OBJECTIVES: Health technology assessment (HTA) agencies evaluate the value of new medicinal products compared to existing clinical practice. Joint HTA reports by several European Member States require a description and analysis of 1) all available data, including real-world evidence (RWE), to assess the relative effects of the medicine on health outcomes, and 2) the degree of certainty of the relative effects based on available data. To evaluate the acceptance of RWE by HTAs, we performed a qualitative assessment of EU-JCA critiques on RWE to support reimbursement decisions.

METHODS: Data were obtained from the EUnetHTA relative effectiveness assessments pilots conducted to date; all medicinal compounds that had undergone EU-JCA were identified and a qualitative review was performed of: 1) the selection of the studies relevant to the assessment, and 2) the conclusions on relative effectiveness and safety. Trends were assessed by comparing two time periods: 2010-2015 (EUnetHTA Joint Action (JA)1 and JA2; n=7) and 2016-2021 (JA3; n=20).

RESULTS: Overall, EU-JCAs primarily relied on randomized clinical trials (RCTs) to support their conclusions for effectiveness and systematically rejected RWE due to methodological issues. However, the external validity of RCTs was frequently criticized and additional larger, long-term, pragmatic RCTs and prospective observational studies were required to supplement existing evidence. Safety analyses within the assessments frequently included observational studies. The more recent JA3 assessments were more inclusive of RWE, especially for orphan drug assessments.

CONCLUSIONS: We found qualitative evidence of increasing acceptance of RWE in HTA decision making. Current EUnetHTA methodology, to be implemented into the EU-HTA Regulation 2021/2282 in January 2025, considers more than ever prospective observational studies fit to address RWE internal validity critiques. It will be interesting to assess the impact of regulation in JCA reports after its implementation in 2025.