1. NIH at the Crossroads: Myths, Realities and Strategies for the Future Elias A. Zerhouni, M.D. Director, National Institutes of Health

2. NIH Budget Facing a “Perfect Storm” in 2006  Federal & Trade Deficits  Defense and Homeland Security needs  Katrina  Pandemic flu  Post- Doubling effects  Physical Sciences focus  Biomedical research inflation- 3 to 5%

3. NIH Budget: Myths and Realities…

4. What is Driving Success Rates?  Is NIH placing more emphasis on applied as opposed to basic science  Is NIH shifting towards solicited research (RFAs and PAs) at the expense of unsolicited, investigator-initiated research?  Is it due to the Roadmap?

5. 56.6% 53.9% 55.2% 56.4% 52.1% 53.0% 55.2% 55.8% 55.2% 56.1% 40.5% 39.2% 38.4% 38.5% 39.8% 40.8% 43.5% 41.0% 40.8% 5.0% 7.0% 3.7% 5.7% 5.5% 5.2% 4.8% 3.6% 3.1% 0.0% 10.0% 20.0% 30.0% 40.0% 50.0% 60.0% FY 1998FY 1999FY 2000FY 2001FY 2002FY 2003FY 2004FY 2005FY 2006FY 2007 Basic ResearchApplied ResearchOther Basic and Applied Research

6. What is Driving Success Rates?  Is NIH placing too much emphasis on translational science at the expense of basic research?  Is NIH shifting towards solicited research (RFAs and PAs) at the expense of unsolicited, investigator-initiated research?  Is it due to the Roadmap?

7. Grants: Unsolicited Far Outnumber Solicited 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% 1994199619982000200220042006 Fiscal Year Percentage of Grants UnsolicitedSolicited 91% 93%

8. What is Driving Success Rates?  Is NIH placing too much emphasis on translational science at the expense of basic research?  Is NIH shifting towards solicited research (RFAs and PAs) at the expense of unsolicited, investigator-initiated research?  Is it due to the Roadmap?

9. NIH Roadmap for Medical Research Roadmap 0.8% ($237 Million) Non-Roadmap 99.2% ($28,520 Million) FY2005 Request = $28,757M  Developed to increase synergy across NIH  Not a single initiative but over 345 individual awards in FY05: ― 40% basic ― 40% translational ― 20% high risk

10. What Is Really Happening? 3 Fundamental Drivers  Large capacity building throughout U.S. research institutions and increase in number of tenure-track faculty  Large increase in applicants and applications occurring after 2003  Budgets: –Appropriations below inflation after 2003 ( +3 % in ‘04, 2.2% in ‘05 and 0% in 06 ) while BRDPI in 2004 was ~ 5% –Budget cycling phenomenon

11. New Grant Applications and Success Rates During and After Doubling Period Success Rates Applications Projected Number of Applications % Success Rate of Grants Funded 31% 19% 0% 5% 10% 15% 20% 25% 30% 35% 1998199920002001200220032004200520062007 0 10,000 20,000 30,000 40,000 50,000 60,000 +8,303 +8,359 22% 49,656 43,069 24,154

12. As Many New Applicants in the Last 2 years as during the previous 5 years! ≈ 26583 - 21249 (2003) – (1999) Period of doubling 5334 31791 - 26583 (2005) – (2003) 5208

13. The Budget Cycling Phenomenon: What Funds are Really Available in Any One Year? NIH Appropriations Committed Funds Uncommitted Funds Budget Increase From ending grants started 4-5 years ago From current year to previous year Continuing grants

14. NIH Congressional Appropriations Billions of Dollars DOUBLING $13.7 $15.6 $17.8 $20.5 $23.3 $27.1 $28.0 $28.6 $0 $5 $10 $15 $20 $25 $30 FY 1998 FY 1999 FY 2000 FY 2001 FY 2002 FY 2003 FY 2004 FY 2005 FY 2006 FY 2007 ?

15. The Bottom Line: Demand for Grants “Took Off” Just as NIH Budget Was “Landing!”  NIH managed well in 2004 and 2005 by shifting “one time” funds from 2003 to 2004, and obtaining small increases in 2004 (2.9%) and 2005 (2%)  Katrina requirements led to a flat 2006 NIH while rest of HHS underwent a 2.5% cut  Budget cycling effect will improve demand vs supply of grants in 2007 but we need to educate public about need for sustainability in research

16. The Question on Everyone’s Mind: “What are MY chances of being funded?”  Payline is not the funding cut-off line!  Success rate per application understates funding rate per applicant  FY 2005- 22.3% success rate for applications, but 27.6% for applicants  FY 2006- 19.8% for applications, but ~25% for applicants

17. Success Rate is Higher than the Percentile Payline 010203040 100 0 - 75 - 50- 25 - Percentile Score Percent R01s Funded >99% of grants under the payline are funded Success Rate per application Payline

18. 0% 5% 10% 15% 20% 25% 30% 35% 40% 199519971999200120032005 Applicant Applications Success Rate for R01 Equivalents Fiscal Year Success Rates are always higher for Applicants than for Applications Success Rate files as of May 3, 2006. Program srf_indiv_060103_rfm Individuals are determined using the pi_profile_person_id in IMPAC-II

19. Where Do We Go From Here? Adaptive Strategies A Vision for the Future

20. Strategies  First: Know the facts  Second: Develop adaptive strategies  Protect the essential: Knowledge and Discovery  Increase number of competing grants (supply/demand management)  Support new investigators  New Pathway to Independence Program  Institutes and Centers efforts to assist new investigators  Third: Convey a unified message  Increase communications about positive impact of NIH at local, regional and national levels  Fourth: NIH’s exciting vision for the future

21. The First HapMap Success Story: Age-Related Macular Degeneration  Two other risk variants have been identified in the last two months  Together these account for 74% of risk, and point to powerful new approaches to prevention and treatment

22. Human Genome Project and HapMap: The Foundation of a New Medical Era 1990 - 1997 1998 - 2002 2003 - 2006  New powerful DNA sequencing technologies  Transformation of Genomics from technology to biology- driven science  2007 Genes, Environment, and Health Initiative –Identify roots of 10 most common diseases within 3 years –Devise new ways of monitoring personal environmental exposures –Guide new treatments 17-year investment per American : ~$16.50 Total Average investment per American ~$1 per year

23. Basic Discovery Today Provides the Foundation for Tomorrow’s Medicine Basic Research and Technology Development Translational Research Clinical Applications

24. The Future Paradigm: Transform Medicine from Curative to Preemptive Preemptive Personalized Predictive Participatory

25. Elias A. Zerhouni, MD, Director, NIHMay 4, 2006 NIH Transforming medicine through discovery