ABSTRACT
Benefit–risk (B–R) assessment underpins premarket drug development, regulators’ decisions to approve drugs for marketing as well as attendant postmarket regulatory actions, and payers’ coverage decisions. In 2012, the Institute of Medicine highlighted the need for a transparent, continuous, and integrated assessment and reassessment of a drug’s B–R profile throughout its life cycle. In the past 10 years, important legislative and policy initiatives pertaining to B–R assessment have been enacted or initiated throughout the world. These initiatives have supported the approval of innovative medical products while increasing the need to study both safety and effectiveness in the postmarket setting owing to the increasing paucity of evidence on these medical products before market approval. In this vein, regulators have withdrawn indications due to a 16negative shift in the B–R balance in light of emergent evidence, introduced risk mitigation strategies in the postmarket setting to ensure the safe use of drugs that have been associated with serious harm, and scaled back risk management programs when safety issues did not pan out after further study. Further, even if a drug is approved for marketing and stays on the market after safety-related regulatory actions, payers may not support the initial or ongoing coverage of the drug based on their own B–R and value assessment. These developments underscore the uncertainty regarding a drug’s B–R profile over time and the importance of regulatory science initiatives designed to enhance the ongoing assessment and management of a drug’s benefits and risks. The ability to reduce the uncertainty regarding the benefits and risks of drugs in the postmarket setting stems initially from the premarket evidence base and the ability to evaluate both benefits and risks in the postmarket setting via valid and accepted approaches. This chapter discusses recent regulatory policy and science initiatives, opportunities, and challenges related to B–R assessment, as well as current regulatory B–R assessment considerations for structured B–R evaluation in medical product development across clinical development phases and beyond. The focus is on policies and initiatives in the United States and Europe, as they substantially influence those in other parts of the world and generally drive the field, although initiatives from other regions are important and are mentioned in brief.
