The approval decision does not represent a singular moment of clarity about the risks and benefits associated with a drug—preapproval clinical trials do not obviate continuing formal evaluations after approval. However, the approval decision is a critical juncture in a product’s lifecycle because it releases a drug to the market, where the public will gain broad exposure to it. In a strengthened drug safety system, that juncture should mark the beginning of another important stage in the lifecycle, when regulators, sponsors, health insurers, health care providers, and independent researchers actively pursue and manage emerging knowledge about risk-benefit relationships and uncertainty and they communicate that knowledge to patients, and health care organizations in a timely manner. Regulatory, health insurance coverage, and treatment decisions over a drug’s lifecycle depend on the quality and timeliness of data collected, evaluated, and transmitted by trustworthy stakeholders in the health care system. In short, a drug safety system oriented around the new paradigm requires:
A culture of safety in CDER supported by strong leadership, effective management, science-based decision making that is, insofar as possible, insulated from outside influences, and a healthy organization that encourages debate, teamwork, and independent scientific inquiry.
Science that is rigorous and that through the individual and joint efforts of sponsors, academic researchers, and health care organizations describes a drug’s risk-benefit profile, patterns of drug use, comparative effectiveness of drugs, behaviors of prescribers and users, and behaviors of institutions that affect prescribers and users.
A regulatory process that is flexible, dynamic (e.g., proactive, responsive), and attentive to safety throughout the lifecycle of a drug, and a regulatory agency that is sufficiently empowered to take actions necessary to protect the public health.
Communication about safety that is timely and effective and that facilitates transparency and enhances credibility.
The committee’s vision of a transformed drug safety system has at its core a lifecycle approach to drug risk and benefit—not a new concept, but one that has been implemented, at best, in a narrow and fragmented manner. For FDA, attention to risk and benefit over the life of a drug requires continuous availability of new data and ongoing, active reassessment of risk and benefit to drive regulatory action (in response to the accumulating information on a given drug), and regulatory authority that is strong both before and after approval. For the industry, attention to risk and benefit over the lifecycle will require more careful assessments of emerging information about possible new risks and timely communication of this information to