precipitate or require a regulatory decision, including the reaffirming of the drug’s current regulatory status. The three stages of the adapted framework include (1) define the public health questions of importance, (2) assess the drug’s benefits and risks, and (3) make, communicate, and implement the regulatory decision. The three-stage framework is designed to be broadly applicable to regulatory decisions, to support decision-makers’ judgment, and to facilitate the resolution of disagreements about the scientific evidence and the best regulatory actions to protect public health. For FDA’s regulatory decisions about approved drugs to be ethical and appropriate, FDA needs to consider the perspectives of patients; and the concerns of consumers, health care providers, and industry; securing this input is an important element of the proposed framework.
Establishing and maintaining a BRAMP document for each drug throughout its lifecycle would also enhance FDA’s ability to respond appropriately to safety evidence. The document would summarize the benefits and risks of the drug, the rationale for FDA’s decisions in light of those benefits and risks, and how any risks will be managed throughout the drug’s lifecycle. The BRAMP document, as proposed by the committee, is designed to support the systematic implementation of the lifecycle approach to regulatory oversight of drugs, to foster collaboration between FDA and drug sponsors in that oversight, and to increase the transparency of FDA’s decisions. Because the benefit–risk profile of a drug can change over time, the BRAMP document would become a living document that is updated when there is new information that warrants re-evaluation of the drug’s benefit–risk profile. Each update would include summaries of the three stages of the decision-making framework discussed above and any plans for identifying or managing risks (such as a risk evaluation and mitigation strategy). In the premarketing setting, the drug sponsor would provide initial information about the benefits and risks of a given drug, uncertainties in the information relevant to the public’s health, and detailed plans to decrease those uncertainties if they exist. FDA should review and finalize the BRAMP document. In the postmarketing setting, FDA staff who did not play a primary role in the drug’s approval process and who have expertise in surveillance, epidemiology, and the evaluation of safety data collected from different observational and clinical trial designs, would review and modify the BRAMP document at pre-specified intervals throughout the lifecycle of the drug and when new information warrants re-evaluation of the drug’s benefit–risk profile.
Disagreements among experts about scientific evidence lead to some of the more challenging regulatory decisions. When such disagreements occur, it is important for FDA to characterize the nature of the disagreements. These can occur because experts have different prior beliefs about the plausibility of a given benefit or risk in light of prior evidence, different views about the quality of the studies supplying the evidence or about the relevance of the new evidence to the public health question that calls for a regulatory decision, or different ideas about