In April 2010, FDA asked IOM to “convene a committee to evaluate the scientific and ethical issues involved in conducting studies of the safety of approved drugs”. The five specific questions posed by FDA appear in Box S-1. In response to FDA’s request, IOM convened a committee of 12 members who have expertise in bioethics, biostatistics, clinical trials, epidemiology, health policy, law, patient safety, pharmacoepidemiology, and regulatory science.

FDA requested two reports: a letter report due in July 20103 and this final report. In its letter report, Ethical Issues in Studying the Safety of Approved Drugs: A Letter Report, released on July 9, 2010, the committee addressed the first question of the committee’s charge by presenting a conceptual framework for analyzing the ethics of postmarketing randomized controlled trials required by FDA. In this final report, the committee addresses all five specific questions posed to the committee by FDA.


The committee met in person six times, including two open information-gathering sessions. The committee used the conceptual framework in its letter report as a starting point for this final report but conducted further research and deliberations related to its full charge. The following underpinnings of that conceptual framework, as well as additional themes that emerged as the committee deliberated its full charge, shaped this report: (1) an understanding of FDA’s public health mission; (2) the importance of adopting a lifecycle approach to drug safety and benefit–risk assessment; (3) FDA’s ethical obligations in making regulatory decisions, including the centrality of transparency and communication to those decisions; and (4) a commitment to using best practices in regulatory science and high-quality evidence in regulatory decision-making.


In Chapter 2, the committee explains the need for FDA to adopt a consistent process for factoring in different evidence in the making of regulatory decisions throughout a drug’s lifecycle. Using a consistent framework for regulatory decision-making will facilitate stakeholder understanding of decisions and the process by which decisions are made, emphasize the dynamic nature of benefit and risk assessments, provide an opportunity to consider the value of additional


3FDA requested that IOM complete the letter report before a July 13–14, 2010, joint meeting of FDA’s Endocrinologic and Metabolic Drugs Advisory Committee and Drug Safety and Risk Management Advisory Committee on rosiglitazone.

The National Academies of Sciences, Engineering, and Medicine
500 Fifth St. N.W. | Washington, D.C. 20001

Copyright © National Academy of Sciences. All rights reserved.
Terms of Use and Privacy Statement