Structured Frameworks to Increase the Transparency of the Assessment of Benefits and Risks of Medicines: Current Status and Possible Future Directions

Abstract

Structured frameworks for benefit‐risk analysis in drug licensing decisions are being implemented across a number of regulatory agencies worldwide. The aim of these frameworks is to aid the analysis and communication of the benefit‐risk assessment throughout the development, evaluation, and supervision of medicines. In this review, authors from regulatory agencies, pharmaceutical companies, and academia share their views on the different frameworks and discuss future directions.

Evaluating Quality of Decision-Making Processes in Medicines' Development, Regulatory Review, and Health Technology Assessment: A Systematic Review of the Literature

“…The 10 QDMPs were developed based on results from semi-structured interview with 29 key opinion leaders from regulatory authorities and pharmaceutical companies to investigate and identify the important issues that influence decision making (Donelan et al, 2015). In addition, the key decision-making frameworks (Hammond et al, 1999; Blenko et al, 2010; SDG, 2011) as well as benefit-risk assessment methodologies (Leong et al, 2015; Pignatti et al, 2015) are also underpinned by these practices. In a subsequent review, these QDMPs were presented to major pharmaceutical companies and regulatory authorities, and were considered as appropriate and relevant (Bujar et al, 2016a).…”

“…In particular, the area of benefit-risk assessment has brought certain concepts in decision making to the forefront through the usage of qualitative and quantitative tools by pharmaceutical companies and regulatory authorities (Guo et al, 2010; EMA, 2011; FDA, 2013; Tafuri, 2013; Leong et al, 2015; Pignatti et al, 2015), as well as in the area of HTA regarding inclusion of multiple decision criteria (Cole et al, 2016) and a structured assessment of comparative added benefit of a technology against the cost of treatment (Cherny et al, 2015; Schnipper et al, 2015). The second key area that has benefitted from more structured decision making is portfolio management, where companies have been using frameworks (Sharpe and Keelin, 1998; Cook et al, 2014) as well as quantitative methods and algorithms (Hassanzadeh et al, 2011; Jekunen, 2014) in order to analyze and optimize the portfolio of medicines and ultimately avoid late terminations in phase III development.…”

Quantifying Preferences in Drug Benefit‐Risk Decisions

“…Appreciating the value of more quantitative approaches, European regulators called for a more explicit approach that includes decision criteria descriptions, data interpretation and valuations, and outcome weighting . The European Medicines Agency (EMA) has adopted a model that tabulates the magnitudes and uncertainties of the most important favorable (i.e., benefits) and unfavorable effects (i.e., risks) in the “effects table.” Construction of an effects table is one of the steps in developing a quantitative benefit‐risk model with a framework, such as PROACT‐URL, belonging to the domain of Multi‐Criteria Decision Analysis (MCDA). In the United States, the US Food and Drug Administration (FDA) has adopted a Benefit‐Risk Framework tool to communicate evidence and uncertainties about relevant benefits and risks taken into account in regulatory decisions .…”

“…The International Council for Harmonization allows for including preference information in marketing authorization applications in its 2016 update to the common technical document . Despite the EMA, the FDA, and the International Council for Harmonization all proposing structured benefit‐risk assessment guidance, they do not explicitly mandate the implementation of quantitative methodologies by applicant companies. Furthermore, the documentation of marketing authorization decisions generally consists of a qualitative description of the importance of the observed effects (clinical relevance) but does not include explicit preference information, such as trade‐offs, at least not in quantitative terms.…”

“…Historically, European regulatory assessment has been justified mainly using implicit value judgments without a formal quantification of acceptable benefit-risk trade-offs. 8 Appreciating the value of more quantitative approaches, European regulators called for a more explicit approach that includes decision criteria descriptions, data interpretation and valuations, and outcome weighting. 9 The European Medicines Agency (EMA) has adopted a model that tabulates the magnitudes and uncertainties of the most important favorable (i.e., benefits) and unfavorable effects (i.e., risks) 10 in the "effects table."…”