OBJECTIVES: Since 2011, newly marketed drugs undergo an early benefit assessment (EBA), in which the drug’s additional benefit (AB) compared to an appropriate comparator (AC) defined by the Federal Joint Committee (G-BA) is assessed. Often, there is no evidence available from head-to-head studies with the AC. In such cases indirect comparisons (IC) may be used to prove an AB against the AC. To investigate the acceptance of IC to demonstrate an AB, EBA were retrospectively analysed.

METHODS: All EBA until January, 5th 2017 were considered in this analysis. The reasons for the passed resolutions („Tragende Gründe“) published by the G-BA were screened for keywords („indirekt“, „historisch“) to preselect potential assessments. Relevant assessments were examined regarding the type of IC (historic i.e. unadjusted vs. non-historic i.e. adjusted), outcome (IC accepted, AB), and reasons for IC rejection by G-BA (if applicable) in each assessed patient population.

RESULTS: A total of 82 assessments were identified during the keyword-screening, of which 68 included an IC for at least one patient population. 24 assessments contained historic ICs, of which 13 were accepted and 12 resulted in an AB (mostly drugs for the treatment of hepatitis C). In contrast, 47 assessments contained non-historic ICs, of which only 8 were accepted and 4 resulted in an AB. Hence, only a small proportion of assessments with an IC resulted in an AB. Most IC were rejected by the G-BA due to methodological issues. Those issues most frequently concerned inappropriate patient populations, inappropriate statistical methods, and incomplete study pools.

CONCLUSIONS: It seems reasonable to plan pivotal studies not only to comply with the requirements for marketing authorization but also with the rules of the EBA. Further promotion of the IC methodology accepted by the G-BA is recommended as this may improve the chances to have an AB granted.