Does Size Matter?

Providing high quality evidence is considered extremely challenging in rare diseases, inter alia due to substantially low patient numbers and high disease burden. However, high-quality comparative evidence is essential for the benefit assessment and price negotiations in Germany. This analysis aims to identify whether there is an evident correlation of population size and evidence quality and to subsequently analyze the potential impact for orphan drugs on price negotiation outcomes in Germany – despite the currently existing privileges.

All orphan benefit assessments were analyzed regarding population size, quality of submitted evidence, G-BA rating and price negotiation outcome by using publicly available data, combining all dossier assessments in Germany and IQWiG/G-BA rulings with GKV-SV price negotiation outcomes (LAUER-TAXE®).

For a German target population of ≥ 1,750 patients in > 95 % of cases, an RCT was submitted. For a population size of < 100 patients still ~55 % were RCT. Concurrently to a higher ratio of RCT/non-RCT, the average GBA benefit rating slightly increased. The overall average net rebate for orphan drugs is 14,86 %. Exemplary, for a target population of < 50 patients in Germany (n = 24), an average net ATC rebate of 13.2 % was negotiated for RCT and 7.1 % for non-RCT.

Despite the evident hurdles in a rare disease setting, high quality evidence for orphan drugs is often submitted for the HTA in Germany. Within all orphan drugs assessed by the GBA in Germany, the negotiation outcome improved with increasing quality of evidence and in general with a decreasing German target population. This trend should be considered when evaluating the business case regarding the conduction of clinical trials. The room for interpretation is restricted due to limited numbers of orphan procedures and potential outliers.