Charge to the Committee

The Food and Drug Administration (FDA) has requested that the Institute of Medicine convene a committee to evaluate the scientific and ethical issues involved in conducting studies of the safety of approved drugs. Questions to be explored by a committee include:

1.  What are the ethical and informed consent issues that must be considered when designing randomized clinical trials to evaluate potential safety risks?

2.  What are the strengths and weaknesses of various approaches, including observational studies, including patient registries, meta-analyses, including patient-level data meta-analyses, and randomized controlled trials, to generate evidence about safety questions?

3.  Considering the speed, cost, and value of studies, what types of follow-up studies are appropriate to investigate different kinds of signals (detected pre-approval or post-marketing) and in what temporal order?

4.  Under what circumstances should head-to-head randomized clinical trials for safety be required?

5.  How should FDA factor in different kinds of safety evidence in considering different kinds of regulatory actions?

cal trials. This letter report does not, however, present a comprehensive literature review of the subject.

Given the short period available for preparing this letter report, the committee focused on identifying a conceptual framework to guide its analysis of the ethics of the design and conduct of postmarketing safety research required by FDA, including key issues that need to be taken into account in assessing ethics and informed consent in randomized controlled trials. In developing this framework, and in its explication in this letter report, the committee relied on the extensive body of codes, regulations and guidance on the ethics of research involving human participants, much of which is built around a commitment to several basic moral principles, including beneficence, respect for persons and their autonomy, and justice. The committee did not enumerate all the ways in which the issues raised in this letter report can affect the ethics of a study, did not detail how the various issues should be weighed against one another, and did not explore in depth issues related to the ethical and scientific justifications of randomized controlled trials. A more detailed analysis of those issues and their implications and effects will be included in the committee’s final report.

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