A Review and Comparative Case Study Analysis of Real-World Evidence in European Regulatory and Health Technology Assessment Decision Making for Oncology Medicines

Objectives: Real-world evidence (RWE) is valuable in supporting regulatory and health technology assessment (HTA) decisions; however, the actual contribution to approvals remains elusive. This study aimed to review RWE approaches and use in oncology medicine approvals in Europe and understand cohesion and discrepancy in the acceptance of the RWE by the European Medicines Agency (EMA) and European HTA bodies.

Methods: This scoping review involved a search of the EMA database, National Institute for Health and Care Excellence (NICE), Gemeinsamer Bundesausschuss (G-BA), and Haute Autorité de Santé (HAS) websites to identify final reports and appraisals for oncology medicines with references to RWE. The selection was guided by research terms associated with RWE study designs, data sources, and outcomes. Qualitative analysis was used to systemize the data. Case studies assessed by more than one agency were selected for comparative assessment of RWE approach, use, and acceptability.

Results: RWE was mainly leveraged as an external control for indirect treatment comparisons or contextualization to support clinical trial results by the EMA, NICE, G-BA, and HAS. However, this approach was mostly rejected due to methodology biases. Comparative assessment of RWE acceptability for the same oncology medicines across agencies suggests discrepancies between EMA and European HTA bodies and among NICE, G-BA, and HAS.

Conclusions: There is diverging acceptance of RWE in EMA and European HTA bodies with no clear consensus on the most effective way to leverage RWE in approvals. With the introduction of the joint European Union Joint Clinical Assessment in 2025, it is crucial for European HTA bodies and EMA to develop synergetic standards for the use of RWE to ensure equitable and timely access to medicines.