From Concept to Claim: An Integrated Lifecycle Roadmap (ILR) for Patient-Centric Endpoints in Clinical Trials and...

Background: Patient-centric endpoints increasingly influence clinical development, regulatory evaluation, and health technology assessment, yet the relevant methodological guidance remains distributed across separate domains. Estimands, digital health technologies, and real-world evidence are often addressed independently, making it difficult for sponsors to apply them within a single endpoint development strategy. This review synthesizes existing guidance and framework literature to organize these elements into a coherent lifecycle perspective for endpoint development. Methods: This semi-structured narrative review used a structured search of PubMed, Embase, and regulatory databases (FDA and EMA) for records published from January 2009 through December 2025. We synthesized authoritative guidance and peer-reviewed validation frameworks, including V3 and STaRT-RWE, and assessed landmark precedents (SV95C, ADAPTABLE, and RW-Response) selected a priori using pre-specified criteria for regulatory relevance, technical reporting, and first-of-kind pathway relevance. Results: The literature supports four recurring requirements for patient-centric endpoint development: early concept elicitation to establish meaningful aspects of health, explicit estimand specification to address intercurrent events, staged validation of digital measures under V3 principles, and formal validation of computable phenotypes for real-world evidence use. Across the reviewed sources, a recurring gap was the lack of an integrated framework linking these components across the evidence lifecycle. To address this, we organize existing guidance into an Integrated Lifecycle Roadmap that connects concept definition, measurement validation, causal inference, and real-world transportability. Conclusions: Patient-centric endpoints are most robust when they are developed as part of a continuous evidence lifecycle rather than as isolated study variables. The proposed roadmap does not introduce a new methodology, but it provides a practical structure for aligning existing regulatory and methodological frameworks to support scientifically rigorous and patient-relevant endpoint development.