OBJECTIVES: Indirect treatment comparisons (ITC) can estimate relative effectiveness when no evidence from a head-to-head trial exists for a new therapy and a relevant comparator. Although ITCs are being included as part of submission packages, there are no guidelines on how this methodology is evaluated as part of health technology assessments (HTA) in Netherlands. This study aimed to evaluate the reimbursement decisions and critiques of ITCs in cost-effectiveness analyses (CEA) reviewed by Zorginstituut Nederland (ZIN).

METHODS: A review was performed of ZIN reimbursement dossiers from April 2018 to June 2023 which included a CEA with an ITC. Data were extracted for ITC methods, ZIN critique, and reimbursement decision.

RESULTS: Six reimbursement dossiers which included a CEA with an ITC were identified. All six CEAs included pivotal single-arm trials of which four CEAs had external patient-level data available to inform the comparator’s survival data, and two used matching-adjusted indirect comparison using aggregated data (one unanchored, one anchored). In all cases, the use of ITCs was criticized. ZIN expressed concerns around the potential bias and uncertainty due to the use of an ITC. This contributed to two CEAs being considered of insufficient quality, resulting in a negative recommendation. Therapies were more likely to receive positive recommendations when results of the ITC were published, or when the certainty in the treatment effect and its direction was substantial. Despite critique on the use of ITCs, no specific methods were rejected in principle.

CONCLUSIONS: This review highlights how ITCs are considered to introduce substantial uncertainty to CEAs as part of HTA submissions to ZIN. The number of pivotal single-arm trials is increasing, necessitating greater use of ITCs in CEAs. Additional guidance from ZIN is needed to demonstrate how uncertainty from ITCs can be appropriately addressed in CEAs.