Discussion: Discussion: Biostatistics in Biostatistics in Public PolicyPublic Policy

Greg Campbell, Ph.D.Greg Campbell, Ph.D.

Director, Division of BiostatisticsDirector, Division of BiostatisticsCenter for Devices and Radiological HealthCenter for Devices and Radiological Health

Food and Drug AdministrationFood and Drug Administration

Statistics in Public Policy, ASA, February 3, 2012Statistics in Public Policy, ASA, February 3, 2012

OutlineOutline

BiostatisticiansBiostatisticians FDA Advisory CommitteesFDA Advisory Committees Guidance DocumentsGuidance Documents Statistical ResearchStatistical Research Biostatistician RolesBiostatistician Roles

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BiostatisticiansBiostatisticians AcademicAcademic

Departments of Biostatistics in Schools of Public Departments of Biostatistics in Schools of Public Health and Schools of MedicineHealth and Schools of Medicine

Statistics Departments and Mathematics Statistics Departments and Mathematics Departments Departments

Federal Government:Federal Government: NIH, FDA, CMS, CDC (including NCHS), EPA, VANIH, FDA, CMS, CDC (including NCHS), EPA, VA

State and local governmentState and local government Industry (pharma, devices, biologics)Industry (pharma, devices, biologics) Contract Research Organizations (CROs) and Contract Research Organizations (CROs) and

Academic Research Organizations (AROs)Academic Research Organizations (AROs)

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Food and Drug Food and Drug AdministrationAdministration

Science-based agency that values transparency and Science-based agency that values transparency and innovationinnovation

Regulates about 25% of the GDP of U.S.Regulates about 25% of the GDP of U.S. Makes enormous amount of pre-market and post Makes enormous amount of pre-market and post

market (adverse event reports) information market (adverse event reports) information available; preliminary information for FDA Adv. available; preliminary information for FDA Adv. Com. and transcripts Com. and transcripts

Companies generate data on which FDA bases Companies generate data on which FDA bases almost all decisionsalmost all decisions

Does not take cost into account in approval Does not take cost into account in approval decisionsdecisions

The tradition of pre-specification in trial planningThe tradition of pre-specification in trial planning

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Federal Advisory Federal Advisory Committee Act (FACA)Committee Act (FACA)

About 1000 committees with a total of About 1000 committees with a total of 45,000 members serving 54 federal agencies 45,000 members serving 54 federal agencies of the US government provide expert advice, of the US government provide expert advice, shaping the programs and policies of the shaping the programs and policies of the U.S. Government.U.S. Government.

Meetings are generally open unless there is Meetings are generally open unless there is a good reason for a closed meeting a good reason for a closed meeting

Meetings and committees announced in the Meetings and committees announced in the Federal RegisterFederal Register

Activities are tracked by GSAActivities are tracked by GSAwww.fido.facadatabase www.fido.facadatabase

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FDA Advisory FDA Advisory CommitteesCommittees

FDA has at the agency level Advisory FDA has at the agency level Advisory Committees for Science Board, Risk Committees for Science Board, Risk Communication, and PediatricsCommunication, and Pediatrics

Center for Drug Evaluation and Research has Center for Drug Evaluation and Research has 1616

Center for Devices and Radiological Health Center for Devices and Radiological Health has 4, one of which is Medical Device Advisory has 4, one of which is Medical Device Advisory Committee, which has 174 members in 18 Committee, which has 174 members in 18 Panels Panels

Center for Biologic Evaluation and Research Center for Biologic Evaluation and Research has 5has 5

Center for Food Safety and Nutrition has 1Center for Food Safety and Nutrition has 1 Center for Vet. Med. has 1Center for Vet. Med. has 1 National Center for Tox. Res. has 1National Center for Tox. Res. has 1

FDA and Advisory FDA and Advisory CommitteesCommittees

Usually one or more statisticians on each Usually one or more statisticians on each panel.panel.

Two types of meetings (all with public Two types of meetings (all with public comment and patient and industry non-voting comment and patient and industry non-voting reps)reps) Advice about a particular submission (PMA, HDE, Advice about a particular submission (PMA, HDE,

sometimes a 510(k)) with presentations by the sometimes a 510(k)) with presentations by the company and FDAcompany and FDA

Advice about trial design or post-market issuesAdvice about trial design or post-market issues All conflicts of participants are reviewedAll conflicts of participants are reviewed All issues are discussed openlyAll issues are discussed openly

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Statistical Issues at Statistical Issues at PanelsPanels

Bayesian StatisticsBayesian Statistics Use of propensity score methodology Use of propensity score methodology

for non-randomized studiesfor non-randomized studies Treatment of missing dataTreatment of missing data Bias in diagnostic studiesBias in diagnostic studies Challenge is to make the issues Challenge is to make the issues

understandable to non-statisticians understandable to non-statisticians on the panel and in the audience.on the panel and in the audience.

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FDA Guidance FDA Guidance DocumentsDocuments

Guidance for Clinical Trial Sponsors: Guidance for Clinical Trial Sponsors: Establishment and Operation of Clinical Establishment and Operation of Clinical Trial Data Monitoring Committees Trial Data Monitoring Committees (March, 2006).(March, 2006).

Statistical Guidance on Reporting Results Statistical Guidance on Reporting Results from Studies Evaluating Diagnostic Tests from Studies Evaluating Diagnostic Tests (March, 2007).(March, 2007).

The Use of Bayesian Statistics in Medical The Use of Bayesian Statistics in Medical Device Clinical Trials (February, 2010).Device Clinical Trials (February, 2010).

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Bayesian GuidanceBayesian Guidance

Finalized February 5, 2010.

http://http://www.fda.gov/www.fda.gov/MedicalDevices/MedicalDevices/DeviceRegulationaDeviceRegulationandGuidance/ndGuidance/GuidanceDocumenGuidanceDocuments/ucm071072.htmts/ucm071072.htm

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Pivotal Clinical Study Pivotal Clinical Study Design Draft GuidanceDesign 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

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Benefit-Risk Draft Benefit-Risk Draft GuidanceGuidance

Issued August, 2011

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Other Draft Guidance Other Draft Guidance DocumentsDocuments

Draft Guidance for Industry and Food Draft Guidance for Industry and Food and Drug Administration Staff - and Drug Administration Staff - Evaluation of Sex Differences in Medical Evaluation of Sex Differences in Medical Device Clinical Studies (December, Device Clinical Studies (December, 2011).2011).

Adaptive Design Clinical Trials for Drugs Adaptive Design Clinical Trials for Drugs and Biologics (issued by CDER and and Biologics (issued by CDER and CBER, February, 2010).CBER, February, 2010).

Non-Inferiority Clinical Trials (issued by Non-Inferiority Clinical Trials (issued by CDER and CBER, March, 2010).CDER and CBER, March, 2010).

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Quantitative Decision Quantitative Decision Analysis Initiative in Analysis Initiative in

CDRHCDRH Led by Telba IronyLed by Telba Irony How FDA makes decisions on the How FDA makes decisions on the

approval or clearance of pre-market approval or clearance of pre-market submissions and on post-market and submissions and on post-market and compliance actionscompliance actions

Quantifying not only risks but also Quantifying not only risks but also potential benefits. potential benefits. HDEs versus PMAs, first-of-a-kind HDEs versus PMAs, first-of-a-kind

devicedevice14

Some Products with Some Products with Public Health Public Health ImplicationsImplications

Prostate Screening Antigen (PSA) testsProstate Screening Antigen (PSA) tests Test for Human Papilloma Virus (HPV)Test for Human Papilloma Virus (HPV) Evaluation of Digital MammographyEvaluation of Digital Mammography Clinical Trial Designs for Left Ventricular Clinical Trial Designs for Left Ventricular

Assist DevicesAssist Devices Pediatrics medical productsPediatrics medical products Personalized medicine (Companion Personalized medicine (Companion

diagnostics, Drug–Diagnostic Co-diagnostics, Drug–Diagnostic Co-developmentdevelopment

Microarrays (MAQC-II)Microarrays (MAQC-II)

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Biostatistical ResearchBiostatistical Research

Funded by NSF, NIH and a little by Funded by NSF, NIH and a little by FDAFDA

Research review of scientists by NIH Research review of scientists by NIH and FDAand FDA Intramural lab reviewsIntramural lab reviews FDA Science Board SubcommitteeFDA Science Board Subcommittee FDA Regulatory Statistical ResearchFDA Regulatory Statistical Research

Internal to CDRH there is a Center Internal to CDRH there is a Center Science CouncilScience Council

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National AcademiesNational Academies

Includes National Academy of Includes National Academy of Science, Institute of MedicineScience, Institute of Medicine

Statistical committees CATS and Statistical committees CATS and CNSTATCNSTAT

ReportsReports The Prevention and Handling of Missing The Prevention and Handling of Missing

Data in Clinical TrialsData in Clinical Trials Small n Clinical TrialsSmall n Clinical Trials

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The Role of the The Role of the BiostatisticianBiostatistician

Communicate wellCommunicate well Understand the subject matter area Understand the subject matter area Educate non-statisticiansEducate non-statisticians Communicate not just point Communicate not just point

estimates but uncertainty (within the estimates but uncertainty (within the model and of the model)model and of the model)

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Closing RemarksClosing Remarks

We need to be sure to communicate We need to be sure to communicate well with non-statisticians.well with non-statisticians.

We need to be able to partner well We need to be able to partner well with decision-makers in many other with decision-makers in many other disciplines.disciplines.

We statisticians can make a We statisticians can make a difference in people’s lives very day!difference in people’s lives very day!

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