BOX 1-1
Charge to the Committee

The US 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 postapproval) 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?

later, after more than 100 deaths, many in children, caused by diethylene glycol in an elixir of sulfanilamide, the Food, Drug, and Cosmetic Act (FDCA)5 was enacted (FDA, 2009a). Under the FDCA, a new drug could not enter into interstate commerce unless its sponsor filed a new-drug application (NDA) with FDA that contained convincing evidence from preclinical toxicity testing that the drug was safe for its intended uses (Daemmrich, 2004a; Marks, 1997a). A drug was to be evaluated only with regard to its toxicity; its sponsor was not required to provide FDA with evidence of effectiveness or benefits. FDA could, however, deem a drug misbranded “if its labeling is false or misleading”.6 Under those conditions, FDA had the authority to withdraw its approval of the drug and to prosecute the drug sponsor (Carpenter, 2010a; Daemmrich, 2004a; Grossman et al., 2007; Marks, 1997a).7


5Food, Drug, and Cosmetic Act, PL No. 75-717, 52 Stat. 1040 (1938).

621 USC § 331(a), (b), (c), (k) (2010).

721 USC § 331 (2010).

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