The Food and Drug Administration (FDA) is responsible for ensuring the safety of prescription drugs. Though all drugs are tested in clinical trials before they are available to the public, the risks of some drugs may not appear until well after they are approved. With the passage of the Food and Drug Administration Amendments Act (FDAAA) of 2007, the FDA can now require clinical trials or other studies to assess the safety of approved drugs. With this new authority, the FDA must decide when it is ethical for the Agency to require or continue to require clinical trials, and how to ensure the safety of trial participants.
The FDA requested that the Institute of Medicine (IOM) examine when and how to conduct clinical trials ethically to evaluate drug safety. The IOM recommended that the FDA should ensure that any randomized, controlled trial to evaluate the efficacy and safety of an approved drug that is suspected of causing serious adverse events is conducted only when a responsible policy decision cannot be made based either on the existing evidence or on evidence from new observational studies. The IOM suggested that observational studies – often done by reviewing insurance claims and other databases – can yield strong enough evidence to make a decision on a marketed drug.
The Agency should determine that questions about a drug’s possible risks or risk-benefit balance rise to the level of requiring a policy decision, such as whether to revise the product’s label. In addition, FDA should make sure that trials are appropriately designed to resolve uncertainties about efficacy and safety and to minimize risks to participants. A conceptual framework broadly applicable to many situations is provided.
This report is part of a larger study of the scientific and ethical issues involved in conducting studies of the safety of approved drugs. A comprehensive report is expected in 2011.