Discussion: Biostatistics in Public Policy

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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

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Outline

• Biostatisticians
• FDA Advisory Committees
• Guidance Documents
• Statistical Research
• Biostatistician Roles

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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)

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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

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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

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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

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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

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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.

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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).

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Bayesian Guidance

• Finalized February 5, 2010.
• http//www.fda.gov/MedicalDevices/DeviceRegulation
  andGuidance/GuidanceDocuments/ucm071072.htm

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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/DeviceRegulation
  andGuidance/GuidanceDocuments/ucm265553.htm

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Benefit-Risk Draft Guidance
Issued August, 2011
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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).

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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

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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,
  DrugDiagnostic Co-development
• Microarrays (MAQC-II)

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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

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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

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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)

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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
  peoples lives very day!