Discussion: Biostatistics in Public Policy

1. Discussion: Biostatistics in Public Policy Greg Campbell, Ph.D. Director, Division of BiostatisticsCenter for Devices and Radiological Health Food and Drug Administration Statistics in Public Policy, ASA, February 3, 2012

2. Outline Biostatisticians FDA Advisory Committees Guidance Documents Statistical Research Biostatistician Roles

3. Biostatisticians Academic • Departments of Biostatistics in Schools of Public Health and Schools of Medicine • Statistics Departments and Mathematics Departments Federal Government: • NIH, FDA, CMS, CDC (including NCHS), EPA, VA State and local government Industry (pharma, devices, biologics) Contract Research Organizations (CROs) and Academic Research Organizations (AROs)

4. Food and Drug Administration Science-based agency that values transparency and innovation Regulates about 25% of the GDP of U.S. Makes enormous amount of pre-market and post market (adverse event reports) information available; preliminary information for FDA Adv. Com. and transcripts Companies generate data on which FDA bases almost all decisions Does not take cost into account in approval decisions The tradition of pre-specification in trial planning

5. Federal Advisory Committee Act (FACA) • About 1000 committees with a total of 45,000 members serving 54 federal agencies of the US government provide expert advice, shaping the programs and policies of the U.S. Government. • Meetings are generally open unless there is a good reason for a closed meeting • Meetings and committees announced in the Federal Register • Activities are tracked by GSA www.fido.facadatabase

6. FDA Advisory Committees • FDA has at the agency level Advisory Committees for Science Board, Risk Communication, and Pediatrics • Center for Drug Evaluation and Research has 16 • Center for Devices and Radiological Health has 4, one of which is Medical Device Advisory Committee, which has 174 members in 18 Panels • Center for Biologic Evaluation and Research has 5 • Center for Food Safety and Nutrition has 1 • Center for Vet. Med. has 1 • National Center for Tox. Res. has 1

7. FDA and Advisory Committees Usually one or more statisticians on each panel. Two types of meetings (all with public comment and patient and industry non-voting reps) • Advice about a particular submission (PMA, HDE, sometimes a 510(k)) with presentations by the company and FDA • Advice about trial design or post-market issues All conflicts of participants are reviewed All issues are discussed openly

8. Statistical Issues at Panels Bayesian Statistics Use of propensity score methodology for non-randomized studies Treatment of missing data Bias in diagnostic studies Challenge is to make the issues understandable to non-statisticians on the panel and in the audience.

9. FDA Guidance Documents Guidance for Clinical Trial Sponsors: Establishment and Operation of Clinical Trial Data Monitoring Committees (March, 2006). Statistical Guidance on Reporting Results from Studies Evaluating Diagnostic Tests (March, 2007). The Use of Bayesian Statistics in Medical Device Clinical Trials (February, 2010).

10. Bayesian Guidance • Finalized February 5, 2010. • http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm071072.htm

11. Pivotal Clinical Study Design Draft Guidance • Discusses several concepts that are fundamental to Good Device Development Practices with respect to clinical trials. • Some of these concepts have always been true, but have not been promulgated widely by the Agency • http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm265553.htm

12. Benefit-Risk Draft Guidance Issued August, 2011

13. Other Draft Guidance Documents Draft Guidance for Industry and Food and Drug Administration Staff - Evaluation of Sex Differences in Medical Device Clinical Studies (December, 2011). Adaptive Design Clinical Trials for Drugs and Biologics (issued by CDER and CBER, February, 2010). Non-Inferiority Clinical Trials (issued by CDER and CBER, March, 2010).

14. Quantitative Decision Analysis Initiative in CDRH Led by Telba Irony How FDA makes decisions on the approval or clearance of pre-market submissions and on post-market and compliance actions Quantifying not only risks but also potential benefits. • HDEs versus PMAs, first-of-a-kind device

15. Some Products with Public Health Implications Prostate Screening Antigen (PSA) tests Test for Human Papilloma Virus (HPV) Evaluation of Digital Mammography Clinical Trial Designs for Left Ventricular Assist Devices Pediatrics medical products Personalized medicine (Companion diagnostics, Drug–Diagnostic Co-development Microarrays (MAQC-II)

16. Biostatistical Research Funded by NSF, NIH and a little by FDA Research review of scientists by NIH and FDA • Intramural lab reviews • FDA Science Board Subcommittee • FDA Regulatory Statistical Research Internal to CDRH there is a Center Science Council

17. National Academies Includes National Academy of Science, Institute of Medicine Statistical committees CATS and CNSTAT Reports • The Prevention and Handling of Missing Data in Clinical Trials • Small n Clinical Trials

18. The Role of the Biostatistician Communicate well Understand the subject matter area Educate non-statisticians Communicate not just point estimates but uncertainty (within the model and of the model)

19. Closing Remarks We need to be sure to communicate well with non-statisticians. We need to be able to partner well with decision-makers in many other disciplines. We statisticians can make a difference in people’s lives very day!