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The recent benefit–risk framework (BRF) developed by the Food and Drug Administration (FDA) is intended to improve the clarity and consistency in communicating the reasoning behind the FDA's decisions, acting as an important advancement in US drug regulation. In the PDUFA VI implementation plan, the FDA states that it will continue to explore more structured or quantitative decision analysis approaches; however, it restricts their use within the current BRF that is purely qualitative. By contrast, European regulators and researchers have been long exploring the use of quantitative decision analysis approaches for evaluating drug benefit–risk balance. In this paper, we show how quantitative modelling, backed by decision theory, could complement and extend the FDA's BRF to better support the appraisal of evidence and improve decision outcomes. After providing relevant scientific definitions for benefit–risk assessment and describing the FDA and European Medicines Agency (EMA) frameworks, we explain the components of and differences between qualitative and quantitative approaches. We present lessons learned from the EMA experience with the use of quantitative modelling and we provide evidence of its benefits, illustrated by a real case study that helped to resolve differences of judgements among EMA regulators. [ABSTRACT FROM AUTHOR]

In the European Medicines Agency ( EMA), the involvement of patients has been increasingly recognized as valuable and necessary. Specifically in scientific committees, patients through patient representatives are actively involved in deliberations and decision making processes. These scientific committees are meant to ensure that licensed medicines have a positive benefit-risk ratio in favour of the patients and users. To investigate what the contributions are of patient representatives in benefit-risk assessment, we interviewed 15 scientific committee members, 10 of whom are/were EU-state regulatory representatives and five are/were patient representatives. We asked the participants questions related to the benefit-risk assessment tasks of their committees, the connection between patient representatives and the patient perspective, and the contribution of patient representatives in the various benefit-risk assessments tasks. We found that the contribution of patient representatives benefit-risk assessment may be a variable of the benefits and the risks involved in the drug such that the necessity of their contribution is strongly felt when both benefits and risks are high, when benefits are almost equal or are equal to risks and when both benefits and risks are low. In terms of the various benefit-risk tasks, patient representatives contribute to benefit-risk analysis by providing criteria that help define the benefit-risk picture. In benefit-risk evaluation, patient representatives aid in providing a specific basis for the values and weights given to specific benefits and risks and in decision making, they provide what may be a crucial patient perspective in terms of the acceptability of risks. Hence, patient representatives provide a specific expertise in these scientific committees. [ABSTRACT FROM AUTHOR]