PNS205 SURROGATE VALIDATION IN GERMAN AMNOG BENEFIT ASSESSMENTS

Abstract

In clinical trials surrogate endpoints are oftentimes used as substitute for patient-relevant endpoints. However, in the early benefit assessment of pharmaceuticals in Germany and in order be able to provide patient-relevant evidence a validation of surrogate endpoints is critical. The aim of this study was to assess the utilization, methodology and acceptance of surrogate validations in AMNOG benefit dossiers. Dossiers for benefit assessment were retrieved from the homepage of the Federal Joint Committee (G-BA). It was assessed whether the pharmaceutical companies performed a surrogate validation and if a surrogate parameter was considered for benefit assessment by the Institute for Quality and Efficiency in Health Care (IQWiG) and later accepted by the G-BA. In total 397 AMNOG dossiers were analyzed. In 105 (26.4%) dossiers a surrogate validation was presented. Of all attempted surrogate validations, 36 (34.3%) were rejected and 51 (48.6%) were not further commented (e. g. due to limitations in study design). In total, 18 validations (17.1% of all attempted validations) were accepted as valid. Validations were only accepted in infectious indications (94.4%) and oncological diseases (5.6%). Accepted endpoints were (sustained) virologic response for reduced risk for hepatocellular carcinoma as well as AIDS-defining diseases/death, CD4 cell count for AIDS-defining diseases/death and disease-free survival (DFS) for overall survival. In most cases the pharmaceutical companies referred to prior benefit assessments. Only for DFS a comprehensive surrogate validation including systematic literature search and statistical calculations was performed. Even though the methodological demands by IQWiG are high, in one quarter of submitted dossiers pharmaceutical companies attempted to validate a surrogate parameter as a patient-relevant endpoint. Overall, the acceptance of validations is possible; however, the success rate is small (17%). Most accepted surrogate validations were within infectious diseases and their validation referred to prior benefit assessments.