OBJECTIVES : The Act on the Reform of the Market for Medicinal Products (AMNOG) requires pharmaceutical companies to specify the size of the target population (TP) in the German statutory health insurance population in module 3 of an AMNOG dossier. The aim of the study was to review data sources used in module 3’s to determine the TP size of orphan drugs and to evaluate corresponding assessments by the Institute for Quality and Efficiency in Healthcare (IQWiG) concerning transparency and plausibility of the determined TP sizes.

METHODS : All module 3’s and respective IQWiG assessments for orphan drugs published until May 14^th, 2019 were screened by two independent reviewers. Number, classification and combinations of data sources were identified. IQWiG assessments concerning the transparency and plausibility of the TP size were classified and frequency of the determined classifications was investigated.

RESULTS : Overall, 90 AMNOG dossiers with 103 module 3’s (some AMNOG dossiers included more than one TP) were assessed. Literature was used in 83.5% (n=86) of the modules making it the most frequent used data source. In 66.0% (n=68) of the modules, more than one data source was used with most modules relying on two sources (49.5%, n=51). In 68.9% (n=71), the approach to determine the TP was transparent according to the IQWiG. However, only in 14.6% (n=15) the IQWiG considered the size of the TP as solely plausible and in 32.0% (n=33) as either plausible, underestimated or overestimated and additionally uncertain. Nevertheless, the IQWiG was not able to provide a final assessment in 9.7% (n=10).

CONCLUSIONS : Results indicated that various data sources must be combined to get plausible estimates. However, the results show that even if information on prevalence is available and a transparent approach is used, determining the TP size of a new pharmaceutical can be challenging.