Approaches to the Assessment of Clinical Benefit of Treatments for Conditions that Have Heterogeneous Symptoms and Impacts: Potential Applications in Rare Disease.

Multi-component, MBS, and adequate relief have been included in FDA-approved labeling claims. Multi-component endpoints, including composite endpoints, were the most frequent way to address heterogenous manifestations of both common and rare diseases. MBS may be acceptable to regulators, whereas MDRI is unlikely to be. The GAS and adequate relief approaches may have potential utility in rare disease trials, assuming the theoretical and statistical challenges inherent in each approach are managed.