HOW TO WRITE AN NIH GRANT

1. HOW TO WRITE AN NIH GRANT Frances E. Jensen, MD

2. 1 page 1 page 6/12 pages R21/R01

3. Basics • Ask yourself are you ready now…or later? • Writing a grant too early without preliminary data is perilous, and will ultimately waste your time • DO NOT use the NIH peer review process as a grant editing agency • You have a profile readily available to the reviewers re how many times you have submitted any/all grant applications, and how may rejections and the scores (via NIHCommons)

4. Basics • Design a grant application around a “WIN-WIN” hypothesis, so that even a negative result will contribute usefully to your field • DO NOT WRITE A GRANT WITHOUT HYPOTHESES • Do not think of questions to which you or your environment/institution is poorly matched • Best if you have something published in a related field that you can use as a starting point or at least to prove feasibilty

5. Try your best to plan ahead • Write an outline out as far ahead as you can • Play with the aims for a while • Order • Content • Novelty • Solicit your colleagues for internal review

6. Before you submit • Look for FOA’s that might apply to your work • Identify (and in some cases talk to) the appropriate Program Officer • Identify a study section appropriate to your work in the CSR website • INCLUDE THIS INFORMATION IN YOUR COVER LETTER – • Do not let nature take its course!

7. The modifications – for NIH grants 13 PAGES! Specific Aims (1 page) Research Plan (12 pages) The Research Plan is restructured and aligned with peer review criteria. Shorter page limits are adopted. The Biographical Sketch now requires a Personal Statement, and encourages applicants to limit the number of publications to 15. Instructions for describing Resources are modified to address the scientific environment and the institutional investment in Early Stage Investigators.

8. http://grants.nih.gov/grants/funding/phs398/phs398.pdf 1 page 1 page 6/12 pages R21/R01

9. http://grants.nih.gov/grants/funding/phs398/phs398.pdf

10. Biosketch • The new personal statement • Highlight your accomplishments so that this complements the minimalistic background/preliminary results section- CUSTOMIZE • Examples This proposal seeks to study …. We hope to also gain insights into the role of ….in the processes of … that may help illuminate … I am particularly well suited to direct this project, I am a …. My lab demonstrated …. I have pioneered…techniques …and published… I have established … My laboratory has the facilities required to carry out …. Additionally, our Center has core facilities including …needed for this project.

11. Resources Identify the facilities to be used (laboratory, clinical, animal, computer, office, other). Describe how the scientific environment in which the research will be done contributes to the probability of success (e.g., institutional support, physical resources, and intellectual rapport and ways in which the proposed studies will benefit from unique features of the scientific environment or subject populations or will employ useful collaborative arrangements. **For Early Stage Investigators, describe institutional investment in the success of the investigator, e.g., resources for classes, travel, training; collegial support such as career enrichment programs, assistance and guidance in the supervision of trainees involved with the ESIs project, and availability of organized peer groups; logistical support such as administrative management and oversight and best practices training; and financial support such as protected time for research with salary support.

12. 1 page 1 page 6/12 pages R21/R01

13. Introduction- for resubmissions only • One page (as opposed to previously 3) • Keep your argument objective, collegial • Write a first version then scrap it • Remember, it takes two to have a misunderstanding! • It is likely that you were not explicit or did not adequately highlight a critical detail • Be exacting in your response to each criticism and point to area in grant that has been revised, changed

14. 1 page 1 page 6/12 pages R21/R01

15. Specific AimsONE PAGE • Use initial paragraph to emphasize impact • Project where this research is going and describe the field to which it is important • How this fits in with an overall goal of the applicant or a research field • How this fills an existing gap in knowledge • Why this approach is superlative to others • Why this is “win-win”

16. Specific Aims • Then list aims as a paragraph each: • Must include hypothesis and method • “To determine whether..xx.. increases/decreases/verb….yy. We hypothesize that xx plays a critical role in regulating…. We will assay yy… in children/cultured neurons following treatment with….using…technique…. • Must be written actively, and also must be important enough that even the null outcome is a contribution to the field

17. 1 page 1 page Significance, Innovation, Approach 6/12 pages R21/R01

18. Research ApproachTOTAL 12 PAGES Significance Innovation Approach

19. Significance • How does your work add to the field • Make a case for the importance of your area of study • Prevalence of the problem • How this area is a foundation for other fields • What is the unmet need/gap in knowledge • You have to make your topic interesting and understandable – work on the angle to capture interest!

20. Innovation • Express how the project is different from anything ever done before in this area • New technology? • New model? • New reagents? • Out of the box thinking? • New approach? • New connection between areas previously not thought to be linked? • New IDEA!!!

21. How to organize the Research Approach? • Can do more conventionally • Brief section each for significance and innovation • Do a minumum background, prelim results then get to Aims in order • OR -Try to follow new structure • Incorporate background into significance • Incorporate prelim results into innovation and spec aims • Use prelim results in aims to support feasibility

22. For introducing background of field • Opportunity to demonstrate scholarly synthesis • Up to date! • Make sure you cover literature that is in disagreement and state how you interpret this. (the review may do a literature search ) • Where possible end paragraphs with leading issues or questions to be addressed and explicitly say so- ie “this important relationship will be explored in Aim 3 of this proposal” • Do not expect the reviewer to infer • Biggest reason for misunderstanding in review • Always be explicit!

23. When presenting preliminary results • Two purposes • Provide important pilot data to lay groundwork for hypotheses • Prove that the experiments are feasible…in your hands! • Showcase data acquisition, analysis, and ability to infer results • Keep highly organized, and present in order of specific aims • At end of each result EXPLICITY state that it relates to Aim ”xx” • Figures, tables, raw data a must here and it must be impeccable in quality • Reflects on your technique • Can insert in any of the 3 sections, most likely Innovation and Approach

24. Experimental design elements • Probably the most important part of the grant • Really separates out those who have thought hard from those who have more superficially dealt with the issues • First draft should be long, and then you can cut • Be hard on yourself • If you are “hiding “ a potential weakness, the reviewers are trained to immediately notice! • It is much easier to criticize a grant than to appreciate its merit – don’t give them a chance!

25. Research Approach - Space constraints • Consider carefully what is worth repeating versus not: • Yes: • Reminders re impact, feasibility, innovation, prior success • No: • Logistical details, detailed data, dwelling on pitfalls (if there are too many pitfalls you probably shouldn’t be proposing it!)

26. Experimental method • State overall flow of experiment • Details largely out, with the exception of key features • critical reagents or conditions, novel paradigms • Stating n’s increases reviewer’s confidence that you have thought this through • Also outcome measures • What are they- what exactly will the numbers, data you will be acquiring? • Mention statistical method

27. Aim *. To determine whether protein kinases are activated following seizures and change phosphorylation state of glutamate receptors. • Rationale and hypothesis. Prior work has shown….our pilot data suggest…based on this we hypothesize that… • Experiment 1. Is CAMKII increased prior to behavioral seizures activity in a model of acute seizures? • Experiment 2. Is glutamate receptor phosphorylation state increased in neurons showing increased CAMKII activity? • Experiment 3… • For each expt, consider the process of (even if you don’t include it all in the final application) • Experimental design • Data analysis • Anticipated results • Problems and pitfalls • Excellent mental hygiene!

28. Anticipated results • MOST important part of experimental design section • Be logical • Be scholarly, relate the expected outcome to the literature, and where does this new data move the field • Demonstrate that data satisfying the null hypothesis is still relevant and moves you and the field somewhere, and say where • Get credit for future directions “not proposed for funding here” or “beyond the scope of this proposal” • Do not make this section lightweight – delve deep – first draft should be muchlonger than you have space for but an important exercise – so not leave to the last!

29. Problems and pitfalls • Do not write this to sabotage yourself • If there are too many pitfalls, you probably should not be doing the experiment that way! • Good place to recognize inherent confounds of subject matter, state how you will control for this • Provide alternate methods if something might fail • Show contingencies, and this will increase confidence of reviewer that something will come of all that money flowing to you!

30. 1 page 1 page 6/12 pages R21/R01

31. Appendix • Can include supporting documents • Up to 3 unpublished “in press” manuscripts, or published but not publically available link • NOT submitted or under review • Larger images of figures used • NIH conversion is not like Nature’s (!) • Clinical IRBs

32. After you submit • Check on where the grant got assigned • If it is a major error use your OSP at your institution to help you make a request for a switch – has to be highly justified though

33. Remember • The reviewer is not a mind reader • Be EXPLICIT, don’t expect them to hunt back and forth for information or necessarily make the link between something said in the background and a preliminary result, or experimental plan • The reviewer is human • Likely to be juggling a toddler or whiney teenager, his/her own grants/pressures while looking at your grant application • Clear font, print, organization • Minimize typos- these reflect on your fastidiousness • Most erroneous criticism comes from the writer’s lack of clarity • The process is human • And thus inherently flawed, so be patient and have backups • Do your best to control the human element: Identify the best fit for program officer and study section

34. Happy Grant Writing!