Refining the benefit-risk framework for the assessment of medicines: valuing and weighting benefit and risk parameters.

A common framework is necessary for the transparent articulation of the benefits and risks of a therapeutic product across disparate stakeholders. The assignment of value and weighting to each component parameter presents challenges deriving from different stakeholder objectives, methods, and perspectives. Building on prior experiences with a validated framework approach, this forum focused on identifying challenges and approaches to the assignment of values and weightings using a case study applied to a hypothetical medicinal product.

Application of the BRAT framework to case studies: observations and insights.

The BRAT Framework is a set of flexible processes and tools that provides a structured approach to pharmaceutical benefit-risk decision making in drug development and post approval settings. A work in progress, it consists of six steps that produce representations of key tradeoffs, with appropriate documentation of the rationale for decisions and the assumptions made in their development. This article describes insights, gained from case studies, into the Framework's performance in a variety of constructed benefit-risk scenarios, focusing on a hypothetical example of a triptan for migraine. The scenarios described illustrate the challenges inherent in arriving at many of the regulatory decisions, including obtaining data for matching populations for all outcomes, finding data of consistent quality, addressing correlated outcomes (e.g., elevated liver function tests and hepatitis rates), dealing with rare but serious adverse events (AEs), and understanding and making decisions based on information for many outcomes simultaneously. The Framework provides a structure for organizing, interpreting, and communicating relevant information, including heterogeneity in results and the quality and level of uncertainty of data, in order to facilitate benefit-risk decisions.