((A-022)) (A-022) Opening the DOOR for Patient-Centric Benefit-risk Evaluation:Highlights from the CIOMS Benefit-risk Working Group

Background: Typically in clinical trials and other research studies that evaluate the effects of interventions, efficacy and safety are evaluated in silos, one outcome at a time. However this approach: fails to incorporate associations between or the cumulative nature of multiple outcomes in individual patients, suffers from competing risk complexities during interpretation of individual outcomes, fails to recognize important gradations of patient responses, suboptimally evaluates treatment effect heterogeneity based on a single endpoint rather than benefit:risk considerations, and since efficacy and safety analyses are often conducted on different populations, generalizability is unclear. In recognition of the limitation of current approached to benefit-risk evaluation, the Benefit-risk Working Group for the Council for International Organizations of Medical Sciences (CIOMS), a multinational multidisciplinary group of benefit-risk experts from industry, government including representation from major regulatory bodies around the world, and academia, recently recommended: (1) transitioning benefit-risk evaluation as a post-hoc exercise to incorporating benefit-risk considerations into clinical trial design, and (2) a pragmatic patient-centric approach to benefit-risk assessment to ensure proper evaluation of the benefits and harms as experienced by patients.

Objectives: To describe and illustrate the desirability of outcome ranking (DOOR), a paradigm for the design, analysis, and interpretation of clinical trials and other research studies based on patient-centric benefit-risk evaluation developed to address these limitations and the CIOMS recommendations, and advance clinical trial science.

Methods: In the DOOR paradigm, “outcomes are used to analyze patients rather than patients being used to analyze outcomes”. The experiences of clinical trial participants in different treatment arms are compared by the desirability of the overall patient outcome, increasing pragmatism and addressing the most important “real world” question to aid clinical decision-making: how do resulting patient experiences, when comprehensively considering benefits and harms, compare between therapeutic alternatives? The DOOR paradigm is described and illustrated using examples.

Results: Not applicable.

Conclusions: The desirability of outcome ranking (DOOR) paradigm is a patient-centric and pragmatic approach to benefit-risk evaluation and the design and analysis of research studies, that advances benefit-risk evaluation science and addresses the recommendations from the CIOMS Benefit-risk Working Group. The DOOR paradigm is described in the CIOMS Benefit-risk Working Group report "Benefit-risk balance for medicinal products".