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A Two-Stage Patient-Focused Study Design for Rare Disease Controlled Trials

We developed a study design for rare disease clinical trials (RDTs) that efficiently evaluate treatments, promotes access to new treatments during treatment development, and optimizes healthcare resource utilization for future treatment allocation, development, and prioritization. Comprehensive literature review and focus group discussion were conducted. To address the multifaceted challenges facing RDTs, four key issues for RDTs must be addressed, which are 1) the opportunity to access the new treatment; 2) assessment of outcomes where clinically validated outcomes may be lacking; 3) patient heterogeneity; and 4) duration of the study and number of patients required. Our proposed study design has two stages. Stage 1 distinguishes patients who respond to the treatment from those who do not respond to the treatment after assigning them all to the experimental treatment. Stage 2 evaluates the treatment effect comparatively among patients responded in Stage 1. In addition to treatment effect evaluation, our design can greatly benefit rare disease patients and clinical practice by increasing opportunities to access experimental treatments and by providing relevant information that can be used for tailoring treatments to certain subgroups, aiding future research in treatment development, and improving healthcare resource utilization.