Report at a Glance
Choosing Appropriate Study Designs
While randomized clinical trials may be the gold standard for studying drug efficacy prior to FDA approval, the committee finds that in practice a number of constraints that arise after approval — such as patients’ refusal to participate once the medicine is readily available —can make the kinds of trials needed for certain safety evaluations impractical. Depending on the frequency, magnitude, seriousness, and timing of a suspected adverse event, in many situations observational studies may be preferred for postmarketing research to assess a drug’s risks. Observational studies provide evidence about the possible effect of a treatment for patients who choose to take or not to take a drug—and are not randomly divided into treated groups and control groups, as is done in randomized clinical trials.
By law, the FDA may require a postmarketing clinical trial only under certain conditions, such as when observational studies cannot provide sufficient information to guide agency actions. As a public health agency, the FDA has an ethical obligation to protect people from unsafe medicines and to safeguard the rights and interests of research participants. The FDA must balance these two obligations in deciding which type of postmarketing study to require, and it will need to work with external boards to strengthen ethics oversight over the course of the research.
The committee concludes that the FDA may be justified in requiring studies that could expose patients to heightened risk—but only if a public health question of pressing importance is at stake, if no other study design could supply the needed evidence, and if the FDA relies on the research findings in a timely fashion in formulating its regulatory response. In addition, appropriate safeguards to protect patients’ rights and interests must be in place to ensure that the additional risk is acceptable, and the study should employ a welldesigned informed consent process tailored for the unique aspects of the postmarketing setting.
An estimated 48 percent of all Americans take at least one prescription drug during any given month, according to a 2010 study by the Centers for Disease Control and Prevention. With such widespread use, improving the FDA’s system for assessing the safety of approved drugs could have a major impact on health nationwide.
The FDA’s current approach to drug oversight in the postmarketing setting is not sufficiently systematic and does not ensure that it assesses the benefits and risks of drugs consistently over a drug’s life cycle. Adopting a regulatory framework that is standardized across all drugs, yet flexible enough to adapt to regulatory decisions of differing complexity, could help make the agency’s decisionmaking process more predictable, transparent, and proactive, allowing the FDA to better anticipate post-approval research needs and improving drug safety for all Americans.