Demystifying grants at NIH

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Demystifying grants at NIH PY 718, Spring
2007 Sylvie Mrug Sources Bruce Freeman, Univ
of Pittsburgh LaShawndra Price, NIMH
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National Institutes of Health
Much of the biomedical research in the United
States is supported by the federal government,
primarily the National Institutes of Health
(NIH). NIH is part of the U.S. Department of
Health Human Services.
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Structure of the NIH

• 27 institutes and centers, e.g.
• NIMH mental health
• NIA aging
• NCI cancer
• NIDA drug abuse
• The institutes and centers are similar in some
  ways, but not others
• Each has its own mission, budget, activities,
  priorities, and ways of doing things
• Make sure to align your application with the
  mission and priorities of the institute where you
  want to send it

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National Institutes of Health
Office of the Director
National Institute on Alcohol Abuse and Alcoholism
National Institute of Arthritis
and Musculoskeletal and Skin Diseases
National Cancer Institute
National Institute on Aging
National Institute of Child Health and
Human Development
National Institute of Allergy and Infectious
Diseases
National Institute of Diabetes and Digestive
and Kidney Diseases
National Institute of Dental and Craniofacial Rese
arch
National Institute on Drug Abuse
National Institute of Environmental Health
Sciences
National Institute on Deafness and
Other Communication Disorders
National Eye Institute
National Human Genome Research Institute
National Heart, Lung, and Blood Institute
National Institute of Mental Health
National Institute of Neurological Disorders
and Stroke
National Institute of General Medical Sciences
National Institute of Nursing Research
National Library of Medicine
National Center for Complementary and
Alternative Medicine
Clinical Center
National Institute of Biomedical Imaging
and Bioengineering
Fogarty International Center
National Center for Research Resources
Center for Information Technology
Center for Scientific Review
National Center on Minority Health and Health
Disparities
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Example the NIMH
NIMHs Mission is to reduce the burden of mental
illness and behavioral disorders through research
on mind, brain behavior.

• Through the support and conduct of research on
  mental disorders and the underlying basic science
  of brain and behavior
• Ensuring rapid and effective dissemination and
  use of research results to improve prevention,
  intervention, treatment, and policy

So in your application, you should state
explicitly how the proposed research will
contribute to reducing the burden of mental
illness in this country
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General Grant Types (NIMH)

• Graduate Student
• T32
• institutional NRSA
• institutional to increase diversity
• F31
• individual NRSA
• individual minority
• R36 mental health dissertation research to
  increase diversity
• R25 mental health education grant
• RPG research supplements for underrepresented
  minorities or disability
• Add-on to research project grants (R, P, others)

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General Grant Types (NIMH)

• Post-doc
• T32
• institutional NRSA
• institutional to increase diversity
• F32 individual NRSA
• R25 mental health education grant
• RPG research supplements for underrepresented
  minorities or disability
• Add-on to existing research project grants (R, P,
  others)
• NEW K99/R00 (kangaroo)

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General Grant Types (NIMH)

• Early career
• Career development (K series)
• K01 mentored research scientist development
  award
• 3-5 years, mainly salary support (75)
• K22 research career award for transition to
  independence
• K99/R00
• Independent grants (R series)
• R03 small, short-term (2 yrs), 50,000/yr
  limit
• R21 exploratory/developmental
• - high risk/high impact
• - short-term (2 yrs)
• - higher limit than R03 - 275,000/2yrs
• R25 mental health education grant

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General Grant Types (NIMH)

• Early career contd
• RPG research supplements (minorities or
  disability)
• LRP extramural loan repayment program for
  clinical or pediatric researchers

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General Grant Types (NIMH)

• Mid- to senior-level
• Career development (K series)
• K02 independent scientist award
• K05 senior scientist award
• K24 midcareer investigator award in
  patient-oriented research
• Independent grants (R series)
• R03 small grant
• R21 exploratory/developmental grant
• R01 large project grant up to 5 years,
  lt500,000/yr
• R25 mental health education grant
• P series
• large multi-investigator grants, program
  projects, research centers, etc.

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Eligibility

• Make sure to check eligibility criteria before
  proceeding
• E.g., US citizenship or permanent residency is a
  requirement for all individual training career
  development awards
• F, K series
• But non-citizens can apply for R grants
• Other eligibility criteria have to do with your
  position (student, postdoc, faculty) and type of
  institution

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More on R grants

• R grants can be
• Investigator initiated
• Or in response to a specific FOA
• FOAs, PAs and RFPs
• To solicit proposal in specific areas of
  interest, NIH institutes issue a number of
  Funding Opportunity Announcements (FOA) each year
• Program announcement (PA) broad, specifies a
  research area, may include set-aside amount of
  money, typically valid for 3 years
• Request for applications (RFP) more narrowly
  defined, typically one-time opportunity

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Facilitating the grant/career timeline
post doc resident
juniorfaculty
seniorfaculty
student
training
F31
F32
K Awards (career dev)
Combining the K and R
research
R01
P01
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First Major Independent Research Support Occurs
at an Ever-Later Age

Average Age of Initial Type 1 R01/R23/R29 Award
for Different Degrees Held

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M.D.-Ph.D.
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M.D.
Average age
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Ph.D.
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1980
1981
1982
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1987
1988
1989
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1997
1998
1999
2000
2001
2002
2003
Fiscal Year
For more information, see http//grants.nih.gov/g
rants/20040712_New_Investigator_Talk.ppt
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NIH Pathways to Independence

• One of current priorities
• Designed to facilitate receiving R01 earlier in
  the career
• K99/R00 kangaroo award
• Provides up to 5 years of support consisting of
  two phases
• Initial 1-2 years of mentored support for highly
  promising postdoctoral research scientists (K99
  Phase)
• Followed by up to 3 years of independent support
  contingent on securing an independent research
  position (R00 Phase)
• Activation of R00 Phase requires offer and
  acceptance of a tenure-track, full time assistant
  professor position (or equivalent)
• Transition is subject to administrative review of
  progress and evaluation of research plan

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Mentored (K99) Phase

• Provides 1-2 years of mentored support for highly
  promising postdoctoral research scientists who
  have terminal clinical or research doctorates
• Total cost per year up to 90,000
• This phase may be submitted on behalf of
  candidate by wide range, but not foreign
  institutions
• U.S. citizens and non-U.S. citizens eligible

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Independent Investigator (R00) Phase

• Application may be submitted on behalf of PI by
  US universities, but not Federal and foreign
  institutions
• Total cost for independent investigator phase may
  not exceed 249,000 per year
• Institution must demonstrate commitment to
  candidate (minimum 75 effort, space, etc.)
• PI expected to apply for independent research
  grant support

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From application to review - The Black Hole of NIH
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Lighting Up The Black Hole of NIH Grants

• NIH (National Institutes of Health) (www.nih.gov)
  (www.niehs.nih.gov)
• 27 Institutes and Centers
• - issue FOAs
• - can help you in the process of writing your
  application
• CSR (Center for Scientific Review)
• - this is where your completed application gets
  reviewed
• ? 20 IRGs (Integrated Review Groups)
  (www.csr.nih.gov/review/IRGDESC.asp)
• ? 250 Study Sections (http//www.csr.nih.gov/Co
  mmittees/rosterindex.aspA)

Program Officers (very important!)
SRAs (Scientific Review Administrators)
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Who is a Program/Project Officer (PO)?

• Each institute / center has a number of POs with
  different areas of expertise
• Each FOA identifies one or more POs
• PO is a scientist and administrator
• manages grants, contracts, cooperative
  agreements
• identifies needs in scientific areas
• identifies scientific areas of special interest
  and communicates the interest (ie, writes FOA)
• monitors scientific progress and reports program
  accomplishments
• advocates for the best science

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How can Program/Project Officer help you?

• Talk with a PO before you start writing an
  application
• Is your project interesting for the institute?
• Is it appropriate for the FOA?
• Is the mechanism appropriate for your career
  level?
• Talk with your PO as you are working on the grant
• Get feedback on specific aims
• Establish a good working relationship
• You want the PO to be on your side
• The PO can help you with post-review revisions
• They are present when your proposal is discussed
• can provide helpful information on top of your
  written reviews

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What Makes for a Competitive Application?

• Hypothesis driven.
• Technically feasible and within your expertise
  (or with support from your mentor). 2 3
  related publications always a plus.
• Not overly ambitious.
• Novel, exciting but not too controversial.
  Challenging an existing paradigm is good, but do
  it to advance the science, not to prove wrong or
  disparage other investigators.
• Convince reviewers that what you propose to study
  is a recognized and important topic.
• READ THE NIH ROADMAP!!!! Whats hot or of
  priority?
• Make sure your proposed research has
  disease-relevance or potential for translational
  studies (for NIH).

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NIH Is Going Electronic

• Learn the Electronic Research Administration
  (eRA) system!
• NIH eRA Commons (https//commons.era.nih.gov/comm
  ons)
• how grants are submitted
• reviewers submit their reviews
• you can find information related to your
  application

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Deciding a Review Panel for Your Grant

• It is a good idea to suggest a specific review
  panel for your grant
• Search the CSR web for descriptions of the
  science addressed by the various study sections
• Search the Study Section rosters
• Try to find one within a relevant IRG with 2 3
  names that you recognize as having expertise in
  your area
• Seek advice from others in your field
• Speak with a Program Officer(s) and the SRA(s)!
• ! Write a cover letter requesting assignment to
  the NIH institute and Study Section you are
  targeting.

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More about the Review Panel

• Your proposal will be reviewed by 2 or 3 fellow
  scientists.
• Primary, Secondary, Reader(s) (Discussant)
• Each reviewer will be assigned about 8 12
  proposals. They do their reviews evenings,
  weekends, last minute
• Probably one reviewer will have direct expertise
  in the area of your proposal
• The fate of your application can and probably
  will be determined by the most informed (or most
  biased) and the most eloquent of the reviewers

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Your Challenge is to

• Help the reviewers grasp the essence of your
  project from the Specific Aims page within 10
  minutes.
• Make sure the reviewers can understand the whole
  of the project during 2 3 hours of interrupted
  study.

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Reviewers What do they have to do?

• Before the meeting rank the proposals.
• Write a detailed critique of each proposal they
  were assigned.
• Formulate and communicate a critique and a
  preliminary score.
• At the study section meeting, discuss the
  proposal, and achieve consensus with fellow
  reviewers.
• Submit a final score.

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NIH Criteria for Evaluation

• Significance
• Approach (75)
• Innovation
• Investigator
• Environment
• Overall Evaluation

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Study Section
Your application
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Scores and What They Mean
Range is 1 5 (actually 100 500). Descriptors
were linked to priority score ranges.

• 1.0 - 1.5 Outstanding
• 1.5 - 2.0 Excellent
• 2.0 - 2.5 Very Good
• 2.5 - 3.0 Good
• Streamlined
• (lower half, unscored, triaged)

• Wow
• Exciting
• Fixable
• Boring (needs major work)
• Fundamental Problems

Under todays budgets and funding priorities, one
has to take a new view of streamlined grants. It
used to be a kiss of death but now there are
uncertainties due to how study sections are
scoring applications.
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Translating the Scores
Funding is based on the percentile, not the
priority score
Priority Score 140 160 180 200 250 280
Old Percentiles 0.8 4.0 11.3 23 40 56
New Percentiles 5.5 14.0 23 32 52 58
The relationships among the score, percentile and
funding level depends on the specific NIH
institute, the review cycle, and the NIH budget.
The percentile is calculated on an average of
voting for 3 review cycles.
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So Now You Want to Write a Grant Application
How long will it take?

• The typical R01 takes ? 4 8 weeks and ? 20-40
  hr/wk in writing time to finish.
• Total preparation time takes about 4 months.
• It requires PLANNING!
• Your very first duty is to turn on the Create
  Back Up File under tools options save! Set
  auto-save to every 5 min helps

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The Structure of the Application
Two Parts Administrative Science

• Administrative (http//grants1.nih.gov/grants/f
  orms.htm)
• Budget and Budget Justification (Modular)
• Biosketches for all key personnel. (4 pages,
  includes other support)
• IRB (make sure that all issues addressed)
• Letters of collaboration, consultation.
• Letters of support from mentors if
  training-related.
• Especially if a new investigator, letter of
  support from your Chair to document departmental
  / institutional commitment.

Finish all admin components 3 wks before deadline!
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Grant Etiquette

• Prepare a draft of letters for consultants and
  send it in plenty of time so they can get it back
  to you.
• If you request input from colleagues and it is
  critical be open-minded and dont argue!
• Give your colleagues a copy of the grant that is
  submitted and be sure to thank them.

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The Science - Focus the reviewers on the science
and not on a distracting hap-hazard presentation.

• Develop and describe ideas and facts clearly, in
  straightforward English. Get help if you need
  it. Let many people read your proposal and
  incorporate their feedback.
• If you have special terminology, explain and
  define it up front. Dont make up confusing
  abbreviations. (NOS ? Nutrient Overload Syndrome)
• Minimize the use of I, we, and us.
• Minimize use of prepositional phrases. (The focus
  of this proposal from us is to begin to study the
  effects of free radicals on the biochemistry for
  which little is known about events that ensue
  from consumption of omega-3 fatty acids by a
  subset of people.)

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The Science How can you help the reviewers
concentrate on the science and not be distracted
by the presentation

• Limit use of qualifiers, no more than one per
  sentence. (e.g., may, perhaps, possibly, etc.)
  (It may be that perhaps the effect is due to a
  possibly unknown factor which at this current
  time probably cannot be fully or partially
  explained.)
• Write in a positive style, be assertive.
• (The reason remains undefined.)
• There is a 25 page limit for R01 (less for
  smaller grants). If you go over, do not change
  the font or remove spacing! Edit your verbosity.

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The Science How can you help the reviewers
concentrate on the science and not be distracted
by presentation.

• Earn good-will by doing the reviewers a few key
  favors. Use a 12 point font and aim for at least
  one page less than the limit.
• Use schemes, cartoons, colorful figures, bold
  headings, paragraph breaks (3 or 6 pt) to break
  up the text and help simplify and organize
  concepts
• Clearly explain complex ideas. Avoid telepathy.
  Remember, reviewers dont know your stuff as well
  as you do

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The Science How can you help the reviewers
concentrate on the science and not be distracted
by presentation.

• Vary the appearance of your pages. Help
  highlight points and break up text via the
  careful use of italics, color, and bullet points.
  Do NOT overdo.
• Make your legends and titles informative. Use a
  bold font for these to help the reader.
• Make absolutely sure that the legends and figure
  labels can be read easily. Cramming in lots of
  text by using small fonts will only help you get
  a worse score.

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Specific Aims
This page is the blueprint for the proposed
research plan It is the most important part of
the application.

• ONE PAGE ONLY!
• Define the problem and key issues first.
• Briefly state the background and rationale (can
  be based on preliminary data) for the hypothesis.
  
• State a clear, succinct, focused, and testable
  hypothesis which stems from the information
  above. Put in bold font.
• List 3 5 one sentence Specific Aims which are
  obvious tests of the hypothesis. Brief
  experimental approaches can be included.
• Finish with a significance statement, i.e., what
  the study means and will reveal if completed.
  The project should have relevance to a human
  health issue.

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Regarding Significance / Impact

• Will original and important contributions be
  made?
• Will the proposed studies change the view of a
  scientific issue or clinical problem?
• Fundamental science and/or clinical relevance
  is important. Be sure to highlight disease
  relevance.
• Studies viewed as observational, correlative,
  phenomenology, fishing expeditions, simple data
  gathering, etc., dont fly.

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Background and Significance

• Refer to and analyze relevant literature with
  current citations.
• Compose short paragraphs to one-half page
  sections with a boldface heading. Use schemes to
  simplify concepts/paradigms.
• Lay the foundation for your preliminary studies
  and experimental aims (establish their
  significance). If you base a statement on your
  preliminary studies, cite page and figure ).
• Identify (diplomatically) gaps in knowledge and
  discrepancies in the literature.
• Summarize key issues and gaps in knowledge that
  you will address in the proposal. Bold, numbered
  or bulleted

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Preliminary Studies
A principal goal of Preliminary Studies is to
provide support for your hypothesis and your
capabilities to perform the proposed work Does
this person walk the walk and talk the talk?

• Show key data using challenging methodologies.
• Preliminary does not mean below publication
  quality!
• Summarize your recent research in 3 5 points.
  Outline what is coming up.
• Say why you are showing specific data. (E.g., a
  key finding that supports your hypothesis,
  documents the workability of a new method,
  demonstrates feasibility to perform the
  experiments, etc.)
• Dont waste space, waste the reviewers time, or
  confuse key issues by showing irrelevant data.

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Research Design and Methods
Experimental Plan (Sequentially organize
Specific Aims) For each Aim Restate Specific
Aim A. General approach and rationale B.
Specific experimental approach C. Methods
(global ones can be grouped first or last) D.
Anticipated results E. Potential pitfalls and
alternative approaches Statistical
Analysis Timetable
Should be at least 10 of your 25 pages.
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Research Design and Methods
Anticipated Results and Potential Pitfalls

• Note what you expect to observe and how these
  results will fill a gap in our understanding of
  this subject.
• Acknowledge potential weaknesses and technical
  limitations in the experimental plan. Be
  introspective and forthright.
• Do not state Since weve already done this
  lots of times before, we anticipate no problems
  with the proposed studies.
• Propose alternative approaches to test or
  circumvent weaknesses, limitations, and
  surprising results.

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The Reviewers Perspective and Written Comments

• Does the application address an important
  question?
• Will it yield new insight to a specific problem?
• Is the proposal disease-related and can the
  results support future translational studies?
• Is there a focused, testable hypothesis?
• Do the experimental design and technical
  approaches test the hypothesis?
• Is the experimental plan logical and cohesive?
• Be wary of one aim being dependent on the
  success of another.
• Are appropriate experimental models (reactions,
  cells, animals, subject populations) used?
• Are methods / analyses / reagents properly
  developed?

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The Reviewers Perspective and Written Comments

• Is the project feasible? (Can the applicants
  accomplish what they propose?)
• Are there preliminary data that supports key
  concepts and methodologies?
• Are there supporting data / publications
  utilizing challenging experimental approaches?
• Does the applicant have the technical resources
  (reagents, instrumentation, techniques, animal
  models, etc.) and institutional commitment to
  accomplish the proposed studies.
• Is the training and track record of the PI and
  Co-Investigators appropriate and sufficient to
  accomplish the stated goals?
• Has the PI thoroughly addressed human/animal,
  biosafety, etc., issues?

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.really dont want that grant funded?

• Let NIH assign your grant.
• Mislabel figures and tables or dont include any
  at all.
• Make legends cryptic or too small, since they are
  taking up valuable text space.
• Propose studies using reagents that you do not
  have and are challenging to generate.
• Ignore the importance of statistical analysis
  procedures in study design and data interpretation

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So you REALLY dont want to be funded?

• Dont include potential pitfalls, alternative
  approaches, or interpretations of the experiments
  you propose.
• We do not envisage any problems with the
  proposed studies.
• Letters of support everyone knows they are
  drafted by the PI anyways, so why bother?
• Take complete inspiration from your mentors
  R01 dont worry, neither your mentor nor the
  study section will notice.
• In a revision, respond to only the reviewers
  comments you agree with. Also, be sure to add
  new specific aims when not prompted by the review.

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The Submission, Review, Resubmission Cycle
1st Submission Feb, June, Oct. Revised
March, July, Nov. Only 3 submissions allowed
(Initial and two revisions)
Jul 06 Start Work
Oct 06 Submit
Feb/Mar 07 Review
May 07 Pink Sheets
Jul 07 or.. Resubmit
Oct 07 2nd Review
Apr 08 Start Date
If you get streamlined on the initial submission
Oct 06 Submit Mar 07 Review (triage) Jul
07 Resubmit Oct 07 Review (12 not funded) Nov
07 Resubmit Feb 08 Review Jul 08 Start
If your 2nd revision requires extensive further
work
Jul 08 Resubmit Oct 08 Review Apr 09 Start
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Useful Websites

• NIH (http//www.nih.gov/)
• CRISP (Computer Retrieval Information on Specific
  Projects) - search for abstracts of funded
  projects (http//www.crisp.cit.nih.gov/)
• Office of Extramural Research (http//grants1.nih
  .gov/grants/)
• Program Announcements (http//grants.nih.gov/grant
  s/guide/pafiles/index.html)
• CSR (http//www.csr.nih.gov/)
• Search for grant opportunities
  (http//fundingalert.cos.com/helptoc.shtml)