Recommendations for the use of clinical outcome assessments in rare disease drug development
Summary There are over 10,000 rare diseases collectively affecting an estimated 250–450 million people globally. While these diseases are rare individually, their cumulative impact on patients, families, healthcare systems, and society is substantial. The incorporation of clinical outcome assessments (COAs) in clinical trials can facilitate patient-focused drug development and treatment evaluation by generating meaningful evidence on how patients feel and function. This work was conducted in three phases: a targeted literature review (searched Aug 2025; updated Feb 2026), a multistakeholder workshop (online, Sept 2025) and, finally, an online survey to ratify final recommendations (responses by March 3, 2026). Of 43 individuals invited, 35 (81%) attended the virtual workshop: 11 researchers (including clinical trialists); 12 patients/caregivers; seven industry experts; four individuals from regulatory agencies and one HTA expert. All were based in the UK or USA. Across three sessions, the workshop explored stakeholder perspectives on considerations and appropriate methodological approaches to COA assessment for rare disease drug development to facilitate the generation of recommendations for future use. A threshold of at least 70% votes was chosen, a priori, for inclusion in the final set of recommendations. Here, we describe the potential benefits of COAs, summarise the key challenges, and provide recommendations to facilitate their effective and consistent integration in drug development for rare diseases.