1. 1 Che594 Lect24 Proposals To NIH

2. All information and opinions are those of Mark A. Shannon, 2007 Objective For Today Overview Of NIH Grants How Grants Are Scored 2

3. All information and opinions are those of Mark A. Shannon, 2007 3 National Institutes of Health The NIH is not a single institute. It is actually a collection of 20 institutes and 7 centers (next page). The individual Institutes are funded at very different levels: The level plays a large role in whether or not your proposal is funded or not. Programs in each institute are also funded at very different levels. You have the choice to send your proposal to different programs and institutes Do your homework to find out which program has both money and fits your proposal best. TALK TO PROGRAM MANAGERS!

4. All information and opinions are those of Mark A. Shannon, 2007 4 National Cancer Institute - Est. in 1937 National Eye Institute - Est. 1968 National Heart, Lung, and Blood Institute - Est. 1948 National Human Genome Research Institute - Est. 1989 National Institute on Aging - Est. 1974 National Institute on Alcohol Abuse and Alcoholism - Est. 1970 National Institute of Allergy and Infectious Diseases - Est. 1948 National Institute of Arthritis and Musculoskeletal and Skin Diseases - Est. 1986 National Institute of Biomedical Imaging and Bioengineering - Est. 2000 National Institute of Child Health and Human Development - Est. 1962 National Institute on Deafness and Other Communication Disorders - Est. 1988 National Institute of Dental and Craniofacial Research Est. 1948 National Institute of Diabetes and Digestive and Kidney Diseases - Est. 1948 National Institute on Drug Abuse - Est. 1973 National Institute of Environmental Health Sciences - Est. 1969 National Institute of General Medical Sciences - Est. 1962 National Institute of Mental Health - Est. 1949 National Institute of Neurological Disorders and Stroke - Est. 1950 National Institute of Nursing Research - Est. 1986 National Library of Medicine - Est. 1956 Center for Information Technology - Est. 1964 Center for Scientific Review - Est. 1946 John E. Fogarty International Center - Est. 1968 National Center for Complementary and Alternative Medicine - Est. 1999 National Center on Minority Health and Health Disparities - Est. 1993 National Center for Research Resources - Est. 1962 NIH Clinical Center - Est. 1953

5. All information and opinions are those of Mark A. Shannon, 2007 5 National Cancer Institute - Est. in 1937 National Eye Institute - Est. 1968 National Heart, Lung, and Blood Institute - Est. 1948 National Human Genome Research Institute - Est. 1989 National Institute on Aging - Est. 1974 National Institute on Alcohol Abuse and Alcoholism - Est. 1970 National Institute of Allergy and Infectious Diseases - Est. 1948 National Institute of Arthritis and Musculoskeletal and Skin Diseases - Est. 1986 National Institute of Biomedical Imaging and Bioengineering - Est. 2000 National Institute of Child Health and Human Development - Est. 1962 National Institute on Deafness and Other Communication Disorders - Est. 1988 National Institute of Dental and Craniofacial Research Est. 1948 National Institute of Diabetes and Digestive and Kidney Diseases - Est. 1948 National Institute on Drug Abuse - Est. 1973 National Institute of Environmental Health Sciences - Est. 1969 National Institute of General Medical Sciences - Est. 1962 National Institute of Mental Health - Est. 1949 National Institute of Neurological Disorders and Stroke - Est. 1950 National Institute of Nursing Research - Est. 1986 National Library of Medicine - Est. 1956 Center for Information Technology - Est. 1964 Center for Scientific Review - Est. 1946 John E. Fogarty International Center - Est. 1968 National Center for Complementary and Alternative Medicine - Est. 1999 National Center on Minority Health and Health Disparities - Est. 1993 National Center for Research Resources - Est. 1962 NIH Clinical Center - Est. 1953 You apply to individual institutes in response to calls for proposals or with unsolicited proposals. Proposals reviewed and ranked by Center for Scientific Review (CSR).

6. All information and opinions are those of Mark A. Shannon, 2007 6 NIH Funding Levels Total NIH funding over $29 Billion a year! Total is misleading for basic and applied research Most of money goes to hospitals and clinics who enrolled patients into treatment modality studies, including pharmaceuticals Money dominated by physician side of NIH Total funding for applied, and basic research on order of $6B This is the only pot universities can apply to NIH has only a very small educational mission. Hence, Universities do NOT dominate basic and applied research funding. Most of this goes to medical research centers, the NIH Institutes (themselves) and companies. Universities compete head on with these. Competition among University research intense: < 1 in 10 is funded, similar to NSF Reported 15 to 20% funding levels misleading: > 20% in SBIR/STTR

7. All information and opinions are those of Mark A. Shannon, 2007 7 Main Types of NIH Grants Largest is “Center-like” Research Grants (in response to Program Announcements (PAs) Very, very hard to get (much less than 5% funded). Evaluated exactly the same as smaller grants, but much more complex, so tends to have worse scores (more later). $ much larger, order $1 million/yr or more in direct costs RO1 - Main funding instrument. Can be up to 5 years funding. Order of $250 to $500 k/yr direct funding for 1 to 4 investigators. MUST HAVE STRONG PRELIMINARY DATA…i.e. the evaluators must be convinced you will be successful R21 - Higher risk, impact, 2 yr. Order $125 k/yr direct. No Prelim data needed, however, it is highly desired. SBIR/STTR for Small Companies - Easiest to get, highest funding ratio. $100k Phase I, $750 k phase II. Phase III possible, but improbable. STTRs have University participation RO3, R15 - Special University focused proposals with educational content $30 to 80 k/yr. Easier to get but still must be evaluated by CSR.

8. All information and opinions are those of Mark A. Shannon, 2007 8 Center for Scientific Review (CSR) All proposals from all institutes evaluate proposals, and are given a score or are unscored (a lot more later on scoring). The score is almost everything. There are many, many Study Sessions, which is the group that does the scoring (more on Study Sessions later). Each proposal is handled by a CSR Official, who is NOT a PM. One typically CANNOT select the CSR Official or Study Session, but there are ways to help influence this MOST IMPORTANT decision by CSR. Talk to PM and research CSR S.S. These are online. If you want a particular S.S., get intellectual area right

9. All information and opinions are those of Mark A. Shannon, 2007 9 Study Sessions (S.S.) S.S. is determined by intellectual content, NOT INSTITUTE! Large number of members 20 to 26, each with one vote Varied backgrounds, including MD’s, scientists, and a few engineers. Bulk are Charter members, which means they serve a 2 to 6 year term giving the S.S. memory of previous proposals. 25% are rotators or ad hoc panelists. Only 7% are allowed to be junior faculty or scientists. Charter members must be nominated by CSR Officers and undergo a tenure review by CSR upper management. Good for Junior to do at least once. Meets 3 to 4 times a year to review 80 to 100 proposals at a time 3 or 4 of the S.S. members read and evaluate proposal Each proposal that is scored considered for about 15 minutes Panel votes on proposal based on evaluation of readers

10. All information and opinions are those of Mark A. Shannon, 2007 10 Connection of S.S. to Institutes Network of S.S., Programs, and Institutes The same PM can send proposals to different S.S., even for the same BAA. Different institutes send to the same S.S. Determined by what area/intellectual content is within the proposal, NOT INSTITUTE! Scores normalized within and across S.S., which is normalized by the scores of the total S.S. mean and StDev. PM 1 PM 2 PM 3 PM 4 S.S. A S.S. B S.S. C Institutes CSR Institute I Institute II

11. All information and opinions are those of Mark A. Shannon, 2007 11 Scoring Streamlining (triage) 60% at every S.S. is now streamlined based on the Primary (P), Secondary (S), and Discussant (D) scores If streamlined, the proposal is UNSCORED, thus you do NOT know where you are with respect to the mean. Low-score is better Scale is from 1 to 5 (old scale from 100 to 500) 1 is considered perfect (typically not permitted by CSR), 3 average, 5 does not allow resubmission Scores and Range 40% remaining are scored. Highest and lowest of P, S, and D score sets range. S.S. members can vote outside range if they speak up before vote. Average of all votes is the score.

12. All information and opinions are those of Mark A. Shannon, 2007 12 Fundable Range Depends on the NORMALIZED Score, Type of Grant, and $ that PM has in a program Everything here is subject to change…moving target RO1 < 5th percentile is considered in fundable range Depends on Institute (Cancer yes, facial cranial, probably no), and if PM has money in program R21 < 10th percentile is considered fundable R03/R15 < 15th percentile R43/44 SBIR/STTR < 25th percentile Training Grants for Young Investigator Development Highly competitive, but good opportunity to look into

13. All information and opinions are those of Mark A. Shannon, 2007 13 How Evaluators Tend to Rank Criteria 1.Medical and/or biological significance: Do not underestimate this 2.Hypothesis-driven specific aims: Can be lost right here, not won. 1.Note: No longer required for engineering or instrumentation proposals, but reviewers still desire them 2.Adequate number, but not too many 1.Need to be related, but common mistake is to have one depend on another 2.R21 - 2 to 3 are good…5 or more too many 3.RO1 - 3 to 5 are good….7 or more too many 3.Ideas: Is the approach to solve the problem innovative and exciting, but still sound? This is what wins proposals. 4.Strength of investigators: Can they do the work proposed? 1.Strong CV and number of papers published essential 2.Preliminary data and previous impact of investigators work 5.Money and timeline 1.Can’t be considered until after scoring, but it still matters. Don’t ask for full 5 years for an RO1, keep budget modular if possible. Given in order of importance that S.S. members look for.

14. All information and opinions are those of Mark A. Shannon, 2007 14 CSR Suggested Format of Reviews SUMMARY AND RECOMMENDATION State briefly the objective of the research plan. Indicate the specific gaps or areas that the proposed plan is going to address. Then, summarize the major strengths and weaknesses. Finally, provide your assessment by assigning one of the flexible priority scores (The range is 1.0 to 5.0, Examples 1.8, 3.5). The aim of the evaluation is the generation of strengths and weaknesses. Limit descriptive comments and emphasize evaluative comments for the following criteria:

15. All information and opinions are those of Mark A. Shannon, 2007 15 CSR Suggested Format of Reviews Criteria Significance Evaluate the importance and impact of the proposed plan on human health, biodiversity conservation, and sustainable economic opportunities and for contributions to scientific advancement in the field. Evaluate the capacity building on research and training for host country. Evaluate progress of the existing project (For relevant applications only), including accomplishments made and published results.

16. All information and opinions are those of Mark A. Shannon, 2007 16 CSR Suggested Format of Reviews Criteria Approach Evaluate whether the methods and analysis are appropriately designed to provide clear answers to the specific aims of the proposed plan and whether the potential problems are addressed and alternatives considered. Innovation Evaluate the creativity of the proposed plan Investigators Evaluate the research competence and evidence of productivity for both US and foreign investigators, in the relevant field of research plan. Environment Evaluate the adequacy of both existing and proposed facilities and resources for the planned research.

17. All information and opinions are those of Mark A. Shannon, 2007 17 CSR Suggested Format of Reviews Other Considerations PROTECTION OF HUMAN SUBJECTS FROM RESEARCH RISKS: Evaluate the application with reference to the following criteria: risk to subjects, adequacy of protection against risks, potential benefit to the subjects and to others, importance of the knowledge to be gained. (If the applicant fails to address all of these elements, notify the SRA immediately to determine if the application should be withdrawn.) If all of the criteria are adequately addressed, and there are no concerns. Write "Acceptable Risks and/or Adequate Protections." A brief explanation is advisable. If one or more criteria are inadequately addressed, write, "Unacceptable Risks and/or Inadequate Protections" and document the actual or potential issues that create the human subjects concern. If the application indicates that the proposed human subjects research is exempt from coverage by the regulations, determine if adequate justification is provided. If the claimed exemption is not justified, indicate "Unacceptable" and explain why you reached this conclusion. Also, if a clinical trial is proposed, evaluate the Data and Safety Monitoring Plan. (If the plan is absent, notify the SRA immediately to determine if the application should withdraw.) Indicate if the plan is "Acceptable" or "Unacceptable", and, if unacceptable, explain why it is unacceptable.

18. All information and opinions are those of Mark A. Shannon, 2007 18 Other Considerations GENDER, MINORITY AND CHILDREN SUBJECTS: Public Law 103-43 requires that women and minorities must be included in all NIH-supported clinical research projects involving human subjects unless a clear and compelling rationale establishes that inclusion is inappropriate with respect to the health of the subjects or the purpose of the research. NIH requires that children (individuals under the age of 21) of all ages be involved in all human subjects research supported by the NIH unless there are scientific or ethical reasons for excluding them. Each project involving human subjects must be assigned a code using the categories "1" to "5" below. Category 5 for minority representation in the project means that only foreign subjects are in the study population (no U.S. subjects). If the study uses both then use codes 1 thru 4. Examine whether the minority and gender characteristics of the sample are scientifically acceptable, consistent with the aims of the project, and comply with NIH policy. For each category, determine if the proposed subject recruitment targets are "A" (acceptable) or "U" (unacceptable). If you rate the sample as "U", consider this feature a weakness in the research design and reflect it in the overall score. Explain the reasons for the recommended codes; this is particularly critical for any item coded "U". CSR Suggested Format of Reviews

19. All information and opinions are those of Mark A. Shannon, 2007 19 Other Considerations GENDER, MINORITY AND CHILDREN SUBJECTS: CSR Suggested Format of Reviews CategoryGender (G)Minority (M)Children (C) 1Both GendersMinority & non-minorityChildren & adults 2Only WomenOnly minorityOnly children 3Only MenOnly non-minorityNo children included 4Gender Unknown Minority representation unknown Representation of children unknown 5Only Foreign Subjects

20. All information and opinions are those of Mark A. Shannon, 2007 20 Other Considerations GENDER, MINORITY AND CHILDREN SUBJECTS: ANIMAL WELFARE: Express any comments or concerns about the appropriateness of the responses to the five required points, especially whether the procedures will be limited to those that are unavoidable in the conduct of scientifically sound research. BIOHAZARDS: Note any materials or procedures that are potentially hazardous to research personnel and indicate whether the protection proposed will be adequate. BUDGET: Evaluate the direct costs only. Do not focus on detail. Determine whether the total budget is appropriate for the project proposed. Provide a rationale for suggested modification in amount or duration of support. OTHERS (for Administrative Notes in the Summary Statement): These comments are useful to NIH but should not influence your overall score. FOREIGN: If the applicant organization is foreign, comment on any special talents, resources, populations, or environmental conditions that are not readily available in the United States or that provide augmentation of existing U.S. resources. In addition, indicate whether similar research is being performed in the U.S. and whether there is a need for such additional research. These aspects do not apply to applications from U.S, organizations for projects containing a significant foreign component. CSR Suggested Format of Reviews

21. All information and opinions are those of Mark A. Shannon, 2007 21 Allowed up to three submissions on same topic PM’s and CSR Officials determine if proposal is on same topic and content. Reviews returned within 2 weeks of CSR Review Wants to have quick turnaround so resubmission can occur. Pay close attention to reviews, take at face value, and respond as affirmatively as possible Since goes back to same S.S. at least one of the previous reviewers will see. Also, all on panel can read and comment. There is institutional memory. Reviewers want to see their comments taken seriously and responded to. Else scores will worsen, not become better on subsequent reviews. New reviews There will be at least one new review each time, which means that addressing previous reviews may not be sufficient. New ideas, innovations, and data can strengthen. What to do With Reviews

22. All information and opinions are those of Mark A. Shannon, 2007 Elements Of An NIH Proposal Executive Summary (1/2 page) Introduction Literature review Specific Aims 1-2 for R21, 3-5 for R01 Detailed Research Plan Methods Preliminary data Risk mitigation strategy References cited Biosketches Current and pending support Supporting Letters 22

23. All information and opinions are those of Mark A. Shannon, 2007 The Executive Summary Shorter version (30 lines max) of the introductions you have already been writing Must cover the Heilmeier Criteria Explain exactly what you are going to do with absolutely no jargon Explain Who cares? If you're successful, what difference will it make? What's new in your approach and why do you think it will be successful? No citations (you do not have to cite an expert) 23

24. All information and opinions are those of Mark A. Shannon, 2007 Elements Of An NIH Budget NIH Uses “Modular budgets” up to $250,000/yr Ask for fixed increments of 25K in direct costs Flat budgets for all years 24

25. All information and opinions are those of Mark A. Shannon, 2007 Typical NSF Budget For Starting Faculty Member 25 Year 1Year 2Total PI0000 Others000 others0000 Grad Students1 @ 50%23,50024,67548,175 Fringe Benefits1,2061,2662,471 Total Salary and Fringe24,70625,94150,646 supplies10,000 20,000 travel3,000 6,000 equipment0 tuition remission13,16013,81826,978 Total Direct Costs50,86652,759103,624 F&A20,73821,41742,156 Total Costs71,60474,176145,780

26. All information and opinions are those of Mark A. Shannon, 2007 Typical NIH R21 Budget For Starting Faculty Member 26 Year 1Year 2Total PI2 months15,00015,75030,750 Others0000 others0000 Grad Students1 @ 50%23,50024,67548,175 Fringe Benefits6,5476,87413,421 Total Salary and Fringe45,04747,29992,346 supplies13,79310,88324,676 travel3,000 6,000 equipment0 tuition remission13,16013,81826,978 Total Direct Costs75,000 150,000 F&A34,01233,65067,662 Total Costs109,012108,650217,662

27. All information and opinions are those of Mark A. Shannon, 2007 NIH Hints For New Investigators Start with an R21 (2 years of support) Instructions say no preliminary data needed, but it IS needed Make budget low ($75K of Direct Costs) Be sure to follow the rules 27

28. All information and opinions are those of Mark A. Shannon, 2007 28 Questions?