In July, the Department of Health and Human Services and the Office of Science and Technology Policy published an advance notice of proposed rulemaking (ANPRM) proposing sweeping changes to the rules governing oversight of research on human subjects—changes aimed at “better protect[ing] human subjects who are involved in research, while facilitating valuable research and reducing burden, delay, and ambiguity for investigators.”1 The process is likely to amend not only the core regulation on human-subjects research (known as the “common rule”), but also regulations governing vulnerable subjects, IRB registration requirements, research regulations of the Food and Drug Administration, and the “privacy rule” of the Health Insurance Portability and Accountability Act. Our goal here is to provide an annotated guide to the proposed changes.
The ANPRM notes that, “Although the regulations have been amended over the years, they have not kept pace with the evolving human research enterprise, the proliferation of multi-site clinical trials and observational studies, the expansion of health services research, research in the social and behavioral sciences, and research involving databases, the Internet, and biological specimen repositories, and the use of advanced technologies, such as genomics.” In fact, ethicists and investigators alike have claimed that the current regulatory framework is both failing to protect participants and hindering research.
Section I of the ANPRM provides a general background on the federal regulations governing human subjects research. Later sections set forth proposals on matching IRB review to the degree of risk posed by the study, allowing single-IRB review of multisite studies, improving consent forms, ensuring data security, improving adverse event reporting, extending federal protection to all U.S. research, and harmonizing regulations among government agencies. Each proposal includes a long list of questions for public input.
Section II: Ensuring risk-based protections. Current regulations allow the stringency of review to vary somewhat according to the risks of a protocol. For example, expedited review is permitted for “minimal risk” protocols—that is, those that entail no more risk for a research participant than she would encounter in her daily life. But there is little guidance provided beyond identifying a “minimal risk” category, and there are sometimes significant differences in oversight between different IRBs reviewing the same proposal.
The 2002 Institute of Medicine report on research oversight recommended calibration of IRB review to research risks.2 To achieve this goal, the ANPRM suggests the following changes:
• establish mandatory data security and information protection standards for identifiable information, and rules protecting against inappropriate re-identification, so IRBs will not need to review informational risks;
• eliminate or modify continuing review requirements for many studies;
• update the list of categories of research that can use an expedited review mechanism;
• update the concept of “exempt” studies to provide standard protections, while at the same time streamlining procedures to request or review exemptions; and
• require written consent for research on biospecimens, but use a standard form that can include open-ended consent to future research.
Several proposals offer relief both to investigators and to the overworked and underfunded IRB system. Given limited time and resources, it makes sense to calibrate initial and continuing review requirements to risk levels; studies with lower risk should need less oversight. Moreover, if the primary “risk” is a breach of confidentiality, then efforts should focus on data security rather than additional oversight. These changes should receive widespread support.
Perhaps more controversial is the suggestion regarding research with biospecimens. Increasingly, institutions are forming biobanks, or linking biological specimens to existing electronic data-banks. These repositories are valuable research tools, and the scope of individual informed consent controlling the use of biospecimens (even de-identified ones) has been a point of significant contention. While the ANPRM requires written consent, it allows a broad, nonspecific authorization to use the biospecimens in future studies without additional permission. Attention should also be given to the implications of broad authorizations for participants’ ability to withdraw from research and the scope of investigators’ obligations to recontact subjects.
Section III: Streamlining IRB review of multisite trials. Investigators frequently complain about the difficulty of navigating multiple IRB reviews for multisite trials. The...