Implications of EU HTA on Future Relevance of Surrogate Outcomes in National Assessment

OBJECTIVES: Acceptance of surrogate outcomes is one key challenge in HTA. EU HTA will set new standards for HTA on the European level and will be more closely connected to the regulatory process. This study analyzes (1) the current problems in accepting surrogate endpoints in (national) HTAs, (2) the methods set out by EUnetHTA and by EMA, and (3) the implications for upcoming national assessments post 2025. German HTA will be analyzed here, as this can be considered being currently the most rigorous national HTA within the EU.

METHODS: Relevant surrogate outcomes are identified by screening G-BA resolutions since 2011, excluding orphan drug assessments. Reasons for acceptance or non-acceptance are extracted and categorized. EU HTA and EMA standards on surrogate outcomes are extracted from respective guidelines.

RESULTS: HTA in Germany is strictly limited to patient relevant endpoints (impression perceived through the senses). So far, only one formal validation of a surrogate outcome has been accepted since 2011. However, in several cases surrogate outcomes have been accepted without formal validation, as they were considered “generally accepted in the scientific community”.

EUnetHTA guidelines provide a clear framework: First, relevant outcomes are defined by the member states. Second, the selection should be guided by close interaction with patients and healthcare professionals. Third, patient preferences are also explicitly mentioned as patient relevant. EU HTA offers the potential of a greater standardization and methodological clarity with regards to surrogate outcomes, although the adoption for the national appraisal remains to be seen.

CONCLUSIONS: It might be anticipated that the closer integration between regulatory and HTA processes as well as the methodological possibilities with regard to surrogate validation will lead to increased acceptance of surrogates, which are essential determinants for the clinical efficacy. This may enrich the available set of instruments for evidence demonstration within Germany and potentially beyond.