Presentation (CTI)

OBJECTIVES: Clinical trials are shifting from laboratory and physiological endpoints towards outcomes meaningful to patients. Clinical outcome assessments (COAs) are measures reflecting how a patient feels, functions or survives. This review compared the COA evidence requirements and methodological guidance of regulatory and Health Technology Assessment (HTA) bodies in Canada, England, Europe, United States (US).
METHODS: A targeted review of publicly available guidance to May 2026 was carried out. Sources: Food & Drug Administration (FDA;US), Canada’s Drug Agency (CDA-AMC), European Medicines Agency (EMA), HTA Co-ordination Group (HTA CG; Europe), National Institute for Health and Care Excellence (NICE; England), Haute Autorité de Santé (HAS; France), Institute for Quality and Efficiency in Health Care (IQWiG; Germany), Ministry of Health (MoH) in Spain. Data were extracted using an eight-domain framework: conceptual framework/fit-for-purpose, instrument design, content validity, psychometric properties, meaningful change, modification/translation, stakeholder governance, impact on the effect estimate.
RESULTS: All requirements were non-binding. FDA guidance was the most comprehensive, addressing all eight domains. EMA addressed seven with less methodological detail. The Joint Clinical Assessment (JCA; Europe) guidance was the most comprehensive HTA guidance, addressing seven domains. CDA-AMC addressed three domains, naming consensus-aligned measurement properties and minimal important differences. IQWiG addressed two, requiring validated instruments and uniquely applied thresholds; NICE addressed one, centred on meaningful change. HAS addressed one domain, a conditional requirement for validated disease-specific quality-of-life scales. The Spanish MoH guidance contained no substantive mention of COAs.
CONCLUSIONS: As clinical studies shift towards patient-meaningful outcomes, COAs are becoming increasingly central to approval and reimbursement. Payer COA guidance has traditionally lagged behind regulatory requirements, potentially because non-COA endpoints were prioritised. JCA guidance sets higher COA evidence requirements, which may signal a trend towards more comprehensive COA requirements among HTA bodies. These results highlight the need for harmonised COA guidance and integrated evidence strategies satisfying regulatory and HTA requirements.