new drug treatment for breast cancer.
Case Study 2: An application proposed to develop and test an antidote for a
chemical agent in an animal model.
Significance: The potential use of chemical agents in wars or related to
terrorist activities is of national security concern. However, the significance of the
project depends on how the project will contribute to the development of effective
therapeutic agents and/or change therapeutic approach.
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•Although such agents may directly affect a very limited number of
individuals and the therapeutic agent(s) may have no other uses, the project
has the strong likelihood of yielding life saving therapeutic agents should an
exposure occur; thus the significance is very high.
•However, if well established clinical practices and multiple effective antidotes
are widely available, contribution to the field of development therapeutics for
chemical agent exposure will be lower and significance diminished.
Overall Impact: What is the likelihood that this project conducted by these
investigators in their environment, with this level of innovation and the proposed
approaches, will have a sustained powerful influence on the field?
•The project resolves an unmet need; there are no effective therapies for this
chemical exposure with high mortality. The reviewers might note the highly
qualified investigators, flawless methods, an excellent animal model, and
therapeutic compounds that will work on various chemical agents — High
Overall Impact.
•While other therapeutic agents exist, the proposed compounds have numerous
advantages in terms of side effect, ease of use and efficacy and will likely be
the treatment of choice — High Overall Impact.
•The project contributes to the enhancement of the therapeutic arsenal but
will not result in major changes to current clinical/therapeutic practices —
Medium Overall Impact.
•While the idea is significant and sound, methodologies are flawed and
investigators have very limited experience in the field. The probability of
achieving the goals is low — Low Overall Impact.
•Technically sound with good investigators, but the animal model has no
relevance to human condition — Low Overall Impact.
NIH has instructed reviewers to weigh all of the individual core criteria
— innovation, significance, approach, environment and investigators — when
examining your application and arrive at an overall impact score. Unfortunately,
there is no magic formula reviewers use to equate your individual criterion scores
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to your overall impact score. Each will likely rate each criterion differently. Some
will base your impact score almost entirely on your experimental approach, as
they did under the former application review process. Others will be much more
concerned with Innovation and Significance.
REMEMBER:
There is no magic
formula reviewers
use to equate
your individual
criterion scores
to your Overall
Impact score.
The specific grant you are seeking will also affect your Overall Impact score.
For an R01, reviewers likely will base the Impact score more on Environment and
Approach, whereas an R21 Impact generally should depend more upon Innovation
and Significance.
Integrate Impact Throughout
There is no template for incorporating Overall Impact into your grant
application. For example, there is no section called “Overall Impact,” and NIH
does not incentivize investigators to add a paragraph labeled as such to their
proposals. Instead, the agency’s Office of Extramural Research indicates that
applicants should describe impact clearly in whatever words are relevant to their
proposed projects.
Some reviewers state that the impact should “bubble up” throughout the entire
application. Others note that you should integrate it so that your Approach supports
your Specific Aims, indicating that you will obtain useful data.
Essentially, reviewers want to see that not only are you addressing a timely and
important problem, but also that you can accomplish it in the period outlined with
the resources requested. Plus, the information you glean will be useful by the next
generation of experiments or possibly be translatable in the near term.
With this in mind, one tactic is to include a simple “impact statement” in each
of the five core criteria sections. For example, in the innovation section, you might
note how your research will affect future efforts in the field, such as the following:
STRATEGY:
One tactic is to
include a simple
“impact statement”
in each of the
five core criteria
sections.
151 “The work will define future vaccine design because scientists and manufacturers
will know that both IgG and IgA antibodies are required to prevent infection.”
The Project Summary/Abstract is also a good place to indicate your research’s
impact because it is one of the first elements of your application reviewers will
read. For instance, consider the following:
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“The end product will be an affordable, accurate blood test for early detection
of colon cancer without colonoscopy. Successful demonstration of this approach
in colon cancer will enable application to other cancers in need of early detection
biomarkers. Future directions of this research also include the application of a
systems biology approach to the large datasets generated in the discovery phase to
provide new insights about the earliest stages of colon cancer.”
Although NIH does not require — or even suggest — that you include such a
statement, making your Overall Impact readily accessible for reviewers can support
your chances that they will more easily recognize it.
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CITE YOUR BIBLIOGRAPHY AND REFERENCES
Direct from NIH:
Provide a bibliography of any references cited in the Project Narrative. Each
reference must include the names of all authors (in the same sequence in which
they appear in the publication), the article and journal title, book title, volume
number, page numbers, and year of publication. Include only bibliographic
citations. Applicants should be especially careful to follow scholarly practices in
providing citations for source materials relied upon when preparing any section of
the application.
Unless otherwise noted in an FOA, this section is required for submissions to
NIH and other PHS agencies. This section (formerly “Literature Cited”) should
include any references cited in the PHS 398 Research Plan form (see Section
5.5 for details on completing that form). When citing articles that fall under the
Public Access Policy, were authored or co-authored by the applicant and arose
from NIH support, provide the NIH Manuscript Submission reference number
(e.g., NIHMS97531) or the PubMed Central (PMC) reference number (e.g.,
PMCID234567) for each article. If the PMCID is not yet available because the
Journal submits articles directly to PMC on behalf of their authors, indicate “PMC
Journal – In Process.” A list of these journals is posted at:
http://publicaccess.nih.gov/submit_process_journals.htm.
Citations that are not covered by the Public Access Policy, but are publicly
available in a free, online format may include URLs or PubMed ID (PMID)
numbers along with the full reference (note that copies of publicly available
publications are not accepted as appendix material). The references should be
limited to relevant and current literature. While there is not a page limitation, it is
important to be concise and to select only those literature references pertinent to
the proposed research.
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What this means:
Essentially, NIH reviewers do not want to be inundated with copies of articles
that they can review online. So if you refer to published studies or information
in your Research Strategy section, then you should cite them in this section. And
unless the publication is not available online or is not part of the NIH or Pubmed
system, you should not include a copy of it with your application.
If you must include a publication with your application, you should offer it as
an appendix rather than including it within the application.
Here is a sample of how your bibliography entries might appear:
1. Kowal J, Tkach M, Théry C. Biogenesis and secretion of exosomes. Curr
Opin Cell Biol. 2014 Jun 21;29C:116-125. doi: 10.1016/j.ceb.2014.05.004.
[Epub ahead of print] Review. PMID: 24959705 [PubMed - as supplied by
publisher]
2.Revenfeld AL, Bæk R, Nielsen MH, Stensballe A, Varming K, Jørgensen
M. Diagnostic and Prognostic Potential of Extracellular Vesicles in
Peripheral Blood. Clin Ther. 2014 Jun 1;36(6):830-846. doi: 10.1016/j.
clinthera.2014.05.008. Review. PMID: 24952934 [PubMed - as supplied by
publisher]
3.Lamichhane TN, Sokic S, Schardt JS, Raiker RS, Lin JW, Jay SM.
Emerging roles for extracellular vesicles in tissue engineering and
regenerative medicine. Tissue Eng Part B Rev. 2014 Jun 23. [Epub ahead of
print] PMID: 24957510 [PubMed - as supplied by publisher]
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CONCLUSION
Because the Research Strategy section of your application includes the
Significance, Innovation and Approach criteria that NIH reviewers will use to
evaluate your proposal, you will spend most of your writing time on this material.
At the same time, your project’s Overall Impact score will likely depend heavily on
this material as well.
As if that were not enough pressure, the agency has limited the number of
pages you can use for your efforts. Nonetheless, you must demonstrate not only
that you have a viable proposal worth funding, but that it is a valuable addition to
your scientific field. n
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Chapter 5: Special Considerations
Chapter 5:
Special Considerations
When outlining your project, if you plan to use human or animal test subjects
— or sample or data from them — you must complete the key portions of the
application associated with these groups.
Both you and your institution must assure NIH that human and animal test
subjects will be protected. NIH cannot award any grant until such assurances are on
file with the agency.
Include enough information so reviewers will have no questions about what
you propose to do. In addition, your research plan must be certified by your
institutional review board (IRB) prior to funding. Although you do not need IRB
approval when you submit your application, you should begin the approval process
early because revisions and final approval can take time.
And before NIH can fund your grant application, there must be a Human
Subject Assurance on file with the Office of Human Research Protections. This is
usually handled at the institutional level.
Similarly, for proposed research using vertebrate animals, there is specific
information you must include regarding the animals’ treatment and the rationale for
including them. Also, an institutional animal care and use committee (IACUC) must
review and approve your proposal before you submit it. At NIH, an Animal Welfare
Assurance must be on file with the Office of Laboratory Animal Welfare (OLAW).
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COMPLETE THE PLANNED ENROLLMENT REPORT
Direct from NIH:
The NIH is mandated by law (Public Health Service Act sec. 492B, 42 U.S.C.
sec. 289a-2) to ensure the inclusion of women and minority groups in clinical
research. The goal is to ensure that individuals are included in clinical research in a
manner that is appropriate to the scientific question under study.
When submitting a new or competing renewal application/proposal to the
NIH that includes NIH-defined clinical research studies, investigators should
address plans for inclusion on the basis of sex/gender, race, and ethnicity as well as
complete the Planned Enrollment Report. At a minimum, the inclusion plan should
describe the proposed sample distributions by sex/gender, race, and ethnicity.
You should justify the proposed sample in the context of the scientific goals of
the proposed study. In addition to Planned Enrollment Reports, investigators
submitting a competing renewal application should also complete a Cumulative
Inclusion Enrollment Report(s) to describe progress on inclusion from the previous
funding period.
When reporting these data in the aggregate, investigators should report: (a)
the number of research participants in each ethnic category; (b) the number of
research participants who selected only one category for each of the five racial
categories; (c) the total number of research participants who selected multiple
racial categories reported as the “number selecting more than one race,” and (d)
the number of research participants in each racial category who are Hispanic or
Latino. Investigators may provide the detailed distributions, including all possible
combinations, of multiple responses to the racial designations as additional
information. However, more detailed data should be compiled in a way that they
can be reported using the required categories.
Key changes in 2013:
• The Planned Enrollment Report will now include the “More than one race”
category. The “More than one race” category will be used for reporting the
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planned number of individuals who you believe will identify with more than
one racial category. Currently, this category has only been available when
reporting actual cumulative enrollment.
• The layout of both the Planned Enrollment Report and the Cumulative
Inclusion Enrollment Report has been modified to reduce confusion about
racial and ethnic information being distinct concepts.
• The modified Planned Enrollment Report and Cumulative Inclusion
Enrollment Report are structured data forms. As such, they will replace
the need to attach enrollment tables as pdf files on electronically submitted
competing grant applications.
What it means:
If your application is a renewal or revision and involves clinical research
studies, you must describe plans for enrollment, or reports on actual enrollment,
of research subjects. This allows you to include summary data on participants
and involves two categories of ethnicity and five racial categories — all based
upon Office of Management and Budget (OMB) reporting standards for race and
ethnicity data. As of late 2013, “more than one race” has been added as a racial
category. All data are intended to be self-reported by research participants.
The Planned Enrollment Form is used to report your expected inclusion when
you are preparing a new grant proposal and is included here:
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Direct from NIH:
Planned Enrollment Report
This report format should NOT be used for collecting data from study participants.
Study Title:
Domestic/Foreign:
Domestic
Comments:
Ethnic Categories
Racial Categories
Not Hispanic or Latino
Female
Male
Female
Male
American Indian/ Alaska
Native
0
Asian
0
Native Hawaiian or Other
Pacific Islander
0
Black or African American
0
White
0
More Than One Race
0
Total
0
PHS 398 / PHS 2590 (Rev. 08/12 Approved Through 8/31/2015)
Page
159 Total
Hispanic or Latino
0
0
0
0
OMB No. 0925-0001/0002
Planned Enrollment Report
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Chapter 5: Special Considerations
Field Name
Instructions
Study Title
Enter a unique title that describes the study that the participants will be
involved in. If there is more than one study, provide a separate Study Title
for each. Follow the instructions provided in the Application Guide and
the FOA regarding the Inclusion of Women and Minorities. Maximum
250 characters. This is a required field.
Domestic/Foreign
Select whether the participants described in the planned enrollment report
are domestic or foreign. At a minimum, domestic and foreign participants
must be reported separately even if for the same study. This is a required
field.
Comments
Enter information you wish to provide about this planned enrollment
report. This includes but is not limited to addressing information about
distinctive subpopulations if relevant to the scientific hypotheses being
studied and/or a study that will have a delayed onset. Maximum 500
characters.
American Indian/Alaska
Native
Enter the expected number of females and males (in the respective fields)
who are American Indian/Alaska Native and Not Hispanic or Latino, and;
enter the expected number of females and males (in the respective fields)
who are American Indian/Alaska Native and Hispanic or Latino. These
are required fields.
Asian
Enter the expected number of females and males (in the respective fields)
who are Asian and Not Hispanic or Latino, and; enter the expected
number of females and males (in the respective fields) who are Asian and
Hispanic or Latino. These are required fields.
Native Hawaiian or Other
Pacific Islander
Enter the expected number of females and males (in the respective fields)
who are Native Hawaiian or Other Pacific Islander and Not Hispanic or
Latino, and; enter the expected number of females and males (in the
respective fields) who are Native Hawaiian or Other Pacific Islander and
Hispanic or Latino. These are required fields.
Black or African American
Enter the expected number of females and males (in the respective fields)
who are Black or African American and Not Hispanic or Latino, and;
Enter the expected number of females and males (in the respective fields)
who are Black or African American and Hispanic or Latino. These are
required fields.
PHS SF424 (R&R) Adobe Forms Version B Application Guide
White
Enter the expected number of females and males (in the respective fields)
who are White and Not Hispanic or Latino, and; enter the expected
number of females and males (in the respective fields) who are White and
Field Name
Instructions
Hispanic or Latino. These are required fields.
More than One Race
Enter the expected number of females and males (in the respective fields)
who identify with more than one racial category and are Not Hispanic or
Latino, and; enter the expected number of females and males (in the
respective fields) who identify with more than one racial category and are
Hispanic or Latino. These are required fields.
Part I: Instructions for Preparing and Submitting the Application
127
Total
The total fields at the bottom are auto-calculated to total all racial
categories for females and males who are Not Hispanic or Latino and all
racial categories for females and males who are Hispanic or Latino. The
total fields at the right are auto-calculated to total all males and females of
both Not Hispanic or Latino and Hispanic or Latino ethnicity in each
racial category.
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Cumulative
Inclusion Enrollment
Report
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In addition, if your study is funded, NIH requires you to report the cumulative
enrollment of subjects and their distribution by sex/gender and ethnicity/race using
the Cumulative Inclusion Enrollment Report form (below) unless your program
official indicates otherwise. If you are conducting more than one study, you should
provide a separate table for each study. This is the form you will use when writing
a renewal application, or when proposing to use data from an existing study in a
new application.
Direct from NIH:
Cumulative Inclusion Enrollment Report
This report format should NOT be used for collecting data from study participants.
Study Title:
Comments:
Ethnic Categories
Racial Categories
Not Hispanic or Latino
Female
Male
Hispanic or Latino
Unknown/
Not
Reported
Female
Male
Unknown/Not Reported Ethnicity
Unknown/
Not
Reported
Female
Male
Total
Unknown/
Not
Reported
American Indian/
Alaska Native
0
Asian
0
Native Hawaiian or
Other Pacific
Islander
0
Black or African
American
0
White
0
More Than One
Race
0
Unknown or Not
Reported
0
Total
0
0
PHS 398 / PHS 2590 (Rev. 08/12 Approved Through 8/31/2015)
161 0
0
0
Page
0
0
0
0
0
OMB No. 0925-0001/0002
Cumulative Inclusion Enrollment Report
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PHS SF424 (R&R) Adobe Forms Version B Application Guide
Field Name
Instructions
Study Title
Enter a unique title that describes the study that the participants will be
involved in. The title should be the same as submitted on the original
Planned Enrollment form for this study. Follow the instructions provided
in the Application Guide and the FOA regarding the Inclusion of Women
and Minorities. Maximum 250 characters. This is a required field.
Comments
Enter information you wish to provide about this Cumulative Inclusion
Enrollment Report. This includes but is not limited to information if
distinctive subpopulations are relevant to the scientific hypotheses being
studied. Maximum 500 characters.
American Indian/Alaska
Native
Enter the number of females, males, and individuals of unknown/not
reported sex/gender (in the respective fields) who are American
Indian/Alaska Native and Not Hispanic or Latino, and; enter the number
of females, males, and individuals of unknown/not reported sex/gender (in
the respective fields) who are American Indian/Alaska Native and
Hispanic or Latino; and enter the number of females, males, and
individuals of unknown/not reported sex/gender (in the respective fields)
who are American Indian/Alaska Native and of unknown/not reported
ethnicity. These are required fields.
Asian
Enter the number of females, males, and individuals of unknown/not
reported sex/gender (in the respective fields) who are Asian and Not
Hispanic or Latino, and; enter the number of females, males, and
individuals of unknown/not reported sex/gender (in the respective fields)
who are Asian and Hispanic or Latino; and enter the number of females,
males, and individuals of unknown/not reported sex/gender (in the
respective fields) who are Asian and of unknown/not reported ethnicity.
These are required fields.
Native Hawaiian or Other
Pacific Islander
Enter the number of females, males, and individuals of unknown/not
reported sex/gender (in the respective fields) who are Native Hawaiian or
Other Pacific Islander and Not Hispanic or Latino, and; enter the number
of females, males, and individuals of unknown/not reported sex/gender (in
the respective fields) who are Native Hawaiian or Other Pacific Islander
and Hispanic or Latino; and enter the number of females, males, and
individuals of unknown/not reported sex/gender (in the respective fields)
who are Native Hawaiian or Other Pacific Islander and of unknown/not
reported ethnicity. These are required fields.
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PHS SF424 (R&R) Adobe Forms Version B Application Guide
Black or African American
Enter the number of females, males, and individuals of unknown/not
reported sex/gender (in the respective fields) who are Black or African
American and Not Hispanic or Latino, and; enter the number of females,
males, and individuals of unknown/not reported sex/gender (in the
respective fields) who are Black or African American and Hispanic or
Latino; and enter the number of females, males, and individuals of
unknown/not reported sex/gender (in the respective fields) who are Black
or African American and of unknown/not reported ethnicity. These are
required fields.
White
Enter the number of females, males, and individuals of unknown/not
reported sex/gender (in the respective fields) who are White and Not
Hispanic or Latino, and; enter the number of females, males, and
individuals of unknown/not reported sex/gender (in the respective fields)
who are White and Hispanic or Latino; and enter the number of females,
males, and individuals of unknown/not reported sex/gender (in the
respective fields) who are White and of unknown/not reported ethnicity.
These are required fields.
More than One Race
Enter the number of females, males, and individuals of unknown/not
reported sex/gender (in the respective fields) who identify with more than
one racial category and are Not Hispanic or Latino, and; enter the number
of females, males, and individuals of unknown/not reported sex/gender (in
the respective fields) who identify with more than one racial category and
are Hispanic or Latino; and enter the number of females, males, and
individuals of unknown/not reported sex/gender (in the respective fields)
who identify with more than one racial category and of unknown/not
reported ethnicity. These are required fields.
Unknown or Not Reported
Enter the number of females, males, and individuals of unknown/not
reported sex/gender (in the respective fields) whose race is unknown/not
reported and who are Not Hispanic or Latino, and; enter the number of
females, males, and individuals of unknown/not reported sex/gender (in
the respective fields) whose race is unknown/not reported and who are
Hispanic or Latino; and enter the number of females, males, and
individuals of unknown/not reported sex/gender (in the respective fields)
who are of unknown/not reported race and of unknown/not reported
ethnicity. These are required fields.
Total
The total fields at the bottom are auto-calculated to total all racial
categories for females, males, and individuals of unknown/not reported
sex/gender who are Not Hispanic or Latino; all racial categories for
females, males, and individuals of unknown/not reported sex/gender who
are Hispanic or Latino, and all racial categories for females, males, and
individuals of unknown/not reported sex/gender who are of unknown/not
reported ethnicity. The total fields at the right are auto-calculated to total
all individuals in a given racial category.
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Note that NIH did not design these forms as data collection devices. Instead,
the agency indicates that you should use for that purpose an instrument that you
prepare for your study, and then use the information you collect to complete the
form.
In addition, you should use the following OMB definitions when applying the
ethnic and racial categories:
• Hispanic or Latino — a person of Cuban, Mexican, Puerto Rican, South or
Central American, or other Spanish culture or origin, regardless of race. The
term, “Spanish origin,” can be used in addition to “Hispanic or Latino.”
• American Indian or Alaska Native — A person having origins in any of the
original peoples of North, Central or South America and maintains tribal
affiliation or community.
• Asian — A person having origins in any of the original peoples of the Far
East, Southern Asia or the Indian subcontinent including, for example,
Cambodia, China, India, Japan, Korea, Malaysia, Pakistan, the Philippine
Islands, Thailand and Vietnam.
• Black or African American — A person having origins in any of the black
racial groups of Africa. Terms such as “Haitian” or “Negro” can be used in
addition to “Black or African American.”
• Native Hawaiian or Other Pacific Islander — A person having origins in any
of the original peoples of Hawaii, Guam, Samoa or other Pacific Islands.
• White — A person having origins in any of the original peoples of Europe,
North Africa or the Middle East.
• Ethnic/Racial subpopulations — In addition to the OMB ethnic and racial
categories, NIH uses the following definition for ethnic/racial subpopulations:
o Subpopulations — Each ethnic/racial group contains subpopulations
that are delimited by geographic origins, national origins and/or cultural
differences. It is recognized that there are different ways of defining and
reporting racial and ethnic subpopulation data. The subpopulation to which
an individual is assigned depends on self-reporting of specific origins and/
or cultural heritage. Attention to subpopulations also applies to individuals
who self identify with more than one ethnicity or race. These ethnic/racial
combinations may have biomedical, behavioral and/or social-cultural
implications related to the scientific question under study.
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The online forms you will use to complete your application will auto-total the
various rows and columns.
OMB’s data collection standards represent minimum requirements, and NIH
encourages researchers to collect additional types of information that could provide
insight into the relationships between race/ethnicity and health. For example, you
might also choose to inquire further for those who choose multiple categories as
to which they primarily identify. Or you might decide to ask participants if they
consider themselves part of a subpopulation — for instance, if a subject indicates
that he is Native American, you might ask him if he identifies as a member of a
particular tribe or nation.
If you do decide to collect this additional information, you do not have to
include it as part of your Planned Enrollment Form. But you should include it as
part of your resubmission/renewal application.
For many more suggestions and FAQs on this topic, see the NIH page on
inclusion at http://grants.nih.gov/grants/funding/women_min/women_min_qa.htm.
UPDATES TO NIH’S PLANNED AND CUMULATIVE
INCLUSION ENROLLMENT FORMS
The following was released by the NIH on April 30, 2014 (Notice Number:
NOT-OD-14-085):
On October 16, 2014, the NIH will transition to a new module within the
eRA Commons (known as the Inclusion Management System, or IMS) used for
reporting sex/gender, race, and ethnicity information as required by the NIH
Policy on the Inclusion of Women and Minorities in Clinical Research (see NOTOD-14-086). The previous system (known as the Population Tracking System) will
be retired this summer.
The NIH is also transitioning to an updated format for reporting sex/gender,
race, and ethnicity information. As noted in NOT-OD-13-092, the NIH has
modified the format used to report sex/gender, race, and ethnicity information of
individuals enrolled in clinical research studies. Applicants submitting competing
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applications have been using the updated formats starting with receipt dates on or
after September 25, 2013.
It is now time to transition to the modified format for Type 5 non-competing
progress report submissions using the PHS 2590 or the RPPR (Research
Performance Progress Report) as we prepare to deploy the Inclusion Management
System.
The notice goes on to say:
When submitting a progress report between July 18, 2014 and October
16, 2014 grantees will be directed to upload a PDF of the updated inclusion
enrollment reporting format in section G.4.b of the RPPR rather than access a link
to a structured data form.
Once the Inclusion Management System is available on October 17, 2014,
grantees submitting non-competing Type 5 progress reports using the RPPR will
have access to a link to the Inclusion Management System in Section G.4.b of the
RPPR that will allow reporting of the inclusion enrollment data using the updated
reporting format.
If using the PHS2590, use the PDF version of the updated inclusion
enrollment reporting format.
Additional Resources: Additional guidance regarding these changes as well as
other topics related to the inclusion of women and minorities in clinical research
can be found at:
http://grants.nih.gov/grants/funding/women_min/women_min.htm.
Along this same line, Notice NOT-OD-15-005, was released on October 2,
2014. Titled ‘ Use of New Inclusion Management System Required as of October
17, 2014’ it states:
The purpose of this NIH Guide Notice is to notify NIH applicants and
grantees about using the new Inclusion Management System (IMS) for reporting
sex/gender, race, and ethnicity information as required by the NIH Policy on the
Inclusion of Women and Minorities in Clinical Research. The existing system
was retired for grantee use in non-competing progress reports in July 2014. The
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new Inclusion Management System will be released October 17, 2014, and will
take advantage of the structured inclusion data being collected on competing
applications to pre-populate inclusion data records and allow grantees to directly
manage their inclusion data in the system throughout the awarded project period.
Key Changes for October 17, 2014, and beyond:
(1) Inclusion enrollment report forms received with competing application
submissions will automatically populate the IMS.
(2) NIH grantees completing their RPPR (Research Progress Performance
Report) will be prompted in Item G.4.b to access and update inclusion records
directly in IMS.
(3) Grantees will be able to access their inclusion enrollment data through the
IMS, found through the eRA Commons Status page, and can review or update their
inclusion data as needed.
(4) NIH will migrate ongoing enrollment information from the previous data
system to the IMS. Because the report format has been adjusted, grantees will be
prompted to update Cumulative Inclusion Enrollment data in the IMS format at the
time of the RPPR. They are encouraged to update Planned Enrollment data as well.
What it means:
The NIH is switching over to a new system for reporting, and now needs
grantees to submit the required information, which hasn’t changed, in a somewhat
different manner.
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INFORMING REVIEWERS ABOUT HUMAN SUBJECTS
Early on NIH’s application, you must indicate whether your proposal involves
using human subjects. If it does, you must later upload several separate documents
indicating who will be involved, why, how they will be impacted and your rationale
for including them.
In fact, there are four such documents you must prepare:
•Protection of Human Subjects
•Inclusion of Women and Minorities
•Targeted/Planned Enrollment Table
•Inclusion of Children
NIH does not place any page count restrictions on these, but it states that you
should “be succinct.” Do not use this section to circumvent the Research Strategy
section’s page limit.
Each of these documents must include specific information regarding the
REMEMBER:
NIH does not
place any page
count restrictions
on the human subjects documents,
but it states that
you should “be
succinct.”
human subjects, and we will look at them individually.
Protection of Human Subjects
This portion contains at least four sections, and NIH suggests you use subheads
to delineate them. Further, if your research includes a clinical trial, you should
have an additional subheading, “Data and Safety Monitoring Plan,” which we will
discuss next.
Direct from NIH:
4.1.1 Risks to Human Subjects
a. Human Subjects Involvement, Characteristics, and Design
•Describe the proposed involvement of human subjects in the work outlined in
the Research Strategy section.
•Describe and justify the characteristics of the subject population, including
their anticipated number, age range, and health status if relevant.
•Describe and justify the sampling plan, as well as the recruitment and
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retention strategies and the criteria for inclusion or exclusion of any
subpopulation.
•Explain the rationale for the involvement of special vulnerable populations,
such as fetuses, neonates, pregnant women, children, prisoners,
institutionalized individuals, or others who may be considered vulnerable
populations. Note that ‘prisoners’ includes all subjects involuntarily
incarcerated (for example, in detention centers) as well as subjects who
become incarcerated after the study begins.
•If relevant to the proposed research, describe procedures for assignment to a
study group. As related to human subjects protection, describe and justify the
selection of an intervention’s dose, frequency, and administration.
•List any collaborating sites where human subjects research will be performed,
and describe the role of those sites and collaborating investigators in
performing the proposed research. Explain how data from the site(s) will be
obtained, managed, and protected.
b. Sources of Materials
•Describe the research material obtained from living individuals in the form of
specimens, records, or data.
•Describe any data that will be collected from human subjects for the
project(s) described in the application.
•Indicate who will have access to individually identifiable private information
about human subjects.
•Provide information about how the specimens, records, and/or data are
collected, managed, and protected as well as whether material or data
that include individually identifiable private information will be collected
specifically for the proposed research project.
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c. Potential Risks
•Describe the potential risks to subjects (physical, psychological, financial,
legal, or other), and assess their likelihood and seriousness to the human
subjects.
•Where appropriate, describe alternative treatments and procedures, including
the risks and potential benefits of the alternative treatments and procedures, to
participants in the proposed research.
What it means:
Section 1: Risks to Human Subjects. When you write this section, NIH
suggests that you break it up into three components:
Section 1A: Human Subjects Involvement, Characteristics and Design.
According to NIH, you should use this section to describe and justify the following:
•The proposed involvement of human subjects in the work outlined in your
Research Strategy section.
•The characteristics of the subject population, including their anticipated
numbers, age range and health status if relevant.
•The sampling plan, as well as the recruitment and retention strategies and the
criteria for including or excluding any subpopulation.
•The rationale for involving special vulnerable populations, such as fetuses,
neonates, pregnant women, children, prisoners or institutionalized individuals.
•If relevant, the procedures for assigning individuals to a study group,
including selecting an intervention’s dose, frequency and administration.
•Any collaborating sites where human subjects research will be performed
and the role of those sites and collaborating investigators in performing the
proposed research, including how data from the site(s) will be obtained,
managed and protected.
Section 1B: Sources of Materials. For this section, indicate the following:
•The research material obtained from living individuals, such as specimens,
records or data.
•Any data that will be collected from human subjects for the project(s)
described in the application.
•Who will have access to individually identifiable private information about
human subjects.
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•How the specimens, records and/or data are collected, managed and protected
as well as whether material or data that include individually identifiable
private information will be collected specifically for the proposed project.
Section 1C: Potential Risks. Here, you must detail the following:
•The potential risks to subjects — physical, psychological, financial, legal or
other — and their likelihood and seriousness to the human subjects.
•Where appropriate, any alternative treatments and procedures, including any
risks and potential benefits, to participants in the proposed research.
For example, this section might read as follows:
Human Subjects Involvement and Characteristics: The focus of this study
is to develop biomarkers of pregnancy over gestation and at the development of
preeclampsia. Pregnant women (who are classified as a vulnerable population),
comprise most of the study population. Because the study is about pregnancy, men
are not eligible to be participants, except for control plasma.
Women would be approached in a manner consistent with university, state,
and federal guidelines. The characteristics of their backgrounds are anticipated to
reflect that of our patient populations. We will follow study eligibility criteria in a
manner consistent with university, state, and federal guidelines.
Sources of Research Materials: As specified in the study protocol, research
materials will involve medical records, pregnancy outcome data, data from research
visits and examinations, newborn anthropomorphic examination, and biological
samples (e.g., maternal blood, placental tissue, and umbilical cord blood).
Potential Risks: It is routine practice in the U.S. for women to undergo
screening for high blood pressure and development of preeclampsia.
Risks associated with blood draw include patient discomfort (pain), bruising,
inconvenience, and increased risk of infection. These risks are minimal.
Given that women and their unborn children are vulnerable subjects, our
IRB requires assurance that these risks area “not greater than minimal risk.” The
university Committee for Protection of Human Subjects requires completion of a
Pediatric Risk Assessment Form by an independent physician “with expertise in
pediatric population.” Potential risks will be described in non-medical terms in the
research consent form.
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Direct from NIH:
4.1.2 Adequacy of Protection Against Risks
a. Recruitment and Informed Consent
•Describe plans for the recruitment of subjects (where appropriate) and
the process for obtaining informed consent. If the proposed studies will
include children, describe the process for meeting requirements for parental
permission and child assent.
•Include a description of the circumstances under which consent will be
sought and obtained, who will seek it, the nature of the information to be
provided to prospective subjects, and the method of documenting consent. If
a waiver of some or all of the elements of informed consent will be sought,
provide justification for the waiver. Informed consent document(s) need not
be submitted to the PHS agencies unless requested.
b. Protections Against Risk
•Describe planned procedures for protecting against or minimizing potential
risks, including risks to privacy of individuals or confidentiality of data, and
assess their likely effectiveness.
•Research involving vulnerable populations, as described in the DHHS
regulations, Subparts B-D must include additional protections. Refer to
DHHS regulations, and OHRP guidance:
•Additional Protections for Pregnant Women, Human Fetuses and Neonates:
http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.html#subpartb
•Additional Protections for Prisoners: http://www.hhs.gov/ohrp/
humansubjects/guidance/45cfr46.html#subpartc
•OHRP Subpart C Guidance: http://www.hhs.gov/ohrp/policy/index.html
•Additional Protections for Children: http://www.hhs.gov/ohrp/humansubjects/
guidance/45cfr46.html#subpartd
•OHRP Subpart D Guidance: hhs.gov/ohrp/policy/populations/children.html
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•Where appropriate, discuss plans for ensuring necessary medical or
professional intervention in the event of adverse effects to the subjects.
Studies that involve clinical trials (biomedical and behavioral intervention
studies) must include a general description of the plan for data and safety
monitoring of clinical trials and adverse event reporting to the IRB, the NIH
and others, as appropriate, to ensure the safety of subjects.
What it means:
Section 2: Adequacy of Protection Against Risks. For this area of the
document, NIH outlines these two sections:
Section 2A: Recruitment and Informed Consent. Here, provide the
following information:
•Plans for recruiting subjects (where appropriate) and the process for obtaining
informed consent. If your project will use children, outline the process for
meeting parental consent and child assent requirements.
•The circumstances under which you will seek and obtain consent, who will
seek it, what information you will provide to prospective subjects and how
you will document consent. If you will seek a waiver of some or all of the
informed consent elements, provide justification for the waiver.
Section 2B: Protections Against Risk. In this section, NIH states that you
should include the following:
•Planned procedures for protecting against or minimizing potential risks,
including risks to the privacy of individuals or confidentiality of data, and
assess their likely effectiveness.
•Research involving vulnerable populations.
•Additional protections for pregnant women, human fetuses and neonates.
•Additional protections for prisoners.
•Additional protections for children.
•When appropriate, plans for ensuring necessary medical or professional
intervention if subjects suffer an adverse effect. If your proposal involves
a clinical trial(s) — such as biomedical or behavioral intervention studies
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— you must include a general description of the plan for data and safety
monitoring of clinical trials and adverse event reporting to the appropriate
organization(s) to ensure the subjects’ safety.
Here’s an example of how this section might read:
Recruitment and Informed Consent: Prior to implementation, we will train
all research and any clinic personnel involved in recruitment for our project.
Informed consent will be obtained in a method consistent with university, state,
and federal regulations. A HIPAA waiver will be sought to allow the ability to
screen clinic charts and/or other medical records, and then eligible women will be
approached by research staff. Written study materials including brochures, flyers,
and signs will be employed to provide information regarding the study. Trained
researcher staff will approach eligible women and explain the study, review the
consent documents, and answer questions as appropriate. All written material is
presented in both English and Spanish. For those languages not spoken by the
immediate staff, the clinics have access to an interpreter hotline.
If interested in participating, women will receive an IRB-approved Patient
Information and Consent Form that describes the study and the terms of potential
participation in the study. If a woman chooses to participate, she will sign the
consent form as will the person seeking consent. A copy of the informed consent
form will be given to the enrolled subject, placed in medical records charts
(hospital or clinic), and in a research chart. All subjects will have the option of
withdrawal from any study at any time.
Protection From Risk: With respect to protections for pregnant women,
fetuses, and neonates, this project meets definitional and procedural criteria and
requirements as outlined in 45 CFR 46 (§46.201-§46.204). Safeguards will be
built into our plan to minimize any risks, including those associated with loss of
confidentiality. Materials will be stored in a protected location with access limited
to research personnel.
All research personnel will also comply with all IRB and OPRR educational
programs and guidelines.
Subject data, when transmitted, will be identifiable only by a study subject
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number. Only personnel with a need to know will have access to any study
information, an access that will require security passwords. All hard copies of subject
data will be kept in locked file cabinets in the co-investigator’s research office.
The university requires that all investigators and members responsible for
the design and/or conduct of research provide evidence of adequate training to
maintain IRB approval of a study. All individuals who will be involved in conduct
of the research have completed (or will complete) the course required by the
university for those who will participate in human subjects’ research.
Direct from NIH:
4.1.3 Potential Benefits of the Proposed Research to Human Subjects and
Others
•Discuss the potential benefits of the research to research participants and others.
•Discuss why the risks to subjects are reasonable in relation to the anticipated
benefits to research participants and others.
What it means:
Section 3: Potential Benefits of the Proposed Research to Human Subjects
and Others. For this section, you should provide the following information:
•The potential benefits of the research, not only to participating human
subjects, but also to others.
•Why the risks to subjects are reasonable compared to the anticipated benefits
to research participants and others.
This section might read as follows:
There may be no direct and immediate benefit to the subjects from their
participation in this research study. Preliminary findings from the study will be
made available to researchers, as well as the general public as soon as possible.
There is likely no direct benefit for the patients, except that in the future, this
noninvasive assay might help diagnose preeclampsia earlier in gestation.
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Direct from NIH:
4.1.4 Importance of the Knowledge to be Gained
•Discuss the importance of the knowledge gained or to be gained as a result of
the proposed research.
•Discuss why the risks to subjects are reasonable in relation to the importance
of the knowledge that reasonably may be expected to result.
What it means:
Section 4: Importance of the Knowledge to Be Gained. For this portion, NIH
states that you should provide details regarding the following:
•The importance of the knowledge gained or to be gained as a result of the
proposed research.
•Why the risks to subjects are reasonable when compared to the importance of
the expected resulting knowledge.
The following is an example of this section:
Our goal is to develop biomarkers that are windows on the physiologic world of
gestation and preeclampsia. We believe this study will provide important data as to
whether a flow cytometric approach will work in the setting of preeclampsia. Thus,
we believe the potential risks to study subjects are limited to the risk associated
with a blood draw and are appropriate for the knowledge to be gained.
Direct from NIH:
4.1.5 Data and Safety Monitoring Plan
The NIH Data and Safety Monitoring Plan Policy is described and referenced
in Section 5.3.
•If the proposed research includes a clinical trial, create a heading entitled
“Data and Safety Monitoring Plan.”
•Provide a general description of a monitoring plan that you plan to establish
as the overall framework for data and safety monitoring. Describe the entity
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that will be responsible for monitoring and the process by which Adverse
Events (AEs) will be reported to the Institutional Review Board (IRB), the
funding I/C, the NIH Office of Biotechnology Activities (OBA), and the
Food and Drug Administration (FDA) in accordance with Investigational
New Drug (IND) or Investigational Device Exemption (IDE) regulations. Be
succinct. Contact the FDA (http://www.fda.gov/) and also see the following
websites for more information related to IND and IDE requirements:
http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.
cfm?CFRPart=312 (IND), http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/
cfcfr/CFRSearch.cfm?CFRPart=812 (IDE).
•The frequency of monitoring will depend on potential risks, complexity, and
the nature of the trial; therefore, a number of options for monitoring trials are
available. These can include, but are not limited to, monitoring by a:
a. PD/PI (required)
b.Institutional Review Board (IRB) (required)
c. Independent individual/safety officer
d.Designated medical monitor
e. Internal Committee or Board with explicit guidelines
f. Data and Safety Monitoring Board (DSMB). NIH specifically requires the
establishment of Data and Safety Monitoring Boards (DSMBs) for multisite clinical trials involving interventions that entail potential risk to the
participants, and generally for Phase III clinical trials. Although Phase I
and Phase II clinical trials may also need DSMBs, smaller clinical trials
may not require this oversight format, and alternative monitoring plans
may be appropriate.
•A detailed Data and Safety Monitoring Plan must be submitted to the
applicant’s IRB and subsequently to the funding IC for approval prior to the
accrual of human subjects. For additional guidance on creating this Plan, see
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-038.html.
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What it means:
Potential Section 5: Data and Safety Monitoring Plan. As stated earlier, if
your proposal includes a clinical trial, NIH states that you must include a section
with this subheading.
You should provide the following details in this section:
•A general description of your monitoring plan for data and safety. Describe
the entity responsible for monitoring and the process by which adverse events
(AEs) will be reported to your institutional review board (IRB), the funding
ICO, the NIH Office of Biotechnology Activities (OBA), and the Food and
Drug Administration (FDA) in accordance with Investigational New Drug
(IND) or Investigational Device Exemption (IDE) regulations.
•The frequency of monitoring will depend on potential risks, complexity
and the trial’s nature. Therefore, you will have a number of options
regarding monitoring trials, which can include, but should not be limited to,
monitoring by a:
a. PD/PI (required)
b.IRB (required)
c. Independent individual/safety officer
d.Designated medical monitor
e. Internal committee or board with explicit guidelines
f. Data and Safety Monitoring Board (DSMB). In fact, NIH specifically
requires establishing DSMBs for multi-site clinical trials involving
interventions that entail potential risk to the participants and generally
for Phase III clinical trials. Although Phase I and Phase II clinical trials
may also need DSMBs, smaller clinical trials may not require them, and
alternative monitoring plans may be appropriate.
•You must submit a detailed Data and Safety Monitoring Plan to your IRB
and subsequently to the funding ICO for approval prior to accruing human
subjects.
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For instance, this section might read as follows:
This is not a clinical trial, although pregnant women will be examined,
blood drawn for study, and they will receive their standard of care from the coinvestigator who is a physician.
The university IRB policies outlined in our IRB Reference Manual will be
followed. The privacy of all subject information will be maintained as per HIPAA
requirements by de-identification of subject information. The local research team
will create and maintain a confidential database on the hospital system. Only
research staff is authorized entry into the hospital system on the computers that will
be used for data storage. All source documents are maintained in locked files in a
locked room. Appropriate firewall and virus scanning software are installed and
updated routinely by the hospital and/or university support staff.
Direct from NIH:
4.1.6 ClinicalTrials.gov Requirements
Public Law 110-85 (also known as the FDA Amendments Act (FDAAA) of
2007) mandates registration and results reporting of “applicable clinical trials”
in ClinicalTrials.gov. Under the statute these trials generally include: (1) Trials
of Drugs and Biologics: Controlled, clinical investigations, other than Phase 1
investigations, of a product subject to FDA regulation; and (2) Trials of Devices:
Controlled trials with health outcomes, other than small feasibility studies, and
pediatric postmarket surveillance. Review the statutory definition of applicable
clinical trial to identify if registration is required to comply with the law (See PL
110-85, Section 801(a), adding new 42 U.S.C. 282(j)(1)(A)).
NIH encourages registration of ALL clinical trials whether required under the
law or not.
Registration is accomplished at the ClinicalTrials.gov Protocol Registration
System Information Website (http://prsinfo.clinicaltrials.gov/). A unique identifier
called an NCT number, or ClinicalTrials.gov registry number, will be generated
during the registration process.
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The NIH implementation of FDAAA requires:
•the registration of applicable clinical trials in ClinicalTrials.gov no later than
21 days after the first subject is enrolled,
•the reporting of summary results information (including adverse events) no
later than 1 year after the completion date for registered applicable clinical
trials involving drugs that are approved under section 505 of the Food, Drug
and Cosmetic Act (FDCA) or licensed under section 351 of the PHS Act,
biologics, or of devices that are cleared under section 510k of FDCA, and
•if an “applicable clinical trial” is funded in whole or in part by an NIH grant
or cooperative agreement, grant and progress report forms shall include a
certification that the responsible party has made all required submissions to
ClinicalTrials.gov.
For competing (new and renewal) applications that include applicable clinical
trials which require registration and results reporting under FDAAA, provide
the NCT number/s, Brief Title/s (protocol title intended for the lay public – see
Definitions), and the identity (name, organization) of the responsible party and
their contact information (e-mail address is required for internal administrative use
only) in the human subjects section of the Research Plan under a section heading
entitled ClinicalTrials.gov. If a new applicable clinical trial is proposed, or if the
grant will support an applicable clinical trial that is ongoing but not yet required
to register under FDAAA (e.g. less than 21 days have passed since enrollment of
the first patient), the human subjects section of the Research Plan must include a
clear statement, under the heading ClinicalTrials.gov, that the project includes an
applicable clinical trial which will require registration in ClinicalTrials.gov.
The entity responsible for registering the trial is the “responsible party”. The
statute defines the responsible party as:
1.the sponsor of the clinical trial (as defined in 21 C.F.R. 50.3) (http://www.
accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=50.3), or
2.the principal investigator of such clinical trial if so designated by a sponsor,
grantee, contractor, or awardee (provided that “the principal investigator is
responsible for conducting the trial, has access to and control over the data
from the clinical trial, has the right to publish the results of the trial, and has
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the ability to meet all of the requirements” for submitting information under
the law) (http://www.gpo.gov/fdsys/pkg/PLAW-110publ85/pdf/PLAW110publ85.pdf). See PL 110-85, Section 801(a), (adding new 42 U.S.C.
282(j)(1)(A)(ix)).
For the complete statutory definitions of “responsible party” and “applicable
clinical trial”, refer to Elaboration of Definitions of Responsible Party and
Applicable Clinical Trial.
The signature on the application of the Authorized Organization Representative
assures compliance with FDAAA.
Additional information can be found on the ClinicalTrials.gov Web site
(http://grants.nih.gov/ClinicalTrials_fdaaa).
What it means:
Potential Section 6: ClinicalTrials.gov Requirements.
If your application includes applicable clinical trials that require registration
and results reporting under the FDA Amendments Act of 2007 (FDAAA, Public
Law 110-85), you should include this section to provide the ClinicalTrials.gov
registry number(s) (NCT), Brief Title(s) (which is the protocol title intended for the
lay public), and the identity (name and/or organization) and contact information
for the responsible party. If your proposal includes a new clinical trial or if the
grant will support an applicable clinical trial that is ongoing but not yet required
to register under FDAAA (that is, less than 21 days have passed since enrolling
the first patient), you must clearly state in this section that the project includes an
applicable clinical trial that will require registration in ClinicalTrials.gov. NIH
further states that the entity responsible for registering the trial — the “responsible
party” — is one of the following:
•The sponsor of the clinical trial, or
•The PI of such clinical trial if so designated by a sponsor, grantee, contractor
or awardee — as long as the PI “is responsible for conducting the trial,
has access to and ability to meet all of the requirements” for submitting
information under the FDAAA.
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Inclusion of Women and Minorities
For this Human Subjects document, you must address NIH’s policy that all
agency-supported biomedical and behavioral clinical research projects must
include women and members of minority groups and their subpopulations unless a
clear and compelling rationale and justification that including them is inappropriate
with respect to the subjects’ health or the research’s purpose.
Direct from NIH:
4.2 Inclusion of Women and Minorities
In the attachment for Item 7, include a heading entitled “Inclusion of Women
and Minorities.” Although no specific page limitation applies to this section of the
application, be succinct. The NIH Policy on the Inclusion of Women and Minorities
in Clinical Research is described and referenced in Section 5.6.
Scientific Review Groups will assess each application as being acceptable
or unacceptable with regard to the inclusion of women and minorities in clinical
research.
In this section of the Research Plan, address, at a minimum, the following four
points:
1.The targeted/planned distribution of subjects by sex/gender and racial/
ethnic groups for each proposed study or protocol using the format in the
Targeted/Planned Enrollment Table. (Instructions for completing this table
are provided below in 4.3.) If using existing specimens and/or data without
access to information on the distribution of women and minorities, so state
and explain the impact on the goals of the research as part of the rationale
that inclusion cannot be described (item 3 below). Alternatively, describe
the gender and minority composition of the population base from whom
the specimens and/or data will be obtained. Include the Targeted/Planned
Enrollment Tables in this section.
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2.A description of the subject selection criteria and rationale for selection
of sex/gender and racial/ethnic group members in terms of the scientific
objectives and proposed study design. The description may include, but is
not limited to, information on the population characteristics of the disease or
condition under study.
3.A compelling rationale for proposed exclusion of any sex/gender or racial/
ethnic group (see examples below).
4.A description of proposed outreach programs for recruiting sex/gender and
racial/ethnic group members as subjects.
4.2.1 Additional Instructions and Requirements When NIH-Defined Phase III
Clinical Trials Are Proposed
If the proposed research includes an NIH-Defined Phase III Clinical Trial,
the section on Inclusion of Women and Minorities also must address whether
clinically important sex/gender and/or race/ethnicity differences are expected from
the intervention effect. The discussion may include supporting evidence and/or
data derived from animal studies, clinical observations, metabolic studies, genetic
studies, pharmacology studies, and observational, natural history, epidemiology
and other relevant studies. The discussion of expected sex/gender and/or race/
ethnicity differences in intervention effect must include selection and discussion of
one of the following analysis plans:
• Plans to conduct valid analyses to detect significant differences in intervention
effect among sex/gender and/or racial/ethnic subgroups when prior studies
strongly support these significant differences among subgroups, or
• Plans to include and analyze sex/gender and/or racial/ethnic subgroups when
prior studies strongly support no significant differences in intervention effect
between subgroups. (Representation of sex/gender and racial/ethnic groups is
not required as subject selection criteria, but inclusion is encouraged.), or
• Plans to conduct valid analyses of the intervention effect in sex/gender and/
or racial/ethnic subgroups (without requiring high statistical power for each
subgroup) when the prior studies neither support nor negate significant
differences in intervention effect among subgroups.
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What it means:
Cost is not an acceptable reason for excluding women or minorities except
when the study would duplicate data from other sources, NIH states.
Consequently, Scientific Review Groups (SRGs) — also known as “study
sections” — will assess your application as being acceptable or unacceptable
regarding the inclusion of women and minorities in clinical research.
At a minimum, NIH states that this document must address the following four
points:
1.The targeted/planned distribution of subjects by sex/gender and racial/ethnic
groups for each proposed study or protocol using the format in the Targeted/
Planned Enrollment Table (which we will discuss in the next section of this
chapter). If you are using existing specimens and/or data without access
to information on the distribution of women and minorities, state so and
explain the impact on your research’s goals as part of the rationale that you
cannot describe inclusion. Alternatively, describe the gender and minority
REMEMBER:
Cost is not an acceptable reason for
excluding women
or minorities except
when the study
would duplicate
data from other
sources.
composition of the population base from whom the specimens and/or data
will be obtained.
2.The subject selection criteria and rationale for selecting sex/gender and
racial/ethnic group members in terms of the scientific objectives and
proposed study design. Include, but do not limit yourself to, information
regarding the population characteristics of the disease or condition under
study.
3.A compelling rationale for excluding any sex/gender or racial/ethnic group.
4.Proposed outreach programs for recruiting sex/gender and racial/ethnic
group members as subjects.
The following are examples of acceptable reasons to justify excluding human
subjects based upon sex/gender:
1.One gender is excluded because of the following:
•Including them would be inappropriate with respect to their health;
•The proposal’s research question is relevant to only one gender;
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•Evidence from prior research strongly demonstrates no difference between
genders; or
•Sufficient data already exist regarding comparable studies’ outcomes in the
excluded gender, and duplication is not needed in this study.
2.The research’s purpose constrains the applicant’s selection of study subjects
by gender (for example, uniquely valuable stored specimens or existing
datasets are single gender; very small numbers of subjects are involved;
or overriding factors dictate selection of subjects, such as matching of
transplant recipients or availability of rare surgical specimens).
3.Gender representation of specimens or existing datasets cannot be accurately
determined — for instance, pooled blood samples, stored specimens or
datasets with incomplete gender documentation — and this does not
compromise the research’s scientific objectives.
For excluding minority groups or subgroups, the following examples show
acceptable justifications:
1.Some or all minority groups or subgroups are excluded from the proposed
research because of one of the following:
•Including them would be inappropriate with respect to their health;
•The proposal’s research question is relevant to only one racial or ethnic
group;
•Prior research strongly demonstrates no differences between racial or
ethnic groups on the outcome variables;
•Your proposal involves a single minority group study to fill a research gap;
or
•Sufficient data already exist regarding comparable study outcomes in the
excluded racial or ethnic groups, and documentation is not needed in this
study.
2.The study’s geographical location has only limited numbers of those
minority groups who would be eligible for the study, and the investigator has
satisfactorily addressed this issue in terms of:
•The study’s size;
•The relevant characteristics of the disease, disorder or condition; or
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•The feasibility of making a collaboration or consortium or other
arrangements to include representation.
3.The purpose of the research limits the applicant’s study subject selection
by race or ethnicity — for example, uniquely valued cohorts, stored
specimens or existing datasets are of limited minority representation; very
small numbers of subjects are involved; or overriding factors dictate subject
selection, such as matching of transplant recipients or availability of rare
surgical specimens.
4.Racial or ethnic origin of specimens or existing datasets cannot be accurately
determined — for instance, pooled blood samples, stored specimens, or
datasets with incomplete racial or ethnic documentation — and this does not
compromise the research’s scientific objectives.
If your proposal includes a Phase III clinical trial, this section also must
address whether you expect clinically important sex/gender and/or race/ethnicity
differences from the intervention effect. This discussion may include supporting
evidence and/or data derived from animal studies, clinical observations, metabolic
studies, genetic studies, pharmacology studies, and observational, natural history,
epidemiology, and other relevant studies. Your discussion of expected sex/gender
and/or race/ethnicity differences in intervention effect must include selecting and
discussing one of the following:
•Plans to conduct valid analyses to detect significant differences in intervention
effect among sex/gender and/or race/ethnic subgroups when prior studies
strongly support these significant differences among subgroups; or
•Plans to include and analyze sex/gender and/or racial/ethnic subgroups when
prior studies strongly support no significant differences in intervention effect
between subgroups; or
•Plans to conduct valid analyses of the intervention effect in sex/gender and/
or racial/ethnic subgroups (without requiring high statistical power for each
subgroup) when the prior studies neither support nor negate significant
differences in intervention effect among subgroups.
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For example, this document could read as follows:
A. Inclusion of Women
The rationale for inclusion of women in this study is that preeclampsia only
occurs in pregnant women. We will also recruit males in the same age and ethnic
distribution as controls.
B. Inclusion of Minorities
We will increase awareness of our study among the diverse minority population
at the research sites. We will strive to create a diverse research team, as a culturally
diverse research staff can enhance enrollment of minorities. We will utilize our
strong presence at the various outpatient clinics and offices to ensure screening and
recruitment opportunities across populations. Any study materials that are created
will be sensitive to the multicultural makeup of our patient population.
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Inclusion of Children
Direct from NIH:
4.4 Inclusion of Children
The NIH Policy on Inclusion of Children is referenced and described in Section
5.7. Instructions for Item 9 of the Research Plan are as follows:
• Create a section entitled “Inclusion of Children” and place it immediately
following the Targeted/Planned Enrollment Table.
• For the purpose of implementing these guidelines, a child is defined as an
individual under the age of 21 years (for additional information see
http://grants.nih.gov/grants/funding/children/children.htm and
http://grants.nih.gov/grants/guide/notice-files/not98-024.html).
• Provide either a description of the plans to include children, or, if children
will be excluded from the proposed research, application, or proposal, present
an acceptable justification for the exclusion (see below).
• If children are included, the description of the plan should include a rationale
for selecting a specific age range of children. The plan also must include a
description of the expertise of the investigative team for working with children
at the ages included, of the appropriateness of the available facilities to
accommodate the children, and the inclusion of a sufficient number of children
to contribute to a meaningful analysis relative to the purpose of the study.
• Scientific Review Groups will assess each application as being acceptable
or unacceptable with regard to the age-appropriate inclusion or exclusion of
children in the proposed research project.
• When children are involved in research, the Additional Protections for
Children Involved as Subjects in Research (45 CFR Part 46 Subpart D)
apply and must be addressed under the Protections Against Risk subheading
(4.1.2.b).
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What it means:
For this Human Subjects document, you should provide the following
information regarding your proposed research’s inclusion of children — which
NIH defines as an individual younger than 21 years of age:
•A description of the plans to include children, or if children will be excluded
from the proposed research, application or proposal, present an acceptable
justification for excluding them.
•If children are included, the plan description should offer a rationale for
selecting a specific age range. The plan also must describe the investigative
team’s expertise for working with children at the ages included, of the
available facilities’ appropriateness to accommodate the children, and the
inclusion of sufficient children to contribute to a meaningful analysis relative
to the study’s purpose.
•SRGs assess each application as being acceptable or unacceptable based
upon the age-appropriate inclusion or exclusion of children in the proposed
research project.
•When you involve children in research, you must address additional
protections placed for their safety in the Adequacy of Protection Against
Risks section within the Protection of Human Subjects document.
At the same time, there are specific instances when NIH indicates you can
justify excluding children — or a specific age range, such as younger than 18 years
of age — from your research. Keep in mind, however, that NIH policy requires
you to include children in all clinical research conducted or supported by the
agency unless there are clear and compelling reasons not to include them. Here are
examples of when you may exclude children from your proposal:
•The research topic is not relevant to children.
•Laws or regulations bar you from including children.
•The knowledge you seek is already available for children or will be obtained
from another ongoing study, and an additional study will be needlessly
redundant. In this case, you should provide documentation of other studies
justifying the exclusions.
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•A separate, age-specific study in children is warranted and preferable,
including such examples as:
a. The condition is relatively rare in children when compared to adults,
meaning that you would need to make an extraordinary effort to include
children, although in rare diseases or disorders where the applicant has
made a particular effort to assemble an adult population, the same effort
would be expected to assemble a similar child population with the rare
condition; or
b.The number of children is limited because most are already involved in a
nationwide pediatric disease research network; or
c. Issues of study design preclude direct applicability of hypotheses and/or
interventions to both adults and children — including different cognitive,
developmental, or disease stages or different age-related metabolic
processes. Although this situation may justify excluding children in some
instances, NIH states that you should consider taking these differences into
account in your study design and expand the hypotheses you are testing
or the planned interventions to allow you to include children rather than
exclude them.
•Insufficient data are available in adults to judge potential risk in children — in
which case one of the research objectives could be obtaining sufficient adult
data to make this judgment. Although you generally should not include children
in the initial research study group, the illness’ nature and seriousness may
warrant their participation earlier based upon careful risk and benefit analysis.
•You concentrate your study designs to collect additional data on pre-enrolled
adult study subjects such as longitudinal follow-up studies that did not
include data on children.
•Other special cases that you can justify and the review group finds acceptable.
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INFORMING REVIEWERS ABOUT VERTEBRATE
ANIMAL TEST SUBJECTS
As with human subjects, if you propose to use live vertebrate animal test
subjects, NIH reviewers will evaluate how you involve them. This means you must
provide additional documentation to support using the animals. Provide this as a
separate document which you will upload when completing your application.
Direct from NIH:
If Vertebrate Animals are involved in the project, address each of the five points
below. This section should be a concise, complete description of the animals and
proposed procedures. While additional details may be included in the Research
Strategy, the responses to the five required points below must be cohesive and
include sufficient detail to allow evaluation by peer reviewers and NIH staff. If
all or part of the proposed research involving vertebrate animals will take place
at alternate sites (such as project/performance or collaborating site(s)), identify
those sites and describe the activities at those locations. Although no specific
page limitation applies to this section of the application, be succinct. Failure to
address the following five points will result in the application being designated
as incomplete and will be grounds for the PHS to defer the application from the
peer review round. Alternatively, the application’s impact/priority score may be
negatively affected.
If the involvement of animals is indefinite, provide an explanation and
indicate when it is anticipated that animals will be used. If an award is made,
prior to the involvement of animals the grantee must submit to the NIH awarding
office detailed information as required in points 1-5 above and verification of
IACUC approval. If the grantee does not have an Animal Welfare Assurance then
an appropriate Assurance will be required (See Part III, Section 2.2 Vertebrate
Animals for more information).
The five points are as follows:
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1.Provide a detailed description of the proposed use of the animals in the work
outlined in the Research Strategy section. Identify the species, strains, ages,
sex, and numbers of animals to be used in the proposed work.
2.Justify the use of animals, the choice of species, and the numbers to be used.
If animals are in short supply, costly, or to be used in large numbers, provide
an additional rationale for their selection and numbers.
3.Provide information on the veterinary care of the animals involved.
4.Describe the procedures for ensuring that discomfort, distress, pain,
and injury will be limited to that which is unavoidable in the conduct of
scientifically sound research. Describe the use of analgesic, anesthetic,
and tranquilizing drugs and/or comfortable restraining devices, where
appropriate, to minimize discomfort, distress, pain, and injury.
5.Describe any method of euthanasia to be used and the reasons for its
selection. State whether this method is consistent with the recommendations
of the American Veterinary Medical Association (AVMA) Guidelines on
Euthanasia. If not, include a scientific justification for not following the
recommendations.
Do not use the vertebrate animal section to circumvent the page limits of the
Research Strategy.
What it means:
NIH states that this section should be a concise, complete description of the
animals and proposed procedures. Specifically, the agency indicates that you must
address the following five points:
1.A detailed description of how you propose to use the animals in the work
outlined in the Research Strategy section. Identify the species, strains, ages,
sex and numbers of animals you plan to use.
Here is an example of how this section might read:
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Addressing the questions proposed above will require the use of specific
pathogen-free, germ-free, or gnotobiotic C57BL/6 and BALB/c wild type mice and
JhD-/-, RAG-/-, and Thy1.1 indicator mice. Some of the mice will be purchased, but
for some strains we will establish breeding colonies here. Since there has been no
reported difference in the effects of the virus in male and female mice and to minimize
unnecessary euthanizing in the breeding colonies, experiments will be performed
using both male and female mice. Young adult mice, 4-6 weeks, will be used for most
experiments. Mice will be orally inoculated with a normal gut the murine strain of
the virus. At times, specified in the proposed studies, fecal samples will be collected
after placing mice in specially designed stainless steel cages for four hours and blood
samples collected by tail vein bleeds. A set of experiments in mice will involve
isolating bone marrow cells from one mouse and retro-orbitally transferring the cells
into irradiated naïve mice of a congenically matched strain (chimeric experiments)
and will allow determination of critical subsets of immune cells that are responsible
for the generation of virus-specific antibody. Another set of experiments will involve
adoptive transfer of purified cells from one mouse to a congenically matched mouse.
A series of experiments will assess the impact of microbiota on the IgA response by
infection of gnotobiotic and antibiotic-treated mice. All experimentally infected mice
will be housed in microisolation or gnotobiotic cages in P2 containment facilities and
routinely assessed in a sentinel program. We estimate we will need approximately 800
mice per year, including breeders.
2.Justification for using the animals, choice of species and the numbers you
plan to use. If animals are in short supply, costly or to be used in large
numbers, provide an additional rationale regarding why you selected them
and at the numbers you indicate.
For instance, this section might read as follows:
The mouse is a well-established model of virus infection that has been widely
used to define the pathogenesis of the virus, the immune response, and to test
potential vaccine candidates. The mouse model of this virus is the best small
animal model to examine the role of different immune components in the induction
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of protective IgA since reagents are readily available and numerous mouse strains
with immunologic defects are available to determine the role each family members
plays in intestinal IgA production. Adult mice will be used to facilitate repeated
sampling and because of the numbers of cells and the size of the tissues that can be
recovered for cell adoptive transfer studies. The experiments have been designed
to obtain the most information using the least number of animals. However, the
inherent variability in performing the proposed experiments requires a repetition
of at least 1-2 times with at least 5 animals per group. For studies on IgA induction
and virus clearance and protection a minimum of 5 mice will be used per group.
A power calculation shows that 4.5 (or 5) animals are required per group when
the following assumptions are made: protection rate of treated group equals 85%,
protection rate in control group equals 10%.
Statistical Analysis and Endpoints. Statistical analyses are performed using
SPSS Version 7.5 for Windows (SPSS Inc., Chicago, IL). Percent reductions in
shedding (protection) between groups are compared using the Man Whitney U test.
Antibody titers prior to and following virus challenge within a group are compared
using the Wilcoxon Signed Ranks test and between groups by using the KruskalWallis test followed by the Mann Whitney U test. Trend analysis is performed by
linear regression and correlation coefficients between specific immune responses.
Means of responses will be calculated based on multiple experiments (2-3)
including a minimum of 5-10 animals or 5-10 pools of 2-5 animals/pool. Most
groups will have 5 mice/group to optimize the possibility of obtaining statisticallysignificant results in each experiment after attrition and outliers. This is justified
by power analysis (One-way ANOVA) on a representative experiment where
responses were compared in 3 groups of mice (e.g., wild type, and two knockout
mouse strains) as follows: N per Group (Power): 2 (0.407); 3 (0.795); 4 (0.746); 5
(0.988); 6 (>.99); 7 (>.99); 8 (>.99).
3.Information regarding the veterinary care the animals will receive.
This section might read as follows:
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Full-time veterinary care will be provided by the veterinary staff of the Center
for Comparative Medicine (CCM). There are four full-time veterinarians and three
veterinary technicians on staff. CCM also has a fully-equipped and staffed clinical
diagnostic and pathology laboratory. All experiments will adhere to the “Guide for
Laboratory Animal Facilities and Care” and are reviewed by an internal animal
care and resources committee (IACUC) prior to initiation.
4.The procedures for ensuring that any animal discomfort, distress, pain and
injury will be limited to that which is unavoidable. Describe the use of
analgesic, anesthetic, and tranquilizing drugs and/or comfortable restraining
devices, where appropriate, to minimize discomfort, distress, pain and injury.
Here is an example of how this section might read:
Discomfort and injury to animals will be limited to that which is unavoidable
for the conduct of these experiments and analgesic, anesthetic, and tranquilizing
drugs will be used where appropriate to minimize discomfort and pain to animals.
Animals will be monitored daily for signs of distress including non-responsiveness,
labored respiration, inability to eat, bleeding, or self-mutilation. Animals will be
deeply anesthetized prior to cervical dislocation. Tail vein or retro-orbital injections
of cells will be performed under mild isoflurane sedation. Restraints will be utilized
during tail vein bleeding and tails will be cleansed with alcohol prior to sampling
to prevent infection. The procedures using these animals will be carried out within
the provision of Public Law 89-544 as amended by the Animal Welfare Act of 1970
(Public Law 91-579; DHEW Publication No. (NIH) 78-23, “Guide for the Care and
Use of Laboratory Animals”; NIH Guide to Grants and Contracts, vol. 7, No. 17
(1/1/79)) and related animal welfare rules and regulations henceforth issued by the
Secretary of Agriculture and/or other federal or state agencies.
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5.Any method of euthanasia you plan to use and the reasons for selecting
it. State whether this method is consistent with the recommendations of
the American Veterinary Medical Association (AVMA) Guidelines on
Euthanasia. If not, include a scientific justification for not following the
recommendations.
Here, you might refer to the following example:
For euthanasia, animals will be deeply anesthetized with rodent combination
anesthetic (37.5 mg/ml ketamine, 1.9 mg/ml Xylazine, 0.37 mg/ml Acepromazine)
and then subjected to cervical dislocation or treated with CO2. These methods are
consistent with the recommendations of the Panel on Euthanasia of the American
Veterinary Medical Association.
REMEMBER:
If you are not sure
your research will
require animal
test subjects, you
must still complete
the additional
documentation.
In addition, if all or part of the proposed research involving vertebrate animals
will take place at alternate sites such as project/performance or collaborating
site(s), you must identify those sites and describe the activities that will take place
at each.
Keep in mind that if you fail to address the five points listed above, NIH can
designate your application as incomplete and defer it from the peer review round.
Alternatively, your impact/priority score could be negatively affected.
If you are not sure if your research will require animal test subjects, you
must still complete this additional document, NIH notes. Be sure to provide an
explanation, and indicate when you anticipate you will use animals. If you win the
grant, you must submit to the NIH awarding office detailed information covering
the five points above and verify approval by your IACUC — all before you may
involve animals in your research.
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INFORMING REVIEWERS ABOUT “SELECT AGENTS”
As in the case of using human or animal test subjects, you must create additional
documentation — which you will upload as a separate document — if your research
involves using “Select Agents.” These are hazardous biological agents and toxins
that the U.S. Department of Health and Human Services (HHS) and Department of
Agriculture (USDA) identify as having the potential to pose a severe threat to public
health and safety, to animal and plant health, or to animal and plant products. You
can find a list of these agents, which the Centers for Disease Control and Prevention
(CDC) maintains, at http://www.selectagents.gov/resources/List_of_Select_Agents_
and_Toxins_2012-12-4-English.pdf.
Direct from NIH:
Select Agents are hazardous biological agents and toxins that have been
identified by DHHS or USDA as having the potential to pose a severe threat
to public health and safety, to animal and plant health, or to animal and plant
products. CDC maintains a list of these agents. See
http://www.selectagents.gov/SelectAgentsandToxinsList.html.
If the activities proposed in the application involve only the use of a strain(s)
of Select Agents which has been excluded from the list of select agents and toxins
as per 42 CFR 73.3, the Select Agent requirements do not apply. Use this section to
identify the strain(s) of the Select Agent that will be used and note that it has been
excluded from this list. The CDC maintains a list of exclusions at
http://www.selectagents.gov/SelectAgentsandToxinsExclusions.html.
If the strain(s) is not currently excluded from the list of select agents and toxins
but you have applied or intend to apply to DHHS for an exclusion from the list,
use this section to indicate the status of your request or your intent to apply for an
exclusion and provide a brief justification for the exclusion.
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If any of the activities proposed in your application involve the use of Select
Agents at any time during the proposed project period, either at the applicant
organization or at any other performance site, address the following three points for
each site at which Select Agent research will take place. Although no specific page
limitation applies to this section, be succinct.
1.Identify the Select Agent(s) to be used in the proposed research.
2.Provide the registration status of all entities* where Select Agent(s) will be
used.
• If the performance site(s) is a foreign institution, provide the name(s) of the
country or countries where Select Agent research will be performed.
* An “entity” is defined in 42 CFR 73.1 as “any government agency (Federal,
State, or local), academic institution, corporation, company, partnership,
society, association, firm, sole proprietorship, or other legal entity.”
3.Provide a description of all facilities where the Select Agent(s) will be used.
• Describe the procedures that will be used to monitor possession, use and
transfer of the Select Agent(s).
• Describe plans for appropriate biosafety, biocontainment, and security of
the Select Agent(s).
• Describe the biocontainment resources available at all performance sites.
If you are responding to a specific funding opportunity announcement (e.g., PA
or RFA), address any requirements specified by the FOA.
Reviewers will assess the information provided in this Section, and any questions
associated with Select Agent research will need to be addressed prior to award.
What it means:
If your research involves only using a strain(s) of Select Agents that has been
excluded from the list, the Select Agent requirements do not apply. Nonetheless,
you should use this document to identify the strain(s) of the Select Agent that you
will use and note that it has been excluded from the list. You can find a list of these
exclusions at http://www.selectagents.gov/SelectAgentsandToxinsExclusions.html.
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On the other hand, if the strain(s) is not currently excluded from the Select
Agent list but you have applied or intend to apply to HHS for an exclusion from the
list, use this document to indicate your request’s status or your intent to apply for
an exclusion and provide a brief justification for the exclusion.
If any of the activities proposed in your application involve using Select Agents
at any time during the project period, regardless of where the research may take
place, you must address the following three points for each research site where
Select Agent research will take place:
1.Identify the Select Agent(s) you plan to use in your proposed research.
2.Provide the registration status of all entities — which NIH defines as
“any government agency (Federal, State, or local), academic institution,
corporation, company, partnership, society, association, firm, sole
proprietorship, or other legal entity” — where you will use Select Agent(s).
Even if the performance site(s) is a foreign institution, provide the name(s)
of the country(ies) where Select Agent research will be performed.
3.Provide a description of all facilities where you plan to use the Select
Agent(s).
•The procedures that you plan to use to monitor possession, use and transfer
the Select Agent(s).
•Your plans for appropriate biosafety, biocontainment and security of the
Select Agent(s).
•The biocontainment resources available at all performance sites.
Here is an example of a select agent section from a successful grant application
(Developing small molecule therapeutics for Ebola hemorrhagic fever virus,
Principal Investigator: Amab Basu, PhD):
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Select Agent
Select Agent to be used:
In vitro:
Ebola Zaire Mayinga
Ebola Sudan Boniface
Marburg Angola
In vivo:
Mouse Adapted Ebola Zaire
Guinea Pig Adapted Ebola Zaire
Organization Name registration status:
Number and expiration date: XXXXXXXXX-XXXX expiration XX/X/XX
The foundation is a select agent registered entity with Health and Human
Services, Centers for Disease Control and Prevention (CDC) and U.S. Department
of Agriculture, Animal Plant Health Inspection Service, National Select Agent
Program. The foundation has been inspected by the CDC National Select Agent
Program for use of HHS Select Agents and Toxins, Overlap Select Agents and
Toxins and USDA Select Agents and Toxins. Per the requirements of 42 CFR 73,
is approved for use of select agents at BioSafety Level 2, 3, and 4 and Animal
Biosafety Level 3 and 4.
Description of Facilities:
Procedures used to monitor possession, use and transfer of Select Agent(s)
The foundation maintains an experienced and trained staff of scientists,
veterinarians, research technicians and veterinary technicians available to perform
studies at high biocontainment and maximum containment. These individuals have
demonstrated proficiency at conducting nonhuman primate studies with the agents
identified in the proposal. The BSL3, ABSL3 and BSL4 Operations and Safety
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Manuals specify policies, procedures, and standard operating procedures (SOP)
for the safe handling of biological materials in biosafety laboratories. The policies,
procedures, and SOPs comply with application federal, state, and municipal
regulations and with the guidelines “Biosafety in Microbiological and Biomedical
Laboratories” issued by the Centers for Disease Control and Prevention (CDC) and
the National Institutes of Health (NIH). Employees are trained from these manuals
on each facility’s mechanical systems, biosafety, biocontainment and security.
Employees are also trained according to project specific and departmental standard
operating procedures.
These procedures apply to all foundation employees and visitors that use,
generate, store, or dispose of potentially infectious materials in foundation
biosafety laboratories and to persons who must enter those laboratories to perform
services. Prior to conducting experiments in the foundation biosafety laboratories,
staff members must read and be trained in the requirements outlined in this manual
and applicable task-specific safety plans.
At the present time, the director is the CDC designated Responsible Official
(RO). Select agent use, transfer or possession is forbidden without the permission
of the Responsible Official or Alternate Responsible Official, the required forms
filed, and written approval received from the CDC Select Agent Program.
Upon approval, the BSK-3/4 Committee will consider select agents proposals
for work in the BSL-3/4 laboratory. BSL-3/4-qualified investigators desiring
to work on a BSL4 project must also submit a Biohazard Application to the
Biohazards and Safety committee. The foundation Biosafety Committee has a key
role in the foundation’s overall biosafety program. The committee is responsible
for evaluating the foundation’s facility, equipment, and staff capabilities for
performing work in a safe manner. The committee is also responsible for:
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•Reviewing protocols and risk assessments submitted by principal
investigators for work involving biological materials or toxins.
•Meeting with PIs prior to the implementation of projects involving biological
materials or biological-derived toxins.
•Evaluating the foundation’s staff, facility and equipment for their ability to
provide the appropriate containment for handling biological materials.
•Assessing the foundation’s compliance with existing federal, state and local
environmental regulations.
Committee membership consists of representatives from technical departments,
management, and administrative staff, among others. The committee communicates
by e-mail with face-to-face meetings at least quarterly and/or more frequently if
necessary.
Plans for appropriate biosafety, biocontainment, and security of the Select
Agent(s)
Infectious cultures, inventory stocks or toxic materials are stored inside the BSL4
laboratory in refrigerators, incubators or freezers that are marked with the universal
biohazard sign. Principal investigators maintain inventories of infectious agents
stocks. A master list of select agents is securely kept by Virology and Immunology in
the BSL4 Scientific Manager’s office. A computerize and bar code inventory system
has been selected for the select agent inventory. All issues relating to select agent
inventory or tracking must be directed to the Responsible Official.
All infectious or toxic materials stored in refrigerators or freezers are properly
labeled and stored in containers capable of withstanding thermal shock of freezing
and thawing. Each container is labeled with the identity of the infectious agents,
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the date of the preparation, the initials or name of the responsible laboratorian
and a reference number that links the material to the more inclusive information
contained in the inventory database.
When work is completed, all infectious cultures and toxins are removed
from workbenches and cabinets and stored in a designated refrigerator or freezer.
Materials to be discarded are placed in a sealable container filled with a suitable
disinfectant. The container is placed in a discard pan containing the disinfectant.
Discard pans are placed in a cart and transported to the autoclave. Labware
containing infectious liquids are stored and transported in leak-proof containers
large enough to contain the fluid in case of leakage.
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CONCLUSION
Finally, if you are using human or animal test subjects and/or select agents,
NIH wants to know how and for what. Consequently, you will have to upload
specific information as part of your grant application. But be sure you do not use
these documents to bypass the Research Strategy page limits. n
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Chapter 6: Budgeting Your Research
Chapter 6:
Budgeting Your Research
When applying for a National Institutes of Health (NIH) grant, in addition to your
proposal’s science, you also have to forecast how much money you will need to complete
your research. Therefore, you should use the budget and associated justifications to
present and support all the expenses required to achieve your proposal’s objectives.
In fact, your budget’s numbers are almost as important as — if not more so
— the words you use to tell your research’s story. This part of your application
communicates to reviewers what you plan to do with the money you are asking
them to invest in your project. Some reviewers even flip to the budget first to get
a snapshot of the proposal and help them understand it. Although they should
not take your budget into consideration as part of the assessment process, the
information is available to them. And reviewers are told to evaluate the application
and assign a priority score based upon the science and feasibility, and some believe
the budget an indicator of feasibility.
There are two types of budget proposals that you can submit:
1.Modular budget
REMEMBER:
Some reviewers
flip to the budget
first to get a
snapshot of
the proposal
that will help them
understand it.
2.Detailed budget
You can use a modular budget for certain research grants if you request
$250,000 or less per year for direct costs. These are simplified, so you would not
submit detailed categorical information with these applications. You will input
details about this type of budget beginning on form PHS 398.
Detailed budgets — also called research and related (R&R) budgets — involve
filling out three separate data entry screens as part of the R01 grant application.
And there are a total of 11 different sections that make up the three data screens. In
addition, you have to complete a separate detailed budget for each year of support
you request. So this can become a rather lengthy process.
Finally, your application’s budget, regardless of the type you use, also includes
several justification documents. These are narratives that you construct to indicate
where you propose to spend your grant-related funds and why.
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Direct vs. Indirect Costs
For budgeting purposes, NIH makes a distinction between “direct” and
“indirect” costs associated with your proposal:
•Direct costs — Those that can be specifically identified with a particular
project or activity.
•Indirect costs — Also called facilities and administrative (F&A) costs, the
grantee incurs these for common or joint objectives that cannot be identified
specifically with a particular project or program.
When formulating a modular budget, you should consider only direct costs.
For detailed budgets, however, you must include both direct and indirect costs.
Keep in mind, however, that universities and other institutions commonly establish
a single, negotiated contracted percentage rate to represent F&A costs for all NIH
grants on their campuses, and you can obtain that information directly from your
organization to include with your application’s budget.
Note: From whatever award money you are granted, your administration
will “take off the top,” for itself, the F&A percentage it has negotiated with the
government.
Also remember that if you have a subcontract or consortium agreement with
another institution, you should treat any costs associated with that agreement as
“direct,” including that subcontracted organization’s indirect costs.
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STRATEGY FOR PLANNING YOUR BUDGET
The NIH application includes both R&R and modular budget components, and
you can use these to continually revise and keep track of your budget’s size during
your application writing process. In fact, this can be a helpful tool in your budget
planning process.
And the National Institute of Allergy and Infectious Diseases (NIAID) suggests
that you should expect to spend time and effort crafting your thorough justification
for your budget. “The more detail you include to justify it, the better — weak
budget justifications are a big problem for many applications,” the institute states.
If your budget expands beyond your grant type or career stage, you should
consider cutting back your experiments or Specific Aims, experts recommend.
Also, remember that NIH allows you to use grant money for certain specific
costs, and it uses the following principles to define which costs you can charge to
your grants:
•Allowable — Also known as “conformance,” this principle centers on
complying with the limitations and exclusions contained in the terms and
conditions of the award, which can vary depending upon the type of activity,
recipient and other characteristics of the specific grant.
•Allocable — You can allocate a cost to your grant if you incur it solely to
advance work under the proposal, it benefits both the project and other work
at your institution, or it is necessary to the overall organizational operation
and is assignable to the grant at least partially.
•Reasonable — A cost may be reasonable if it and its associated costs reflect
an action a prudent person would take under the circumstances prevailing
when the decision to incur the cost was made.
•Consistency — You, as the Principal Investigator (PI), must consistently
assign costs to cost objectives.
These four principles apply regardless of the type of budget you use.
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Another key aspect to your budget strategy is knowing how much money to
request. As the “Goldilocks” fairytale says, “Not too much, not too little, but just
right.” You should ask only for enough money to do the work you propose, but do
not think that a “low ball,” unrealistic budget will curry favor. In fact, you should
keep the following in mind:
STRATEGY:
You should ask
only for enough
money to do the
work you propose,
but do not think that
a “low ball,” unrealistic budget will curry
favor.
•NIH reviewers search grant applications for reasonable costs and judge
proposals based on whether your Specific Aims and methods support your
request.
•Reviewers also read the percent effort you list for each key person and judge
whether they are in sync with their expectations based upon your application.
•If you significantly over- or underestimate your budget, reviewers often take
this as you not understanding your work’s scope.
Consequently, NIAID recommends that you should calculate salaries as 60
percent to 80 percent of your total budget request. When you formulate the PI’s
salary, remember the mandatory cap, which changes each year. You can find the
salary cap information on NIH’s Web site: http://grants.nih.gov/grants/policy/
salcap_summary.htm. And do not ask for anything that might appear extravagant,
such as too much travel.
You should also use your budget to mention any discounts you receive. For
example, you use a large number of antibodies from a single source for your
project, and that supplier gives you a 25 percent volume discount. You should note
this in your budget documents because reviewers will want to know that you have
established this relationship.
NIAID also recommends that you should not request funds for equipment or
resources you have already listed as available in your Research and Other Related
Project Information forms. If you do, reviewers will delete these items, and it may
tarnish your credibility.
Alternatively, once you have determined the resources you will need for your
project, identify what your institution can provide. Once you have this information,
NIAID recommends that you ask the following:
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•Does your institution offer you a budget for purchasing needed equipment?
•Will you have access to the necessary equipment, especially any large
equipment (for instance, that costing more than $10,000) that you can share?
•If not, is there someone with whom you can collaborate who has access to
that equipment?
At the same time, if you decide to request funds for equipment as part of your
budget, NIAID offers the following guidelines:
•Requesting funds for small equipment or items not usually shared is fine.
•New investigators generally should avoid asking for expensive equipment.
Study sections are more likely to approve such requests once you have firmly
established yourself and are in charge of a larger group.
If you find yourself needing the expensive equipment as an absolute necessity
for your proposal, however, make sure it is essential and justify it well, NIAID
notes. You can create a separate module for that equipment, make it a one-time
cost, and do not add it to your base amount.
Also keep in mind any service contracts associated with such equipment. If
NIH funds the instrumentation, the agency will want to ensure it stays functional,
and this includes grant funding for service contracts. Even if you share the
equipment, you also share service contracts for this equipment, and you should
reflect this in your budget.
When deciding how much to ask for, experts recommend that you consider that
each grant mechanism has a cap. For example, R01s have a $250,000 yearly cap
for modular budgets. And if you request $175,000 or $200,000 instead of $250,000,
as a new investigator, you can show reviewers that you are easing your way into
the field, which could be a good thing, some experts note.
On the other hand, if you are performing human subject or animal studies, you
may need the full amount because such research is expensive. Therefore, be sure
to explain in your budget request the expensive nature of the animal/human testing
and your type of research.
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TIP:
When deciding
how much to ask
for, experts
recommend that
you consider
that each grant
mechanism has
a cap.
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To ensure that you include everything you should in your financial plan, some
experts recommend that you have someone else review it to search for anything
that you have missed. Another option is to work closely with your sponsored
programs office to ensure you complete your budget section correctly.
Not a Review Criterion, But …
Generally, NIH reviewers are not supposed to take your budget into
consideration as part of the assessment process. They are there to evaluate the
application and assign a priority score based upon the science and feasibility.
The budget, however, is there if reviewers wish to look at it — and many do —
and factor it into their scores even though it does not appear on the official summary.
After all, they say, the budget is one measure of a PI’s experience and judgment.
If the reviewer considers your budget inadequate, you may be told that your
proposal is “ambitious.” Although excellent science is necessary to receive a
good score, that is not sufficient. NIH is equally concerned with whether you will
likely accomplish the goals and milestones you lay out in your application. Less
experienced investigators often will try to show that they are a “bargain,” thinking
that the more “bang for its buck” the agency receives, the more impressed reviewers
will be. This is not a good calculation because they usually do not care about a
bargain. Instead, they care about you successfully completing the proposed study.
REMEMBER:
If the reviewer
considers your
budget inadequate,
you may be told
that your proposal
is “ambitious.”
Moreover, less experienced investigators often think, “I’ll say what I have to in
the application to get the funding. I’ll worry about actually carrying out the work
after I have the money.” On that note, be careful what you wish for.
The last thing you want is to win a grant award, and then spend as many as five
years trying to fulfill your commitments with inadequate resources. In particular,
one place where you can easily cut your budget is the amount of effort you allocate
for you and/or your co-investigators. Keep in mind, however, that this will likely
leave you overwhelmed because no matter what you list as your percent effort, you
still have to do or oversee all the work or end with a poorly run grant.
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So if your budget is too low, you make it difficult on yourself once you are
funded. And you run the risk of failing to honor your commitments to NIH, which
may cost you in the long run.
Note: Many comments in this section courtesy of William Gerin, PhD, Professor of Biobehavioral Health
at Pennsylvania State University.
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CREATE YOUR BUDGET
When you create your budget, remember that reviewers often use it to judge
your competence by comparing it to your project’s scope.
If you are from a domestic institution and request $250,000 per year or less
in direct costs for your proposed project, you can use a modular budget. This is
a simplified method for requesting funds, meaning you do not need to submit
detailed categorical information with your application.
Using modular budgets, PIs request funding in $25,000 increments. Keep in
mind, however, that this funding mechanism offers no inflationary increases for
future years, which requires you to plan your entire budget at the outset.
REMEMBER:
Modular budgets
offer no inflationary increases for
future years, which
requires you to plan
your entire budget
at the outset.
On the other hand, if you are applying for a grant from a foreign institution or
for more than $250,000, you will need to submit an R&R budget. This will require
the following:
•Using the R&R budget component forms (Application Sections A-K).
•Requesting a salary below the annual cap.
•Ensuring your direct institutional costs are consistent on all budget forms.
•Using whole numbers for person months and percent effort, and dollars for
costs. Rounding calculations to the nearest dollar, but institutional costs do
not need to be in whole numbers.
Modular or Detailed Budget?
To determine whether you should choose a modular or R&R budget, use the
following flow chart from NIH:
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Do your direct costs
(minus any consortium/subcontract F&A costs)
equal less than $250,000 per year?
No
Use detailed budget
(SF424 (R&R) Budget Form)
Yes
Are you applying for an
R01, R03, R15, R21 or R34 grant?
Chapter 6: Budgeting Your Research
No
Yes
Is that applicant organization based
in the United States?
Yes
No
Use modular budget
(PH S398 Modular Budget Form)
http://grants.nih.gov/grants/funding/modular/modular.htm.
Source: National Institutes of Health
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MODULAR BUDGETS HAVE A LIMIT
Direct from NIH:
Modular budgets are applicable to certain research grant applications from
domestic organizations requesting $250,000 or less per year for direct costs.
International organizations and others that do not fall under this definition
should use the detailed budget forms described in Section 4.7. Note, consortium/
contractual F&A costs are not factored into the direct cost limit. They may be
requested in addition to the $250,000 limit. Modular budgets are simplified;
therefore, detailed categorical information is not to be submitted with the
application.
For all modular budgets, request total direct costs (in modules of $25,000),
reflecting appropriate support for the project. There will be no future year
escalations. A typical modular grant application will request the same number of
modules in each year. Provide an additional narrative budget justification for any
variation in the number of modules requested.
What this means:
Once you have determined your budgetary needs in $25,000 increments —
not to exceed $250,000 — you must support your monetary request. For modular
budgets, you will do this by completing three narrative “justifications”:
1.Personnel Justification
2.Consortium Justification
3.Additional Justification
Some applicants might be tempted to add details of their scientific approach to
the budget justifications sections to boost their chances of getting all the funding
they seek. Although reviewers do carefully consider these financial planning
documents, they generally are only making sure the budget is appropriate for the
proposed experiments.
Therefore, details about your experimental approach are inappropriate for this
section because you cannot be sure your reviewers will read it. If your approach
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requires something that is unusually expensive, such as lots of animal costs for a
transgenic study, however, then definitely do point that out in the budget section.
Note that your budget request should not factor in your overall impact
score because it is in the “other” category, which is discussed after a score is
assigned. On the other hand, if reviewers think your request is excessive, they
will recommend cuts. And there may be “budget envy” among some reviewers,
especially if your salary structure looks high — as at a private company or national
lab. Be sure to explain your salary structure in the Personnel Justification if you
think that might be an issue.
Personnel Justification
Direct from NIH:
List all personnel, including names, percent of effort and roles on the project.
NIH and other PHS agencies use the concept of person months as a metric for
determining percent of effort. To assist applicants unfamiliar with this concept,
resources are available on the web at http://grants.nih.gov/grants/policy/person_
months_faqs.htm. Frequently asked questions and a conversion calculator are
available.
No individual salary information should be provided. Since the modules
should be a reasonable estimate of costs allowable, allocable, and appropriate for
the proposed project, applicants must use the current legislatively imposed salary
limitation when estimating the number of modules. For guidance on current salary
limitations contact your office of sponsored programs.
NIH grants also limit the compensation for graduate students. Compensation
includes salary or wages, fringe benefits and tuition remission. This limit should
also be used when estimating the number of modules. See:
http://grants1.nih.gov/grants/guide/notice-files/NOT-OD-02-017.html
What this means:
For the Personnel Justification, you should list all personnel working on the
project, their roles and the number of person months they will devote to the project.
A “person month,” according to NIH, is the measure you should use to indicate the
amount of time PIs, faculty and other senior personnel devote to your project.
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To calculate person months, multiply the percentage of your effort associated
with the project by the number of months of your appointment. NIH offers the
following examples:
•25% of a 9-month academic year appointment equals 2.25 person months (9 x
0.25 = 2.25)
•10% of a 12-month calendar year equals 1.2 person months (12 x 0.10 = 1.2)
•35% of a 3-month summer term appointment equals 1.05 person months (3 x
0.35 = 1.05)
In addition, your personnel justification should briefly describe each person’s
responsibilities in enough detail to justify the person’s level of effort. But you
should not include salary information in this document. And you should include
all key personnel even if you know they will be gone when the application is
funded, NIH says.
Budgeting Effort Can Be Delicate Task
When budgeting effort for the PI and/or co-investigators, you should start
with a pragmatic analysis. How much time will the particular investigator need to
allocate to accomplish his project-related duties? Think in these terms: There are
40 hours in a standard workweek, and 20 percent effort would mean that person in
theory would work on the project one full eight-hour day each week.
STRATEGY:
As for co-investigators who will do
the work outlined
in your proposal,
you have to find the
balance between
what they have
to do, how much
you can afford and
what would appear
questionable to a
reviewer.
217 And there are additional considerations. For example, you plan to list a senior
colleague as a co-investigator. You actually do not expect him to do much, but his
well-known name will be useful perhaps as a political expedient, and you might
feel awkward if you left him out. Consequently, you might list him at 5 or 10
percent effort. Also keep in mind that even at such a limited level, including such a
senior-level salary on your budget could add approximately $25,000 or more.
As for co-investigators who will do the work outlined in your proposal, you have
to find the balance between what they have to do, how much you can afford and what
would appear questionable to a reviewer. For instance, if you budget a co-investigator
in charge of all the lab work at only 3 percent of her salary, the reviewer likely would
find this unreasonable. Or if a co-investigator’s main job is to help with data analysis
that does not begin until Year 4, the reviewer likely would be concerned if you budget
him at 20 percent effort for all five years of the grant.
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To avoid this, you should determine effort allotments based upon the
following criteria:
1.Actual effort as matched to the anticipated work level
2.“Political” and personal considerations
3.Funds that are available
4.Appropriateness of the effort level as perceived by reviewers.
When considering effort for consultants, you will use the budget justification
section to describe not only what she will do, but also how many days per year she
will spend on the project and at what fee per day. You can break the cost down by
days or number of hours.
The consultant’s fee will vary depending on specialty, seniority and the
credentials she has. A lower-level consultant, for example, might be someone from
another university with a Masters degree in psychology who will score your heart
rate variability data. You might budget this person at $30 per hour, or roughly $250
per day. A more senior consultant might require $500-$1,000 per day, depending on
seniority and fame. Keep in mind that if you pay one consultant too much per day,
you run the risk of a reviewer flagging your application negatively.
Follow This Example
The following is an example of a Personnel Justification taken from a
successful R01 grant application (Method for Guiding Ablative Therapy of Cardiac
Arrhythmias. Principal Investigator: Antonis Armoundas, PhD):
Personnel Justification:
[Dr. PI (9.6 Calendar Year person months)]: The Principal Investigator is a
junior faculty at the [hospital], an independent investigator within the CVRC
and an Assistant Professor. He has extensive experience in the development of
biomedical signal processing algorithms and in conducting animal and human
studies. He will have overall responsibility for this project. He will supervise and
participate in all studies, perform data analysis, and prepare reports, manuscripts
and abstracts.
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[Dr. A], (Other Significant Contributor): [Dr. A] is an Attending
Electrophysiologist at the [hospital] and an Instructor in Medicine. [Dr. A’s]
research interests are focused on making advances in catheter mapping and
ablation of atrial and ventricular arrhythmias. Furthermore, he has been involved
in developing novel approaches and technologies for the management of cardiac
arrhythmias. He will provide hands on experience in the planning, execution and
troubleshooting of the proposed animal experiments.
[Dr. B], (Other Significant Contributor): [Dr. B] is an Attending
Electrophysiologist at the [hospital] and an Assistant Professor in Medicine. His
research interests are largely related to catheter ablation procedures and device
therapy. He will provide critical expertise and be involved in the planning phase
but also to actively participate in conducting and troubleshooting in the proposed
animal experiments and the data analysis and interpretation. Furthermore, his
experience as an Attending Electrophysiologist will be academically valuable, both
in theory and experimentally.
[Dr. C], (Other Significant Contributor), [Dr. C] is an Assistant Professor in
Medicine and a Staff Electrophyiologist at the [hospital]. She is currently the
Director of Interventional Electrophysiological Laboratory. She has extensive
experience with catheter ablation procedures, implantation and management of
pacemakers, defibrillators and cardiac resynchronization devices. She will provide
valuable hands on training and guidance in planning and troubleshooting the
electrophysiological experiments. She will participate and perform the catheter
ablation procedures, and she will also provide support in the optimization of the
electrophysiological experiments.
[Dr. D), (Other Significant Contributor): [Dr. D] is an Attending
Electrophysiologist at the [hospital] and an Assistant Professor in Medicine. [Dr. D’s]
group has been focused on making advances in catheter mapping and ablation of atrial
and ventricular arrhythmias. He is the Director of the Cardiac Resynchronization
Clinic, which is involved with developing novel approaches and technologies
for the management of cardiac arrhythmias. He will provide all the necessary
electrophysiological equipment for the experiments and hands on experience in the
planning, execution and troubleshooting of the proposed animal experiments.
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Postdoctoral Fellow: to be named (12.0 calendar months effort): He or she will
be involved in conducting the animal experiments and will have the day-to-day
responsibility for this project.
Graduate Student, [(9.6 calendar year person months effort in Year 1, 10.8
calendar year person months effort in Years 2-4)]: [The graduate student] has
worked for 6 years at [a hospital’s] Cardiac Rhythm Management Division as a
Clinical Engineer, Staff Scientist, and program manager before pursuing a PhD. He
has extensive experience in processing intracardiac signals and assembling cardiac
electrophysiology related hardware. He will have responsibility for developing
the signal processing algorithms and assembling and testing the hardware for this
project. He will also participate in all studies and the data analysis.
Consortium Justification
Direct from NIH:
Provide an estimate of total costs (direct plus Facilities and Administrative) for
each year, rounded to the nearest $1,000. List the individuals/ organizations with
whom consortium or contractual arrangements have been made. List all personnel,
including percent of effort, using the metric of person months, and roles on the
project. No individual salary information should be provided. Indicate whether
the collaborating institution is foreign or domestic. While only the direct cost
for a consortium/contractual arrangement is factored into eligibility for using the
modular budget format, the total consortium/contractual costs must be included in
the overall requested modular direct cost amount.
What this means:
Consortiums are agreements between the applicant and a collaborator, which
can be an individual or an organization, to carry out a portion of the grant-supported
research. If you receive an NIH grant, you will be directly and primarily responsible
for the funds, as well as accountable to the agency for performing the project.
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In the Consortium Justification, you must provide details of any consortium
agreements. This includes total costs associated with each such agreement rounded
to the nearest $1,000. You should also outline any personnel considerations,
including the roles and person months, and whether the consortium involves a
foreign individual or organization.
Here’s an Example
The following is an example of a Consortium Justification taken from a successful
R01 grant application (Tumor Necrosis Superfamily Ligands and Lymphocytes Role
in Liver Regeneration. Principal Investigator: Robert A. Anders, MD):
Consortium Justification:
A consortium arrangement with the University of Chicago, a domestic
institution, will be established in the estimated amount of $108,000 per year for a
total of $538,000, direct and F&A costs.
[Professor A, MD, PhD — 9 Calendar Year person months]
[Dr. A] is a Professor of Pathology at the University of Chicago. He is an
immunologist and has significant experience with the lymphotoxin system. [Dr.
A’s] lab cultures the hybridoma cell lines and purifies the LTbeta receptor-Ig,
and agonistic LTbeta receptor antibody and performs the quality control analysis
for each of these biologic agents. [Dr. A’s] research interest focuses on lymph
node development, autoimmunity and tumor immunology. He will serve as coinvestigator and will devote [36] calendar months to the project. He will oversee
and advise Dr. B.
[Assistant Professor B, MD, PhD — 9 Calendar Year person months]
[Dr. B] is a Research Associate (Assistant Professor) at the University of
Chicago. He has significant experience with selective ablation of the TNF
superfamily members in mice. He developed the T and B cell specific TNF
and lymphotoxin deficient mice. He has also developed the hepatocyte specific
lymphotoxin beta receptor deficient mice. [Dr. B’s] research interest focuses
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on development of the peripheral immune system (spleen, Peyer’s patches,
limb lymph nodes) and more recently how the central immune system controls
autoreactive T cells in thymus medulla. He will serve as a co-investigator on this
project and will devote [36] calendar months to the project.
Additional Narrative Justification
Direct from NIH:
If the requested budget requires any additional justification; e.g, variations in
the number of modules requested, save the information in a single file and click the
add attachment button to complete this entry.
What this means:
In most cases, applicants request the same number of modules each year, except
for special needs like equipment. If the number of modules you request vary from
year to year, this section is where you will explain why.
Use This Example
The following is an example of Additional Justification taken from a successful
R01 grant application (Engineering Fibrin Polymers for Enhanced Angiogenesis.
Principal Investigator: Thomas H. Barker):
Additional Narrative Justification:
TIP:
In most cases,
applicants request
the same number
of modules each
year, except for
special needs like
equipment.
Consultant fees
Funds have been requested for the consultation of [Dr. F] in years 1 through 4.
Travel
Funds have been requested to allow presentation of research results to the
scientific community. Over the course of the project, we are proposing the
presentation of results at 2-3 primary conferences per year.
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Materials and supplies
Funds have been requested for general M&S. These funds will be used
for standard laboratory supplies in support of the research objectives such as
expression systems, molecular biology supplies, cell culture plastics, culture media,
antibodies and reagents for detection and imaging as well as the purchase and
housing of animals, surgical supplies, and histology.
Publication costs
Funds in years 2-5 have been requested to offset the cost of manuscript
publication.
Equipment
In addition to the above requested funds, we are requesting additional funds
for equipment. Specifically, we are requesting funds in year 1 ($15,000) and
2 ($10,000) for two separate and necessary upgrades to our standard inverted
fluorescent microscope (Nikon TiE). These upgrades allow for 1) enhanced Z-axial
imaging resolution necessary for microfluidic experiments (both fibrin polymers
alone and in vitro angiogenesis assays) and 2) imaging of live cultures over time.
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FORM A DETAILED BUDGET
Direct from NIH:
If funds are being requested for more than one budget period, you must
complete a separate detailed budget for each year of support requested. To navigate
to screens for the next budget period, click the Next Period button at the top of
the 3rd budget screen (Sections F through K). You must complete all the required
information (i.e., those fields that are highlighted and outlined in red) and/or
confirm/update any pre-populated information before the Next Period button is
activated. If no funds are requested for a required field, enter “0.” Note the Budget
Justification is also a required item and must be attached before the Next Period
button is activated.
What this means:
If you are submitting a detailed budget, there are 11 separate sections
(designated A-K) that you will have to complete. These break down as follows:
•A: Senior/Key Person
•B: Other Personnel
•C: Equipment Description
•D: Travel
•E: Participant/Trainee Support Costs
•F: Other Direct Costs
•G: Total Direct Costs (A through F)
•H: Indirect Costs
•I: Total Direct and Indirect Institutional Costs (G+H)
•J: Fee
•K: Budget Justification
The NIH application breaks these sections into three separate screens as you
complete the form online:
•Screen 1: Sections A and B (Personnel)
•Screen 2: Sections C, D and E (Equipment, Travel, and Trainee Costs)
•Screen 3: Sections F through K (Other Direct and Indirect Costs and the
Budget Justification)
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Now, let’s examine each of these sections by screen.
Start With Personnel
NIH devotes the two sections on the first screen to detailing your proposal’s
personnel needs.
Direct from NIH:
A. Senior/Key Person
This section should include the names of all senior/key persons at the applicant
organization who are involved on the project in a particular budget year. Include
all collaborating investigators, and other individuals meeting the senior/key person
definition if they are from the applicant organization. Details of collaborators at
other institutions will be provided in the Subaward budget for each subaward/
consortium organization. Personnel listed as Other Significant Contributors who are
not committing any specific measurable effort to the project should not be included in
the Personnel section of the budget since no associated salary and/or fringe benefits
should be requested for their contribution. Consultants designated as senior/key
persons in the Senior/Key Person Profile Form can be included in Budget Section A
only if they are also employees of the applicant organization. Otherwise, consultant
costs should be included in Consultant Services.
What this means:
This section offers a series of data fields for each Senior/Key Person, including
the following:
•First, middle and last name, along with any prefixes or suffixes
•Project role — identify each Senior/Key Person, including project directors/
principal investigators, postdoctoral associates and other professionals
•Base salary — enter the annual compensation paid by the employer
•Calendar, Academic or Summer months — indicate the number of person
months devoted to the project for each individual (based upon the appropriate
calendar, academic or summer designations)
•Requested salary — regardless of the number of months each Senior/Key
Person devotes to the project, you must identify only the salary amount you
are requesting for this budget period
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•Fringe benefits — enter the cash value of any applicable fringe benefits for
each person. According to the NIH “the fringe benefits rate is based on your
institution’s policy; the NIH does not have a pre-set limit on fringe benefits.
More information on what is included as fringe benefits can be found in the
Grants Policy Statement at http://grants.nih.gov/grants/policy/nihgps_2013/
nihgps_ch7.htm#Fringe_Benefits. If you have questions about what rate to
use, consult your institution’s sponsored programs office.”
•Funds requested — here, note the requested salary and fringe benefits.
For Section B (Other Personnel) on this application budget screen, you will
identify the number of people in each project role rather than name individuals. In
fact, Section B includes the following data fields for each role:
•Number of personnel — identify the number of people you are proposing for
each project role category
•Project role — the form already lists Post Doctoral Associates, Graduate
Students, Undergraduate Students and Secretarial/Clerical, and you should
count only those not already listed in Section A. You can list additional
project roles in the additional data fields provided.
•Calendar, Academic or Summer months — indicate the number of person
months devoted to the project for each project role category (based upon the
calendar, academic or summer designations)
•Requested salary — show the amount of salary/wages you are requesting for
each project role
•Fringe benefits — enter the cash value of any applicable fringe benefits for
each project role
•Funds requested — note the requested salary and fringe benefits for each
project role
Screen 2 Means Direct Expenses
NIH devotes three sections on the second screen to specifics regarding any
equipment, travel and support costs associated with your proposal.
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For Section C, you will separately list any equipment costing more than
$5,000. NIH defines equipment as “an item of property that has an acquisition cost
of $5,000 or more (unless the organization has established lower levels) and an
expected service life of more than one year.” The agency further notes that it will
allow items limited to research equipment and apparatus that you do not already
have available to conduct your work. And it usually will not cover general-purpose
equipment, such as personal computers, unless you use them exclusively or
primarily for conducting your proposed research.
In this section, you also have to list the estimated cost of each piece of
equipment, including shipping and any maintenance costs and agreements.
In Section D, you must outline your travel costs. There are separate data fields
for domestic and foreign travel, which NIH breaks down as follows:
•Domestic travel — In this field, include the total funds you are requesting for
travel within the United States, Canada, Mexico and U.S. possessions.
•Foreign travel — Here, you list the total funds you request for travel beyond
North America and U.S. possessions.
For both types of travel, you must note in your budget justification document
the purpose, destination, travel dates (if known) and number of individuals for
each trip. If you do not know when the travel will take place, you must estimate the
trip’s length (for example, three days).
And although the application includes Section E for participant/trainee support
costs, NIH states the following:
Unless specifically stated otherwise in an announcement, NIH and other PHS
agencies applicants should leave blank Section E. Note: Tuition remission for
graduate students should continue to be included in Section F. Other Direct Costs
when applicable.
At the same time, if you must complete this section, you will provide the total
requested funding amounts related to participants and trainees involved in your project
for tuition/fees/health insurance, stipends, travel and subsistence, among others.
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Keep Track of Other Direct Costs
The third screen of the detailed budget form includes Sections F-K, which
consist of the remaining costs associated with your proposed research.
NIH reserves Section F for Other Direct Costs. This is where you must detail
the following:
•Materials and supplies — Here, you note general categories
•Publication costs
•Consultant services
•ADP/computer services
•Subawards/consortium/contractual costs
•Equipment or facility rental/user fees
•Alterations and renovations
•Other, which might include such costs as patient care and tuition remission.
For Section G (Total Direct Costs), you report the sum of the totals for
Sections A-F.
In Section H, however, you will provide information regarding Indirect Costs,
breaking them down by type, such as salaries and wages. Keep in mind that your
institution should have this information because it usually contracts with NIH for
an indirect cost rate that applies to all research conducted at the organization.
For Section I, Total Direct and Indirect Costs, you simply add the totals
for Sections G and H. And Section J (Fee) is usually left blank because a fee
is generally not allowed on a grant unless specifically noted in a program
announcement. In that case, you should enter the requested fee.
Finally, Section K is the Budget Justification.
Direct from NIH:
Use the budget justification to provide the additional information requested
in each budget category identified above and any other information the applicant
wishes to submit to support the budget request. The following budget categories
must be justified, where applicable: equipment, travel, participant/trainee support
and other direct cost categories. Only one file may be attached. The attachment is
required.
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Use this section to list the names, role (e.g., PostDoc or Graduate Student),
associated months, salary and fringe benefits for all Postdoctoral Associates and
Graduate Students included in Budget Section B. Other Personnel.
Include a justification for any significant increases or decreases from the initial
year budget. Justify budgets with more than a standard escalation from the initial
to the future year(s) of support. Also use this section to explain any exclusions
applied to the F&A base calculation.
If the application includes a subaward/consortium budget, a separate budget
justification is submitted for that budget. See Section 4.8 Special Instructions for
Preparing Applications with a Subaward/Consortium.
What this means:
Section K is a single narrative that you will upload to support the need for the
requested funds in your application’s detailed budget from Sections A-J. And you
have to address each cost individually.
STRATEGY:
The budget
narrative can be
your opportunity to
expand upon your
proposal without
affecting your
scientific content
related to explaining
your research.
Because most PIs focus on their science, they frequently wait until the last
minute to write the budget justification. But this is your chance to expand upon
the project without taking up precious pages in the Research Strategy. In fact, the
budget narrative does not count against your application page limit. Therefore,
it can be your opportunity to expand upon your proposal without affecting your
scientific content related to explaining your research.
This budget justification also allows you to show reviewers that you have
adequately planned for your project, you have done this before, and you know
what you are doing. To support this, make sure that your justification matches
your overall project narrative. These two items should go hand-in-hand because
you do not want a reviewer to be surprised to find an item in the budget that is not
mentioned in the research strategy.
Here is a sample Section K from a successful R01 grant (Capsid-Targeting
HIV-1 Antivirals. Principal Investigator: Christopher Aiken, PhD):
Budget Justification — Year 1:
Personnel
[Dr. X], Principal Investigator ([9.6] Calendar Months)
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[Dr. X] will devote [80 percent] of his effort to the project. His involvement
will include: overseeing the activities of the other personnel on the project,
providing critical input regarding experimental design and analysis of data. [Dr.
X] has extensive experience in molecular studies of HIV-1 infection, including
experience in the analysis of drug resistance and antiviral mechanisms. He will
communicate directly with the collaborators, and will directly participate in the
presentation of results at meetings and in publications.
[Dr. Y], Research Instructor ([9.6] Calendar Months)
[Dr. Y] will devote [80 percent] effort to the project. He has performed HIV
research in [Dr. X’s] lab for 11 years and has extensive experience with studies
of HIV-1 maturation inhibitors. He will perform the studies described in Specific
Aims 3 and 5, and will report the results directly to the PI.
[Dr. Z], Research Fellow ([3.6] Calendar Months)
[Dr. Z] will contribute [30 percent] effort to the project. He joined [Dr. X’s]
laboratory as a postdoc in March 2009 and is currently studying the mechanism of
cyclophilin A-dependent HIV-1 restriction, which will be completed in May 2010.
He will perform the studies described in Specific Aim 4.
Senior Research Specialist ([9.6] Calendar Months)
[The Senior Research Specialist] has worked in [Dr. X’s] lab for six years
and has extensive experience with virus propagation, assays of HIV-1 infectivity,
uncoating, and host restriction as well as cell culture and protein purification. She
will provide technical support to the other two scientists during the initial two years
of the project, including cell culture, molecular cloning, purification of recombinant
proteins, and routine infection assays. She will contribute [80 percent] of her effort
to the project during Years 1 and 2, after which her effort will be reduced to [40
percent] in Year 3 and eliminated in Year 4, due to a reduced need for technical
support in the later stages of the project.
Fringe Benefits
Fringe benefit calculations are derived from the current [university]
guidelines. Fringe benefits are calculated at a rate of 21.9% and 26.8% for faculty
and staff, respectively.
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Equipment ($10,000)
Spectrophotometer (Nanodrop: $10,000): Funds are requested to replace our
existing spectrophotometer, which is 10 years old. The instrument will be used for
the quantitation of solutions containing DNA, protein, and drugs.
Supplies ($38,000)
Cell culture ($10,000): The proposed studies involve intensive cell culture
experiments, including media, antibiotics, fetal bovine serum, and disposable
plasticware.
Protein production ($12,000): Funds are requested for supplies for expression
and purification of recombinant CA proteins, including competent E. coli strains,
IPTG for induction, buffer components (Tris, NaCl, EDTA, 2-mercaptoethanol),
dialysis cassettes, columns for chromatographic purification and protein analysis,
and precast gels for analysis.
Biochemicals ($5,000): Funds are requested for specialty chemicals, including
X-gal for infection assays, cyclosporine A, reverse transcriptase assay components,
and supplies for p24 ELISA.
Molecular biology reagents ($8,000): This category includes enzymes and
kits for DNA purification, PCR, and molecular cloning, as well as oligonucleotide
primers. The proposed work involves intensive cloning for identification of viral
mutations conferring resistance.
BSL-3 supplies ($2,400): Funds are requested to cover the cost of consumables
and safety equipment for work in the BSL-3 laboratory, including protective
gowns, shoe covers, gloves, bags for sterilization and waste disposal, antiseptic for
decontamination of liquid waste, and eye protection.
Pipettors ($600): Funds are requested for purchase and maintenance
of micropipettors, including multichannel pipettors that are needed for the
proposed studies.
Travel ($2,500)
Funds ($2,500) are requested for travel of both the PI and postdoc to one national
meeting per year (e.g., Cold Spring Harbor Retroviruses, Keystone Symposium, and
Symposium on Antiviral Drug Resistance) to present results from the project.
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Other Expenses ($6,800)
Publication Costs ($2,000): Funds are requested to cover the costs of one
publication per year during the project period.
Service contracts and certifications ($2,400): Funds are requested to cover
a portion of the service contracts for the 2 ultracentrifuges, the Li-Cor Odyssey
imager, and the flow cytometer according to their anticipated use on the project.
Funds are also requested to cover the costs for annual certification of 3 biosafety
cabinets (2 in the BSL-3 and one in the BSL-2 laboratory).
Laboratory Analysis/Core Charges/Computer ($2,400): Funds will cover
the cost of approximately 200 sequencing reactions for identification of viral
mutations. Other funds in this category include autoclaving and glasswashing
services that are recovered by the Department on a fee-per-use basis. Additionally,
funds requested in this category include the cost of various software upgrades and
computer devices required for collection, analysis, storage, and sharing of data.
Consortium Costs ($236,312)
[University A] ($33,737):
The proposed studies will require analysis of HIV-1 capsid dissociation in target
cells by fluorescence microscopy. This approach requires careful quantitation of CA
protein levels associated with GFP-labeled cores following viral entry into target
cells. For these specialized services, we have proposed to collaborate with [Dr. M]
at [University A], whose lab has pioneered this approach for the study of HIV-1
uncoating. Should funding be provided for the proposed investigations, we will enter
into a consortium agreement (subcontract) with [University A]. The subcontractor’s
proposed budget and agreement to enter an NIH consortium is included.
[University B] ($202,575):
The proposed studies will also require detailed structural studies of synthetic
assemblies of HIV-1 CA protein and native HIV-1 cores. For these specialized
services, we propose to collaborate with Drs. [N and O] in the Department
of Structural Biology at [University B]. [Dr. N] is an experienced X-ray
crystallographer and has recently determined a novel high-resolution structure
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of HIV-1 CA that will soon be reported. Her group will perform the proposed
crystallographic studies. [Dr. O] is also a structural biologist specializing in
electron microscopy, and her group will perform experiments involving EM (both
negative stain and cryo-EM). [Dr. O’s] group has recently determined the structure
of cylindrical assemblies of HIV-1 CA, leading to the identification of a novel
intersubunit interface that is critical to HIV-1 capsid function. Importantly, both
of these investigators are members of the Center for HIV-Protein Interactions, in
which [the PI] actively participates. Should funding be provided for the proposed
investigations, we will enter into a consortium agreement (subcontract) with
[University B]. The subcontractor’s proposed budget and agreement to enter an
NIH consortium is included.
Budget Justification — Year 2:
All recurring costs are incremented at a rate of 3% over year 1 to account for
inflationary increases.
Budget Justification — Year 3:
The effort of the Sr. Research Specialist will be reduced to [40 percent] as we
anticipate a reduced need for her technical services during the third year. All other
recurring costs are incremented at a rate of 3% over year 2.
Budget Justification — Year 4:
No effort is requested in Year 4 for the Sr. Research Specialist. All other
recurring costs are incremented at a rate of 3% over year 3.
On the other hand, if you are submitting a revision or supplemental application,
you only need to include those budget items for which you request additional
funds. And NIH says that if the initial budget period of the supplemental/revision
application is less than one year, you can prorate the personnel costs and other
appropriate items in your detailed budget.
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NIH Has Special Instructions for Subaward/Consortiums
If your application includes a subaward or consortium agreement, NIH requires
each consortium grantee organization to complete a subaward/consortium budget
component, which includes a budget justification section. The agency requires this
only for those organizations that perform a substantive portion of the project.
And this is necessary only when the prime grantee is submitting a detailed
(R&R) budget. This is not needed if you are using a modular budget.
Remember, though, the NIH is expecting someone to be designated as the
consortium lead investigator responsible for ensuring proper conduct of the
project or program at that site. However, when completing the Project Role for the
consortium lead investigator, the project role of “PD/PI” should only be used if the
entire application is being submitted under the Multiple PI policy.
Institutions Have Deadlines, Too
Most universities and other grant-seeking organizations will not allow you to
wait to submit your budget. Usually, they set a deadline of three or four weeks
before the NIH submission date for you to give them your proposed budget,
including all the appropriate sign-offs and consortium agreements.
In fact, many experts suggest that you address your budget as soon as you
outline your grant proposal to ensure you complete it on time.
Therefore, you should check with your grants submission department to
TIP:
Many experts
suggest that you
address your
budget as soon
as you outline
your grant propsal
to ensure you
complete it on time.
ensure you correctly understand all the institution-specific applicable deadlines
for your application.
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CONCLUSION
Whether you request a modular or detailed budget for your R01 application,
your financial planning to support your research likely should fall within the early
stages so you can complete it on time — either to meet your institution’s deadlines
or those for NIH.
And although modular budgets may appear easier to plan, you are limited
to no more than $250,000 per year in direct costs attributed to your proposal.
Alternatively, you can request more funds with detailed budgets, but the planning
process is more intensive and time-consuming.
In either case, how you explain your monetary request plays a key role in NIH’s
funding decision because the justification narratives may be studied at multiple
levels of the agency’s review process.
Keep in mind also that although reviewers are not supposed to include the
budget as part of their overall assessment of your application, they may use it to
judge your proposal’s feasibility. Therefore, you should consider it a key portion of
your application. n
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Chapter 7: Submitting Your Application
Chapter 7:
Submitting Your Application
Before you submit your R01 application, take time to review the finished product. Make sure your proposal works as a whole rather than a group of parts. Remember your ultimate goal is to communicate that your research deserves funding,
you’re the right person to conduct it, and your institution is the right place to do it.
That’s why reviewing your proposal for content is important. Ensure all of the
sections communicate your message adequately. Your research strategy must include strong specific aims and address your project’s significance, innovation and
approach. Your project summary should be a compelling synopsis of your proposed
research. And your budget should be in synch with your research strategy.
Reviewing your proposal for writing quality is just as important. You may want
to ask colleagues or non-experts to read your proposal and provide feedback. Or
you may need to hire a professional editor.
You must also construct a cover letter to introduce your proposal. This is part
of the National Institutes of Health’s (NIH’s) application upload process, and the
agency encourages you to include one. If you are submitting a changed or corrected
TIP:
Your Research
Strategy must
include strong
Specific Aims and
address your
project’s Significance, Innovation
and Approach.
application, the cover letter is mandatory.
In addition, make sure you have included all of your application’s necessary
components. Don’t forget any attachments, and confirm that all attachments adhere
to NIH requirements. The agency used to provide a two-day window during which
applicants could fix errors, but that is no longer available. Therefore, it is extremely
important to ensure all of your documents are uploaded.
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Include All the Necessary Components
Arguably the most important step in reviewing your R01 application is making
sure it is complete. There are certain components that are mandatory for all applicants, and there are parts that are required only under certain circumstances.
Direct from NIH:
A completed application includes data in the following components:
Required Components
•SF424 (R&R) (Cover component)
•Research & Related Project/Performance Site Locations
•Research & Related Other Project Information
•Research & Related Senior/Key Person
•PHS398 Cover Page Supplement
•PHS398 Research Plan
•PHS398 Checklist
•PHS398 Modular Budget or Research & Related Budget, as appropriate
Optional Components
•PHS398 Cover Letter File
•Research & Related Subaward Budget Attachment(s) Form
For certain applicants, NIH requires additional components. You must take extra steps if your research involves multiple institutions or requires multiple principal investigators (PIs). The same is true if you are submitting a revision application
or if you belong to a foreign institution applying for U.S. dollars.
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Foreign Organizations
Applicants from foreign organizations must:
•Prepare their budgets in U.S. dollars
•Create detailed budgets for all applications (complete the research and related
budget component of the SF424 application forms, not the PHS398 modular
budget component)
•Omit any charge-back of customs and import fees
•Comply with the format specifications, which are based upon a standard U.S.
paper size of 8.5” x 11,” within each PDF
•Facilities and administrative (F&A) costs should be 8 percent of your total
direct costs, less equipment
•Comply with federal/NIH policies on human subjects, animals and biohazards
•Comply with federal/NIH biosafety and biosecurity regulations
Applications With Multiple PIs
If your project has multiple PIs, one of you must be the primary NIH contact.
This person is responsible for all communication, for assembling the application
materials and for coordinating progress reports. At the same time, this PI may not
REMEMBER:
The primary PI is
responsible for all
communications,
for assembling the
application materials
and for coordinating
progress reports.
have other special roles or responsibilities within the project team.
The contact’s information should be entered on the SF424 (R&R) cover component. All other PIs should be listed in the research and related senior/key person
component as PIs. The commons (login) ID of each PI must be included in the
credential field of the research and related senior/key person component. If it is not,
NIH will reject the application.
You must also include a multiple PI leadership plan. The plan should describe
your rationale for having more than one PI as well as the leadership team’s organizational structure. You should detail communication plans, the decision-making
process for scientific direction and procedures for resolving conflicts. If you have
planned budget allocation, you should describe how resources will be distributed to
the project’s specific components or individual PIs.
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Applications Involving Multiple Institutions
When multiple institutions are involved in a project, you must designate one as
the prime institution. This facility must administer a subcontract to request funding
for the other(s).
The prime institution should submit a detailed budget using the research and
related budget component. Attach all of the other facilities’ budgets separately to
the research and related subaward budget attachment(s) form.
For a modular budget, the prime institution completes the PHS398 modular
budget component only. The facility must then provide information concerning
the consortium/subcontract budget in the budget justification. Separate budgets for
each consortium/subcontract grantee are not required.
Revision Applications
A revision application is a competing supplemental application that asks for
support for a significant expansion of your project’s scope or research protocol. If
you’re submitting one, don’t forget these requirements:
•A one-page introduction — “Introduction to application” section of the PHS
398 research plan — describing the supplement’s nature and the impact it will
have on your original proposal
•Adequate details from the original application for reviewers to evaluate the
revision in the context of the original
•Budgetary changes for the remainder of the current grant’s period
•A specific response to criticisms in the prior summary statement
The NIH Cautions:
Applications for revisions are not appropriate when the sole purpose is to restore awards to the full SRG-recommended level if they were administratively reduced by the funding agency. A revision application should not be submitted until
after the original application has been awarded and must not extend beyond the
term of the current award period.
8.
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ENSURE ALL ADDITIONS ARE ATTACHED AND
COMPLY WITH GUIDELINES
Just like the application components, some additions are mandatory for all
applicants, and others are required only under certain circumstances.
Conditional additions include documents that describe the use of consultants,
consortium/contractual arrangements, plans for resource sharing, how you will
handle select agents and how you plan to protect human subjects. Reference letters
are also required conditionally.
Conversely, all applicants must include additions describing facilities and other
resources, as well as a bibliography. If your research requires documents such as
informed consent forms or surveys, you must include them in an appendix.
Appendix Materials
The appendix should only contain supportive or supplemental information. Do
not include essential information in the appendix in an attempt to circumvent the
research plan’s page limitations.
You are allowed a maximum of 10 PDF attachments. If you require more than
10, you can combine the information into attachment No. 10.
New, resubmission, renewal and revision applications may include the following materials in the appendix:
1)Although publications are not allowed as appendix materials in most cases,
applicants may sometimes submit up to three of the following types of pub-
TIP:
Do not include
essential
information in
the appendix in
an attempt to
circumvent the
research plan’s
page limitations.
lications:
a. Manuscripts and/or abstracts accepted for publication but not yet published.
b.Manuscripts and/or abstracts that have been published, but a free, online,
publicly available journal link is not available.
c. Patents directly relevant to the project.
Do not include unpublished theses or abstracts/manuscripts submitted (but
not yet accepted) for publication.
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2)Clinical protocols, informed consent documents and data collection instruments such as surveys and questionnaires
3)For materials that cannot be submitted electronically or materials that cannot be converted to PDF format (e.g., medical devices, prototypes, DVDs,
CDs), contact the scientific review officer (SRO) for instructions. Be as
concise as possible, and submit only information essential for the application’s review.
Do not include these items in the appendix:
1)Photographs or color images of gels, micrographs, etc. You must include
these images in the research strategy PDF. However, images embedded in
publications are allowed.
2)Publications that are publicly accessible. Include the URL or PubMed submission identification numbers in the bibliography, the progress report publication list section or the biographical sketch section.
Bibliography
There is no specific format to which your bibliography must adhere. Just ensure
that it includes all references cited in the research plan, and references are arranged
in the same sequence as they appear in the document. Each listing must include the
names of all authors, the article and journal title or the book title, the volume number, page numbers and year of publication.
Only include bibliographic citations. Follow scholarly practices in providing
citations for source materials relied upon when preparing any application section.
The location of this information is slightly different in the SF424 R&R and the
PHS398. Be sure to read the application instructions carefully for the application
you are using.
Facilities and Other Resources
Make sure you have identified the facilities you will use (laboratory, animal,
computer, office, clinical and other). If appropriate, indicate their capacities, pertinent capabilities, relative proximity and availability to the project. Describe only
those resources directly applicable to your work.
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Consortium/Contractual Arrangements
Explain the programmatic, fiscal and administrative arrangements between the
applicant organization and the consortium organization(s).
Consultants
Attach letters from all consultants that confirm their project roles. The letters
should include the charge for consulting services.
Protecting Human Subjects From Risk
NIH will not distribute awards unless human protection assurances are on file
with the Office for Human Research Protections (OHRP).
Resource-Sharing Plan(s), Including Data-Sharing Plans
You must share final research data for applications that seek $500,000 or more
in direct costs in any year of the grant. The same is true for some program announcements and all genome-wide association studies. Describe your resourcesharing plan — or justify its absence — in a brief paragraph in your research plan.
Select Agents
Have you identified any select agents to be used in the proposed research?
These are hazardous biological agents and toxins the U.S. Department of Health
and Human Services (HHS) or U.S. Department of Agriculture identify as able to
pose a severe threat to public health and safety, animal and plant health, or animal
and plant products.
If your proposed research involves using select agents, your application has to
detail how you’ll use them. But how can you best convey to reviewers that you’ve
thoroughly considered safely handling these dangerous substances? Following
these recommendations can help:
•Resist the temptation to merely “touch up” the boilerplate language your
university provides. True, customary information from your institution gets
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you started. But reviewers are looking for more than that. They want your
plan’s specific details.
•Double-check information security. Regulators want to know you’ll protect
against accidental release of agents that can harm people, animals and plants.
They also recognize that some of the biohazards have the potential for bioterrorism. So outline your information security measures.
•Explain your backup plans. Reviewers know what can go wrong and want
to know that you’ve considered it. A short description addressing common
problems goes a long way toward establishing your credibility.
•Focus on existing facilities, equipment and experience. Lacking any of
these will hurt you. NIH doesn’t want to pay for your learning curve or
expensive facilities.
Reference Letters
Note there are two types of reference letters:
1)A letter of recommendation is from a faculty member or other person qualified to evaluate your proposal’s merit and your qualifications.
2)A letter of support is typically from an outside individual whose assistance
you will need to ensure your project’s success. This letter is meant to establish your credibility, convince the review board your project is feasible and
detail the type of support promised.
You can only include reference letters if they are specifically requested in the
funding opportunity announcement (FOA) or application guide. You can submit
them as soon as the FOA opens, even prior to sending in your application.
Reference letters are linked by FOA number and your Commons user ID. If you
don’t provide these values or enter them incorrectly, the letter never connects to the
application. Orphaned letters are deleted from eRA Commons after six months.
If you are submitting a changed or corrected application to address eRA-identified errors/warnings, the reference letters will automatically move to the most
recent application submission for a specific opportunity deadline. Reference letters
that come in electronically must be uploaded electronically via eRA Commons.
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If your original application was rejected, and you decide to resubmit as an A1
application, you cannot use the same reference letter(s). You must submit new ones
for each opportunity.
Unless stated, the aforementioned attachments do not influence your application’s
rating (priority score). Your reviewers will comment on the attachments’ adequacy,
however. Any concerns they have may negatively affect and postpone an award.
Frequently Asked Questions About Attachments
Q. What type of attachments does NIH accept?
A. PDFs. But if an attachment can’t be submitted electronically, the agency will
accept a hard copy.
Q. Who is responsible for generating the PDF documents?
A. The applicant or his institution’s grant office.
Q. How does an applicant submit appendix material that he cannot send electronically?
A. Mail “hard” appendix materials, such as a video or heart valve, to the SRO
and then the reviewers.
Q. How does NIH accommodate appendix material?
A. There is an attachment upload available. You can include up to 10 separate
PDF attachments. The appendix attachment upload feature is in the PHS 398 research plan component.
Q. How does NIH accommodate supplemental/additional/correction material
submitted after the application?
A. Supplemental/additional/correction material must be submitted through,
and at the discretion of, the assigned SRO. Some FOAs prohibit the submission of
supplemental/additional/correction materials.
Q. How does the NIH handle administrative supplements?
A. Individual institutes and centers handle them.
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CREATE A COVER LETTER
Although it’s not always required, NIH strongly recommends that you submit
a cover letter with your grant application. Keep in mind the agency likely will use
the letter to help assign your proposal to the right study section.
Direct from NIH:
The cover letter is only for internal use and will not be shared with peer reviewers.
The letter should contain any of the following information that applies to your application:
•Application title
•Funding opportunity (PA or RFA) title of the NIH initiative
•Request of an assignment (referral) to a particular awarding component(s) or
Scientific Review Group (SRG) [PHS (Public Health Service) makes the final
determination.]
•List of individuals (e.g., competitors) who should not review your application
and why
•Disciplines involved, if multidisciplinary
•For late applications, include specific information about the timing and nature
of the cause of the delay
•When submitting a Changed/Corrected Application after the submission date,
a cover letter is required explaining the reason for the Changed/Corrected application. (If you already submitted a cover letter with a previous submission
and are now submitting a Changed/Corrected Application, you must include
all previous cover letter text in the revised cover letter attachment. The system
does not retain any previously submitted cover letters until after an application
is verified; therefore, you must repeat all information previously submitted in
the cover letter as well as any additional information.)
•Explanation of any subaward budget components that are not active for all
periods of the proposed grant
•Statement that you have attached any required agency approval documentation for the type of application submitted (This may include approval for applications $500,000 or more, approval for Conference Grant or Cooperative
Agreement (R13 or U13), etc.)
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Your cover letter can also include requests for peer review assignment. The
Division of Receipt and Referral, Center for Scientific Review, is responsible for
assigning applications to institutes/centers and SRGs. The division asks that applicants make requests in the following format:
•List one request per line.
•Place the institute/center and SRG review requests on separate lines.
•Place positive and negative requests on separate lines.
•Include the name of the institute/center or SRG, followed by a dash and the
acronym. Do not use parentheses.
•Provide explanations for each request in a separate paragraph.
Making Peer Review Suggestions
There are tips you should keep in mind when making peer review suggestions
in your cover letter. First, never request individual reviewers by name. But you can
ask for reviewers with a specific area of expertise.
Analysis has shown that requests for expertise (as long as reviewers go
unnamed) are a valuable source of information when NIH selects peer reviewers.
When you make this suggestion, you can include any of the following:
•Suggestions of study sections or funding agencies best suited to a proposal.
Include advice you received from a program director or SRO about a study
STRATEGY:
Although you should
never request
individual reviewers
by name, you can
ask for those with
a specific area of
expertise.
section or institute.
•For multidisciplinary applications, highlight the application’s main
disciplinary/methodological thrust.
•Include a list of research disciplines critical to understanding your
application.
It’s also perfectly acceptable for you to learn about peer reviewers by viewing
SRG rosters at https://public.era.nih.gov/pubroster/. But you should never
communicate directly with a review group member about an application, either
before or after review. Peer reviewers must report to SROs any direct or attempted
contact by applicants.
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Communicating Conflict of Interest
Include information regarding a conflict of interest, or a potential conflict,
in your cover letter. For example, say you request a specific study section to
review your application. But the roster indicates that a direct competitor, a former
mentor or a former student is a member of that study section. To request the
exclusion of a reviewer:
•List the individual in the cover letter.
•Provide a brief description of why the person should not be involved in
reviewing your application.
Cover Letter Template
NIH offers the following template as a guide for creating a cover letter.
Application title.
Funding Opportunity Announcement number:
Please assign this application to the following: Please note the outline of
indentations.
Institutes/Centers
National Cancer Institute – NCI
National Institute for Dental and Craniofacial Research – NIDCR
Scientific Review Groups
Molecular Oncogenesis Study Section – MONC
Cancer Etiology Study Section – CE
Please do not assign this application to the following:
Scientific Review Groups
Cancer Genetics Study Section – CG
The reasons for this request are [provide a narrative explanation for the request(s)].
List of individuals (e.g., competitors) who should not review the application
and why.
Disciplines involved, if multidisciplinary.
Statement that required NIH approval documents are included. (e.g., budget
over $500K/year; approval for conference grant; cooperative agreement, etc.)
For late applications, if applicable, include explanation of the delay as part of
the letter.
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REVIEW YOUR PROPOSAL FOR CONTENT
So you’ve assembled the necessary components, included the required attachments and written a comprehensive cover letter. Now, it’s time to review your proposal’s content. Examine the most important sections closely. Ensure your abstract
is a compelling, detailed summary of your research. Make certain your budget is
in synch with your research strategy. Evaluate your specific aims, and assess how
you’ve described your project’s significance, innovation and approach.
Project Summary/Abstract
Your project summary should succinctly describe every major aspect of your
project. But it should not exceed 30 lines. If an abstract is too long, NIH will flag it
as an error.
Your project summary must include these parts.
•A brief background of the project
•Specific aims, objectives or hypotheses
•The significance of your research and its relevance to public health
•Your project’s unique features and innovation
•The methodology (action steps) to be used
•Expected results
•Description of how your results will affect other research areas
REMEMBER:
Your Abstract is
the first component
reviewers read, and
it may actually be
the only part they
read, setting the
tone for your entire
application.
Remember that your abstract is the first component reviewers read, and it may
actually be the only part they read. It sets the tone for your application and should
be a good predictor of the proposal that follows. It also becomes the primary
identifier for your project and may be used for public dissemination in the future.
Make sure your project summary:
•Follows the proposal’s logic and order
•Is composed of short, direct sentences
•Clearly details your hypothesis
•Has been proofed and edited rigorously
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Don’t:
•Just cut and paste sections from your proposal
•Forget to describe the problem
STRATEGY:
Tell reviewers why
testing your
hypothesis is worth
NIH’s money, why
you are the person
to do it and how
your institution
can give you the
support you’ll need
to get it done.
•Include too much obvious background information
•Use jargon, acronyms, symbols and abbreviations
•Include figures, tables or references
Budget
Your budget tells reviewers more than just how much money you want. Make
sure it accurately reflects the resources you will need and the expenses you expect
to incur. Were you realistic in your request? Both padding and deliberately underbudgeting reflect naiveté, and reviewers will notice.
Special forms are provided for the budget and justification. NIH recommends
the budget and justification cover personnel, consultants, equipment, supplies, travel and other expenses (for example, animal maintenance). Make sure you provided
brief descriptions of duties for all budgeted positions, with the number of personmonths requested each year and any anticipated fluctuations. Try to eliminate as
many “to be named” personnel designations as you can. They’re often deleted by
reviewers.
If you use a modular budget, you do not need to detail supplies, equipment and
travel costs. But for non-modular budgets, make sure you justified all equipment
purchases. Details are important, especially for non-project specific equipment,
such as a fax machine and computers.
Also, be sure to check indirect costs. Some institutions have on-campus and
off-campus rates. If applicable, also provide documentation of institutional rates for
animal maintenance and acquisition. Exceptionally large numbers of animals will
need detailed justification.
If you have any questions or concerns, review the budget with your institution’s
budget department. Requirements and terminology tend to differ from agency
to agency and award to award. For example, a PI may only have experience
measuring effort in percentages. Therefore, the NIH approach of measuring effort
in “person-months” may prove confusing.
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You should also verify cost estimates with internal and external experts. This
can help you accurately estimate and plan project tasks (for instance, international
travel considerations, conference venues and equipment quotes).
Reviewing your budget and the project description simultaneously can be
helpful as well. This ensures your project scope does not exceed the agency’s
REMEMBER:
maximum budget request.
Some grant
programs are
subject to
legislatively imposed
salary limitations,
and any salary
limit adjustments
are made at the
time of award.
Compensation
includes salary or
wages, fringe
benefits and
tuition remission.
Research Strategy
The Research Strategy is organized into three sections: significance, innovation and approach. Reviewers’ assessment of these sections will largely determine
whether your application is recommended for funding.
Ensure all sections are internally consistent and dovetail each other. Did you
use a numbering system and make sections easy to find? Did you lead the reviewers through your research plan? Make sure your research strategy section answers
these questions:
•What do you intend to do?
•Why is it worth doing? What is the research’s significance? How is it innovative?
•What have other researchers done in this field? Use appropriate references.
What will your work add to the field of knowledge?
•What have you (and your collaborators) done to establish your project’s feasibility?
•How will you accomplish the research? Who will do it, where will they do it,
and when?
Specific Aims
For the section on Specific Aims, make sure you include a brief narrative describing your project’s long-term goals or objectives and your hypothesis. Then follow with your list of aims.
You should only include three or four. That’s because one or two aims likely
will not have a broad enough scope to provide any real impact on a field. But more
than four aims will be difficult to fully develop.
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In crafting an effective and convincing Specific Aim, consider the aim’s
characteristics and its relationship to the others. It is best if one aim is not strictly
dependent on the success of the others. If your aims are sequential, tell the
reviewers what you intend to do if you get an unexpected result in the first one —
that is, why the whole project would not collapse.
Significance
Ensure you cover the state of existing knowledge, including literature citations
and highlights of relevant data. You should also include the proposed research’s rationale, any knowledge gaps the project will fill, and the potential contribution your
research will make to science and public health.
Clearly state what is significant about your research. You want to point out what
you are going to achieve that’s different from other research projects.
Cautionary example: “HIV is a retrovirus that has caused a worldwide
epidemic of AIDS. More than 33 million people are affected with HIV globally. As
a retrovirus, HIV integrates into the host chromosome. Anti-virals are not without
complications; resistance to current drugs occurs frequently.”
This is basic information, and it’s correct. But it doesn’t indicate what the
researchers plan to do or what is significant about the proposal.
Better: Include a clear statement that follows the above, such as, “This
proposal is designed to discover more about anti-viral drugs and see what can be
done to reduce resistance.”
Innovation
This section should explain why your concepts and methods are novel. Focus
on innovation in study design and outcomes. And summarize findings to be presented as preliminary data in the Approach section.
Keep in mind that a reviewer’s response to scientific innovation will vary.
This will depend upon how extensively he has read in his own field, how broadly
his knowledge extends to other fields, and how much novelty and risk he is
willing to tolerate.
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Reviewers tend to be on the conservative side when it comes to awarding
grants. They hesitate to support work at the earlier, potentially more innovative
stages. Science that is truly revolutionary threatens the existing order, putting at
risk the significance and validity of current dogma.
Additionally, reviewers often believe a grant must have enough preliminary
data to eliminate significant uncertainty about the central hypothesis but not so
much that further investment won’t yield additional high-impact papers.
Approach
This section should include the following:
•Your preliminary studies, data and experience relevant to the project design
•An overview of the experimental design
•A description of methods and analyses that will accomplish the project’s specific aims
•A discussion of potential difficulties and limitations and how these will be
overcome
•Expected results and alternative approaches that will be used if unexpected
results occur
•A projected sequence or timetable (work plan)
•If the project is in early stages, a description of any strategy to establish feasi-
REMEMBER:
Reviewers tend
to focus on the
Approach section
because they can
assess logical and
technical flaws there
more objectively
than in other
sections.
bility and the management of any high-risk aspects
•A detailed discussion of the way results will be collected, analyzed and interpreted
•A description of new methodology and why it represents an improvement
over the existing ones
Reviewers tend to focus on the Approach section because they can assess
logical and technical flaws there more objectively than in other sections.
Last year, NIH’s Office of Extramural Research looked at the five reviewing
criteria (Approach, Significance, Innovation, Investigator and Environment) and
how well scores for each factor correlate with an application’s Overall Impact
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score. The score for Approach turned out to be the best predictor of Overall Impact,
correlating to Overall Impact in 82 percent of funded applications.
The Approach section is also where many new PIs make one or more standard
errors that are relatively easy to identify:
•The applicant is “overly ambitious”
•One or more aims are “unfocused” or “underdeveloped”
•An aim is just a “fishing expedition” for a missing gene or interactions
•There’s too little description of results analysis
•Over-reliance on a preferred hypothesis
•An aim is just too “risky”
Anticipating these critiques when reviewing your proposal is one of the best
defenses you have. Knowing that the Approach score provides the strongest
correlation to your Overall Impact rating shows this section is where you should
devote most of your reviewing time.
After you’ve reread your research plan, ask yourself these questions:
•Did you include preliminary data or a progress report?
•Did you avoid excessive experimental detail by referring to publications that
describe the methods to be employed? Publications cited should be by you, if
possible.
•Did you, if relevant, explain why one approach or method will be used over
others? This shows you did not simply overlook the alternatives.
•If you’re employing a complex technology for the first time, did you take extra care to demonstrate familiarity with it?
•Did you explain how data will be collected, analyzed and interpreted?
•Did you develop alternative strategies for potential problems?
•Did you include any resource-sharing plans?
•Did you document proposed collaborations and offers of materials or reagents
of restricted availability with letters?
•Did you point out any procedures, situations or materials that may be hazardous to personnel and describe precautions to be exercised?
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REVIEW YOUR PROPOSAL FOR WRITING QUALITY
Once you’ve assessed your application’s content, look at the quality of your writing. Does your proposal clearly communicate the message you want to convey? Is it
concise and to-the-point? Are there grammatical, spelling or punctuation errors?
Take these NIH-recommended editing steps:
•Allow enough time so you can put the completed application aside and later
edit it from a fresh vantage point. You may only need to break for a few
hours, or you may need a few days. When you go back to your proposal, try
reading it aloud.
•Allow at least a few weeks for an internal review by collaborators, colleagues
and mentors. Make revisions/edits from that review. If possible, have experts
in your field and those who are less familiar with your science provide feedback. The application should be easily understood by all.
•If more than one investigator has contributed to the application, the writing
may not be cohesive. Employ one overall editor to ensure the sections work
together.
•Have zero tolerance for typographical errors, misspellings, grammatical mistakes or sloppy formatting. A disorganized application may convince reviewers you will conduct your research in the same manner.
•Perform a final proofread of the entire grant application.
Writing Examples
Unclear writing: “It is important to realize that, due to the highly ruminant
nature of giraffes, there exists an opportunity for deleterious or unpredicted
results. Some results may include: a) generation of unreasonable and/or potentially
unviable offspring, b) depletion of the natural environment of foliage and c)
desecration/obliteration of migrational pathways.”
An improvement: “Highly ruminant giraffes may produce harmful or unexpected
results, such as generation of unreasonable or otherwise unviable offspring, depletion
of foliage, and desecration or obliteration of migrational pathways.”
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The second example is 28 words, versus the initial 49. But nothing significant
from the first version is missing from the second. We substituted “harmful” for
“deleterious;” that’s two easy-to-understand syllables for five fancy ones. The
giraffes, the subjects of the research, are in their rightful place as subjects of the
sentence. We took out an unnecessary statement — “It is important to realize that”
— but there’s still more trimming to do.
Further improvement: “Ruminant giraffes may generate unreasonable
or otherwise unviable offspring, deplete foliage, and desecrate or obliterate
migrational pathways.”
The final example is a mere 17 words. The scientific sense is still there, with
a 65 percent saving in word count over the original version. In the course of a 15page proposal narrative, that’s like giving yourself 10 extra pages to explain your
research. Now, look back at the first version of this paragraph and ask yourself
what job the extra 32 words were doing. The answer is, nothing useful, and a lot
that hurts the proposal’s chances.
Hiring a Professional Editor
You may want to hire an editor to ensure your application is error-free. A professional can ensure your proposal says what you really mean. Editors-for-hire can
provide these services:
•Copy editing or line editing, which includes correcting style; clarifying expression; making suggestions for structure; and ensuring proper use of grammar, diction and syntax. Professional editors can improve these fairly quickly
if there are no underlying problems with the science.
•Content review. What appears to be a writing problem may actually be a content problem. These boil down to two kinds:
1)You’re not sure what you’re really trying to say.
2)There’s a problem with the concept itself. You should be able to say: “This
study was conducted this way and produced these results, with these caveats and limits.”
Example: “There is evidence of the efficacy of cognitive-behavioral therapy
in reducing chronic pain in some subsets of the population.” This naturally
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leads the reader to ask a series of questions: Which subset? How were these
isolated? What kinds of testing uncovered these results? How much was
learned, and how much remains unknown? The structure of the improved paper can now be visualized.
Consider hiring an editor if:
•You don’t have enough time to polish or hone your application. Or you’ve
lost focus and will lose a lot of time trying to find it.
•You’re not a very good writer. A professional grant writer can offer you form
compositional structures that will allow readers to easily understand what
you’re saying.
•Many researchers are involved. The application can easily lose focus if the
investigators can’t agree. Sometimes a third party can step in and find ways to
create a single vision.
•English isn’t your first language.
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11 SIMPLE MISTAKES THAT CAN DERAIL YOUR
GRANT APPLICATION
Often, the simplest, most basic errors can hurt grant applicants the most. Here
are 11 of them:
1) Failing to allocate enough time to write. Typically, you can assume you will
need 120 hours to write, review and revise an NIH application for a threeto five-year grant. A smaller, non-governmental grant can take three or four
months to complete. Bottom line: Overestimate the time you think you’ll
need, and plan all your timelines accordingly.
2) Skipping the instructions. Do not bend, modify or get creative with them.
Follow rules regarding font, font size, margins and word count. Pay attention to details on allowable budget expenses. When in doubt, contact the
TIP:
Don’t assume the
reader understands
your jargon and
can follow the
compelling rationale
or breach the gaps
in your logic.
program officer.
3) Poor writing. Don’t assume the reader understands your jargon and can
follow the compelling rationale or breach the gaps in your logic. Lead the
reviewer to logical and natural conclusions. Keep abbreviations, strange acronyms and jargon to a minimum.
4) Failing to edit. As mentioned previously, you should edit your proposal
yourself and ask others for feedback.
5) Inadvertent plagiarism. The NIH runs all grant proposals through plagiarism programs. Before submitting yours, do the same. Programs include
iThenticate, Plagiarism Detector and Copyscape. You can even enter sections of your proposal into a search engine to be sure you haven’t inadvertently copied from someone else’s research.
6) Forgetting the responsible conduct of research plan. You are required to
have one for all students (graduate or undergraduate) or postdoctoral researchers who receive a salary from your grant. This ensures appropriate
training and oversight. Discuss your plan with your compliance office to be
sure you have the right measures in place.
7) The reviewers did not find your central scientific question interesting. Arguably,
the single most common reason for a grant receiving a low score is reviewers’
perception that your central scientific question lacks significance. Reviewer
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uninterest in your question could stem from your failure to communicate its
significance clearly, an overly narrow focus, or a lack of novelty and originality
that suggests you are addressing a problem already solved.
One way to test your proposal’s significance is to provide a non-expert colleague with a three-sentence description. If he or she can appreciate why
you are doing the work, then you are on the right track.
8) The preliminary data are weak and call into question your proposal’s feasibility. Or there is an overly large gap between your hypothesis and your
preliminary data.
9) The overall success of your project depends upon the outcome of a key experiment, which you have not performed. There is a natural tendency to organize experiments in a linear and sequential fashion. For a research grant,
however, this strategy can be risky. If the succeeding aims all depend on a
positive outcome of Aim One (which is yet unproven), your whole project
depends on that first experiment’s success.
10)The project’s scope is too ambitious, with multiple hypotheses or rationales
that pull the grant in disparate directions. This is called “spaghetti syndrome,”
in which every good hypothesis, experiment or reagent in the PI’s pantry is
thrown at the problem. This approach rests on the assumption that reviewers
will find at least a few good ideas stuck on the proverbial wall, and this will
raise their enthusiasm. In reality, this approach diminishes enthusiasm. It suggests a PI is unable to prioritize among the project’s various facets, which can
lead to an inefficient deployment of people and resources.
11)The PI or research team lacks the experience to carry out the proposed
work. For first-time and early investigators, reviewers will assess training
and accomplishments during the postdoctoral years. For more senior investigators, reviewers will look at past career experience and productivity. If a
particular approach is unproven with respect to your lab, the most reliable
strategies are:
a)Identifying and soliciting an outside collaborator with a published track
record in the method
b)Devoting existing lab efforts to generate the preliminary data and remove doubts about your ability.
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MAKE THESE FINAL CHECKS
Below is a list of some of the more common errors made by applicants, based
on historical information accumulated by the NIH :
•Does the data universal numbering system number on the SF424 (R&R)
cover form match the system for grants.gov and commons registration?
•Did you include the eRA commons ID in the credential field of the R&R
senior/key person profile form for all PIs? This is critical to NIH’s ability to
post errors, warnings and the assembled application image in eRA commons.
•Did you include the organization name for all senior/key people listed on the
R&R senior/key person profile form?
•Did you follow the page limits specified in the FOA and application guide?
•Did you used an allowable font type and size?
•Did you provide the correct type of submission, federal identifier and type of
application information on the SF424 (R&R) cover form?
On initial submission, the type should be set to “application.” For subsequent
submissions, it should be set to “changed/corrected.”
Changed/corrected applications sent in before the due date do not require a
cover letter. Any application submitted after the due date must include one. For
electronic submissions, the cover letter is a PDF attachment to the PHS 398 cover
letter file component in the optional documents section.
There are nine application types you can use to identify the stages in a grant’s
life cycle. The type defines the procedures and specifies the documents required to
process the award. You can only choose one.
1)New: A request for support of a project that has not been funded
2)Competing continuation: An appeal for an additional support period based on
a previously funded project
3)Supplement: A solicitation for additional funds, either for the current operating year or for any future year, to cover increased costs (noncompeting) or to
expand the scope of work (competing)
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4)Extension: A request for additional time and/or funds beyond those previously awarded. These are typically limited to certain mechanisms, including
Merit (R37), Developmental/Exploratory (R21/R33) and Fast-Track Small
Business Grants SBIR/STTR (R42/R44). These grants do not compete for
available funds.
5)Noncompeting grant progress report: An appeal to pay the next budget increment of a current award. This does not compete for available funds.
6)Change of institute or division: A request for NIH’s acceptance of a change
in business structure, such as successor-in-interest, name change or merger
7)Change of grantee or training institution: An appeal for support of a funded
project to be transferred from one grantee or training institution to another
8)Change of institute or center: A noncompeting continuation to be transferred
from one institute to another
9)Change of institute or center: A competing continuation that has been transferred from one institute to another
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TIP:
NIH uses the HHS
logo within the
application guide to
flag agency-specific
instructions and
clarifications for
fields on federalwide forms. Pay
special attention to
the HHS logo, or
you may miss key
NIH requirements.
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SUBMITTING THE APPLICATION
Typically, the authorized organization representative (AOR) will submit all application materials. A PI can submit materials with the AOR’s approval, but NIH
won’t accept materials that have not been approved.
To submit your proposal, go to the grants.gov login page and enter your username and password. Once you are logged in, the application package will be automatically uploaded to the website. A confirmation screen appears once the upload
is complete, and a grants.gov tracking number is provided. Keep this number for
your records.
If everything is acceptable, no further action is necessary. The application will
automatically move forward to the Division of Receipt and Referral in the Center
for Scientific Review for processing.
On the other hand, if some part of the proposal was lost or did not transfer correctly during the submission process, the AOR can reject it and submit a changed/
corrected application. In these cases, you should contact the eRA help desk to
ensure the issues are addressed and corrected. Once you’ve rejected the proposal,
follow the instructions for correcting errors, including the requirement for cover
letters on late applications.
Also use the reject feature if you determine that warnings are applicable to your
proposal and must be addressed now. Remember, warnings do not stop the application process. If a submission results in warnings (but no errors), it will automatically move forward after two weekdays. Work with your AOR/signing official to
determine when the reject feature is appropriate.
You may find you need to submit supplementary or corrective material after
your due date — for example, revised budget pages, updated biographical sketches,
letters of recommendation or publications that have been accepted but not published. Acceptance of those materials is at the discretion of the NIH SRO. Be sure
to send any additional documents as PDF attachments to emails.
You must submit additional materials to the SRO with the consent of your
AOR, and the AOR should be copied on correspondence to the SRO.
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Direct from NIH:
SHOULD YOU WITHDRAW THE APPLICATION?
There are two ways to stop the application from moving forward for peer review. You can withdraw it or you can simply reject the application image. Your application will undergo peer review as is unless your scientific review officer [SRO]
allows you to send additional information or you have withdrawn it. You should
consider withdrawing your application in the following circumstances:
•You feel the application is not up to snuff.
•You’ve run out of time for corrections and can’t send additional data.
Remember that your goal is to impress your reviewers with the best possible
application. Balance the severity of the problems with the amount of time you have
left to correct them in the same review cycle. Compare that with the time lost if
you wait for the next due date.
To withdraw your application from consideration, ask your organization to fax
a signed letter to the Center for Scientific Review’s Division of Receipt and Referral at 301-480-1987. Provide your NIH accession number.
If you plan to withdraw the application and resubmit for the same deadline, be
careful. Once you no longer have an active application in the system, you will have
the same disadvantages as anyone else who applies at the last minute. Allow at
least two days to get your corrected application into the system.
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CONCLUSION
Congratulations on your submission. You made the application deadline and
there were no errors that could sidetrack your proposal’s advancement towards
review. Since you planned and executed the writing of your proposal well in
advance, and are comfortable and confident on its content, there should be no
reason for you to withdraw your application. n
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Chapter 8: The NIH Application Review Process
Chapter 8:
The NIH Application Review Process
This chapter outlines the National Institutes of Health’s (NIH) review process.
It describes how the Center for Scientific Review assesses applications and assigns
them to review groups. It also explains how your application moves from an
integrated review group (IRG) to a scientific review group (SRG) to an institute or
center’s advisory board or council.
You’ll learn the four steps of the initial peer review process and how an SRG
(otherwise known as a study section) rates your application. We describe how five
criteria — Significance, Innovation, Approach, Investigators and Environment —
are used to score your proposal. We explain the importance of Overall Impact, what
percentiles mean, and how to interpret summary statements.
Also included in this chapter is information on tracking your application and
steps to take once you’ve received a response from NIH. You’ll learn about just-intime information and how to resubmit your application if it is not funded the first
time around.
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Chapter 8: The NIH Application Review Process
NIH REVIEW PROCESS: A BRIEF OVERVIEW
Once you have submitted your application to NIH, it goes through a few levels
of review. First, the Center for Scientific Review performs a cursory assessment,
checking for errors that automatically disqualify an application.
If there are no errors, the center sends your proposal to the group of reviewers
known as the IRG. From there, your application goes to a study section (SRG).
The SRG is composed of roughly 20 scientists, mostly non-federal, who have
expertise in relevant disciplines and current research areas. The scientific review
officer (SRO), who is an NIH staff member, leads this group and appoints a few
key reviewers to analyze your proposal in detail. The remaining members scan
your application, reading only certain sections in depth.
The study section votes and scores your application on the five review criteria:
Significance, Innovation, Approach, Investigator(s) and Environment. The group
also evaluates your project’s Overall Impact. The SRO compiles a summary
statement that includes your application’s scores as well as a more detailed critique.
After the SRG’s assessment, your application goes to institute/center national
advisory councils for review. Councils are composed of both scientists and lay
members chosen for their expertise and activity relating to health and disease. Your
application is only eligible for funding if both the study section and the institute/
center advisory council recommend it.
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Chapter 8: The NIH Application Review Process
NIH CHECKS YOUR APPLICATION
As soon as NIH receives your proposal, it goes to the Center for Scientific
Review for a cursory review. The staff there makes sure it conforms with
administrative and formatting requirements.
NIH calls this check a potential failure point because the agency may return
your application without a peer review. This would happen if you:
•Didn’t list other support
•Failed to include sufficient human or animal documentation, data, assurances,
or other required documentation
•Omitted pre-approval documentation for submitting an application requesting
$500,000 or more in direct costs for any one year
•Left out pre-approval documentation for an investigator-initiated clinical trial
•Didn’t show documentation of approval for using select agents
•Included a detailed budget when it should have been a modular one
•Improperly formatted your application (wrong font size and margins)
•Submitted the forms in the wrong way — for example, emailing them instead
of submitting through grants.gov
•Didn’t meet the requirements of a request for applications or institute-specific
program announcement, if responding to one of the initiatives
•Contacted a reviewer
•Submitted your application late.
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Chapter 8: The NIH Application Review Process
YOUR APPLICATION GETS AN NIH ID NUMBER
The Center for Scientific Review gives your application a unique identification
number that looks like this: 1 R01 AI183723 02 A1 S1. Each part of the identifier
provides a snippet of information about your application.
•The first number is the application type; for example, a new application
is Type 1. This tells NIH whether your application is a new, renewal,
noncompeting or other type of application.
•Next is the activity code, or the type of grant you’ve applied for; in your case,
an R01 research grant.
•The next two-letter abbreviation is the institute code. For example, the
National Institute of Allergies and Infectious Diseases code is AI.
•Next is the unique serial number Center for Scientific Review assigns.
•Then comes the suffix showing the support year for the grant.
•The final two are codes for a resubmission, supplement or fellowship
institutional allowance.
In the eRA Commons, the website where you submit your application
(https://commons.era.nih.gov/commons/), you’ll see this NIH number. You’ll also
see the old grants.gov tracking number. But NIH staff will typically refer to your
application using the NIH number.
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Chapter 8: The NIH Application Review Process
YOUR APPLICATION IS ASSIGNED TO AN IRG, SRG
AND INSTITUTE/CENTER
The Center for Scientific Review assigns your application to an IRG and then to
a study section for the first round of peer review. It assigns institute/center advisory
boards (sometimes more than one per application) for the next review level as well.
You can request review assignments in your cover letter. But keep in mind the
center is not required to honor your requests. It may make different assignments
based on NIH referral guidelines and workload factors.
Within three weeks of your submission deadline, your assignment should
appear in the eRA Commons. Here’s how to access it:
Log in to the commons to check. If you don’t see your assignments within three
weeks, call the eRA Commons Help Desk at 1-866-504-9552.
At first, you might not see the expected study section. Instead, that field may
show the umbrella organization, the IRG. This will be updated over the next few
REMEMBER:
You can request
review assignments
in your cover letter.
But keep in mind
the CSR is not
required to honor
your requests.
days, when your application is assigned to the SRG that will actually perform the
initial peer review.
If the Center for Scientific Review gives you an assignment you’re not happy
with, you can request a change.
After the funding agency receives your application, it is assigned to a program
division using internal referral guidelines. The program officer, grants management
specialist and SRO fields will be blank initially in the eRA Commons.
Call if You’re Not Satisfied With an Assignment
Follow these steps if you are not happy with your study section or institute/
center assignment:
1)Inform your SRO of the problem well before initial peer review begins.
Speak up if a committee member has a conflict of interest or you feel the
group doesn’t have adequate expertise.
2)Check the Center for Scientific Review study section roster index to find an
alternative.
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3)Discuss the alternative you prefer with the chief of the IRG for your assigned
study section. You can get his contact information from your SRO.
4)Fax a letter to the center at 301-480-1987 stating your reasons for
requesting a change. Here is an example of an acceptable request and an
unacceptable one:
a. Acceptable: “The focus of study section X seems to be more on the
structural biology of molecules of immunologic importance. Since my
application proposes to develop new antibodies for phase 1 human
studies, the clinical perspective of reviewers on study section Y is critical
to appreciate the approaches I have taken.”
b.Not acceptable: “I don’t want study section X due to lack of expertise Z.”
5)If that does not resolve the problem, appeal to the Center for Scientific
Review’s director of receipt and referral by calling 301-435-0715.
6)Be sure to talk to your program officer about the situation.
Waiting for the next receipt date is often better than getting reviewed by the
wrong study section. You also have grounds for an appeal if the group doesn’t have
the expertise required for an effective peer review and, as a result, the assessment
turns out poorly.
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Chapter 8: The NIH Application Review Process
SUBMITTING ADDITIONAL INFORMATION
You may add certain information to your submitted application, even though it’s
sitting in the eRA Commons database waiting for review. But there are restrictions on
what you can add, guidelines on how to add it, and a deadline you should know.
NIH policy allows you to submit new material up to 30 calendar days
before the peer review meeting. But only material that results from “unforeseen
administrative issues” is acceptable. This includes:
•Relocation information. If you accept a job at a new institution or a new
position with your current organization, you can write a letter notifying NIH
of that.
•Issues from natural disasters. For example, notify NIH if flooding damages
the lab where you plan to conduct your research.
•Letters of support. If you decide to change key personnel and add a
TIP:
NIH policy allows
you to submit new
material up to 30
calendar days
before the peer
review meeting.
collaborator, you may submit a letter of support from that person.
•Biographical sketch changes. If an investigator suddenly leaves or you hire
new lab personnel, you can alter Biographical Sketches.
•Articles. If publications were in press when you turned in the application, but
they’ve now been accepted, you want to let NIH know.
•Budget revisions. For example, say you require the same piece of equipment
for overlapping grant proposals, and your other grant was funded. You can
submit a budget revision removing that equipment from the proposal about to
be reviewed.
The SRO will determine whether your information will be included with your
application. Post-submission materials NIH will not accept include:
•Support letters that don’t result from a key personnel change
•Updated Research Strategy or Specific Aims pages
•Late-breaking research findings.
These guidelines will apply to all unsolicited, investigator-initiated
applications. There are exceptions, however, for certain Funding Opportunity
Announcements, training grants and Requests for Applications.
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Follow These 5 Steps
There are essentially five steps to the post-submission process.
1)Contact your institution’s Sponsored Programs Office or Sponsored
Research Office.
2)Secure the NIH-required signature from the signing official at your
institution. NIH won’t accept materials that are sent without it.
3)Follow NIH guidelines for the pages you’re submitting. For example,
updates or changes to a Biographical Sketch or a budget will require a form
page. If a form page is not needed, however, NIH guidelines indicate you
must limit each letter or explanation to one page. Also remember to follow
NIH policies regarding margins, paper size and font size.
4)Prepare a description of the material you’re submitting. If you’re sending data,
as an exception to one of the grant mechanisms listed above, you should:
•Design a concise table or graph to represent the data.
•Succinctly describe the experiment’s design, results and conclusions.
•Indicate the significance to the proposal.
•Note results that will add to the proposal’s innovative nature.
•Use a bullet-point format.
•Include the grant number and title.
5)Send the post-submission material to the SRO. NIH prefers you send the
information electronically as a PDF. You should include:
•A note to the SRO with a brief description of your attachment
•One or two sentences about why you are submitting it
•The grant number and title
•All post-submission materials in one email.
If the SRO accepts your material, it will be uploaded to eRA Commons. You’ll be
able to find it by checking the “Additions for Review” section of your application.
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Chapter 8: The NIH Application Review Process
INITIAL PEER REVIEW
Direct from NIH:
Your application’s most significant test is initial peer review. Your peers —
successful scientists in your field and related ones — use the information in your
application to assess the merit of the science you’ve proposed and your ability
to get the work done. Peer review results in a numerical value indicating the
reviewers’ judgment of the likelihood that your project will have a powerful impact
on its area of science. That number is the most important factor in determining your
application’s success.
How SRGs Operate
The SRG is made up of scientists who have expertise in relevant scientific
disciplines and current research areas. Each study section is led by an SRO, who is
a staff scientist with the NIH’s Office of Extramural Research. The SRG also has a
chair, who serves as moderator for discussing applications’ scientific and technical
merit and is a peer reviewer.
Study sections are typically composed of about 20 reviewers. It is their duty to:
•Declare conflicts of interest with specific applications following NIH guidance
•Receive access to the grant applications approximately six weeks prior to the
peer review meeting
•Prepare a written critique (using review critique fillable templates) for each
application assigned per the SRO, based on review criteria and judgment
of merit
•Assign a numerical score to each review criterion
•Make recommendations concerning the scientific and technical merit of
applications, in the form of final written comments and numerical scores
•Make recommendations concerning protections for human subjects; inclusion
of women, minorities and children in clinical research; welfare of vertebrate
animals; and other areas as applicable for the application
•Make recommendations concerning appropriateness of budget requests.
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Federal officials who are not part of the review board are allowed to attend
review meetings. But they must have advance approval from the responsible SRO.
These individuals may provide programmatic or grants management input at the
officer’s discretion.
What SROs Do
Direct from NIH:
Your SRO does an initial check of your application to make sure the key parts
are there. If you’re responding to a request for applications, program staff will
check to ensure it is responsive to the request for application.
Before sending your application to reviewers, SROs look at it more
thoroughly to make sure it’s complete, and they may contact you if anything is
missing. If this happens, send in the information quickly so reviewers receive it
well before the review.
The SRO ensures each application receives an objective and fair initial peer
review, making certain all applicable laws, regulations and policies are followed.
The officer performs the following tasks:
1)Analyzes application content and checks for completeness
2)Documents and manages conflicts of interest
3)Recruits qualified reviewers based on scientific and technical qualifications
and other considerations, including:
a. Authority in scientific field
b.Dedication to high-quality, fair and objective reviews
c. Ability to work collegially in a group setting
d.Experience in research grant review
e. Balanced representation
4)Assigns applications to reviewers for critique preparation and designation of
individual criterion scores
5)Attends and oversees administrative and regulatory aspects of peer review
meetings
6)Prepares summary statements for all applications reviewed
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Chapter 8: The NIH Application Review Process
The SRO selects at least three reviewers to examine each proposal and report
on it to the rest of the study section. These individuals are highly influential in how
the SRG grades each application. In fact, for your grant to score well, all three must
become enthusiastic advocates of your proposal.
The assigned reviewers are typically those panel members who are most familiar
with your area of research. If none of the members have the necessary expertise, the
SRO will find at least one ad hoc reviewer with the appropriate credentials.
In most cases, the primary reviewer will be best acquainted with your work and
will take the lead in presenting your application to the panel. The second reviewer
will likely be nearly as familiar, having published in the same field or a related one.
These two reviewers will scrutinize all aspects of your research plan
carefully, taking into account significance, feasibility and innovation, as well
as your qualifications to perform the proposed work. With their expertise, they
are positioned to decide whether your planned studies will significantly advance
the field, rather than merely provide incremental progress on an already well-
REMEMBER:
The SRO selects
at least three
reviewers to
examine each
proposal and report
on it to the rest of
the study section.
characterized system.
The third reviewer, who is often called the “discussant,” is usually different. He
will probably not be an expert in your field but will have a general knowledge of it.
For example, the discussant may have learned about your field by teaching certain
aspects of it in a survey course. For this person, the crucial part of your proposal
will often be the “Significance” section.
The discussant will look for details regarding specific ways your research, if
successful, will affect fields other than your own. Consequently, the better you
can establish that your findings will have important implications at large, the
more likely this reviewer will appreciate your work’s significance and convey
enthusiasm for your research to the study section.
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BASIC LAYOUT OF INITIAL PEER REVIEW
The peer review process has four steps:
1)Applications are reviewed based on established criteria.
2)Assigned reviewers summarize their prepared critiques for the group.
3)The entire panel discusses the application.
4)Final scoring of Overall Impact/priority scores is conducted by private ballot.
After the SRO opens the meeting, the primary reviewer presents your
application to the group. Those with conflicts of interest should have already left
the room. The remaining individuals review applications in the order of their
preliminary Overall Impact scores, which helps them calibrate final scores. This
also helps reviewers gauge when it is appropriate to stop discussing applications, as
they generally do not discuss about half of the applications.
At that point, the group decides if other applications merit discussion. They
explore differences of opinion, interacting heavily during the discussion, which
generally lasts 10 to 15 minutes. Other study section members ask the assigned
reviewers questions and skim the application during the discussion.
Generally, once the group has found a fatal flaw everyone agrees to, they stop
discussing the application. Examples of fatal flaws include not protecting the
safety of lab workers or animals, proposing too much work for the award time, not
recognizing a key paper in the field or including a factual inaccuracy.
Where possible, study sections evaluate applications from new and early-stage
investigators before the more experienced researchers. That way, the SRGs review
at least half of applications for new investigators, and NIH can meet its targets for
funding them. Review materials are confidential, so reviewers are not allowed to
divulge any information outside the meeting. At the end of the meeting, NIH staff
collect and destroy all materials used in the review.
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Chapter 8: The NIH Application Review Process
Most Reviewers Scan Each Application
Generally, only assigned reviewers will read your application before the review.
Others mostly read just your Abstract, Significance and Specific Aims. SRGs
receive dozens of applications for each meeting, totaling thousands of pages to read
in a few weeks, and members have full-time jobs. They couldn’t possibly read all
applications in depth.
Keep in mind that all of the study section members will score your application,
even though only a few will have read it in depth. That’s why you write and
organize your Specific Aims for both audiences. You must make a strong case for
your research so the assigned reviewers can readily read, understand and explain
your project to the group.
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Chapter 8: The NIH Application Review Process
HOW REVIEWERS SCORE APPLICATIONS
Before the SRG meets to discuss the applications, each reviewer and discussant
assigned to an application gives a separate score for the five criteria — Significance,
Investigator(s), Innovation, Approach and Environment. In addition, they assign a
preliminary Overall Impact score to an application. Applicants will receive a report
or summary statement detailing the individual scores of the assigned reviewers and
discussant(s), even if the full committee does not discuss the application.
Noncompetitive Applications Get a Streamlined Review
Direct from NIH:
NIH uses a process called “streamlining” so reviewers can focus on
applications that have a chance of being funded. Review committees don’t review
any application the group unanimously feels is roughly in the bottom half of
applications being reviewed at the meeting. That percentage varies by grant type as
well as by study section. Because no institute funds 50% of applications assigned
to it, there’s no need to review the bottom half. Here is how streamlining works:
•One week before the study section meets, SROs ask members for a list of
applications they feel should not be reviewed and prepare a combined list.
•If any reviewer disagrees with a call, the group will review that application.
Non-Numeric Scores
1)Not discussed (ND). Applications unanimously judged by the peer review
committee to be less competitive are not discussed. These applications do
not receive a numerical impact/priority score, but they do receive individual
criterion scores. No set number of applications is discussed; in some
meetings, the ND option may not be used.
2)Not recommended for further consideration (NRFC). A majority of reviewers
must vote in favor of NRFC for an application to be designated as such.
Members will vote for NRFC in the following scenarios:
a)The application lacks significant and substantial merit.
b)The project presents serious ethical problems regarding the protection of
human subjects.
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c)The research poses serious ethical problems in the use of vertebrate
animals, biohazards and/or select agents.
NRFC-scored applications do not proceed to the second level of peer review
(national advisory council/board) because they cannot be funded.
3)Other non-numeric scores
a)Deferred (usually due to lack of sufficient information, quorum or to
allegations of research misconduct)
b)Abstention (used rarely)
c)Conflict (score put in by a reviewer who is in conflict with the application)
d)Not present
Competitive Applications: Five Criteria Determine the Score
The reviewers and discussant(s) assign scores for the five criteria related to your
proposal’s scientific and technical merit. The scores are based on the 1-to-9 scale.
Your application does not necessarily need to be strong in all categories to be judged
likely to have major scientific impact. For instance, a project that is not necessarily
innovative may be essential to advance a particular scientific field. Now, let us
examine the five individual score criteria used to evaluate your grant proposal.
Significance
For this criterion, reviewers determine if your proposed project addresses an
important problem or a critical barrier to progress in your field. They also examine how
scientific knowledge, technical capability and/or clinical practice will be improved
if you achieve your project’s aims. And they seek to understand how successfully
completing the proposal’s aims will change the concepts, methods, technologies,
treatments, services or preventive interventions that drive the particular field.
Investigator(s)
This criterion represents the PI’s qualifications. If it involves early-stage or new
investigators, reviewers want to see experience and training. If the researchers are
established, the SRG will look for an ongoing record of accomplishments that have
advanced the fields involved. And if the proposal includes collaborative or multiple
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PIs, investigators should have complementary and integrated expertise. They must
also have a leadership approach, governance and organizational structure that is
appropriate for the project.
Innovation
The study section wants to see that an application challenges and seeks to
shift current research or clinical practice paradigms by using new interventions,
instruments, theoretical concepts, approaches or methodologies. The SRG wants
to ensure that these factors are new to one research field or new in a broad sense.
And the reviewers look for refined, improved or new applications of interventions,
instruments, theoretical concepts, approaches or methodologies.
Approach
Approach represents a proposal’s overall strategy, methodology and analyses.
Reviewers want to ensure these aspects are well-reasoned and appropriate for
accomplishing your project’s Specific Aims. Address any potential challenges,
alternative strategies and benchmarks for success. If the project is in its early
stages, the Approach should include a strategy to establish feasibility and manage
any particularly risky aspects of the research. If the project involves clinical
research, the Approach should delineate plans for protecting human subjects
from research risks and plans to include minorities, members of both genders and
children. It should also include any justifications of the proposed scientific goals
and research strategy.
Environment
Reviewers want to ensure that PIs will have the resources — the institutional
support, equipment and other physical assets — they need to successfully complete
the proposed research. Additionally, the SRG wants to know if there are any
unique features of the scientific environment, subject populations or collaborative
arrangements that will benefit the project.
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Role of the Review Criteria
Direct from NIH:
Peer reviewers don’t score applications strictly by the review criteria; rather,
the criteria are gauges for assessing merit and feasibility. Your assigned reviewers
give your application a score for each criterion as well as the whole application;
other reviewers score just the whole application. It’s important to understand how
review criteria relate to your score:
•Overall impact and merit. A final score reflects a judgment of the likelihood
of a project to have a powerful impact on its area of science.
•Ideal application. To a large extent, reviewers judge your application based
on their ideal outstanding application in your field of science. This is similar
to a dog show, where dogs are judged for “best of breed” and different breeds
do not compete with each other. So there is not a one-to-one relationship
between how your application measures up to the review criteria and your
score.
•Usage varies. Adherence to the criteria varies by committee.
•Weight varies. An application does not need to be strong in all review criteria
to get a high Overall Impact score, though all criteria can affect your score.
Two examples: Reviewers may assign an exceptional score to a proposal for
important work that is not innovative but is essential to move a field forward.
An application with high significance may receive an outstanding Overall
Impact score even if reviewers are less enthusiastic about the other criteria.
Assigning an Overall Impact Score
The Overall Impact reflects the SRG’s assessment of the likelihood that your
project will exert a sustained, powerful influence on the research field(s) involved
based on the five review criteria. The study section arrives at an Overall Impact
score by following these steps.
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REMEMBER:
The Overall Impact
reflects the SRG’s
assessment of the
likelihood that your
project will exert a
sustained, powerful
influence on the
research field(s)
involved based
upon the five
review criteria.
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1)Before the meeting, the assigned reviewers score each criterion and
determine a preliminary Overall Impact score.
2)The discussion may prompt them to change their initial score.
3)The SRG votes. Assigned reviewers enter their official scores for each
criterion and an Overall Impact score on the vote sheet. The other members
can see these and give an Overall Impact score (and usually have an option
of scoring each criterion).
Overall Impact Scores Range From 1 to 9
The SRG uses the preliminary score to determine which applications the group
will discuss in full. Each member’s score reflects his evaluation of the Overall
Impact the project likely will have on the research field(s) involved, rather than
being a calculation of the reviewer’s scores for each criterion.
The scoring system uses a nine-point scale. The Overall Impact score for each
discussed application is determined by calculating the mean score from all the
eligible members’ impact/priority scores and multiplying the average by 10. The
final Overall Impact score is reported in the summary statement.
Use the following table to understand Overall Impact scores:
Impact
High
Score
1
2
Medium
3
4
5
Descriptor
Exceptional
Outstanding
Additional Guidance on Strengths/Weaknesses
Exceptionally strong with essentially no weaknesses
Extremely strong with negligible weaknesses
Excellent
Very good
Good
Very strong with only some minor weaknesses
Strong but with numerous minor weaknesses
Strong but with at least one moderate weakness
6
Satisfactory
Some strengths but also some moderate weaknesses
7
Fair
Some strengths but at least one major weakness
8
Marginal
A few strengths and a few major weaknesses
Low
9
Poor
Very few strengths and numerous major weaknesses
Minor weakness — An easily addressable weakness that does not substantially lessen impact
Moderate weakness — A weakness that lessens impact
Major weakness — A weakness that severely limits impact
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Percentiling
Your Overall Impact score will be expressed on your summary statement in a
percentile. This is the approximate percentage of applications that received better
Overall Impact scores from the SRG during the past year. Keep in mind that only
a portion of all applications receive percentiles because different NIH institute/
centers assign them to different types of applications. And your summary statement
will identify the base that NIH used to determine your percentile.
Direct from NIH:
For appropriate applications — certain activity codes or request for applications
— scores will be percentiled to the appropriate base (e.g. study section base if the
number of R01 applications > 25; CSR-all or IC-all base if <25). All percentiles are
rounded to a whole number. Until a base has been established from three rounds of
review, percentiles are based on less than three application rounds.
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ADDITIONAL REVIEW CRITERIA
In addition to the five scored criteria and the Overall Impact, there are other
aspects of your application reviewers consider. Depending on their applicability to
the proposed research, the SRG will evaluate the following additional items while
determining scientific and technical merit and the Overall Impact/priority score.
But the study section does not assign the following elements a separate score:
•Protections for human subjects. This is for research that involves human
subjects but does not involve one of the six categories of research that are
exempt under 45 CFR Part 46. Reviewers evaluate the justification for
involving human subjects and the proposed protections from research risk
according to the following five review criteria:
oRisk to subjects
oAdequacy of protection from risks
oPotential benefits to the subjects and others
oImportance of the knowledge to be gained
oData and safety monitoring for clinical trials.
•Inclusion of women, minorities and children. If your proposal involves
clinical research, the committee will evaluate your application for inclusion
of minorities and members of both genders, as well as whether it includes
children as potential subjects. There is a federal law (Public Law 103-43) that
requires women and minorities to be included in all NIH-supported clinical
research projects involving human subjects unless a clear and compelling
rationale establishes that inclusion is inappropriate. Similarly, NIH requires
that children — defined as those younger than 21 years of age — be involved
in all human subjects research supported by the agency unless there are
scientific or ethical reasons for excluding them.
•Vertebrate animals. The review committee also evaluates your proposal
for any involvement of live vertebrate animals according to the following
five points:
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oProposed use of the animals and species, strains, age, sex and numbers to
be used
oJustifications for the use of animals and for the appropriateness of the
species and numbers proposed
oAdequacy of veterinary care
oProcedures for limiting discomfort, distress, pain and injury to that which
is unavoidable in the conduct of scientifically sound research, including the
use of analgesics, anesthetic and tranquilizing drugs, and/or comfortable
restraining devices
oMethods of euthanasia and reason for selection if not consistent with the
American Veterinary Medical Association Guidelines for Euthanasia.
•Biohazards. Reviewers assess your application to determine if any materials
or procedures proposed are potentially hazardous to research personnel
and/or the environment and, if needed, determine whether adequate
protection is proposed.
•Resubmission (A1). When reviewing a resubmission application, which
was formerly known as an amended application, the review committee will
examine the application as presented, taking into consideration the responses
you made to comments from the previous scientific review group and changes
made to the project.
•Renewal. When examining a renewal application, which was formerly called
a competing continuation application, the reviewers will consider the progress
you have made in the more recent funding period.
•Revision. For a revision application, which was once called a competing
supplement application, the committee considers the appropriateness of the
proposed expansion of the project’s scope. If the revision relates to a specific
line of investigation in the original application, the committee will consider
whether your responses to comments from the previous SRG are adequate
and whether any substantial changes are clearly evident.
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There are also certain elements that, if applicable to your proposal, reviewers
will consider, but again, they will not score them individually. These include:
•An application from a foreign organization. The SRG will assess whether
the project will further research programs by using unusual talent, resources,
populations, or environmental conditions that are either not readily available
in the United States or augment existing U.S. resources. Reviewers generally
do not comment on the foreign component of domestic applications as
part of this consideration, but any remarks will appear with those about the
application’s Approach section.
•Select agents. The study section will assess the select agent(s) to be used
in the proposed research; the registration status of all entities where
select agent(s) will be used; the procedures for monitoring possession,
use, and transfer of select agent(s); and plans for appropriate biosafety,
biocontainment, and security of the select agent(s).
•Resource-sharing plans. Reviewers will comment on whether the three
following plans — or the rationale for not sharing these resource types —
are reasonable:
oData-sharing plan. Applications requesting more than $500,000 in direct
costs in any year of the proposed research should include a data-sharing
plan. Certain program announcements may request a data-sharing plan for
all applications, regardless of the amount of direct costs.
oSharing model organisms. If you expect to develop model organisms, you
must include a specific plan for sharing and distributing that information.
Or state why such sharing is not possible. A model organism sharing plan
is not subject to a cost threshold of $500,000 or more in direct costs in any
one year.
oGenome-wide association studies. If your application includes these
studies, your proposal must describe a plan for submitting the data to
the NIH-designated repository or an appropriate explanation for why
submission will not be possible.
•Budget and period support. Reviewers will consider whether your budget and
requested period of support are fully justified and reasonable in relation to
your proposed research.
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SUMMARY STATEMENTS
Once the study section has scored your application, the SRO prepares a
summary statement. The document includes bulleted critiques from your assigned
reviewers, a brief summary of the discussion, your Overall Impact score, your
percentile, the SRG’s recommended budget, human and animal subjects codes, and
any administrative comments.
If your summary statement has an issue with human subjects, animals, or
biohazards, NIH will assign it a code that prevents your application from receiving
an award. The agency can’t give you funding until you resolve the issue, so contact
your program officer immediately.
Note that a summary statement is not an exhaustive critique. It is not a teaching
tool containing every point reviewers found to be problematic in your application.
But you can use it to revise a fixable application, if necessary.
Frequently Asked Questions About Summary Statements
Direct from NIH:
Q. How have summary statements changed?
A. The order of the review criteria has changed: Investigator(s) and Approach
swapped positions; the new order (for research applications) is Significance,
Investigator(s), Innovation, Approach and Environment. A table at the beginning of
each critique summarizes the reviewer’s scores for each criterion.
Q. How are the criterion scores displayed in the summary statement?
A. Criterion scores are added automatically by the Internet-Assisted Review
(IAR) system as a table at the beginning of each reviewer’s critique.
Q. What if the scores in the table do not agree with scores that may have been
entered with the written critique?
A. The scores that IAR inserts in the table are accepted as final. Reviewers
are instructed not to enter scores with their critiques and that errant scores in the
critiques may be removed in finalizing the summary statement.
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If You Have Additional Questions
You can contact the appropriate awarding component program official, whose
name is in your summary statement, to ask any questions. The contact can:
•Discuss the review outcome of the application and give guidance
•Provide feedback and answers to any questions about the summary statement
•Explain the meaning of a numerical designation pertaining to human subjects
or vertebrate animals in the summary statement
STRATEGY:
If problems are
fixable, start
revising quickly.
If your application
misses the payline
or is not discussed
and its faults are
fixable, start
revising as soon as
you can, because
you may not have
much time to
revise after you
get the summary
statement.
287 •Relay the funding status of an application
Direct from NIH:
Applicant investigators must not communicate directly with any review group
member about an application either before or after the review. Failure to strictly
observe this policy will create serious breaches of confidentiality and conflicts
of interest in the peer review process. From the time of assignment to the time
the review of your application is complete, applicant investigators must direct
all questions to the SRO. This individual is in charge of the review group and is
identified in the eRA Commons.
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SECOND LEVEL OF REVIEW: INSTITUTE/CENTER
ADVISORY COUNCIL OR BOARD
Once the SRG has weighed in on your application, the institute/center’s
advisory council or board performs a second review. The boards are made up of
scientists from the extramural research community and public representatives who
are approved by the U.S. Department of Health and Human Services. The President
of the United States also appoints members for certain committees.
During this second review process, NIH staff examine applications, Overall Impact
scores, percentile rankings and summary statements. They provide the advisory board/
council with a grant-funding plan. The board considers the institute/center’s goals
before advising the director, and the director makes the final funding decision.
Applications that do not fall within the current payline but are aligned with NIH’s
priorities are placed on the “select pay” list. NIH staff create this list, prioritize it, and
present it to the advisory board. If there is money left over at the end of the funding
cycle, these selected applications will be funded in the order listed.
If your application receives an award, you will be working closely with the
institute/center program officer on scientific and programmatic matters and a grants
REMEMBER:
During the second
review process,
the advisory board/
council considers
the institute/
center’s goals
before advising
the director, who
makes the final
decision.
management officer regarding budgetary or administrative issues.
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WHEN YOU CAN EXPECT TO HEAR BACK
Your scores will be available in the eRA Commons three business days after
the review is complete. Your summary statement should appear there within three
weeks, although it is usually available earlier for new investigators.
Tracking Your Application
Direct from NIH:
The eRA Commons provides a valuable resource for applicants and PIs to track
an application throughout various phases of the grants process. Within the eRA
Commons , the Status tab is where most of the tracking information is found.
1)Use eRA Commons to track status. eRA Commons provides the status
of your grant application and allows you to review detailed information
associated with your applications/grants.
a)Log in to eRA Commons with your user name and password
b)Click the Status tab on the blue navigation bar across the top of the screen
c)Find the application/grant of interest d)Click on the application ID.
The Status screen contains the most current status and relevant documents for
that application/grant.
2)Watch for email notifications. Email notices are sent to notify the PI and/or
signing official to check the eRA Commons for a change in status.
3)Tracking during Peer Review phase.
a)Score and percentile. Following the review group meeting, any available
score and percentile information can be found in the application
information section of the Status screen.
b)Summary statement. Approximately three weeks after the review
meeting a full summary statement is available in the other relevant
documents section.
4)Tracking during Pre-Award and Award phase.
a)Just-in-time (JIT). Some application information (other support,
institutional review board and/or Institutional Animal Care and Use
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Committee approval dates and human subjects education information) is
requested just prior to a final award decision. If needed, NIH will send a
request for this information.
b)Notice of award (NoA). The NoA is the official grant award document
notifying the grantee and others that an award has been made and stating
the terms and conditions of the award. You will find a link to the NoA
under the other relevant documents section of the Status screen. NoAs can
also be automatically emailed to the grantee organization. Organizational
officials can maintain an NoA email address in the eRA Commons
institutional profile.
5)Tracking during Post-Award Management phase. Several post-award tasks
can be managed through the eRA Commons.
a)Electronic Streamlined Non-Competing Award Process (eSNAP). eSNAP
allows extramural grantee institutions to submit an electronic version
of a PHS 2590 progress report. This information is needed to receive a
non-competing award. An eSNAP link is available under actions in your
Status list of grants.
b)Closeout. Electronically submit required closeout documents including
Final Status Report (FSR), Final Progress Report and Final Invention
Statement. At the appropriate time, a Requires Closeout link is available
under actions in your Status list of grants.
c)No-cost extension. You can extend the final budget period of the project
one time for up to 12 months beyond the original expiration date on your
NoA as long as no cost or scope change is involved. At the appropriate
time, an Extension link is available under actions in your Status list of
grants. This may be completed electronically up to one day prior to the
end of the project period.
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JUST-IN-TIME INFORMATION
NIH may request just-in-time information if your application scored roughly
within the top 20 percent. Although you may not get funded, you should prepare
this information anyway. Ensure it is accurate and current.
Notify NIH of any substantive changes to previously submitted just-in-time
information up to the time of an award, including changes in PI or key personnel
status, as well as the use or approval of vertebrate animals or human subjects.
Other support information is always just-in-time. The funding agency also
requests any of the following documentation relevant to your research that you did
not include in your application:
1)Human subjects
a)Assurance number
b)Certification of institutional review board approval of research plan
c)Certification of human subjects education
2)Animals
a)Animal welfare assurance number
b)Certification of institutional animal care and use committee approval
3)Human embryonic stem cells (hESCs)
a)Identify the hESC line from the NIH Human Embryonic Stem Cell
Registry
Other Support Submission
As a just-in-time filing, you’ll need to send a list of other financial support —
existing funding you have and any you may gain from the current application. If
you have no other source of aid, your funding agency will need a letter from your
institution’s business office stating that fact.
Have any support information ready well before the award is made. It should
show the following:
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•No other organization is supporting the research you outlined in your plan:
scientific overlap.
•Your time is not committed more than 100 percent: commitment overlap.
•You have not requested funding for items paid for by another source:
budgetary overlap.
End-of-Year Warning
Funding agencies may skip over your application if it comes up for funding at
the very end of the fiscal year and your just-in-time submission is not ready.
Your institution’s business office should submit other support and human
subjects training information within two weeks of receiving a just-in-time notice.
You don’t need to sign this information because you have a signature assurance
on file with your institution. Because institutional review board and institutional
animal care and use committee certifications may take more than two weeks, your
business official may submit these approvals at the earliest date possible.
Whether you send the certifications with your application or as a just-in-time
filing, they should be sent together. NIH prefers that your institution submit the
documentation through the just-in-time feature of the eRA Commons in PDF format.
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RESUBMISSION (A1)
Nearly every PI who submits a proposal to the NIH is denied the first time out.
In fact, the estimated first-time rejection rate is 75 percent or more. Fortunately,
NIH allows resubmissions for R01 proposals, and an estimated 35 percent of
resubmitted applications get funded. The trick is knowing how to revise your
application in a way that improves your funding chances.
Is Resubmitting Worthwhile?
Before you begin revising your application, ask yourself if resubmitting is
worth it. Will you be rewriting more than half of the proposal? If so, creating a new
one might be a better use of your time.
Have you pursued the research and continued to gather results, or did you move
on to something else? Revising and resubmitting takes time and commitment,
so the research should be meaningful to you. You may want to start over with a
different project, a different institute or program, and/or a new deadline.
Identify the Reasons for Rejection
If you decide to revise and resubmit your proposal, your first step is to identify
the reason(s) for rejection. Carefully analyze the peer reviewers’ summary
statements. Read them more than once so you can identify your application’s
specific weaknesses and strengths. Look for critiques mentioned multiple times.
You will likely see a pattern of issues you need to address in your
resubmission.
In a case study of 605 rejected NIH proposals, researchers found three areas
that attributed to rejection the most:
1.Approach: 73 percent
2.Problem: 58 percent
3.Investigator: 55 percent
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Other reasons included institutional setting, unrealistic budget requests,
inadequate personnel, lack of PI time, unconvincing project and sloppy
presentation.
Respond to Reviewers’ Comments
You have no control over issues with your institution, and you can’t bend
administrative, regulatory or agency guidelines. But you can respond to reviewers’
comments about your approach, problem, experience, budget requests, personnel,
overall project and presentation.
If space permits, your resubmitted application should include a reply to each
comment. Highlight your explanations and changes [in brackets or boldface]. If
you’re making significant alterations in the text, say so in your introduction.
Tips for Resubmitting
Get second opinions. Once you receive your reviews, you should seek out
TIP:
If space permits,
your resubmitted
application should
include a reply to
each comment,
and highlight your
explanations and
changes.
colleagues for their feedback on the reviews. They can be particularly helpful in
advising on resubmission and ways to resolve problems identified in the comments.
The most important second opinion you get may be from your program officer;
they will better be able to tell you if you have an innovative idea worth pursuing in
a resubmission.
Provide sufficient evidence to justify your project. Include specific
background data. Highlight compelling new data you gathered while waiting
for the initial response, and cite newly published research papers. Ensure your
outcomes/objectives are measurable, obtainable and specific. Be sure to connect
your research to its impact on the field and create a clear budget narrative.
Your Personnel Statement. With some imagination and creativity, there are
ways you can use this statement to increase your chances of successfully being
awarded funds.Make sure to describe your experience related to the subject matter
being proposed in the application. In so doing, you must strike a balance between
describing accomplishments and appearing boastful.
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Focus on your writing. Create a strong introduction that keeps reviewers
engaged and sets your proposal’s tone. Be sure to label the progression of ideas,
and keep your narrative concise by writing in short sentences and paragraphs.
Familiarize yourself with review process changes. Take note of new
requirements like page limit reductions, and adhere to them.
NIH Policy Change on Resubmitting Applications
The NIH still allows only one resubmission of an unfunded application
(see NOT-OD-09-016 at http://grants.nih.gov/grants/guide/notice-files/NOT-
REMEMBER:
OD-09-016.html), which must be submitted within 37 months of the new (A0)
It is important to
read the initial
RFA or program
announcement
you applied under
carefully to see if
there are any
special rules
regarding A1
resubmissions.
application (see NOT-OD-10-140 at http://grants.nih.gov/grants/guide/notice-files/
NOT-OD-10-140.html). If the resubmission is not funded, the previous policy
stated that the application had to substantially differ in both content and scope
in order to be eligible for submission as a new application. However, for all
application due dates after April 16, 2014, if your resubmission application (A1)
was unsuccessful at receiving funding, you may now submit the same idea as a
new (A0) application for the next appropriate new application due date (see NOTOD-14-074 at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-14-074.
html). This change in resubmission policy applies to applications submitted to all
grant and cooperative agreement funding opportunities that allow resubmissions,
including all fellowship, training, and career development awards.
Direct from NIH:
http://grants.nih.gov/grants/policy/amendedapps.htm
TIP:
The revised proposal
requires a one page
introduction that
explains how the
investigator has
revised the grant.
295 Per NOT-OD-14-074 (see http://grants.nih.gov/grants/guide/notice-files/NOTOD-14-074.html), for application due dates after April 16, 2014:
•
following an unsuccessful resubmission (A1) application, applicants may
submit the same idea as a new (A0) application for the next appropriate due
date.
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Chapter 8: The NIH Application Review Process
NIH will not assess the similarity of the science in the new (A0) application to
any previously reviewed submission when accepting an application for review.
This policy applies to all NIH Funding Opportunity Announcements (FOAs) that
allow resubmissions, including FOAs for research grants, the NIH Small Business
Innovation Research (SBIR) and Small Business Technology Transfer (STTR)
programs, Career Development Awards, Individual Fellowships, Institutional Training
Grants, Resource Grants, Program Projects, and Center Grants.
NIH’s policy for accepting overlapping applications remains in effect (see NOTOD-09-100 at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-09-100.html).
The NIH will not accept duplicate or highly overlapping applications under review at
the same time. This means that the NIH will not review:
• a new (A0) application that is submitted before issuance of the summary
statement from the review of an overlapping new (A0) or resubmission
(A1) application.
• a resubmission (A1) application that is submitted before issuance of the
summary statement from the review of the previous new (A0) application.
REMEMBER:
Not counting the
introduction, a
revised proposal
must keep to the
same page limits as
other proposals.
• an application that has substantial overlap with another application pending
appeal of initial peer review (see NOT-OD-11-101 at http://grants.nih.gov/
grants/guide/notice-files/NOT-OD-11-101.html).
NIH will not accept a resubmission (A1) application that is submitted later than
37 months after submission of the new (A0) application that it follows (see NOTOD-12-128 at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-12-128.
html and NOT-OD-10-140 at http://grants.nih.gov/grants/guide/notice-files/NOTOD-10-140.html).
Applicants should check the individual FOA to determine whether resubmission
applications are allowed. Resubmissions normally are not permitted for applications
received in response to a Request for Applications (RFA) unless it is specified in the
FOA, in which case only one resubmission will be permitted. Since an RFA often has
special considerations of eligibility, scientific scope, and review criteria, unfunded
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Chapter 8: The NIH Application Review Process
applications to an RFA must be submitted as new applications to another FOA,
using that FOA’s target due date for new applications.
Similarly, a change of grant activity code (e.g., from an R01 to an R21 or from
an R03 to an R01) usually involves a change of eligibility criteria, application
characteristics, dollar limits, time limits, or review criteria. These applications also
MUST be prepared as new applications. More information on these policies can be
found in the NOT-OD-03-019 (see http://grants.nih.gov/grants/guide/notice-files/
NOT-OD-03-019.html).
The Purpose of this Policy Change
The new policy allows for ideas that were unsuccessfully submitted as
a resubmission to be presented in a new grant application without having to
substantially redesign the content and scope of the project. This policy change from
the requirement that previously reviewed applications be substantially redesigned
in order to be accepted as a new application is in response to researcher’s concerns
that changing the scope to be accepted as new resulted in many meritorious
research ideas being deemed ineligible for resubmission. It was argued that this
previous policy was especially hard on new investigators, since finding new
research directions can be quite difficult during this phase of their career. Likewise,
established investigators expressed concern about the need to redirect the research
focus of productive labs in order to submit future NIH applications.
TIP:
If you had an
unsuccessful
resubmission before
this new policy
was issued, this
previously rejected
A1 is now eligible
for submission as a
new A0 application.
Resubmission of an idea as new means that the application will be considered
without a connection to a previous submission. As such, the applicant will not
provide an introduction to describe how this application has changed or specifically
respond to previous reviewer critiques. During review, the reviewers will be
instructed to evaluate the submission as a new idea, even if they have seen this
project in prior cycles. While there may not be major changes to the research
direction of these previously reviewed ideas, the NIH does expect that applicants
will still take advantage of previous comments to bolster the application for each
submission. Also, if you had an unsuccessful resubmission before this new policy
was issued, this previously rejected A1 is now eligible for submission as a new A0
application.
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Chapter 8: The NIH Application Review Process
What Does This Mean in Practice?
• You may now submit a new A0 following an unsuccessful new A0
• Unless you would like the opportunity to address reviewer comments
directly, you do not have to resubmit as an A1
• The new resubmission policy does not limit the number of times an
application may be submitted as new
• Following an unsuccessful A1, you can submit as an A0 having the same
title if you wish; it is not a requirement that you change the title
• As a new submission, it will receive a new grant number
• You still need to have received your summary statement before you can
submit an unsuccessful A1 as an A0
Keep in mind, these rules refer to grants submitted through a general
program announcement, not necessarily requests for applications (RFA). Most
RFAs, which are one time competitions to meet a specific need, do not allow
resubmissions. If an investigator wants to resubmit an RFA with revisions under a
regular program announcement, that would be considered a new proposal.
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Chapter 8: The NIH Application Review Process
CONCLUSION
This final chapter describes the review process, from receipt of your application
by the NIH to ‘just in time’ procedures in the event that an award may be made
to you. The information that you can expect to receive, as well as the timing of
when to anticipate this information becoming available, is also described. The
NIH realizes that you spend a lot of time getting to this point and they strive to
keep you up-to-date with you application’s progress. Remember that the majority
of applications received by the NIH are not awarded. So, if your application is not
funded the first time around, shake off the initial disappointment, heed the reviewer
comments, and submit again. n
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Appendix A: R01 Checklist
Appendix A:
R01 Checklist
Preparation
Your research idea matches NIH’s stated goals
Your research idea matches the goals of one of NIH’s Institutes, Centers or
Offices
Your institution qualifies for NIH support
The R01 is the right grant mechanism for your proposal
Generate a focused, testable hypothesis
Write a provisional title
Choose the date to submit your application
Create a writing schedule
Project Summary/Abstract and Project Narrative
Review individual ICO requirements and include the required information
Use proper formatting
Stay within length requirements
Include the following in your Project Summary:
•Brief background of the project
•Specific aims, objectives or hypotheses
•Proposal’s significance and relevance to public health
•Project’s unique features and innovation
•Methodology
•Expected results
•How results will affect other research areas
Use storytelling tactics to engage reviewers
Examine samples from winning grants
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Appendix A: R01 Checklist
Biographical Sketch
Use the NIH form
Determine Senior/Key Personnel
Use Personal Statement to briefly describe why your experience and
qualifications make you particularly well suited for your role
In Positions and Honors, list your previous positions in chronological order,
concluding with your present one.
Try to list no more than 15 peer-reviewed publications or manuscripts.
For Research Support, list both selected ongoing and completed research
projects, beginning with the most relevant to the current proposal.
If you’re an early-stage investigator, stress your independence from others at
your institution.
Write a desired draft of a letter of support for the person to review and sign,
but do not make all of your supporting letters look the same.
Environment
Explain what facilities you will use.
Detail how the scientific environment in which you perform your research
will contribute to your success.
For early-stage investigators, outline the following:
•Institutional investment in your success
•Collegial support
•Logistical support
If multiple sites are involved, describe the resources available at each site.
List your available equipment
If applicable, generate your Data-Sharing Plan, Sharing Model Organisms
Plan and/or Genome-Wide Association Studies Plan.
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Research Plan
Keep Specific Aims to one page.
Follow individual NIH ICOs’ instructions for crafting your Specific Aims.
Make sure your Specific Aims are not sequential. If they are, show that you
are prepared for unexpected results.
Break your Specific Aims down into three sections: rationale, experimental
approach, and outcomes and alternatives.
In the Significance section of the Research Strategy, include the following:
•Importance of the problem or critical barrier to progress in the field your
project addresses.
•How your proposal will improve scientific knowledge, technical capability
and/or clinical practice.
•How your project will change concepts, methods, technologies, treatments,
services or preventive interventions.
For the Innovation section, explain the following:
•How your proposal challenges and seeks to alter current research and
clinical practice standards.
•New theoretical concepts approaches or methodologies; instrumentation
or interventions you plan to develop or use; and how these are better than
existing ones.
•Refinements, improvements or new applications or theoretical concepts,
approaches or methodologies, instrumentation or interventions.
In the Approach, include the following:
•Overall strategy, methodology and analyses you plan to use to accomplish
your Specific Aims.
•Potential challenges, alternative strategies and benchmarks for success.
•For early-stage projects, any strategies to establish feasibility and how to
change any high-risk aspects.
•Any hazardous procedures, situations or materials and precautions you will
use to address them.
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Appendix A: R01 Checklist
Provide preliminary data to support your proposal.
Include a simple impact statement to each of the core criteria sections.
Complete the Inclusion Enrollment Report.
Cite your Bibliography and references.
Special Considerations
Prepare your Protection of Human Subjects document and use subheads to
delineate the four sections.
Provide a justification if you plan to exclude women, minorities and/or
children.
Complete the Targeted/Planned Enrollment Table.
Address the five points of the live vertebrate animal test subjects section.
For Select Agents, complete the three points for each research site where the
agents will be used.
Budget
Ask only for enough money to do the work you propose, but do not “low
ball” with an unrealistic budget.
Review the cap for your grant mechanism.
Choose your budget type: modular or detailed.
If you’re using a modular budget, generate the needed justifications:
•Personnel
•Consortium
•Additional
For a detailed budget, complete the 11 separate sections on the application.
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Appendix A: R01 Checklist
Review Your Proposal for Content
Your Project Summary/Abstract should describe all major aspects of your
project.
Ensure your budget accurately reflects the resources you need and expenses
you will incur.
Make certain your Research Strategy addresses Significance, Innovation and
Approach.
Assess Writing Quality
Have colleagues review your proposal for clarity.
Perform your own proofread, looking for misspellings, grammatical errors,
etc.
If necessary, hire a professional editor.
Include All Necessary Components
SF424 (R&R) (Cover component)
Research & Related Project/Performance Site Locations
Research & Related Other Project Information
Research & Related Senior/Key Person
PHS398 Cover Page Supplement
PHS398 Research Plan
PHS398 Checklist
PHS398 Modular Budget or Research & Related Budget, as appropriate
PHS398 Cover Letter File (optional)
Research & Related Subaward Budget Attachment(s) Form (optional)
Attach appendix materials as PDFs (no more than 10).
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Appendix B: Index
Appendix B: Index
TermPages
Abstract����������������������������������������������������������������49, 151, 240, 248
Appendix��������������������������������������������������������������61-64, 138, 153-154, 240-244
Approach��������������������������������������������������������������110, 113, 116, 120-127, 131-138,
140, 147, 149-152, 215, 219, 232,
248-249, 250-253, 258, 264-265,
277, 279, 286
Attachments���������������������������������������������������������240, 244, 248, 265
Bibliography��������������������������������������������������������116, 120, 124, 153-154, 240
Biographical Sketch���������������������������������������������51-75, 142, 241, 261, 270
Biohazards������������������������������������������������������������81, 83, 85, 201, 238, 243, 278, 284,
286
Budget������������������������������������������������������������������206-239, 245, 247-250, 257, 260261, 266, 270, 285, 288, 290, 292
Budget justification����������������������������������������������208, 215, 218, 224, 227, 233, 239
Children, inclusion of�������������������������������������������168-173, 188-190, 272, 279, 283
Citations���������������������������������������������������������������53, 61, 66, 113, 123, 153, 241, 251
Consortium justification���������������������������������������215, 220-221
Cover letter�����������������������������������������������������������15, 236-237, 245-248, 259, 261, 268
Detailed budget����������������������������������������������������206-207, 213-215, 224, 228-229, 233
Direct costs�����������������������������������������������������������91-92, 206-207, 213-215, 224, 227228, 235, 238, 242, 266, 285
Early-stage investigator���������������������������������������55, 82-83, 86, 109
End-of-year warning��������������������������������������������292
Environment���������������������������������������������������������80-82, 85, 87, 109, 125, 136, 138,
147, 149-151, 202, 252, 254, 264265, 277, 279, 284-286
Equipment������������������������������������������������������������74, 80, 86, 89, 109, 201, 209, 219,
222, 231, 243, 249-250, 270, 279,
301
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Appendix B: Index
Facilities and other resources�������������������������������72-88, 95, 109, 239-243
Final checks���������������������������������������������������������301
Foreign organizations�������������������������������������������238, 285
Genome-wide association studies (GWAS)���������91-92, 104, 107, 242, 285
Hiring a professional editor���������������������������������255
Human subjects����������������������������������������������������104-105, 168-171, 175, 177, 182,
184, 189, 191, 238, 240, 242, 272,
277, 279, 283, 286-287, 290, 303
Hypothesis�����������������������������������������������������������21-24, 29, 31, 37, 110-117, 143,
248-253, 258
Impact������������������������������������������������������������������See Overall Impact
Inclusion Enrollment Report��������������������������������157-162, 166-167, 303
Indirect costs��������������������������������������������������������207, 224, 228, 249
Innovation������������������������������������������������������������110, 113, 120-125, 131-136, 147,
149-151, 155, 236, 251, 264, 274
Institute/Center Advisory Board/Council������������244-246, 264, 268, 288
Integrated Review Group (IRG)��������������������������264-265, 268
Intellectual property���������������������������������������������77, 100-103, 108
Just-in-time information���������������������������������������291-292, 306
Letters of support ������������������������������������������������72-74, 270
Minorities, inclusion of����������������������������������������160, 165-168, 182-184, 187, 272,
279, 283
Modular budget����������������������������������������������������206-208, 210, 213-215, 220, 235,
237-239, 249
Multiple institutions/sites�������������������������������������81, 85, 169-170, 237-239
Multiple principal investigators���������������������������33, 75, 238
New investigator��������������������������������������������������55-57, 72, 81, 116, 135, 210, 275
Non-numeric scores���������������������������������������������277
Overall Impact�����������������������������������������������������110, 113, 125-126, 137, 147-152,
155, 216, 252-253, 264-265, 275,
277, 280-283, 286, 288
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Appendix B: Index
Peer review�����������������������������������������������������������35, 53-54, 58-61, 64, 66, 70, 100,
142, 191, 196, 245-246, 262-280,
287, 289, 293, 296, 301
Peer review suggestions���������������������������������������See Review suggestions/requests
Personal Statement�����������������������������������������������32, 52, 54-59, 66, 70
Personnel justification������������������������������������������215-218,
Planned Enrollment Report����������������������������������157-168, 182, 184, 188
Positions and honors��������������������������������������������53-54, 60, 70
Preliminary data���������������������������������������������������20, 28, 39, 55, 63, 113, 116-117,
122, 127, 131-133, 136, 139-144,
251-253, 258
Project Narrative��������������������������������������������������48-50, 153, 229
Project Summary �������������������������������������������������See Abstract
Publications in press��������������������������������������������53-55, 58-59, 61-64, 270
Qualifications�������������������������������������������������������17, 52-66, 70, 83, 243, 273, 278
Reference letters���������������������������������������������������240-243
References �����������������������������������������������������������See Bibliography Renewal applications�������������������������������������������24, 28, 56-57, 115, 121, 146, 157158, 161, 165, 180, 240, 267, 284
Research Strategy�������������������������������������������������29, 110, 112, 120-122, 131, 134,
136, 142, 154-155, 168, 170, 191192, 204, 229, 236, 241, 248, 250,
270, 279
Research support��������������������������������������������������53-54, 70-71
Resource sharing��������������������������������������������������See Sharing plans
Resubmission�������������������������������������������������������18, 24, 165, 240, 267, 284, 293298
Review layout������������������������������������������������������266-276
Review process����������������������������������������������������264-292
Review suggestions/requests�������������������������������246-248, 270-271
Reviewer conflict of interest��������������������������������247, 268
Revision application���������������������������������������������24, 121, 146, 233, 237, 239-240,
284
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Appendix B: Index
Scientific Review Group (SRG)/study section����35, 184, 189, 239, 245-246, 264268, 272-288
Scientific Review Officer (SRO)�������������������������241, 244, 246, 261-262, 265, 268277, 286-287
Scoring your application��������������������������������������275-281
Select agents���������������������������������������������������������81, 121, 197-204, 242, 266, 278,
285
Sharing model organisms�������������������������������������91, 98, 285
Sharing plans��������������������������������������������������������91-93, 107, 134, 242, 253, 285
Significance����������������������������������������������������������26, 29, 36-46, 67, 110-155, 236,
248, 250-252, 257-258, 264-265,
271, 278, 280, 286
Specific Aims�������������������������������������������������������24, 29, 34-37, 40-43, 46, 76, 110122, 134-136, 142, 146, 151, 208209, 230, 236, 248, 250, 252, 270,
276, 279
Submitting the application�����������������������������������261
Summary Statements�������������������������������������������264, 273, 286, 288, 293
Title of project �����������������������������������������������������8, 24-29, 31, 39, 41, 43
Tracking your application������������������������������������289-290
Vertebrate animals������������������������������������������������156, 191-192, 196, 272, 278, 283,
287, 291, 303
When to apply������������������������������������������������������23, 28
Withdrawing your application�����������������������������262
Women, inclusion of��������������������������������������������157, 160-174, 179, 182-187, 272,
283
Writing schedule��������������������������������������������������6, 8, 29-31
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About the Consulting Editor —
Dorothy E. Lewis, PhD
Dr. Lewis has had continuous NIH funding since 1985, experiencing both times
of multiple grants and reduced funding. She is a member of the AIDS Immunology
and Pathogenesis study section (2007-2011) and became chair in 2009. She is thus
very familiar with the new NIH application system and new methods of review,
which focus greatly on impact. She has more than 140 publications, a few book
chapters and reviews. And she has mentored many graduate students, fellows and
other faculty members in grant writing, both in a formal course on the subject in
the 90s, and then as the chair of the mentoring committee for the Center for AIDS
(BCM/UTHEALTH), which was recently renewed in its fourth cycle.
Currently, Dr. Lewis is supported by NIH via an R37 that examines T cell
dysfunction in HIV patients, the abovementioned CFAR as the Immunology core
director, and a grant that examines how HIV might affect fat differentiation with a
colleague at BCM. She is also supported by Novartis to develop a method to enrich
fetal DNA from the maternal circulation for the purpose on noninvasive genetic
diagnosis. She teaches medical students and graduate students at UTHEALTH and
mentors various predoctoral and postdoctoral candidates, including in fellowship
and grant writing.
Dr. Lewis received her PhD in Microbiology in 1978 from the University of
Arizona in Tucson. She then did an NIH-supported postdoctoral fellowship at
the University of New Mexico School of Medicine in Albuquerque under the
mentorship of Dr. Noel Warner. She worked on an autoimmune model in mice
trying to determine which immunologic abnormalities were genetically associated.
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She became acquainted with flow cytometry during her fellowship and used
instruments in Los Alamos to characterize murine T and B cells.
She was on a chartered study section from 1992-1996 and then participated
in multiple review panels related to HIV or flow cytometry in the 1990s. She
served on the NIAID council from 2002-2006 on the DAIDS subcommittee, which
exposed her to policy matters and how topics are chosen by program.
Principal Investigators Association | www.principalinvestigators.org
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