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?
postmarketing studies, and minimize delays and increase transparency in the agency’s decisions. The committee proposes a three-stage framework that FDA could apply to regulatory decisions prompted by new information that could affect a drug’s benefit–risk profile, and to use for periodic re-evaluations of the benefit–risk profile during a drug’s lifecycle.4 Central to the framework is the importance of eliciting and incorporating the perspective of the patient.5 In the first stage (Stage I) of the framework, FDA should define the public health question that prompted the need for a regulatory decision, including identifying the specific characteristics of the drug and health problem at issue, available information about the drug, alternative treatments that are available, and plausible regulatory actions and their potential consequences. In the second stage (Stage II) of the framework, FDA should evaluate the quality of evidence on both the benefits
4Given its charge, the committee focuses on the use of the framework in the postmarketing setting, but it could also be useful in the premarketing setting.
5FDA should ensure that patient advocacy groups represent the views of patients rather than the views of commercial entities that provide funding to the organizations.