Bridging Evidence Worlds: Policy and Practice Pathways for Integrating Clinical Trials and Real-World Data in Drug Development and HTA

Alexandros Sagkriotis^*

• HELIOS ACADEMY LIMITED, London, United Kingdom

The integration of clinical and real-world evidence represents one of the most critical transformations in modern drug development and health technology assessment (HTA). Despite increasing regulatory openness, however, clinical trial evidence and real-world data (RWD) still operate largely as parallel rather than fully complementary systems. This review commentary argues that experimental and observational research are not competing paradigms but two interdependent components of a unified evidence ecosystem, each capturing distinct yet equally essential dimensions of patient reality. Randomized controlled trials (RCTs) typically enrol highly selected populations and are optimised for internal validity, whereas RWD reflect the heterogeneity, comorbidities, and lived experiences of patients in routine clinical practice. Integrating these two evidence streams is therefore fundamental for personalised medicine, where the objective is to generate evidence that is both scientifically rigorous and meaningfully reflective of individual patient needs. This narrative Policy & Practice Commentary synthesises regulatory guidance, methodological literature, and applied case examples to examine how leading regulatorsThis Policy & Practice Review examines how leading regulators and HTA agencies, including the U.S. Food and Drug Administration (FDA), European Medicines Agency (EMA), Medicines and Healthcare products Regulatory Agency (MHRA), Pharmaceuticals and Medical Devices Agency (PMDA), and National Institute for Health and Care Excellence (NICE), are developing frameworks to support the use of RWD and real-world evidence (RWE) in regulatory approval and reimbursement decision-making. Areas of convergence and divergence are explored, with particular emphasis on methodological transparency, data provenance, causal inference, and reproducibility as shared quality anchors across jurisdictions.