Failure due to formal reasons within German benefit assessment of medicinal products: the dilemma between marketing authorization and HTA.

Objective: Due to the impact of the Federal Joint Committee's (FJC) appraisal on following price negotiations, it is crucial to understand the underlying reasons of failure in early benefit assessment (EBA) of medicinal products in Germany. Methods: Medicinal products for which no added benefit was granted, the underlying reasons given by the FJC were extracted and grouped into respective categories according to predefined working definitions. Several reasons may hold for one subgroup. Furthermore, binomial proportion analysis was performed to gather proportions and their precision for each therapeutic area regarding possible failure. Results: 293/427 subgroups did not receive an added benefit. For 265/293 the following main formal reasons were stated: deviation of label to the pivotal studies (59%), wrong comparator (20.5%), and methodological deficiencies of indirect comparisons (12.3%). The proportion of failure in EBA is heterogeneous and therapeutic area depending (p = 0.0005). For most of the therapeutic areas, the confidence intervals of binomial proportions include 50%. Conclusion: Various different reasons led to the failure of EBAs in the past. Despite different objectives, a better alignment between the requirements and methods in the marketing authorization procedure and the EBA might facilitate the design of pivotal studies, which may be useful in both procedures. [ABSTRACT FROM AUTHOR]