OBJECTIVES: Acceptance of real-world evidence (RWE) is one key challenge in HTA. The upcoming European HTA will set new standards on the European level. Hence, recently published guidelines by EUnetHTA on RWE might have an impact on the national level. This study analyzes (1) the current problems in accepting RWE in (national) HTAs, (2) the methods are set out by EUnetHTA, and (3) the implications for upcoming national appraisals post 2025. German HTA will be analyzed here, as it can be considered one of the most rigorous national HTA within Europe.

METHODS: Submitted RWE is identified by screening G-BA resolutions since 2011. Reasons for acceptance or non-acceptance are extracted and categorized. EU HTA standards on RWE are extracted from recently published guidelines.

RESULTS: Even though G-BA methodology explicitly acknowledges RWE, in only few resolutions RWE has been taken into account by G-BA (e.g., cerliponase alfa, sebelipase alfa, asfotase alfa). Reasons for not considering RWE have been methodological issues, i.e., lack of or insufficient confounder analysis and differences in the definition of endpoints. Besides, method documents from IQWiG and G-BA do not provide any methodological guideline for RWE.

EUnetHTA guidelines provide general methodological considerations as well as detailed requirements for reporting. This provides clarity and (hopefully) predictability which might have important implications. Once RWE is accepted within EU HTA, it will be interesting to observe how the clinical assessment is incorporated in the subsequent national appraisal.

CONCLUSIONS: So far it is difficult to achieve acceptance of RWE in German HTA. EUnetHTA guidelines promise to open new routes of evidence demonstration for both European and national HTA. It remains to be seen if reality meets this promise.