FDA to require a postmarketing study and what types of studies to require when that is the case, how best to protect the rights and interests of patients who serve as participants in the research that it requires, and how it should use the information from the required postmarketing studies and from other available research (for example, studies initiated by academic researchers) in making regulatory decisions. The present committee’s charge to evaluate the scientific and ethical issues involved in conducting studies of the safety of approved drugs reflects those challenges.

In this chapter, the committee summarizes its responses to the specific questions in its charge (see Box 1-1) and gathers its broad findings and recommendations.2


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

In response to this question, the committee notes that no single algorithm can determine how to factor different kinds of safety evidence into regulatory decision-making, but does specify processes and principles to guide how this should occur. The committee identifies five actions, discussed below, that FDA can take to improve its decision-making processes in response to different kinds of safety evidence: (1) adopt a specified decision-making framework; (2) create a Benefit and Risk Assessment and Management Plan (BRAMP) document for each drug that is maintained across the drug’s lifecycle; (3) characterize the nature of any disagreements about the evidence of benefits or risks; (4) create effective multidisciplinary teams with wide-ranging expertise, including in observational study design and interpretation, outcomes research and pharmacoepidemiology, Bayesian methods and modern causal inference approaches, and (5) adhere to the principles of reproducible research.

The committee proposes that FDA use a three-stage framework—adapted from 2009 Science and Decisions: Advancing Risk Assessment (NRC, 2009) and consistent with a framework recommended by A Risk-Characterization Framework for Decision-Making at the Food and Drug Administration (NRC, 2011)—any time in the lifecycle of a drug that FDA needs to make a regulatory decision, and for planned reviews of regulatory decisions. Given its charge, the committee focuses on the use of the framework in the postmarketing setting where it could be employed, for example, when the emergence of a serious safety signal may


2The committee presents the questions in the order they are discussed in the previous chapters, not the order they are presented in the charge.

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