Randomized clinical trials are the gold standard for evaluating the benefits and harms of interventions and yet may not provide the evidence needed to inform medical decision-making, an ultimate goal for clinical research. Commonly used design and analysis approaches are often not suited to answer the most important questions to inform clinical practice, specifically how do resulting patient experiences, when comprehensively considering benefits and harms, compare between therapeutic alternatives? The standard approach of siloed analysis of one outcome at a time: (i) does not incorporate associations between multiple outcomes; (ii) does not recognize the cumulative nature of multiple outcomes in individual patients or recognize important gradations of global patient response; (iii) suffers from competing risk complexities during interpretation of individual outcomes; (iv) provides for ambiguous generalizability with respect to benefit:risk since efficacy and safety analyses are often conducted on different populations. Evaluation of treatment effect heterogeneity to identify subgroups for treatment or avoidance of treatment is typically evaluated based on a single efficacy or safety endpoint and rarely evaluated based on the overall benefit:risk. Methods that quantify and compare the patient experience are needed. The desirability of outcome ranking (DOOR) is a paradigm for the design, monitoring, analysis, interpretation, and reporting of clinical trials and other research studies based on patient-centric benefit:risk evaluation, developed to address these issues and advance clinical trial science. Aligning the clinical research strategy with the relevant question for clinical practice will enhance research applicability. Careful design and comprehensive analyses are critical for DOOR paradigm application. We provide a recommended statistical analysis plan for research studies implementing DOOR, describe its elements, and illustrate analysis application using examples. A freely available online tool for the recommended analyses and the design of studies implementing the DOOR paradigm is provided.ClinicalTrials.gov ID: NCT05641298.
Tanna et al. (Fri,) studied this question.