Clinical trials in neurosciences: Need for standards for innovation on clinical outcomes

Advances in understanding neurobiological factors underlying neurologic and psychiatric conditions have yet to be adequately translated into successful treatments. In neuroscience therapeutic areas, a high percentage of clinical trials fail to demonstrate safety and efficacy, resulting in a lower innovation index compared to other fields. Developing new treatments requires innovative strategies for outcome decision-making, including tailoring existing instruments or creating novel measurement tools to address validity gaps and capture the clinical benefits of new therapeutic approaches. The interdisciplinary expert group forming the Network on Clinical Outcomes in Early-Phase Clinical Trials within the European College of Neuropsychopharmacology (ECNP) promotes harmonization of outcome research practices to increase the likelihood of identifying safe and effective treatments in neuroscience. Consensus-based recommendations on outcome selection standards were issued to guide researchers designing clinical trials aligned with regulatory agency guidelines (Zaragoza Domingo et al., 2024). This paper highlights two common concerns regarding outcomes in neuroscience clinical trials. First, the availability of reliable, sensitive, and fit-for-purpose (FFP) clinical outcome assessment (COA) tools. In fact, several well-established instruments would not meet current qualification requirements, despite their continued use. Second, instruments validated in one clinical context are being applied to a different condition without confirming validity, compromising content validity and measurement properties. A 7-step standard framework is presented to operationalize outcome decisions across early-to-late-phase pharmacological research, reinforcing content validity and psychometric rigour. A recent expert survey broadly endorsed this framework, and future plans include piloting the method across challenging therapeutic fields and engaging regulatory agencies.