Impact of Federal Regulatory Changes on Clinical Pharmacology and Drug Development: the Common Rule and the 21st Century Cures Act.

Abstract

The Federal Policy for the Protection of Human Subjects, generally referred to as the "Common Rule," is the basis for the human research protection policies of 16 signatory federal agencies and governs virtually all federally funded research involving humans. The Common Rule was originally published in 1991. It has been recognized that changes to the Common Rule are needed to accommodate changes in the research environment and advances in information technology. The Department of Health & Human Services (HHS) issued an Advance Notice of Proposed Rulemaking in the Federal Register in 2011 and a Notice of Proposed Rulemaking in 2015. The final rule was published on January 19, 2017, just prior to the change in presidential administrations. The long gestation of the new Common Rule reflects the difficulty of obtaining consensus on a number of controversial issues. HHS received more than 2100 public comments on the proposed rule. The revised rule introduces important changes that may be particularly relevant to clinical pharmacology research and drug development. These include: (1) revised informed consent requirements, (2) procedures for "broad consent" to facilitate secondary research use of identifiable private information and/or biological specimens, (3) a mandate to promote review by a single institutional review board (IRB) for oversight of federally funded domestic cooperative research involving multiple institutions, (4) expansion of the categories of exempt research, and (5) removal of the requirement for annual continuing IRB review of research in which the remaining activities are limited to data analysis or accessing clinical follow-up data. Also noteworthy are proposed revisions not included in the final rule, including one to extend the Common Rule to multicenter studies that are not federally funded and one to require informed consent for research use of de-identified biological specimens. Major changes could also be coming for approval of new drugs by the Food and Drug Administration (FDA), although it is not a signatory to the Common Rule. The 21st Century Cures Act, which became law in December 2016, enables faster drug approvals by expanding the kinds of evidence, beyond traditional clinical trials, that the FDA can consider when reviewing new drug applications. For example, the law allows greater use of surrogate markers and data from "real-world experience" to evaluate a drug's efficacy. The Cures Act requires HHS and the FDA to harmonize differences between the Common Rule and FDA regulations for protection of human subjects in research.