Ram Tiwari, Ph.D. Office of Biostatistics Center for Drug Evaluation and Research

1. Office of Biostatistics Center of Drug Evaluation and Research, FDAPresented at ASA Caucus of Academic Representatives Ram Tiwari, Ph.D. Office of Biostatistics Center for Drug Evaluation and Research U.S. Food and Drug Administration Ram.tiwari@fda.hhs.gov

2. Outline • FDA location and Organizational Charts • What FDA statisticians do - Review of Drug Products - Presentations at Advisory Committees - Write Guidance Documents for Industry - Regulatory Research and Professional Activities - Training, Communication and Outreach • Career Opportunities at FDA

3. FDA White Oak Campus, Silver Spring, MD OB/Building 21

4. New Center 10 70 150 10 40 10 290 Statisticians at FDA and Growing!

5. CDER ORGANIZATIONa condensed version

6. CDER Office of BiostatisticsDirector: Robert T. O’Neill

7. Typical Activities for an OB Statistician • Review the statistical aspects of the drug development process • Present at the advisory committee meeting • Provide the statistical perspective to policy and guidance working groups • Continue to develop professionally: • Conduct research on regulatory science • Participate/ Present at Professional Meetings

8. CDER Drug/Biologic Review Team • Clinicians • Statisticians • Clinical Pharmacologists • Chemists • Pharmacologists /Toxicologists • Microbiologists • Safety Reviewer • Project Managers • Other Scientists, if needed

9. Micro Chem Stats Clinical Pharm/Tox ClinPharm Communication Dynamics between FDA and Industry Industry Project Team Project Manager Regulatory Affairs

10. Types of Applications • IND: Investigational New Drug Application • NDA: New Drug Application • BLA: Biologics License Application

11. Statistical Review of NDA/BLA • Review study protocol and conduct of trial and sponsor’s analyses • Perform additional analyses, if necessary • Re-analyze the primary efficacy data • Conduct sensitivity analyses • Review proposed label

12. Advisory Committee Meetingshttp://www.fda.gov/AdvisoryCommittees/default.htmhttp://www.fda.gov/ohrms/dockets/ac/acmenu.htm • Typical issues at these meetings • Safety, efficacy, risk/benefits questions • Dosing concerns • Target population or labeling issues • Guidelines/Study/Protocol designs • Appeals of FDA decision

13. CDER Special Government Employees(Partial List) Victor De Gruttola Thomas Flemming David Harrington Richard Gelber James H. Ware Daniel Oakes Lee-Jen Wei Stephen George Marvin Zelen Daniel Gillen Dianne Finkelstein Michael Ginsworld David Schoenfield Robert Hamer Scott Evans Joan Hsu Phillip Lavin Andrew Leon Janet Anderson James Neaton John C. Crawley David MeMets Li Ming Dong Weichung Shih Dianne Sisfo Thomas Ten Have Robert Woolson Mary Lindstrom Ying Lu Warren B. Bilker Daniel Sargent

14. Guidance for Industry Adaptive Design Clinical Trials DRAFT GUIDANCE This guidance document is being distributed for comment purposes only. Comments and suggestions regarding this draft document should be submitted within 90 days of publication in the Federal Register of the notice announcing the availability of the draft guidance. Submit comments to the Division of Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852. All comments should be identified with the docket number listed in the notice of availability that publishes in the Federal Register. For questions regarding this draft document contact Robert O’Neill or Sue-Jane Wang at 301-796-1700, Marc Walton at 301-796-2600 (CDER), or the Office of Communication, Outreach and Development (CBER) at 301-800-835-4709 or 301-827-1800. U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER) Center for Biologics Evaluation and Research (CBER) January 2010 Clinical/Medical

15. Guidance for Industry Non-Inferiority Clinical Trials DRAFT GUIDANCE This guidance document is being distributed for comment purposes only. Comments and suggestions regarding this draft document should be submitted within ___ days of publication in the Federal Register of the notice announcing the availability of the draft guidance. Submit comments to the Division of Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852. All comments should be identified with the docket number listed in the notice of availability that publishes in the Federal Register. For questions regarding this draft document contact Robert O’Neill or Robert Temple (CDER) at 301-796-1700, or the Office of Communication U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER) Center for Biologics Evaluation and Research (CBER) January 2010 Clinical/Medical

16. Guidance for Industry Multiple Endpoints in Clinical Trials DRAFT GUIDANCE This guidance document is being distributed for comment purposes only. Comments and suggestions regarding this draft document should be submitted within ___ days of publication in the Federal Register of the notice announcing the availability of the draft guidance. Submit comments to the Division of Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852. All comments should be identified with the docket number listed in the notice of availability that publishes in the Federal Register. For questions regarding this draft document contact Mohammad Huque, Robert O’Neill or Robert Temple (CDER) at 301-796-1700, or the Office of Communication U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER) Center for Biologics Evaluation and Research (CBER) January 2010 Clinical/Medical

17. Work in Progress on Other TWO Guidance Documents • Prevention and Treatment of Missing Data in Clinical Trials- National Academy of Sciences Report • Meta-Analysis for Safety Evaluation

18. Professional Meetings/ Research Activities • 4th Annual FDA/DIA Statistics Forum • Midwest Biopharmaceutical Statistics Workshop • DIA Annual Meeting • ICSA 2010 • Applied Statistics Symposium • Joint Statistical Meetings 2010 • FDA/Industry Statistics Workshop

19. The Critical Path to New Medical Products • Better Evaluation Tools • Streamlining Clinical Trials • Adaptive Trial Designs • Non-inferiority Trials • Multiple Endpoints in Clinical Trials • Enriched Trial Designs • Harnessing Bioinformatics • Moving Manufacturing into the 21st Century • Developing Approaches to Address Urgent Public Health Needs • Sentinel Initiative* • Specific At-Risk Populations -- Pediatrics http://www.fda.gov/ScienceResearch/SpecialTopics/CriticalPathInitiative

20. Regulatory Science and Review Enhancement (RSR) • CDER Regulatory Science and Review • Enhancement Program • RSR MaPP • Overview of 2011 RSR Program • RSR 2011 Cycle *Updated* (Deadline July 16, 2010) • Call for 2011 RSR Applications • Guidelines for RSR 2011 • RSR 2011 Application Form • Instructions for Completion, Approval and Submission of RSR Application Form • RSR Presentations and Awardees (2007-2009)

21. CDER Science Projects and Publications Databases • The CDER Science Projects Database contains basic information about all CDER science and research projects and programs in a searchable format. The database was developed as an information and research management tool. It provides an opportunity for each investigator to clearly communicate the rationale, impact and relevance of their project/program to a broad audience. • All CDER science projects and programs must have an entry in the Research Database. If your project is not in the database, please contact your Division Director. They can contact Jorge Urrutia. • The CDER Publications Database captures publications and abstracts from the entire FDA. CDER publications resulting from research projects in CDER link back to the corresponding project description in the CDER Science Project Database. • Please check that your publications are in the database by performing a Custom Search using your last name in the Author field. If some of your publications are missing, please click on Add Entry link on the Publications Database page to enter them, or email the citations to Tom Maudru.

22. FDA Commissioner’s Fellowship Program • Two-year Program, which provides an opportunity for health professionals and scientists to receive training and experience at the FDA. • Designed to provide in-depth understanding of science behind regulatory review, drugs, devices, biologics and cosmetics • OB Preceptor: Dr. Ram C. Tiwari, Associate Director • http://inside.fda.gov:9003/EmployeeResources/EmploymentOpportunities/CommissionersFellowshipProgram/default.htm

23. Internship Program • Oak Ridge Institute for Science and Education (ORISE) Internship program • The Office of Biostatistics has contracted with ORISE to administer a summer internship program to enable graduate students in statistics to work with some of our staff on important research projects. • http://see.orau.org/ • Internships through CP and RSR Projects

24. For More Information about Careers in Statistics at FDA: • For Links to employment information: http://www.fda.gov/cder/Offices/Biostatistics/ • http://www.fda.gov/jobs/positions08.html • For U.S. Citizens: http://www.usajobs.opm.gov • For U.S. Citizens and non-U.S. Citizens, both with and without green cards: Contact/send resumes to S. Edward Nevius, Deputy Director, FDA/CDER Office of Biostatistics: SEdward.Nevius@fda.hhs.gov

25. Concluding Remarks • The Office of Biostatistics, CDER, would welcome academic institutions’ increased participation in: • FDA Advisory Committees • OB Ambassadors Program • Commissioner’s Fellowship • Internship Program • Sabbatical/Visitors