Public Law 110-85, the Food and Drug Administration Amendments Act of 2007 (FDAAA 2007; PL 110-85) expanded the US Food and Drug Administration (FDA) authorities and responsibilities over drugs1 during the postmarketing period (that is, after a drug is approved to enter the US market). The expanded authorities, many of which were recommended in The Future of Drug Safety: Promoting and Protecting the Health of the Public (IOM, 2007), provide FDA with additional regulatory tools, such as requiring clinical trials or other studies after a drug has been approved, to protect the health of the public. With the expanded postmarketing authorities comes the recognition that critical decisions regarding the study of drugs after approval raise new challenges and questions, both ethical and scientific, for the agency to consider. FDA therefore asked the Institute of Medicine (IOM) to “convene a committee to evaluate the scientific and ethical issues involved in conducting studies of the safety of approved drugs.” The specific questions that the committee was asked to evaluate are presented in Box 1. In light of the scheduling of a joint meeting of FDA’s Endocrinologic and Metabolic Drugs Advisory Committee and Drug Safety and Risk Management Advisory Committee on July 13–14, 2010, FDA requested a letter report addressing question 1 of the charge—“What are the ethical and informed consent issues that must be considered when designing randomized clinical trials to evaluate potential safety risks?”—by July 2010.


In response to FDA’s request, IOM convened a committee of persons who had expertise in clinical trials, epidemiology, pharmacoepidemiology, bioethics, law, patient safety, biostatistics, public health, and health policy. Those experts agreed to prepare both this letter report, which focuses on question 1 of the charge, by July 2010 and a final report that addresses all the questions in the charge by 2011.

For the present letter report, the committee held one meeting, which included an open session in which it heard from representatives of FDA and representatives of the Agency for Healthcare Research and Quality (AHRQ) and the National Institutes of Health (NIH), which funded this report with FDA. The committee provided an opportunity for other stakeholders to present their perspectives and concerns at the meeting. The committee conducted searches of the literature on the ethics of clinical trials and informed consent relevant to postmarketing clini-


1For simplicity, the committee uses the term drugs throughout this report, but similar considerations would apply to biologics.

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