Presentation (CTI)

OBJECTIVES: The EU Joint Clinical Assessment (JCA) aims to harmonise clinical evidence evaluation across Member States, including the use of surrogate endpoints (SEs) when mature clinical outcomes are unavailable. While SEs can expedite access to innovative therapies, their acceptance varies widely. In Germany (IQWiG/G-BA) applies strict criteria to validate SEs, which can pressure patient access in line with the JCA framework. This study investigates how SEs have been assessed in Germany’s early benefit assessments (EBAs) since the AMNOG law implementation in 2011. It aims to identify patterns in acceptance, understand decision rationales, and explore implications for pharmaceutical companies under the evolving EU JCA framework.
METHODS: All EBAs conducted between 2011 and June 2025 were reviewed. Assessments involving SEs were identified and analysed by therapeutic area, validation level, and appraisal outcome. These were compared against the surrogate validation framework outlined in the EU JCA guidance.
RESULTS: Among 151 EBAs referencing surrogate endpoints, only 6 distinct SEs were accepted by IQWiG/G-BA. Accepted SEs include virological response and CD4 cell count (HIV), oral glucocorticoids’ reduction (asthma and lupus), HbA1c change (type 1 diabetes), and sustained virological response (hepatitis C). Even though there is a substantial overlap between the EU JCA’s Level 1 and 2 surrogacy evidence requirements and the validation criteria applied by IQWiG/G-BA, formal attempts by pharmaceutical companies to validate SEs with IQWiG/G-BA continue to fail.
CONCLUSIONS: Although the decision on SEs acceptance remains at the national level, the JCA guidance outlines three levels of surrogacy evidence. Germany requires Level 1 or 2 evidence per IQWiG standards. Despite the frequent use of SEs in clinical development, their acceptance in EBAs is rare. This underscores the importance of early strategic planning, feasibility assessments, and alignment with HTA expectations to improve the likelihood of successful submissions under both national and EU frameworks.