- •Evaluating the clinical benefit of interventions aimed at treating conditions with heterogeneous symptom and impact presentations is challenging. The same condition can present quite differently across individuals and change within individuals over time. This occurs frequently in rare diseases. The purpose of this review was to identify (1) assessment approaches used in clinical trials to address heterogeneous manifestations that could be relevant in rare disease research and (2) Food and Drug Administration-approved labeling claims that used these approaches.
- •A total of 6 approaches to assessing clinical benefit of interventions for conditions with heterogeneous symptom and impact presentations were identified: composite or other multicomponent endpoints, multidomain responder index, most bothersome symptom, goal attainment scaling, sliding dichotomy, and adequate relief. Based on Food and Drug Administration-approved labeling claims, multicomponent endpoints have been the most successful approach in common and rare diseases. The most bothersome symptom, goal attainment scaling, multidomain responder index, and adequate relief approaches may also have potential applications in rare disease trials.
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