FDA issued guidelines last week that identify which adverse events arising during clinical studies need to be reported to institutional review boards (IRBs) and that clarify the process for reporting unanticipated events. FDA also released a final rule requiring all U.S. IRBs that review FDA-regulated trials to register with FDA. Adverse events often become fodder for plaintiff attorneys in mass tort litigation concerning approved products, as plaintiffs attempt to argue that early risk “signals” were missed or downplayed– as they employ the benefit of 20-20 hindsight.

FDA regulates clinical studies under sections 505(i) (drugs and biologics) and 520(g) (devices) of the Food, Drug, and Cosmetic Act. All such clinical studies must be reviewed and approved by an IRB before the study is initiated, in accordance with the requirements of 21 CFR part 50 (Protection of Human Subjects), part 56 (Institutional Review Boards), and either part 312 (Investigational New Drug Application) or part 812 (Investigational Device Exemptions) (see §§ 50.1, 56.101, 312.23(a)(1)(iv), 312.40(a), 812.2(b)(1)(ii), 812.2(c) and 812.62(a)).

After the initial review and approval of a clinical study, an IRB must conduct continuing review of the study at intervals appropriate to the degree of risk presented by the study, but at least annually. The primary purpose of both initial and continuing review of the study is to assure the protection of the rights and welfare of the human subjects. To fulfill its obligations during the conduct of a clinical study, an IRB must have, among other things, information concerning unanticipated problems involving risk to human subjects in the study, including adverse events that are considered unanticipated problems

This new guidance is intended to assist the research community in interpreting requirements for submitting reports of unanticipated problems, including certain adverse events reports, to the institutional review board. FDA developed this guidance in response to concerns raised by the IRB community, including concerns raised at a March, 2005 public hearing, that increasingly large volumes of individual adverse event reports submitted to IRBs—often lacking in context and detail—are inhibiting, rather than enhancing, the ability of IRBs to protect human subjects.