1. Discussion: Biostatistics in Public Policy
Greg Campbell, Ph.D.
Director, Division of Biostatistics Center 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 Federal Government: 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

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.

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

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!