# Presentation: 354834

## Grants: Going from an Ideato a Winning ProposalNIDDK Network of Minority ResearchInvestigators Meeting19 April 2007 • Bethesda MD

*Robert Ferry, Jr., M.D.*
*Associate Professor*
*Division of Pediatric Endocrinology*
*University of Texas Health Science Center at San Antonio*
*bob@uthscsa.edu*

## Acknowledgements

*Writing Your First Grant*
- Career Development Workshops, The Endocrine Society James D. Shull, Ph.D.
- Eppley Cancer Institute
- University of Nebraska Medical Center
*How To Succeed in Academics*
- Edward McCabe, M.D., Ph.D.
- Department of Pediatrics
- University of California at Los Angeles

## Workshop Discussion Topics

- funding mechanisms
- hypothesis development
- application planning
- application preparation
- review process
- real world scenarios
- implementation

## Funding Agencies

- National Institutes of Health
- American Diabetes Association
- Juvenile Diabetes Foundation International
- American Cancer Society
- Department of Defense
- State / University Research Programs
- Private foundations

## NIH Awards

- _F32_: NRSA Individual Postdoctoral Fellowship Award
- Stipend plus $4,000/year; 3 years
- _K01_: Mentored Research Scientist Development Award
- Salary plus research development support; 3-5 years
- _K08_: Mentored Clinical Scientist Development Award
- Salary plus research development support; 3-5 years
- _K23_: Mentored Patient-Oriented Research Career Development Award
- Salary plus research development support; 3-5 years
- _R01_: Investigator Initiated Research Proposal
- Salary, research support; 3-5 years

## Hypothesis

- Must be important (clinically relevant).
- Must be novel.
- Must be testable.
- Must be supported by clear rationale.
- State it clearly and often.

## Hypothesis Development

- KNOW YOUR STUFF!
- Read the _**primary**_ literature and evaluate it critically.
- “A year in the laboratory can save an hour in the library.”
- Attend seminars and meetings.
- Write literature review.
- Present lecture or chalk talk.
- Challenge dogma.
- Search CRISP database: *http://crisp.cit.nih.gov/*
- Evaluate your strengths and weaknesses.
- How well do you know your area of research?
- How enthusiastic are you for your hypothesis?
- Discuss ideas with trusted colleagues and/or mentor.
- Keep file on new research ideas!

## Hypothesis Development

- MAKE PROTECTED TIME!
- Unstructured as well as structured time.
- “Unanswered questions are better than unquestioned answers.”
- Prioritize your efforts.
- Family first
- First author articles second
- Chapters and reviews third
- Cautiously recruit collaborators.
- Collaborators must be motivated to work with you.
- Loss of control over project

## Planning a Grant Application

- Assess your strengths and weaknesses.
- training history, publications, track record, etc.
- resources
- intellectual
- preliminary data: how novel? how much? how good?
- laboratory staff
- co-investigators and collaborators
- physical
- facilities
- equipment
- clinical materials or populations
- Identify the appropriate source(s) of funding.
- Identify the appropriate funding mechanism.

## Planning - continued

- Know which research and disease areas the NIH or other agency consider to be of high priority.
*NIH Guide*
- Program announcements (PA)
- Requests for applications (RFA)
- Supplements to existing grants
- Translational research
- Disease targeted research

## Planning - continued

- Identify overall goals of proposed research.
- Prepare draft of specific aims.
- Discuss with colleagues/mentor.
- Discuss with NIH program staff.
- identify institute
- identify Initial Review Group (IRG, or “study section”)
*http://cms.csr.nih.gov*
- Draft the application.
- Review internally with trusted, critical colleagues.
- Revise.  _Be your own toughest critic_!
- Submit.

## START EARLY!!

- Plan development 		over 6-18 months
- First draft				takes 1 month
- Internal review			takes 1-2 weeks
- Revisions				take 2-4 weeks
- Budget and justification	takes 1-2 weeks
- Regulatory issues		up to 6 months
- IRB
- IACUC
- recombinant DNA
- Institutional signatures		1-14 days

## Rules for Success 

- Recruit the reviewer as your advocate!
- Read and follow instructions for PHS form 398.
- Use current agency forms (update biosketches).
- Write application in clear and concise manner!!
- Use descriptive section headings.
- Incorporate clear graphics for data and models.
- Goal: craft the “perfect” application.
- Know the strengths and weaknesses in the research plan.
- Maintain positive dialog with NIH staff.
- Never contact members of the Scientific Review Group (SRG); aka Initial Review Group (IRG) and study section.

## Sections of Application

- Abstract						200 words
- Biosketch						3 pages
- Budget and budget justification
- A. Specific Aims				1 page
- B. Background and Significance		2-3 pages
- C. Preliminary Data / Progress Report	6-8 pages
- D. Research Design and Methods		8-14 pages
- Sections A through D cannot exceed 25 pages
- Resources
- Human subjects
- Vertebrate animals
- Appendices

## Abstract

- Write last!
- Don’t underestimate importance!
- Center for Scientific Review (CSR) staff use for assigning application to Institute and IRG, regardless of your request for assignment.
- Reviewers use for “describing” application to IRG members.
- Abstract is entered into CRISP database if grant is funded.

## Biosketch

- The biosketch defines you as the applicant.
- training history
- employment history
- research productivity
- first author publications; number and quality of journal
- other publications; number and quality
- honors and activities relevant to research
- community service awards for a community-based project
- competitions for basic research
- service to scientific and professional communities
- other sources of funding (other support)

## Budget and its Justification

- Modular budget: $25,000 per module
- maximum modular budget is $250 K/year
- average is approximately $175-200 K/year
- Categories
- Personnel
- Equipment
- Supplies
- Travel
- Other expenses
- Direct vs. Indirect Costs

## Direct vs. Indirect Costs

- Direct costs fund the research.
- Budget under control of P.I.
- You must know and understand your institution’s expectations prior to preparing your grant application for submission.
- Indirect costs support research infrastructure at your institution.
- utility bills
- core facilities
- faculty recruitment
- IRB staff
- fundraising

## Tips for Budget Preparation

- Resources:
- your department chair
- your institution’s grants management office
- NIH program staff
- colleagues and mentor
- Make effective use of spread sheet.
- Develop budget simultaneously with research plan.
- As experimental design changes, spread sheet recalculates approximate cost of experiment.

## Budget: Personnel

- Request salary plus benefits.
- P.I. Salary: 15-75% depending on other grants and non-research activities.  Cap is $161,200.
- Co-investigators: 3-15% depending on role in project.
- Postdoctoral Fellows: up to 100%
- Research Technologists: up to 100%
- Graduate Students: up to 90% (must allow time for classes and other activities)
- Provide names and biosketches for all personnel.
- Justify each individual by explaining role in project.
- Sacrificial postdoc?
- No more than one minor position as “to be named”

## Budget: Equipment

- Defined as >$5,000 in cost.
- –80°C freezers
- microscopes/digital cameras
- Usually requested in year 1.
- Must be well and clearly justified.
- Provide evidence of need.
- Indicate use in project.

## Budget: Supplies

- Specialized supplies
- antibodies, molecular biology reagents, etc.
- General supplies
- chemicals, pipettes, bench paper, gloves, etc.
- Cell culture supplies
- media, sera, plastic ware, etc.
- Animal purchase and shipping
- Approximate $10-15 K per FTE (full-time employee)
- List by category or by item if need is atypical.
- Justify (no page limit on budget justification)!

## Budget: Travel

- 1-2 trips per year
- National domestic meeting
- P.I. and Postdoctoral Fellow
- $1,000-1,500 per trip
- Specify meeting in justification
- “annual meeting of The Endocrine Society”

## Budget: Other Expenses

- Animal care
- Histology and other service charges
- Costs associated with clinical trials or studies
- Publication page charges, reprints
- Phone, fax
- Equipment maintenance
- Service contracts

## Specific Aims

- Most important (arguably) section of application.
- Most reviewers start reading here.
- Make it perfect!!
- Hook the reviewers early and set the hook hard.
- Remember that your responsibility is to recruit the primary and secondary reviewers as your advocates.

## Specific Aims - continued

- defines the research question and relates question to human health
- states the overall hypothesis
- states the overall goal of the proposed research
- states each Aim clearly and concisely
- relates each aim to overall hypothesis or a secondary hypothesis
- summarizes research model and approach
- states how completion of research will enhance knowledge and/or impact human health
- sets stage for future research

## Tips for Specific Aims

- Limit to 3-5 highly focused Aims.
- Stress mechanistic aspects wherever possible.
- Don’t make feasibility or significance of an Aim contingent upon success in a previous Aim.
- need independent aims
- Stay focused and realistic.
- Avoid being “overly ambitious”.
- if you made 1 transgenic animal in the past 24 months, then do _not_ propose making 3 new transgenics over the next 12 months

## Background and Significance

- relates human health issues to proposed research
- summarizes current knowledge
- identifies deficiencies in knowledge
- illustrates whether or not P.I. is knowledgeable in the area of research
- illustrates whether or not P.I. understands key technologies
- defines and  justifies the model system

## Tips for Background and Significance

- Educate yourself!!
- Know the primary literature.
- Know the experimental model.
- Educate the reviewer!!
- Don’t assume the reviewers are experts.
- Don’t force reviewers to do literature search to understand the research area.
- Imagine the reviewer is a near-sighted, 54-year-old guy, drinking a scotch at 11 P.M., reading your proposal after reviewing his pending divorce decree
- Write clearly and concisely.  Don’t cloud with minutia (buffer concentrations, etc.).

## Preliminary Data

- Illustrate feasibility of proposed work and capabilities of P.I.
- Data presented should relate directly to and support the hypothesis.
- Self assess strengths and weaknesses.
- Incorporate high quality figures, tables, etc.
- Figures must copy clearly.  Reviewers often receive poor quality copies in black & white.
- Provide full-size copies of key figures, in color if necessary, as appendices.  Contact staff to provide additional copies of the full color proposal.
- Don’t use abstracts from publications verbatim.
- Append pertinent publications
- Don’t assume reviewers will read appendices!

## Research Design and Methods

- Organize by specific aim.
- Restate aim.
- Summarize experimental approach.
- Define and justify the model system!!
- Describe key experiments.
- Indicate priorities.
- Use figures as necessary.
- Predict outcomes.
- State anticipated pitfalls.
- Propose alternative approaches.
- Detail methods.
- Discuss statistical considerations.
- How did they impact experimental design?
- How will they be used for data analysis and interpretation?

## Research Design and Methods

- Illustrate your strengths!
- Cite your publications in which techniques were used and/or developed.
- Indicate how co-investigators and collaborators will contribute.
- Highlight strengths of your institution.
- Cite and append letters of support and collaboration.
- Highlight innovativeness!
- State how can you do this work better than anyone else.
- State how the approach is unique.

## Research Design and Methods

- It is more important to illustrate that you completely understand each method than to tell the reviewer how to do it.  “Write a good short story, not a cookbook.”
- Present a time line.
- Reveal how key observations will enhance understanding of human biology.
- Briefly indicate how findings may impact future research.

## Resources and Environment

- Discuss cores and support services.
- biostatistics shared resource
- animal care facilities
- molecular biology core laboratories
- clinical research facility
- NMR, mass spectrometry, etc.
- Highlight institutional grants.
- SPORE and Center Grants
- Training Grants and Programs
- Get letters of support from key Core Directors, collaborators, and anyone supplying essential reagents.
- Collaborate if you don’t have what you need.

## Assignment for Review

- Staff of CSR assign application to *Initial Review Group* (IRG) and Institute.
- Craft title and abstract to increase probability of assignment to IRG and Institute of your choice.
- Write cover letter requesting specific assignment.
- Check status on ERA Commons.
- If assignment is incorrect, call scientific review administrator as soon as possible for a possible change (well before the review).

## Review Process

- Reviewer assignment
- IRG meeting
- primary review – makes it or breaks it
- secondary review
- tertiary review
- general discussion
- individual scoring 1.0-5.0 (average merit score x 100; “percentile”)
- 100 is perfect and 500 is “acceptable”
- Fundable scores vary by institute and Congressional appropriation, but usually range 100-150.
- 300 and above are usually “unscored” or “triaged” without full review
- Discussion of budget
- Overlap with other funded projects?
- Appropriate in time and amount?
- Discussion of human subjects, animal issues, etc.

## Review Process

- Secondary review by Council
- approve recommendation of IRG
- comply with Congressional and institutional mandates
- fund applications that may exceed pay line, but are in high priority areas
- resolve appeals from P.I.

## R01 Review Criteria

- Significance
- Approach
- Innovation
- Investigator
- Environment

## F32 Review Criteria

- Candidate
- Sponsor and training environment
- Research proposal
- Training potential

## K01, K08 and K23 Review Criteria

- Candidate
- Career development plan
- Training in responsible conduct of research
- Research plan
- Mentor
- Environment and institutional commitment
- Budget

## “Fatal Flaws”

- lack of originality or significance
- too ambitious, lacks focus
- not “hypothesis driven”
- “a technique in search of a hypothesis”
- “fishing expedition”; i.e., totally descriptive
- not supported by preliminary data
- entire proposal depends of success in key experiment or aim
- P.I. lacks experience or knowledge

## What to do if not funded.

- Study the critique.
- Share with colleagues and mentors.
- Recognize that applicant and reviewer share responsibility for an unfavorable critique.
- Discuss critique with NIH program staff.
_**Revise**_ and re-submit.  NIH allows 2 revisions (A1 and A2).
- If critique is flawed, ask SRA to assign new reviewer(s).
- Request new IRG?

## Real World Scenarios

- Junior investigator deserves “benefit of the doubt”.
- Risk of this not happening may be proportional to the total budget requested.
- Don’t assume this will happen when preparing your application.
- “Good Ole Boy” network rules?
- Institutional and geographic bias; does it exist?
- Tenacity is key.
- Whiners go hungry?

## Implementation

- Perform self-assessment twice yearly.
- Experiments on schedule?
- Publications?
- Revision of research plan required?
- Begin planning for renewal immediately.
- “Time flies when you’re having fun.”
- Communicate with NIH program staff
- Give them informative annual progress reports.
- Seek them out at meetings.

## Ferry’s Laws of Professionalism

- #10	Always remain courteous.  The other person is always busier than me and also has a personal life.  Someday, that other person will write a confidential letter, which will impact my trainees and me though we may never see it.
- #9	I’ve been with parents who lost a child, and I’ve seen young people die in combat.  When it truly matters, few words say it.  Family and friends first!  Don’t sweat the small stuff, and everything else is small stuff.
- #8	Attend key details...your anniversary, your hypothesis.
- #7	Discover someone’s reputation before you meet them.  You might be swimming with sharks or rubber duckies.
- #6	The second-in-command is more helpful to you than the commander, but the commander signs the paperwork.  Groups at the #2 spot usually work harder than those at #1.

## Ferry’s Laws of Professionalism

- #5	In a grant application, toot your own horn.  Toot your trainee’s horn whenever you have the chance...“selfless service”.
- #4	Never give up, and always speak your mind and conscience.  Be prepared for the consequences upon you and others from speaking your mind and conscience.
- #3	You’re never alone, even when you feel that way.
- #2	Tomorrow, your biosketch will be stronger, so revise and re-submit your grant applications and manuscripts.
- #1	When you feel discouraged, feed a baby in the nursery at the hospital.  You will recall that achieving the most worthwhile mission requires patience, enjoying what you do, and serving someone larger than yourself.  Babies will probably live longer than you or me.

## Extracurricular Reading

- Cousteau V. How to swim with sharks: a primer. *Perspectives in Biology and Medicine* 1973;16:525-528.
- Johns RJ. How to swim with sharks: the advanced course. *Transactions of the Association of American Physicians* 1975;88:44-54.
- Simone JV. Understanding academic medical centers: Simone’s maxims. *Clinical Cancer Research* 1999;5:2281-2285.
- McCabe E. *How to Succeed in Academics*.