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”  Federal Deficit, Defense and Homeland Security priority requirements, Katrina, Pandemic flu and domestic budget cuts (- 2.7% for HHS)  Congressional support for Physical Sciences for competitiveness  Overall support for NIH is still strong  Biomedical research inflation in 2004 ~ 5.5%

3. NIH Budget: Myths and Realities…

4. Why Are Success Rates So Low?  Is NIH placing too much emphasis on translational science at the expense of basic research?  Is NIH over-investing in big projects and initiatives at the expense of 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. Why Are Success Rates So Low?  Is NIH placing too much emphasis on translational science at the expense of basic research?  Is NIH over-investing in big projects and initiatives at the expense of investigator- initiated research?  Is it due to the Roadmap?

7. 0.0 2.0 4.0 6.0 8.0 10.0 12.0 14.0 19951996199719981999200020012002200320042005 Fiscal Year Number of Announcements/$Billion $0 $5 $10 $15 $20 $25 $30 $35 Appropriations in Billions RFAs per $Billion PAs per $Billion Appropriations NIH is Committed to Investigator- Initiated Research 10.8 8 5.9 5.8 8.2 12.2 10.8 11.2 8 11.1 7 7.6 8.7 6.6 8.1 5.8 10.9 8.8 8.6 6.3 8.3 10

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

9. Why Are Success Rates So Low?  Is NIH placing too much emphasis on translational science at the expense of basic research?  Is NIH over-investing in big projects and initiatives at the expense of investigator- initiated research?  Is it due to the Roadmap?

10. NIH Roadmap for Medical Research  Developed to –Increase synergy across NIH –Respond to concerns about the perceived “balkanization” of NIH (Congress, IOM report)  Developed with wide extramural input  Beyond the scope of a single Institute or Center and benefits all –Emerging areas of science –High risk/high impact research –Enabling science infrastructure

11. NIDA and the NIH Roadmap  Co-lead on an Interdisciplinary Research Initiative  Development of innovative methodology in social and behavioral sciences research  Involved in the development of clinical trials networks  Supports the Molecular Libraries and Imaging Roadmap Initiative

12. Roadmap in FY05: 0.8% of Total Budget Roadmap 0.8% ($237 Million) Non-Roadmap 99.2% ($28,520 Million) FY2005 Request = $28,757M Roadmap in FY06:  1.2% of budget  133 institutions, 33 states

13. 0 100 200 300 400 500 600 FY04FY05FY06FY07FY08FY09  Not a single initiative but over 345 individual awards in FY05: –40% basic –40% translational –20% high risk  Creates “Incubator Space” to accelerate critical research efforts that address major cross- cutting NIH priorities  This “Incubator Space” is now a permanent part of NIH: Office of Portfolio analysis and Strategic Initiatives (OPASI) Roadmap Funding 1.2% - 1.7% NIH Budget NIH Roadmap for Medical Research

14. Nature, 440:358-362 (March 16, 2006) Science, 331:1600-1603 (March 17, 2006) NIH Director’s Pioneer Award Program  New program designed to support individuals with high-risk, potentially groundbreaking ideas  Example: Sunney Xie of Harvard University –First to show translation of a gene at the level of a single protein molecule in a live cell –His work published in Science and Nature simultaneously

15. What Is Really Happening? 3 Fundamental Drivers  Large capacity building throughout U.S. research institutions and dramatic 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 ~ 5.5% –4-year budget cycling phenomenon

17. Comparing the % of Grant Applications Funded (or “Success Rate”) with the Number of New Applications Success Rates Applications Projected Number of Applications % Success Rate of Grants Funded 31% 32% 31% 30% 22% 19% 40,862 34,710 30,069 28,368 27,798 26,407 24,154 46,50 1 49,656 0% 5% 10% 15% 20% 25% 30% 35% 1998199920002001200220032004200520062007 0 10,000 20,000 30,000 40,000 50,000 60,000 43,069 +8,303 +8,359 25%

18. ≈ 43069 - 34710 (2005) – (2003) As Many New Applications in the Last 2 years as During the Doubling Period of doubling 34710 - 26407 (2003) – (1999) 83038359

19. As Many New Applicants in the Last 2 years as During the Doubling ≈ 26583 - 21249 (2003) – (1999) Period of doubling 5334 31791 - 26583 (2005) – (2003) 5208

20. 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

21. 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 ?

22. Why is the Transition so Painful?  Demand for grants “took off” (2002- 2006) just as the NIH budget was ”landing” (1999-2003)  More increase in demand for grants in last 2 years than in the full 5 years of the doubling  NIH budget increases below inflation  Budget cycle effects- uncommitted pool in 2006 comes from 2001-2002 when doubling did not yet occur  2003 commitments will become available in 2007, allowing for a 3% increase in competing grants (even with a flat budget)

23. The Question on Everyone’s Mind: “What are my chances of being funded?”  Because number of applications per applicant has increased from 1.2 to 1.5, success rate understates funding rate - Translates to approximately 15,000 extra applications  FY 05- 22.3% success rate for applications, but 27.6% for individual applicants  FY 06- 19.8% for applications, but ~25% for individual applicants  Payline is not the funding cut-off line!

24. Where Do We Go From Here? The Vision for the Future

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

26.  63% decrease in mortality  ~ 1 million early deaths averted per year  $2.6 trillions in economic return  New effective treatments  More effective prevention  Successfully reduced cholesterol levels in the population  New discoveries being developed by industry Coronary Heart Disease Today 500 400 300 200 100 505560657075808590 95 00 Deaths per 100,000 Year ~ 514,000 Actual Deaths in 2000 ~ 1,329,000 Projected Deaths in 2000 0 5 10 15 20 25 30 35 1960-621971-74 1976-801988-94 1999-02 % population with high serum cholesterol Total investment per American over the past 30 years : ~$110 Average annual investment per American ~$3.70

27. Cancer Today  For the first time annual cancer deaths in the United States have fallen  10 million survivors  Early detection and screening are more effective  New targeted, minimally invasive treatments for cancer have multiplied  New discoveries make it possible for the first time to personalize cancer treatment Survivorship Millions of People 1971 198619902003 9 6 3 Total investment per American over the past 30 years : ~$260 Average annual investment per American ~$8.60

28. Orders of magnitude more effective Expensive in financial and disability costs Understanding preclinical molecular events and ability to detect patients at risk Did not understand the molecular and cellular events that lead to disease Intervene before symptoms appear and preserve normal function for as long as possible Treat disease when symptoms appear and normal function is lost 21 st Century20 th Century Need to Transform Medical Research in the 21st Century

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

30. Tolerable Intolerable Preclinical Time Cost Molecular preemption Curative treatment Symptom management Disease Burden Cost Savings The Future Paradigm: Preempt Disease

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

32. NIH Competing Funds Remain Relatively Constant Amount of NIH Extramural Awards (Excluding R&D Contracts) 0 $5,000 $10,000 $15,000 $20,000 $25,000 19981999200020012002200320042005 Fiscal Year Dollars Awarded (Millions) Competing Noncompeting

33. Predictive: End Stage Renal Disease  End Stage Renal Disease (ESRD): –$22.8 billion in U.S. public and private spending (2001) –In the past decade, the absolute number of ESRD patients more than doubled and the incidence rate doubled –More than 85,000 new cases per year  Apolipoprotein E (APOE): –Variation predicts kidney disease progression –Prediction independent of diabetes, race, lipid and non- lipid risk factors

34. Predict which patients need chemotherapy Impact:  100,000 women each year can make a more informed choice  70,000 women do not have to undergo chemotherapy  Reduces routine cost of treating these patients Test tumor samples for mutations in these genes Personalize: Cancer Treatment Identified 16 informative genes

35. Preemptive: HPV Vaccine  Human Papillomavirus (HPV) infects over 80% of 15-50 year old women and can cause cervical cancer  Prevent sexually transmitted HPV infection = prevent cervical cancer  Anti-viral vaccines are among the most cost effective public health interventions (e.g., smallpox, polio, & measles)  NIH has two vaccines currently in clinical trials