OBJECTIVES: In recent years, multiple pharmaceuticals have been submitted to health technology assessment (HTA) bodies based on data from single-arm trials (SATs). Since this trial design lacks a comparator arm, this places additional challenges on analyzing the cost-effectiveness of these pharmaceuticals. This study aims to provide an overview of previous economic evaluations by Zorginstituut Nederland (ZIN) assessing pharmaceuticals based on SATs.

METHODS: ZIN assessments of pharmaceuticals receiving market authorization by the European Medicines Agency (EMA) based on SATs in the period of 2018-2020 were investigated. If a cost-utility analysis (CUA) was performed, then the approach used to create a comparator arm, the main critique points from the scientific advisory board (WAR), and the final conclusion of the economic assessment were obtained.

RESULTS: Of the 22 included EMA-approved pharmaceuticals: 12 were assessed by ZIN, whilst only 3 of 12 included a CUA. The reasons why a CUA was not conducted were: joint EUnetHTA assessment (N=1), does not comply with established medical science and medical practice (N=3), budget impact below €10 million (N=1), equal therapeutic value claim by manufacturer (N=4). The methods to obtain a comparator arm in the 3 economic assessments were: literature-based cohort (N=2) and intracohort control (N=1). The main critique of the WAR in all 3 assessments was the high level of uncertainty of the indirect comparison used to determine the relative effectiveness. This resulted in no incremental cost-effectiveness ratio being presented in 2 of the 3 assessments. All 3 assessments concluded that the pharmaceutical was not cost-effective.

CONCLUSIONS: SAT-based EMA approvals put significant challenges on HTA bodies to determine the cost-effectiveness of a pharmaceutical. This is mainly caused by the high uncertainty of an indirect comparison to determine relative effectiveness. Future research should explore more robust methodologies to obtain a comparator arm.