1. Current Plan for Critical Path Initiative Janet Woodcock, M.D. Acting Deputy Commissioner For Operations November 5, 2004

2. Public Health Significance of Critical Path Initiative l l Overall goal: Improve health by increasing efficiency, effectiveness, and informativeness of medical product development process l l Problem: The development process is stagnating due to lack of scientific attention l l Approach: Modernize development process using new scientific tools

3. Public Health Significance of Critical Path: Consequences of Stagnation l l Fewer products for important health needs: e.g., vaccines & antibiotics l l Disincentives to develop preventive, Rx targeted, or individualized therapies l l Disincentives to develop therapies for less common diseases l l Diminished competition l l Fewer diagnostics

4. Public Health Consequences: Slowed Biomarker Development l l Today’s biomarkers are tomorrow’s diagnostics l l Diagnose and subset disease; monitor response to therapy; evaluate need for additional therapy; establish prognosis l l Biomarkers and targeted therapies should be developed concurrently (e.g., HIV viral copy number/protease inhibitors) l l Current climate is inhibitory

5. Activities to Date l l Publication of White Paper: March ‘04 l l Analysis of docket submission l l Extensive discussion with external stakeholders l l Extensive discussion with internal stakeholders

6. Tremendous Number of Opportunities Identified: Also Common Themes l l Improving Clinical Phase of Product Development l l Accelerating Development and Regulatory Acceptance of Biomarkers and Surrogate Markers l l Mining FDA’s Databases

7. Common Themes l l Develop additional science-based FDA standards in numerous areas: computer modeling, product testing, statistical analysis, data l l Develop additional science-based FDA test protocols reagents, etc l l Perform all the above using professional society – academic-industry-FDA consortia

8. Next Steps l l Obtain science board input on priorities l l Publish Opportunities List l l Initiate (’05) limited set of projects based on available resources

9. Initiatives We Will Begin this Year l l Clinical Trials Improve the clinical phase of medical product development Standardize data collection and handling l l Development of Biomarker and Surrogate Markers

10. Clinical Development: Facilitating Medical Device Development l l Improving Premarket – Postmarket Balance l l Leveraging outside expertise with the Medical Device Fellowship Program l l Working (with CDER) to develop surrogate endpoints for HIV induced lipoatrophy treatments

11. Clinical Development: Early Drug Development l l Quantitative disease modeling and trial simulation l l Incorporation of early PK/PD data l l October DIA meeting on “Dose-response” to begin dialog on improvement of early clinical trials

12. Clinical Trial Process: Streamlining Data Collection & Analysis l l Many comments to docket l l Offers from potential collaborators l l Opportunity to save time and money without decreasing quality l l FDA can convene & lead effort

13. Accelerate Development and Regulatory Acceptance of Novel Trial Designs l l Various enrichment, sequential, and Bayesian designs have been widely discussed l l Use not widespread due to concerns about regulatory acceptance l l Need concrete demonstration projects or guidance (or both) to move field along

14. Develop Scientific Consensus on Specific Methodologic and Analytic Issues l l Treatment of multiple endpoints l l Design/analysis of non-inferiority trials l l Treatment of missing data in longer term trials

15. Corresponding Internal FDA Assessment: Corresponding Internal FDA Assessment: FDA oversight of clinical trials process – “Bioresearch Monitoring” (BiMo) and IRB inspections Project recently initiated – in formative stages Evaluate objectives and effectiveness of programs Modify programs in concert with other parts of the initiative Evaluate regulatory obstacles to clinical trial process

16. Accelerate Development and Regulatory Acceptance of Biomarkers and Surrogate Markers l l Public discussion and consensus development on the general framework for working up and accepting surrogate markers Public workshops White paper or other document l l Further progress on pharmacogenomics as a worked example

17. Collaboration on Specific Biomarker Projects l l Cooperative research with industry on safety biomarkers l l Potential data mining projects l l Evaluate use of consortia to advance specific markers l l “Imaging as biomarker” project

18. Other Important Projects l l Antimicrobial/antiviral vaccine development l l Pediatric drug/device development l l Biomarkers in adolescent depression l l Many more

19. Summary l l Many important projects identified l l FDA seeks the Science Board’s advice on prioritization l l FDA will undertake a few projects in ’05 where consensus and resources exist l l FDA will seek collaborators to accomplish additional work