Regulation of Clinical Trials Robert Silbergleit, MD Department of Emergency Medicine NETT Clinical Coordinating Center

FDA 21 CFR Common Rule 45 CFR PI IRB DSMB Good Clinical Practice (GCP) Sponsor Funder/IC

FDA 21 CFR Longest history of regulation of clinical trials Helsinki principles +/- (1964) Investigational New Drug (IND) or Investigational Device Exemption (IDE) applications Sponsors - initiate and monitor Investigators - plan and perform IRBs - review and approve All drugs and devices in clinical research unless exempt

+ Common Rule 45 CFR Belmont Principles (1979) Beneficence Justice Respect for persons IRB + informed consent requirements Agriculture, Energy, Commerce, HUD, Justice, Defense, Education, VA, Transportation, Homeland, NSF, NASA, EPA, AID, SSA, CIA, CPSC Federally funded research, or research conducted by an institution with an FWA

+ Common Rule 45 CFR Previously OPRR within NIH Compliance oversight Mostly institutional Policy and assurances Federal Wide Assurance (FWA) Registration of IRB’s Education and development Provides guidance Educational programs SACHRP International Federal Wide Assurance (FWA) is a commitment by an institution to the HHS to comply with the common rule.

Good Clinical Practice (GCP) International Conference on Harmonization Helsinki Principles (13 actually) Designing, conducting, recording, reporting trials E6: GCP Consolidated Guideline 1996 Reflect FDA regulations and/or guidance Are conditions for FDA accepting non-US trials Distinct from WHO guidelines for GCP

PI DSMB Funder/IC NIH provides Peer review - content expertise Methodology Human subjects protection Funding Ongoing review CSR

PI IRB DSMB Sponsor Funder/IC Institutional or independent role of central IRB’s Implement/interpret the reg’s Composition Relatively little content expertise Consider local context Communicate with investigators Review and approve applications Review ongoing safety and conduct Unfunded mandates Accreditation controversy

PI IRB DSMB Sponsor Funder/IC Work for Sponsor or the Funder Advice on safety/performance during the ongoing trial Composition variable Mandate is variable

FDA 21 CFR PI IRB DSMB Good Clinical Practice (GCP) Sponsor

+ Common Rule 45 CFR PI IRB DSMB Funder/IC

FDA 21 CFR Common Rule 45 CFR PI IRB DSMB Good Clinical Practice (GCP) Sponsor Funder/IC

FDA 21 CFR PI IRB DSMB Sponsor Funder/IC

FDA 21 CFR Common Rule 45 CFR PI IRB DSMB Good Clinical Practice (GCP) Sponsor Funder/IC