Developing a Research Proposal

1. Developing a Research Proposal Ralph Nitkin, Ph.D. - RN21E@nih.gov National Institutes of Health (NIH) and Robert Jaeger, Ph.D. - robert.jaeger@va.gov Department of Veterans Affairs (VA)

2. NIH and VA Research • NIH much larger than VA • Budget • Number of Review Panels • Many Similarities – Scientific Quality • Some Differences • Use of LOI – assignment to Panels • Role of “Program Managers” • Local Review at VAMC – allow extra time if needed

3. Background work • Review current literature and ideas with mentors and colleagues; refine the problem under study • Why hasn’t this been done before? • What are the most direct methods or approaches to achieve your goals? Consider alternatives • Develop hypotheses and likely outcomes • Will your approach be conclusive? • How would it impact on the field? • Consult with a statistician in the design phase

4. VA Investigators • Veteran-Centric • Is DoD Collaboration Possible? • Larger studies possible (CSP, Central IRB, QUERI) • Multi-Center Studies may get easier • ITI (“Information Technology ‘Issues’) • “LOI” – typically not used at NIH • Interaction with Program Manager • Local Review at VAMC – allow extra time if needed

5. Preliminary Data • Demonstrate your competence, commitment, and standards • Demonstrate feasibility of approach • Address potential theoretical hurdles • Document success with difficult or highly specialized techniques: Personal mastery: past publications, preliminary data, writing style Recruit collaborators with appropriate expertise It may not be required but it never hurts…

6. New and Early-Stage Investigators • NIH encouraging support for new investigators • “New investigator” status highlighted in the peer-review process • Extended paylines • Shortened review cycle • See NIH websites for specific policy New Investigator = never been PI on an R01 grant Early Career = New and within 10yrs of terminal research degree

7. VA Early-Stage Investigators • Plan to get on the “CDA Track” • CDA-1; CDA-2; Transitional; Research Career Scientist; Senior Research Career Scientist • RR&D began offering Career program in 1997 • Over 100 awardees trained • Career program is growing • Currently receive over 30 applications per cycle • ~ 5-fold increase over past 5 years • “Commitment to VA”

8. Preparing the NIH Application • Abstract • Background/Introduction • Specific Aims • Progress and Preliminary Data • Experimental Design • Significance • Other assurances • Budget Leave a few extra weeks for electronic submission

9. Preparing the NIH Application Take a deep breath - what belongs in each section? Ask senior colleagues for copies of their NIH applications NHBLI sample Career Development application: www.nhlbi.nih.gov/funding/training/redbook/k08.pdf NIAID has an annotated R01 and summary statement: www.niaid.nih.gov/ncn/grants/app/default.htm

10. Information on grant writing, peer review, and funding “Everything you wanted to know about the NCI Grant process but were afraid to ask” http://www3.cancer.gov/admin/gab/02gpb/nci_grants_bk.pdf “Answers to Frequently asked Questions about NIH Grants” http://grants1.nih.gov/grants/funding/giofaq.htm “Tips for New Applicants” from NIGMS: http://www.nigms.nih.gov/funding/tips.html Specific information for bioengineers: http://www.nibib.nih.gov/research/investigators.htm

11. Preparing the NIH Application Do not provide a comprehensive review of the field, but only that literature necessary to appreciate the studies proposed Provide a clear logic flow that motivates each experiment; defend your choices Discuss likely outcomes and interpretations; admit potential pit-falls and provide alternative approaches Include a time-line and be realistic Eliminate experiments that are do-able, but do not directly contribute to the goals of the study What are the outcomes are primary vs. secondary? What are your benchmarks for “success”?

12. Abstract and Specific Aims • Write this last – but it will be the first thing that reviewers read • Specific Aims provide broad rationale and motivation • Each Aim should have its hypothesis or motivation, outcome, and interpretation • Should be very precisely articulated, because they dictate everything that follows • Choose a Title that is true to your aims; don’t oversell

13. Think about the review criteria that will be applied to your application • Individual criterion for NIH applications: • Significance • Investigator • Innovation • Approach • Environment

14. Cover letters One-page letter addressed to “Referral Officer” • Briefly review the goals of your proposal • Request Institute(s) assignment • Suggest appropriate study section (visit CSR website for expertise and rosters or talk to NIH Program Staff)

15. VA Letters of Intent • Submitted in Advance of Application Deadline • Allows VA Program Managers to • Be sure a full application should be submitted • Discuss any pre-submission concerns with PI • Direct the application to the most appropriate panel in advance • Allow extra time to secure additional reviewers if needed

16. Revisions: Be Persistent Build in time for resubmissions Make sure you understand the message in the summary statement: Did they understand what you were proposing? What are major criticisms and what are just minor suggestions? Do they want to see it again? Talk to NIH staff or let colleagues read the critiques Don’t rush it – you have only one revision Take time to improve and update the application

17. Center for Scientific Review The “Judiciary Branch” of the NIH Over 100 standing study sections in following areas: AIDS and Related Research Biobehavioral & Behavioral Proc   Biological Chem and Macromolecular Biophysics   Biology of Development & Aging Bioengineering Sci and Tech Brain Disorders & Clinical Neurosci Cell Biology   Cardiovascular Sciences Digestive Sciences Endocrinology, Metabolism, Nutrition and Reproductive Sciences   Genes, Genomes and Genetics Health of the Population Hematology Immunology Infectious Diseases and Microbiology Integrative, Functional, and Cognitive Neuroscience Molecular, Cellular, and Developmental Neuroscience   Musculoskeletal, Oral & Skin Sciences Oncological Sciences   Respiratory Sciences Risk, Prevention & Health Behavior Renal and Urological Sciences Surgical Sci, Biomedical Imaging, & Bioengineering

18. VA Merit Review System • Similar to NIH • Only 4 Research Services in ORD • Basic Laboratory R & D • Clinical Science R & D • Cooperative Studies Program – Large clinical trials • Rehabilitation R & D • Health Services R & D • Structure may change with adoption of NIH eRA – a time of flux!

19. Winning over Reviewers, part 1 Develop a focused application, with explicit goals Consistent format carried through each section Provide a mechanistic basis for your approaches (where ever possible) and defend your choices Raise an interesting question (basic or clinical) and propose the most direct solution Use the most appropriate means to critically address the issues at hand

20. Winning over Reviewers, part 2 Discuss your proposal in the context of previous studies, current clinical practice If this is so clever, how come it hasn’t been done before? For a major grant give preliminary data on all of your major aims if possible Have a draft read by a merciless colleague with NIH grant experience

21. Winning over Reviewers, part 3 Write to your likely peer-review audience in a style that is logical, interesting and readable Avoid verbosity and clutter - an open looking grant is more readable Use figures and tables, rather than text; Minimize appendices Follow agency guidelines; make sure your application is neat, accurate, consistent & complete Despite professional pressures, do not submit until it is your best possible effort

22. Human Subjects Research • Define the subject population; inclusion/exclusion criteria • “Power calculation” to justify numbers of subjects in each group (based on inherent variability & expected effect size) • Document access to adequate subject population • Work with your Initial Review Board (IRB) to anticipate possible human subject issues (NIH does not require IRB approval at time of submission, only if/when funded) • Understand NIH policies on inclusion of women, of minorities, and of children • HIPAA regulations for confidentiality

23. VA Human Subjects • New VA Central IRB • VA Office of Research Oversight • “JIT”