Developing and Submitting an NIH Grant Application

1
Developing and Submitting an NIH Grant
Application

• Steven O. Moldin, Ph.D.
• DC Office of Research Advancement
• Office of the Vice Provost for Research
  Advancement
• September 27, 2006

2
Course Objectives

• Familiarity with NIH organizational structure
• Identification of NIH Institute priorities
• Understanding NIH grant programs (mechanisms)
• Clarification of submission review process
• Advice on building relationships
• Advocacy tips

3
NIH Organizational Structure

• Largest agency of Department of Health Human
  Services (DHHS)
• Headquarters Office of the Director
• NIH organized into 27 institutes centers
• One center conducts most NIH peer reviews
• Two centers support intramural activities
• 24 institutes provide extramural research support
• Organized according to disease focus

4
NIH Organizational Chart
OD
CC
CSR
ICT
NCRR
NCMHD
NCCAM
FIC
NEI
NCI
NIAID
NHLBI
NIDA
NIDCR
NIDDK
NIA
NIAAA
NIGMS
NIMH
NIDA
NINR
NHGRI
NIDCD
NIEHS
NICHD
NIAMS
NINDS
NIBIB
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NIH Institutes Centers

• NCI Cancer
• NHLBI Heart, Lung Blood
• NIDDK Diabetes Digestive Kidney Diseases
• NIDA Drug Abuse
• NIAAA Alcohol Abuse Alcoholism
• NIBIB Biomedical Imaging Bioengineering
• NINR Nursing Research

• NIA Aging
• NICHD Child Health Human Development
• NIDCD Deafness Other Communication Disorders
• NIAID Allergy Infectious Diseases
• NEI Eye Institute
• NHGRI Human Genome Research
• NIMH Mental Health

6
NIH Institutes Centers

• NLM National Library of Medicine
• NCMHD - National Center on Minority Health
  Health Disparities
• NCCAM National Center for Complimentary
  Alternative Medicine
• CSR Center for Scientific Review
• CC Clinical Center
• CIT Center for Information Technology
• OD Office of the Director

• NIAMS Arthritis Musculoskeletal Skin
  Diseases
• NIDCR Dental Craniofacial Research
• NINDS Neurological Disorders Stroke
• NIEHS Environmental Health Sciences
• NIGMS General Medical Sciences
• FIC Fogarty International Center
• NCRR National Center for Research Resources

7
National Institutes of HealthFY 2006 Budget, Top
10 ICs
Total NIH Budget, 28.59 Billion
8
NIHs Electronic Receipt Goal

• By the end of September 2007, NIH plans to
• Require electronic submission through Grants.gov
  for all NIH grant applications
• Transition from the PHS 398 application form to
  SF424 (RR)

Announced in the NIH Guide, Aug. 19, 2005
http//grants.nih.gov/grants/guide/notice-files/NO
T-OD-05-067.html Modification to the timeline
announced Feb. 7, 2006 http//grants.nih.gov/grant
s/guide/notice-files/NOT-OD-06-035.html
9
NIH Planned Transition Dates of Mechanisms for
Electronic Submission Using the SF424 (RR)
Resource (G7, G8, G11, G13, G20), Career
Development (K), S11, S21, S22 (Jun. 1, 2007)
SBIR/STTR (Dec. 1, 2005)
R13/U13 (Dec. 15, 2005)
R18/U18, R25, C06/UC6 (Oct. 1, 2006)
Fellowship (F) (Aug. 5, 2007)
R36 (Feb. 17, 2006)
Potential R01 Multi-PI Pilot (Oct. 1, 2006)
R15 (Feb. 25, 2006)
Training (TD), U45, D71/U2R (Sep. 10, 2007)
S10 (Mar. 22, 2006)
X02 (April 18, 2006)
DP1(Jan. 22, 2007)
X01 (May 18, 2006)
Project/Center (P), G12, M01, S06, R10/U10, U01,
U19, U54, U56, R24/U24 (Oct. 1, 2007)
R01(Feb. 1, 2007)
R03, R21/R33, R34(June 1, 2006)
03
10
08
10
08
12
11
05
07
12
09
01
02
03
04
05
01
02
04
06
06
07
09
2006
2007

• Current as of February 2, 2006. Visit the Web
  site for the latest version http//era.nih.gov/El
  ectronicReceipt/

Mechanism Abbreviation Key C06/UC6 Research
Facilities Construction Grants DP1 NIH Directors
Pioneer Award Program D71/U2R International
Training Cooperative Agreement/
Phase 2 of FIC mechanism D71 R01
Research Project Grant Program R03
Small Grant Programs R10/U10 Cooperative
Clinical Research Grants R13/U13 Support for
Conferences Scientific Meetings R15
Academic Research Enhancement Awards
(AREA) R18/U18 Research Demonstration and
Dissemination Projects
R21/R33 Exploratory/Development
Research R24/U24 Resource Related Research
Projects R25 Education Projects R34
Clinical Trial Planning Grant Program R36
Research Dissertation Grant Program SBIR
Small Business Innovation Research STTR
Small Business Technology Transfer S06,S10,S11
Biomedical Research S21,22 Health Disparities
Endowment Grants U Cooperative
Agreement Awards X02 Preapplication
10
What are NIHs Research Priorities?

• Before you start writing, is what you want to do
  of interest to NIH?
• What science is of interest to NIH?

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Broad Scientific Areas of Interest to NIH

• Research of direct or strong indirect relevance
  to understanding and preventing disease
• Research on basic biological and psychological
  processes of potential interest if there is
  disease relevance

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NIH Research Priorities

• Solicitated applications
• NIH Roadmap
• Strategic Plan for Obesity Research
• Neuroscience Blueprint
• Biodefense
• Vaccine development
• Genomics
• Bioinformatics/bioengineering
• Unsolicited applications
• Institute priorities
• Government priorities

16
NIH Roadmap

• Framework for NIH priorities
• Vision for biomedical research
• Big Science
• Solicited research proposals in key areas
• Three major initiatives

17
NIH Roadmap Initiatives

• New Pathways to Discovery
• Building Blocks, Biological Pathways Networks
• Molecular Libraries Molecular Imaging
• Structural Biology
• Bioinformatics Computational Biology
• Nanomedicine

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NIH Roadmap Initiatives

• Research Teams of the Future
• High Risk Research
• Interdisciplinary Research
• Public-Private Partnerships

19
NIH Roadmap Initiatives

• Re-Engineering the Clinical Research Enterprise
• Clinical Research Networks
• Clinical Research Policy Analysis Coordination
• Clinical Research Workforce Training
• Dynamic Assessment of Patient-Reported Chronic
  Disease Outcomes
• Translational Research

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NIH Research Outcome GoalsHigh Risk
 
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NIH Research Outcome GoalsModerate Risk
5a By 2007, evaluate the efficacy of three new
treatments strategies for HIV infection in phase
II/III human clinical trials in an effort to
identify drugs that are more effective, less
toxic, and/or simpler to use than the current
recommended HIV treatment regimen. 5b
Establishing the efficacy of statins in
preventing progression of atherosclerosis in
children with Systemic Lupus Erythematosus (SLE
or lupus).  5c Expand the range of available
methods used to create, analyze, and utilize
chemical libraries, which can be used to discover
new medicines. Specifically, use these chemical
libraries to discover 10 new and unique chemical
structures that could serve as the starting point
for new drugs.  5d By FY 2007, identify 20 small
molecules that are active in models of nervous
system function or disease and show promise as
drugs, diagnostic agents, or research tools.
 
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NIH Research Outcome GoalsLow Risk
 
23
Deciphering NIH Grant Mechanisms

• Over a hundred different types of grant programs
  (mechanisms)
• Several have Institute-specific criteria
• Major categories
• Fellowship Programs
• Research Career Programs
• Research Program Projects Centers
• Research Projects
• Institutional Training Programs
• Cooperative Agreements
• Research and Development-Related Contracts

24
Popular Grant Mechanisms

• Fellowship Programs
• F31 Predoctoral Individual National Research
  Service Award
• F32 Postdoctoral Individual National Research
  Service Award

• Research Career Programs
• K01/K02 Research Scientist Development Awards
• K05 Research Scientist Award
• K07 Academic/Teacher Award
• K08 Clinical Investigator Award
• K12 Physician Scientist Award
• K18 Career Enhancement Award
• K20/K21 Senior Development Awards
• K22 Career Transition Award
• K23 Mentored Patient-Oriented Research Career
  Development Award
• K24 Midcareer Investigator Award in
  Patient-Oriented Research

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Grant Mechanisms

• Research Projects
• R01 Research Project
• R03 Small Research Grant
• R21 Exploratory/ Developmental Grants
• R41/R42 Small Business Technology Transfer
  (STTR) Grants
• R43/R44 Small Business Innovation Research
  Grants (SBIR)

• Research Program Projects Centers
• P01 Research Program Projects
• P20 Exploratory Grants
• P30 Center Core Grant
• P50 Specialized Center

26
NIH Career Development Awards

• Grant to do research on small scale and obtain
  training in scientific area
• Mentored v. nonmentored awards
• Basic v. clinical research
• Traditionally easier to get than traditional
  Research Project (R01) award BUT
• http//grants1.nih.gov/training/careerdevelopmenta
  wards.htm

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NIH Grant Mechanism Timetable
Approx. Stage of Research Training and
Development
Mechanism of Support

Predoctoral Institutional Training Grant (T32)
GRADUATE/ MEDICAL STUDENT
Predoctoral Individual NRSA (F31) Predoctoral
Individual MD/PhD NRSA (F30)
Postdoctoral Institutional Training Grant (T32)
Postdoctoral Individual NRSA (F32)
POST DOCTORAL
Mentored Research Scientist Development Award
(K01) Mentored Clinical Scientist Development
Award (K08) Mentored Patient-Oriented RCDA
(K23) Mentored Quantitative RCDA (K25)
EARLY
Small Grant (R03) AREA Grant (R15)
CAREER
Independent Scientist Award (K02)
MIDDLE
Research Project Grant (R01)
Midcareer Investigator Award in
Patient-Oriented Research (K24)
Exploratory/Developmental Grant (R21)
SENIOR
Senior Scientist Award (K05)
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Number of NIH K AwardsFiscal Years 1994 - 2005
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NIH Research Projects

• R01 grants Unsolicited (investigator-initiated)
  grants from one or more labs
• Cornerstone of NIH funding
• Reflect scientists interests, assessment of the
  field, and feasibility
• R03 grants Small, self-contained research
  projects feasibility
• R21 grants High-risk / high-return
• Time and dollar limits Institutes differ
• Less stringent need for preliminary data
• R41/R42, R43/R44 grants Small businesses
• SBIR small business, commercialization
• STTR same, with a university component
• Phases (1, 2, fast-track)

32
FY 2006 AppropriationTotal NIH Budget
Authority28.578 Billion
33
The NIH Grant Code

• Whats with all those numbers?
• 1 R01 NS012345-01A1
• Type (1,5,2 new, non/competing renewal)
• Mechanism
• Institute
• Serial number
• Year
• Revision status/supplement (if applicable)

34
How Does an Application Get Funded?

• Application submitted to CSR
• Regular receipt date (unsolicited apps)
• Special receipt date (solicited apps)
• Application assigned to Institute for funding
  consideration
• Application assigned to peer review committee
• Multiple levels of review
• Grants Management Office of Institute collects
  necessary information

35
NIH Grants and ContractsUnsolicited Applications

• Traditional bread butter NIH grant support
• Regular receipt deadlines
• Review by pre-existing (standing) review
  committees (typically CSR)
• Increased likelihood of success if fits in with
  Institute priorities
• NIH permission needed if budget exceeds 500K in
  any one year

36
Submitting an Unsolicited Grant Application

• Assignment to Institute for funding consideration
• Assignment to particular review committee

37
You Have Control

• Receipt and Referral
• All NIH grant applications sent to CSR
• CSR assigns them to Institutes and peer review
  committees
• Based on referral guidelines /or PI request in
  a cover letter /or an ARA from Program staff
• You can request which Institute program you
  want to be assigned for funding consideration
• Letter to CSR contact with Program official
• You can request which committee you want to
  conduct the peer review
• Letter to CSR contact with Program official

38
Multiple Levels of Evaluation

• Peer review, scientific review committee
• Members drawn from extramural scientific
  community
• Major effect on probability of being funded
• Approval of review, Scientific Advisory Council
• Each institute has its own Council
• Members drawn from extramural scientific
  community
• Nonscientific members
• Typically, minimal effect on probability of being
  funded
• Program evaluation
• Evaluation for agreement with Institute
  priorities
• Greatest effect on probability of being funded

39
Understanding the Review System

• Critical difference between program and review
  staff firewall between the two
• Program staff make funding decisions
• Former scientists, specific areas of expertise
• Based at individual Institutes
• Take Institute priorities, review scores into
  account
• Review staff Scientific Review Administrators
  (SRAs)
• Former scientists who coordinate study sections
  at CSR or within Institutes
• Oversee standing review committees or special
  emphasis panels (SEPs)
• Based at CSR or individual Institutes

40
Review and Award Cycles
41
Dates to Remember

• Process Takes 10-12 Months check deadlines
• http//grants.nih.gov/grants/funding/submissionsch
  edule.htm
• February 1, June 1, October 1
• Unsolicited applications
• No exceptions, stricter enforcement - NEW
• Revised applications, competing continuation
• March 1, July 1, November 1
• Training
• Institute proposals due earlier, individual apps
  later

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NIH Grants ContractsSolicited Applications

• Request For Applications (RFA)
• Set-aside
• Special review
• Special deadline
• Program Announcements (PA)
• Typically no set-aside
• Typically regular receipt dates apply
• Typically review is by standing committees
• PAS for some grants above payline
• PAR specific review
• Cooperative Agreements (Us)
• Significant government participation
• Clinical Trials, Translational grants
• Request for Proposals (RFP)
• Contract solicitation
• Acquisition govt buys a product

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General Peer Review Criteria

• 5 criteria for most NIH applications
• Significance problem, results, methods,
  concepts
• Approach conceptual framework, hypotheses,
  design, appropriate analyses, feasibility
  (preliminary results), methods, overall
  integration, potential problems
• Innovation aims, concept, methods
• Investigator training, suitability, experience
• Environment quality, uniqueness, institutional
  support
• Additional criteria
• New PI, Animals Human Subjects, Data-Sharing
  Plan

44
Specific NIH Review Criteria

• Significance Does this study address an
  important problem? If the aims of the application
  are achieved, how will scientific knowledge be
  advanced? What will be the effect of these
  studies on the concepts or methods that drive
  this field?
• Approach Are the conceptual framework, design,
  methods, and analyses adequately developed,
  well-integrated, and appropriate to the aims of
  the project? Does the applicant acknowledge
  potential problem areas and consider alternative
  tactics?
• Innovation Does the project employ novel
  concepts, approaches or methods? Are the aims
  original and innovative? Does the project
  challenge existing paradigms or develop new
  methodologies or technologies?
• Investigator Is the investigator appropriately
  trained and well suited to carry out this work?
  Is the work proposed appropriate to the
  experience level of the principal investigator
  and other researchers (if any)?
• Environment Does the scientific environment in
  which the work will be done contribute to the
  probability of success? Do the proposed
  experiments take advantage of unique features of
  the scientific environment or employ useful
  collaborative arrangements? Is there evidence of
  institutional support?

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Additional Considerations

• Protection of human subjects from research risk
• The involvement of human subjects and
  protections from research risk relating to their
  participation in the proposed research will be
  assessed.
• Inclusion of women, minorities and children in
  research
• The adequacy of plans to include subjects from
  both genders, all racial and ethnic groups(and
  subgroups), and children as appropriate for the
  scientific goals of the research will be
  assessed. Plans for the recruitment and retention
  of subjects will also be evaluated.
• Animal welfare
• Express any comments or concerns about the
  appropriateness of animal welfare procedures.
  Animals should be confined, restrained,
  transported, cared for, and used in experimental
  procedures in a manner to avoid any unnecessary
  discomfort, pain, or injury.
• Budget
• The reasonableness of the proposed budget and
  the requested period of support in relation to
  the proposed research.

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Ranking and Priority Scores

• 2-3 assigned reviewers discuss a grant, and
  may be the only ones who read it
• All reviewers (30) vote on all grants, based on
  discussion at the meeting
• If its not in the 25 pages, they dont have to
  read it (appendices, and last minute data)
• Grants are scored from 1.0 (best) - 5.0 (worst)
• Reviewers should unscore half of all grants
  spread scores. You still get the written
  reviews
• Unscored Dont Panic! Often fixable, wait for
  comments

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Good Grantsmanship Principles for Success

• Understand the Agency Mission
• Understand Peer Review
• Secure collaborators for areas in which
• you lack experience and training
• There are no competitors in science, there are
  only potential collaborators.
• Grant writing is a learned skill
• Grantsmanship is a full time job
• You are in control of your life

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Priority Scores

• Scores are percentiled against grants in the
  CSR base
• The percentile is typically what counts
• Relative to an Institutes payline
• Paylines differ, as do their policies for funding
  any or all grants above or below it
• Some mechanisms only have priority scores
• Reviewers also comment on budget years
• They can cut Program may need to cut also

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A Few Last Points on Review

• Program staff can attend reviews, but cant
  influence reviewers
• You will be sent a score and percentile after
  review SRAs release summary statements in 6-8
  wks
• (They are NOT available to Program till then,
  either)
• USE https//commons.era.nih.gov/commons/ !!
• You can request (with good reason) that someone
  not review your grant, but cant suggest
  reviewers

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Try, Try Again

• Paylines leave some flexibility
• Grants (esp. near payline) may be selected for
  HPP
• Try not to get discouraged appeals rarely help
  unscored is not the end of the world
• Wait till you see the summary sheets
• Revised applications later due date include an
  introductory section to address changes. This
  response is important
• You have up to 3 tries (no time limit anymore)

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NIH Funding StatsResearch Project Grants

• In FY 2005, NIH
• Reviewed Awarded Success
  Rate
• New 35,874 6,739 18.1
• Continuation 7,025 2,809 40.0
• Competing Supp. 170 51 30.0
• ____________________________________
• Totals 43,069 9,599 22.3

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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

45
44
44
44
43
42
42
MD-PhD
41
MD
Average age
40
40
39
PhD
38
38
37
37
36
35
1980
1981
1982
1983
1984
1985
1986
1987
1988
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
Fiscal Year
53
New Investigators

• Havent been PI on a PHS-supported grant
• Except R03, Fs, mentored K-awards, AREAs
• Check the box on the face page, put it in
  biosketch
• Reviewers should keep in mind limited experience
  and resources (some actually do)
• Emphasis on demonstrating techniques, not track
  record training, potential, institutional
  commitment
• New PIs are often over-ambitious FOCUS
• Reality check with colleagues, Program Staff

54
Percentage of New Investigators in Competing R01
Awards Continues to Decrease FY 1962 - FY 2003
100
Established Investigator
80
60
40
New Investigator
20
0
1963
1967
1971
1975
1979
1983
1987
1991
1995
1999
2003
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Budgets Modular vs. Non-

• Modular Not over 250,000 in any year
• 25,000 modules justify personnel equipment
• Justify timeline, animals in the experimental
  design
• Be REALISTIC - ask for enough to do the work
• Cuts Review and Administrative
• Non-modular gt250K, supply full budget detail
• Administrative cuts are higher
• gt500K you must notify Program 6 wk before
  deadline

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How to Write Your Proposal

• There are several outstanding Web sites devoted
  to tips
• Develop your strategy carefully - dont rush the
  application
• Publish the papers--submit the best application
  you can
• Have funded colleagues read your drafts
• Look for cite relevant Program Announcements
• If you have questions, ask Program Staff

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Advice Writing the Proposal

• Abstract and Specific Aims clearly state what
  you propose to do - why and how, without
  distracting detail
• State hypotheses clearly and design clear answers
  from your experiments
• Address interesting and significant issues
• Make the design win-win by assuming the worst
• Develop alternative strategies for potential
  problems
• Preliminary Data prove you can do the work,
  analyze the results, and draw sound conclusions
• Avoid being overly ambitious

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Advice Writing the Proposal

• Make it easy for the primary reviewer
• S/he will present your case
• Clear significance, fair literature review
• Clear and sound hypotheses
• Demonstrate productivity and feasibility
• Logical experimental design
• Avoid Aims that may make next step impossible
• Dont assume they know what you mean, tell them
• Make it sexy
• Present it in readable, attractive format
• Spell check avoid too many acronyms

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New Direction in Autism Research
Neuroimaging The autistic brain is no longer a
black box
Structure Function Chemistry Connectivity
60
Clinical Studies and Trials

• Clinical studies involve additional policies
• Human subject means a living individual about
  whom an investigator (professional or student)
  conducting research obtains (1) data through
  intervention or interaction with the individual,
  or (2) identifiable private information. be
  aware of HIPAA
• Inclusion of Women and Minorities must be
  addressed
• Office for Human Research Protections regulates

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Critical Relationships to Build

• Program Staff funding decisions
• Review Staff scientific review

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Advocacy Tips

• Make sure there is close match between your
  research Institute priorities
• Work with Program Staff early
• Identify right person
• Respect hierarchy
• Get advice
• Build enthusiasm enlist him/her as your
  advocate
• Send papers, data
• Avoid at all costs pressure, manipulation,
  shameless self-promotion

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Summary

• Identify work with Program Staff
• Direct app to Institute and program
• Direct app to review committee
• Write best proposal you can tightly focused,
  sexy
• Enlist program staff as your advocate
• Be patient and tenacious

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Helpful Websites

• NIH - www.nih.gov
• NIH peer review
• www.csr.nih.gov/review/peerrev.htm
• www.csr.nih.gov/review/irgdesc.htm
• NIH Guide for Grants Contracts
• grants.nih.gov/grants/guide/index.html

65
How to Write a Grant Application http//grants2.n
ih.gov/grants/grant_tips.htm http//www.niaid.nih
.gov/ncn/grants/ http//www.nnlm.nlm.nih.gov/scr/e
dn/grants-resources.htm http//www.nigms.nih.gov/f
unding/tips.html http//www.nigms.nih.gov/funding/
moregrant_tips.html http//deainfo.nci.nih.gov/EXT
RA/EXTDOCS/gntapp.htm http//12.46.245.173/cfda/cf
da.html http//cpmcnet.columbia.edu/research/writi
ng.htm
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And one final assertion
One of the chief causes of poverty in science is
imaginary wealth. The purpose of science is not
to open the door to an infinitude of wisdom but
to set some limit to the infinitude of error.
Brecht, Life of Galileo
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DC Office for Research Advancement

• Additional questions, advice
• Dr. Steven Moldin
• moldin_at_usc.edu