Advancing structured decision‐making in drug regulation at the FDA and EMA

Abstract

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.

Structured benefit–risk evaluation for medicinal products: review of quantitative benefit–risk assessment findings in the literature

“…Despite the multiple public and private initiatives in developing different benefit-risk frameworks and tools, there is still a lack of a clear guidance and understanding on how regulatory bodies expect structured benefit-risk to be conducted, on how to integrate patients' preferences and when to use quantitative methods. 35 Regulatory bodies should continue to collaborate with multiple stakeholders, including academia, industry, health-care professionals, patients and others to strengthen regulatory science and to address many critical knowledge gaps. 36 More research is warranted to address the inherent limitations and concerns related to the use of quantitative methods in benefit-risk assessments.…”

A WHO tool for risk‐based decision making on blood safety interventions

“…Multi‐Criteria Decision Assessment is increasingly applied to support the appraisal of new medicines 8–10 . This has evolved in the development of various methods for balancing the benefits and risks of medicines to support more transparent and consistent decision making 11–14 . The core of a multicriteria decision‐making process is a safety interventions and outcomes table as shown in Table 2.…”

Early Health Technology Assessment during Nonalcoholic Steatohepatitis Drug Development: A Two-Round, Cross-Country, Multicriteria Decision Analysis

“…These sizes have been shown to be optimal, allowing efficient group processes to emerge while preserving individuality, as they are large enough to represent all major perspectives but small enough to be able to work toward agreement. 8 A summary of participant numbers and stakeholder groups in each meeting together with each DC duration is shown in Table 1.…”

“…Decision analysis methods and, specifically, quantitative modeling approaches such as MCDA can be used to aid medical decision making, to explicitly integrate objective measurement with value judgment while managing subjectivity transparently. This is useful for drug evaluation contexts because, although the clinical evidence concerning different treatments’ performance might be objective in nature, the understanding of its value requires subjective interpretation; for example, relating to the relevance of data for the disease of interest, the meaningfulness of improvement in health benefit, and the value trade-offs with possible risks 8 .…”