1. Critical Path Public Docket: Overview for the FDA Science Board November 5, 2004

2. Presentation Overview  Themes  Caveats and Cautions  Biggest Concerns  Other Priority Hurdles  Other Messages  For More Information

3. Overwhelming Support  Overwhelming Concurrence With Critical Path Diagnosis: recognition of science infrastructure problem.  Overwhelming Concurrence With CP Rx: Initiative focus on research, science-based standards, and collaboration.

4. Overwhelming Support  We Heard This From : drug industry and groups, patient groups, device companies and groups, biotech companies, others.  Recognition of Unique FDA Role: "FDA stands at the gateway between the research laboratory and the patient's bedside, FDA is uniquely positioned to understand the scientific and regulatory hurdles associated with bringing innovative medicines to the marketplace.” -- PhRMA

5. What Patients are Telling Us  “FasterCures is strongly supportive of and encouraged by the FDA’s new Critical Path Initiative. This effort has the potential to contribute to the goal of saving lives by saving time in making new therapies available for use sooner.” -- FasterCures  “…We heartily endorse the FDA for its leadership in launching the Critical Pathway Initiative.” -- Prostate Cancer Foundation

6. What Patients are Telling Us  “We particularly welcome the Critical Path Initiative’s attention to improving models and technology for enhancing the clinical relevance and predictive value of preclinical assays, especially those related to pharmacology and toxicology.” -- AIDS Treatment Activist Coalition  “We commend you for the serious effort you are making to resolve the dilemma we face, and offer you our support and help as we address these challenging questions.” -- National Osteoporosis Foundation

7. What Industry Is Telling Us  “AdvaMed compliments FDA on this effort to develop an organized approach to identifying impediments to and improving the process by which we bring medical products to market. We remark particularly on the recognition that there is more to speeding up the overall process of getting a product to market than simply revising the FDA review and approval process.” -- Advamed  “Baxter applauds the initiative taken by FDA in publishing its report, and is supportive of potential collaborative efforts between industry, academia, and FDA" -- Baxter

8. What Industry Is Telling Us  “A new product develop toolkit is urgently needed to improve predictability and efficiency along the Critical Path. We appreciate the Agency’s efforts to take the lead on this initiative…” --Johnson & Johnson  "BMS agrees with the agency’s overall goal of creating a new generation of performance standards and predictive tools that will provide better information about the safety and effectiveness of an investigational product at an earlier stage in the drug’s development.” -- Bristol-Myers Squibb Co.

9. Call For FDA Action  Submitters call for FDA to undertake research, develop guidances, initiate collaborations, and convene consensus development activities on a wide range of scientific issues.  Docket submitters offer to work with FDA.

10. Demand Exceeds Supply  Docket Demand for FDA Action Exceeds FDA Capacity: Far more proposed than FDA can undertake.  Principles for setting priorities for FDA actions are on Science Board agenda.

11. Presentation Overview  Themes  Caveats and Cautions  Biggest Concerns  Other Priorities  Other Messages  For More Information

12. Caveats and Cautions  This Docket Overview Is Not Comprehensive –Major themes –Flavor of specifics  Docket Is Not the Only Source of Input

13. Presentation Overview  Themes  Caveats and Cautions  Biggest Concerns  Other Priorities  Other Messages  For More Information

14. Overriding Concerns  Clinical Trials  Biomarkers and Endpoints

15. Clinical Trials  New Statistical Tools and Analytic Methods to Support Innovative Trial Design –Bayesian methods, methods for imputing missing data –Adaptive designs, non-inferiority designs, proof of concept trials, enrichment designs  Modeling and Simulation, looking for first steps

16. Clinical Trials  Standardization of Trial Administration –Data collection and submission –Investigator contracts  IT Issues -- encourage development of electronic tech for data collection, monitoring, and reporting

17. Clinical Trials  Disease-specific trial protocols  Patient recruitment, enrollment, and retention  Consortiums and registries  Collaborations with NIH and others  Harmonization of IRB and consent requirements

18. Clinical Trials  Alternative approaches to clinical trials for performance of bacterial detection devices.  Create epilepsy clinical trial consortium.  Create career model for clinical researchers.  Articulate how FDA views use of inadequate therapies as controls.  Educate public about value of trial participation.

19. Biomarkers / Endpoints  Getting to Yes: Clarify Process for Validating Surrogate  Clarify Steps and Evidence for Using Biomarkers for Other Purposes  Work to Establish Biomarkers for Specific Conditions

20. Biomarkers / Endpoints  Requests to publish lists of biomarkers – Diagnostic markers that may be used to enrich study designs –Promising or valid pre-clinical biomarkers, including biomarkers from gene expression studies in animals  Guidance on accepting post-approval studies to validate biomarkers  Standards/guidance on imaging as biomarker

21. Biomarkers / Endpoints  Numerous requests for FDA to work with stakeholders to identify better endpoints in specific conditions: sepsis, SLE, diabetes, Alzheimer’s, variety of cancers, obesity, aging, CF, epilepsy, infectious diseases.  Patient-centered endpoints.

22. Presentation Overview  Themes  Caveats and Cautions  Biggest Concerns  Other Priorities  Other Messages  For More Information

23. Submissions Ask for Attention to Wide Array of Conditions Alzheimer's disease, lupus, scleroderma, cancer in general, prostate cancer, pancreatic cancer, infectious diseases, cystic fibrosis, cardiovascular disease, epilepsy, metabolic diseases/diabetes, osteoporosis, gastroesophageal reflux disease, Parkinson's disease, obesity, rare disorders in general, MS, sepsis, HIV/AIDS, irritable bowel syndrome, ALS, stroke, gastrointestinal diseases in general. Pediatric Therapies

24. Cancer  New approaches to clinical trials (alternative study designs and streamlined administration)  Identify and validate new biomarkers and surrogate markers.  Need for public-private partnerships to boost trial participation, develop plan on specific cancers

25. Cancer  Validate PET for tumor progression  Allow testing earlier in disease  Prioritize oncology drugs for study in pediatric population  Move away from survival as primary endpoint

26. Other Priority Hurdles  In Vitro Diagnostics  Data Pooling / Mining, and Models  Mining FDA-held Data  International Harmonization  Antibiotics

27. Other Priority Hurdles  Modeling/Simulation  Path for Combination Products  Industrialization of Biologics  Medical Countermeasures Against Bioterrorism

28. Presentation Overview  Themes  Caveats and Cautions  Biggest Concerns  Other Priorities  Other Messages  For More Information

29. Regulatory Messages  CP must not substitute for improvements to review process  New CP tools should replace old ones, not constitute new requirements  Clarify regulatory pathways for certain types of products (e.g. combination products, tissue engineered products)

30. Guidances Messages  Do More  Do Them Faster  Keep Them Up To Date  Use Collaborative Process

31. Communications Messages  Lack of consistency within and across divisions, and over time  Create venues for collaboration  More, earlier meetings with FDA

32. Resources Messages  Do Not Divert Resources From Review  Adequate/Consistent Staffing  Does FDA Have Enough?

33. Presentation Overview  Themes  Caveats and Cautions  Biggest Concerns  Other Priorities  Other Messages  For More Information

34. For More Information  Start at FDA website (www.fda.gov)www.fda.gov  Click on the Dockets link  On Docket web page, go to “Dailies”  Click on 2004  Under docket # 2004N-0180, click on the individual days to view CP comments. (The system will not display a cumulative view of submissions.)

35. For More Information http://www.fda.gov/oc/http://www.fda.gov/oc/initiatives/criticalpath/