PURPOSE: To illustrate the challenges and solutions for identifying and validating clinical outcome assessments (COAs) to measure treatment benefit in rare disease (RD) clinical trials. DESCRIPTION: Conformance to regulatory guidance is taken into account regarding how measures and methods can be developed, adapted and adapted recognizing the unique challenges of rare diseases (i.e., heterogeneity of disease presentation, unknown or incomplete natural history, vulnerable populations, and the significant, often progressive, disability or cognitive impairments in affected patients, etc.). Furthermore, the completion of ratings, readings and performance tests plus small population size can complicate establishing measurement properties. The task force draws on the COA framework specified in the US FDA Roadmap to Patient-Focused Outcome Measurement in Clinical Trials for the evaluation and proof of treatment benefit using COA endpoints. These recommendations provide practical implementable solutions to these specific challenges. The authors will use a case study of systemic amyloidosis, a rare disease affecting multiple organs that can lead to progressive disability or death. This example will illustrate the issues in measuring treatment benefit from the patient perspective: 1) when the condition is highly heterogeneous and 2) where patients may experience a wide range of symptoms that vary across subtypes. The workshop will be useful to researchers, clinicians, and others involved in developing or evaluating rare disease treatments. Presented by the ISPOR COA Measurement in Rare Disease Clinical Trials — Emerging Good Practices Task Force