Benefit–Risk Assessment, Communication, and Evaluation (BRACE) throughout the life cycle of therapeutic products: overall perspective and role of the pharmacoepidemiologist

Purpose: Optimizing a therapeutic product's benefit–risk profile is an on-going process throughout the product's life cycle. Different, yet related, benefit–risk assessment strategies and frameworks are being developed by various regulatory agencies, industry groups, and stakeholders. This paper summarizes current best practices and discusses the role of the pharmacoepidemiologist in these activities, taking a life-cycle approach to integrated Benefit–Risk Assessment, Communication, and Evaluation (BRACE). Methods: A review of the medical and regulatory literature was performed for the following steps involved in therapeutic benefit–risk optimization: benefit–risk evidence generation; data integration and analysis; decision making; regulatory and policy decision making; benefit–risk communication and risk minimization; and evaluation. Feedback from International Society for Pharmacoepidemiology members was solicited on the role of the pharmacoepidemiologist. The case example of natalizumab is provided to illustrate the cyclic nature of the benefit–risk optimization process. Results: No single, globally adopted benefit–risk assessment process exists. The BRACE heuristic offers a way to clarify research needs and to promote best practices in a cyclic and integrated manner and highlight the critical importance of cross-disciplinary input. Its approach focuses on the integration of BRACE activities for risk minimization and optimization of the benefit–risk profile. Conclusion: The activities defined in the BRACE heuristic contribute to the optimization of the benefit–risk profile of therapeutic products in the clinical world at both the patient and population health level. With interdisciplinary collaboration, pharmacoepidemiologists are well suited for bringing in methodology expertise, relevant research, and public health perspectives into the BRACE process.