Grantsmanship and Navigating through the NIH

William C. ParksDirector, Center for Lung Biology

Department of MedicinePulmonary and Critical Care Medicine

University of Washington School of MedicineSouth Lake Union Research Center

What’s the Big Deal with NIH Grants?

• The major source of research dollars in US• Extramural budget. 2003: $27.173 billion

2004: $28.028 billion (3.1%)2005: $28.757 billion (2.6%)2006: $28.845 billion (0.7%)

• The gold standard of extramural funding

• Essential for advancement and promotion

• Most important: Indirect Costs: $1 = $0.52

Significant Growth in the Last Decade

Top Recipients of Taxpayers Largesse

•JHU•UW •Penn•UCSF•Science Applications

International Corp.*•Wash U•U Mich•UCLA•Pitt•Duke *1 contract, ~$300 mil

Top 10 - 2005

• 2816 institutions/companies/organizations ranked• #2814 ($1):New York City Technical College

Stillman College, ALSouth Bank University, London

*

*~2,000 Submitted

NIH Funds at UW50% of Research Funds at UW Come from the NIH

Appropriations

CancerHeart, Lung & Blood

Diabetes, Digestive, Kidney

Allergy & Infectious Dis.Neurol. Disorders & Stroke

Research Resources

General Med. Sci.Child Hlth. & Human Dev.

Deafness & Communication Disorders

Appropriations

The Bulk of NIH Funds Fund Extramural Research

Most Extramural NIH Funds Support Research Grants

Bye-bye Growth

Paylines at NIGMS

Whose Getting the Grants?

Middle-age to Old PhDs in Basic Science Departments

Award Mechanisms

• Training Awards (Apr, Aug, Dec)• F32 (NRSA): 0-7 yrs post MD or PhD

• Career Development Awards (K’s) (Feb, Jun, Oct)• K01: Mentored Research Scientist (Ph.D.)• K08: Mentored Clinical Scientist (M.D., M.D./Ph.D.)• K23: Mentored Patient-Oriented Research• K99/R00: Pathway to Independence• Several others• Institute-specific rules.

• Investigator Initiated Awards (Feb, Jun, Oct)• R03: Small Research Grants - innovative, high-risk ($50K/yr, 2 yr)• R23: Exploratory and Development Grants• R01: Independent Research Grants - 3-5 yr, renewable, variable budgets• Multi-PI Grants

• Roadmap Initiatives

New Investigator

• Not previously a PI on any PHS-supported research project other than on a• Small grant (R03)• Academic Research Enhancement Award (R15)• Exploratory/developmental grant (R21)• Certain research career awards directed principally to physicians,

dentists, or veterinarians at the beginning of their research career (K01, K08, and K12).

• Recipients of Independent Scientist and other non-mentored career awards (K02, K04) are not new investigators.

• Breaks for Young Investigator (NHLBI)• Separate payline 5 points higher• Fund all 5 years• Expedited review if missed payline by 5 points or less

Grant Preparation

• Formulate your ideas: testable hypothesis that advances a field• Establish your independence (R series)• Generate preliminary data

• Supports hypothesis• Confirms feasibility

• Seek mentoring and advice• Advisory committee• Read successful applications!• Seek advice

• Enlist collaborators, consultants• Special reagents, techniques, advice• Obtain letters

Grant Preparation (cont)

• Think • Know the literature & be critical

• Issues• Questions• Controversies• Unfounded dogma• What gaps will your work fill?

• Give yourself plenty of time• Don’t submit until ready • Know what Institute to target and what they are in interested in

• RFA• Program announcements

• CRISP (Computer Retrieval of Information on Scientific Projects)• Where to submit (which institute)• Know the competition

NIH

CRISP

Grant Preparation (cont)

• Start writing• Take care of the administrative stuff

• Budgets and justification• Human, animal, biohazards approvals (Just in Time)• Resources• Supporting letters• Biosketch

• Separate abstracts/reviews from papers, please.

• Grant sections (15 [K] - 25 [R01] pages)• Specific Aims• Background and Significance• Preliminary Data• Experimental Plan

• Going to on-line submission

Specific Aims - 1 page

• Introductory paragraphs• State purpose and importance• Concise summary of key findings• A clearly stated hypothesis: “Our hypothesis is…”• Relate how aims will address the big picture (long-term goals) and

advance the field• List of aims (3-4)

• Importance for Reviewers• Many say this is the most important section

Background and Significance 3-5 pages

• Critically review the literature• No limit on number of citations • Do not be afraid to say you disagree with something (but explain why and

how you will correct this travesty)• Question dogma• Limit discussion to things (pathways, diseases, molecules, etc.) you will

study• Justify your overall experimental approaches and models• Provide graphics (cartoon, model, pathways, etc.)

• What new information will your work provide?• Don’t be shy

• Use first-person pronouns (I, we)

• Show your enthusiasm• Know your audience

• CSR databases

Preliminary Data 4-8 pages

• Summarize relevant experience and contributions• Provide interesting data• Demonstrate your ability to do things• Demonstrate feasibility of doing new things• Critically interpret your own data - say what it means• Make figures clear• Number the figures• Include legends (but not overly detailed)

Experimental Plan - 10+ pages

• This is the meat• More narrative than technical• For each aim, provide:

• Rationale• Approach• Experiments• Expected Results and interpretation• Potential pitfalls and alternative strategies• Future directions (short)

• Quantification and statistics• Methods

• Justify selection of techniques• Detailed methods are boring, but…• Give priority to new or difficult methods• Kit Rule

Aim Description YR 1 YR 2 YR 3 YR 4 YR 5

1A Role of matrilysin in ischemia-reperfusion repair

1B Neutrophil activation in vivo

2A Neutrophil binding to KC/syndecan-1 complexes

2B Requirement of syndecan-1 shedding

2C Syndecan-1 association with integrins

3A Binding sites of KC:syndecan-1 interaction

3B Neutrophil activation with disrupted KC/syndecan-1.

3C Inhibit KC/syndecan-1 interaction in vivo

• Priorities• Time line at the end of this section

• Logical flow from aim to aim• Caution: do not make an aim

dependent on a preceding aim

Presentation and Style

• Clean, concise English• Grammar and syntax• Active vs. passive voice• Avoid unneeded words: “…has been shown to…”• Read: Strunk and White, The Elements of Style• Read: Robert A. Day,

How to Write and Publish a Scientific Paper

• Paragraphs and spaces• Don’t make it look overly dense or cluttered

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Presentation and Style

• Zero tolerance for typos• Figures should be self explanatory

• Legends• Label the X and Y axes• Point to or demarcate key features

• Avoid excessive abbreviations• Avoid vague terms: e.g., ‘affects’, ‘influences’• Cite complete references• Take the reviewer by the hand

• Don’t make them think• Don’t require them to look elsewhere for information

• Look at successful applications

A February 1 Deadline

• Jan - Dec: Think, advice, preliminary data, manuscripts• Nov - Jan: Download forms, write, seek advice, get feedback• Jan 31: FedEx (soon upload)• Feb - Mar: Sorted by CSR

• Assigned an unique number: R01-HL077765-01• Assigned to a Study Section

• Feb-Mar: Reviewers picked and assigned by SRA• Early Apr: Applications sent to reviewers• Late Apr: Supplementary data• May: Study section meets• May-June: Scores sent to applicant• June: Summary statement sent to applicant• July: Institute Council• Sept 1: $$$$ or resubmit (now: R01-HL077765-01A1)

CSR: Center for Scientific Review

• Receives, assigns and reviews• 64,178 in FY2003 (70% of total)• 200 SRA (Scientific Review

Administrators)• ~11,000 reviewers per year• ~220 Study Sections/Special

Emphasis panels

Study Sections

• Organized into IRGs (Integrative Review Groups)• 12-24 members, essentially all from academia

• Plus about another 12+ ad hoc reviewers

• 60-100+ applications per meeting• ~10-14 per member• 3-4 or 5 reviewers per applications

• Information from CSR web site:• Study section scope• Roster of reviewers• Policies• Schedules

CSR

Why Join a Study Section?

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Review Process

• Applications sent to reviewer 6-8weeks before the meeting

• Streamlining• 1-2 weeks before, grants in the “lower

half” are identified• Streamlined grants are triaged, i.e., not

discussed

• Written critiques submitted up to 2-4 days beforehand

Review Criteria

• Significance• Is the work important, relevant?• Will it have an impact?

• Approach• Meat of the critique• Design, methods, plans, etc.

• Innovation• Novel concepts, methods, and/or approaches

• Investigator• Training and experience• Productivity• Productivity

• Environment• Institution, facilities

Review Process

• 8 am• Done alphabetically or by institute• Reviewers state scores

• 1.0 - 5.0• Adjectives:

• Outstanding (1.0 - 1.5)• Excellent (1.5 - 2.0)• Very Good (2.0 - 2.5)• Good (2.5 - 3.0)• Acceptable (3 - 4)• Find another job (4 -5)

• Discussion • 15-20 min per application

• Scores• Budgets and administrative issues• Next application• 6-7 pm• Bar, eat, bar, sleep, repeat next day

Scores and Summary Statement

• Priority score: mean of all scores• Percentile

• Relative rank within a Study Section• Averaged over 3 meetings.

• Pay line• Varies among institutes• ~14% (19% for NI) at NHLBI

0

25

50

75

100

Pe

rce

nti

le

0 100 200 300 400 500 600

Priority ScoreSummary Statement

Paylines

Top Reasons Why Grants Don’t Get Funded

1. Lack of new or original ideas.

2. Diffuse, superficial, or unfocused research plan.

3. Lack of knowledge of published, relevant work.

4. Lack of preliminary data and/or experience with essential methodologies.

5. Uncertainty concerning future directions (where will it lead?).

6. Questionable reasoning in experimental approach.

7. Absence of an acceptable scientific rationale.

8. Unrealistically large amount of work.

9. Lack of sufficient experimental detail.

Didn’t Make It

• Revised Application • A1, A2, then new proposal

• Consider the critique (without emotion)• Address concerns in an Introduction

• 1-2 pages before Specific Aims• Be agreeable but not obsequious

• Do not re-submit until all is in order• Must avoid the A2 Curse

• Seek advice