is indicated. However, premarketing data used in approval applications are collected from studies that involve small numbers of participants2—often only a few hundred or a few thousand—over a relatively short period of time (IOM, 2007a), so not all risks associated with a drug are known at the time of approval. Warnings or restrictions may be added to the product label, or a drug may be removed from the market because unexpected or greater than expected morbidity or mortality is identified only after a drug enters widespread use. The discovery of new adverse events in the postmarketing setting is part of the normal, natural history of approved drugs. The timely identification of and response to drug-related risks are central to the mission of FDA.

Recent advances in information technology, including electronic health records, and changes in FDA laws, such as the Food and Drug Administration Amendments Act (FDAAA) of 2007,3 provide the opportunity to improve the system for ensuring that drugs are safe and effective. Previous Institute of Medicine (IOM) reports have made recommendations about improving aspects of drug-related patient-safety issues to FDA, other federal agencies, and Congress (IOM, 2002, 2004, 2007a,b). However, no report has focused specifically on the ethical and scientific issues that arise in the postmarketing environment, including how these issues intersect with the authority of FDA to require manufacturers to conduct postmarketing research and how FDA should integrate that authority and evidence, into its regulatory decision-making. The present report addresses those issues in response to the committee’s charge (see Box 1-1) and offers specific recommendations about the ethics and science of FDA required postmarketing research and about the decision-making process about approved drugs when safety issues arise.


Food and Drug Administration Authority Before 2007

FDA’s regulatory authority has evolved over the last 100 years, often as a result of serious drug-related adverse events or deaths. Table 1-1 presents some milestones in FDA’s regulatory history. The initial grant of authority to FDA’s predecessor agency began in 1906 with the passage of the Pure Food and Drug Act,4 which, for drugs, focused on misbranding and adulteration. Thirty years


2Throughout this report, the committee uses the term participants or research participants rather than human subjects. The committee recognizes that both terms have been used in policy discussions on this topic for decades and that neither term perfectly captures the nature of the relationship between the persons who are studied in research (who are both subjects of research and participants in research) and those who are conducting the research.

3Food and Drug Administration Amendments Act of 2007, PL No. 110-85, 121 Stat. 823 (2007).

4Pure Food and Drug Act of 1906, PL 59-384, 34 Stat. 768 (1906).

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