Presentation (CTI)

OBJECTIVES: The EU Health Technology Assessment Regulation (2021/2282) mandates binding evidentiary standards for Joint Clinical Assessments (JCAs), requiring real-world evidence (RWE) that is comparative, patient-centered, and generated through methodologically rigorous post-authorization studies. Conventional single-source observational designs are poorly suited to meet these requirements across diverse patient populations and health system contexts. There is need for flexible, multi-source study architectures integrating primary and secondary data collection while maintaining analytical coherence and regulatory defensibility. This paper describes a hybrid framework combining site-based primary data collection with registry-based secondary data linkage, assessing its applicability to JCA requirements in a multi-country post-authorization setting.
METHODS: The framework draws on three complementary data sources, each serving a distinct evidentiary role. First, prospective data capture via electronic data capture (EDC) systems provides structured, query-controlled collection aligned to pre-specified protocol endpoints. Second, automated EHR extraction reduces transcription burden, improves data completeness, and enables near real-time access to longitudinal clinical information without additional site workload. Third, secondary use of established national registries extends geographic reach and sample size, leveraging population-level data for subgroup and comparative effectiveness analyses. Patient-reported outcomes are collected digitally at pre-specified intervals to meet patient-relevance standards required in HTA submissions. All sources are harmonized into a single analytical dataset. Study design elements are prospectively mapped to JCA PICO requirements, with data quality controls aligned to Good Pharmacoepidemiology Practice (GPP) and ICH E6(R3) standards.
RESULTS: Application of this framework yields a harmonized, JCA-ready dataset from three complementary sources. The modular architecture accommodates variable national digital infrastructure, enabling consistent cross-country implementation regardless of site-level health system maturity.
CONCLUSIONS: This hybrid framework demonstrates that post-authorization studies can be designed prospectively to meet evolving EU JCA evidentiary standards without sacrificing real-world representativeness. The approach is therapeutic-area-agnostic and adaptable across sponsor contexts, offering a replicable model for generating fit-for-purpose RWE within the European regulatory landscape.