Characterizing and Communicating Uncertainty in the Assessment of Benefits and Risks of Pharmaceutical Products
Background and Meeting Objectives:
There is increasing attention on the need for enhancing the evaluation and communication of the benefits and risks associated with pharmaceutical products, thereby increasing the predictability, transparency, and efficiency of pharmaceutical regulatory decision-making. In 2006, the IOM’s Forum on Drug Discovery, Development, and Translation held a workshop to explore the complex tradeoff between drug benefits and risks and examine approaches for better quantifying this balance and informing the public and the medical community. Since that time, FDA has worked to develop an enhanced structured approach to the assessment of benefits and risks in drug regulatory decision-making to better communicate this aspect of the human drug review process. FDA envisions that this framework will serve as a template for product reviews, as well as a vehicle for explaining the basis for FDA’s regulatory decisions. FDA’s work in this area coincides with efforts by other regulatory agencies, academia, and the pharmaceutical industry.
As FDA’s draft PDUFA V Implementation Plan (the Plan) indicates, an extensive body of evidence informs regulatory decisions on the safety and efficacy of a proposed product, but in many cases, FDA must draw conclusions from imperfect data. Identifying and evaluating sources of uncertainty (e.g., absence of information, conflicting findings, marginal results) in a regulatory application is an important part of reviewers’ work; however, drawing conclusions in the face of uncertainty can be a complex and challenging task. Effectively communicating regulatory decisions necessarily includes explanation of the impact of uncertainty on decision-making. Uncertainty may arise from many sources; however two particular areas of uncertainty that could benefit from additional attention are (1) the translation of pre-market clinical trial data to the post-market setting in which an approved drug is used in a much wider patient population, and (2) new findings that emerge in a post-marketing setting where the basis for the finding comes from sources of varying levels of rigor.
This two-part public workshop series will address the opportunity to advance the development of more systematic and structured approaches to characterize and communicate (a) the sources of uncertainty in the assessment of benefits and risks; and (b) their implications for pharmaceutical regulatory decisions. Specifically, the workshop series will explore potential analytical and communication approaches and identify key considerations on their development, evaluation, and incorporation into the assessment of benefits and risks in pharmaceuticals. This workshop series will consider the entire drug development lifecycle, including pre-market drug review and post-market safety surveillance.
For more information on the first workshop in this series, please click here to view the meeting page.