Use and Outcomes of Cost-Effectiveness Analyses and Additional Considerations in Pharmaceutical Reimbursement in the Netherlands

BACKGROUND AND OBJECTIVE: In the Netherlands, the National Health Care Institute (ZIN) assesses pharmaceuticals and advises the Minister of Health, Welfare, and Sport (MoH) on their reimbursement. Since 2015, two policy reforms-the introduction of willingness-to-pay reference values and the lock procedure, which temporarily withholds high-budget hospital pharmaceuticals from reimbursement pending assessment and price negotiations-have changed the decision-making process and expanded the role of cost-effectiveness analysis (CEA). This study provides a comprehensive overview of the use and outcomes of CEAs in Dutch pharmaceutical reimbursement over the past decade. Additionally, we identify how additional considerations beyond cost-effectiveness were used in reimbursement recommendations. METHODS: We analysed reimbursement dossiers and recommendations published by ZIN between 2015 and 2024. Descriptive methods were used to provide insight into characteristics of assessments, CEA outcomes, and recommendations. For a subset of pharmaceutical indications with a CEA and a recommendation to negotiate, we performed a content analysis of ZIN's appraisal and recommendation letters to identify how additional considerations influenced the reimbursement recommendation alongside cost-effectiveness. RESULTS: ZIN advised the MoH on 330 unique reimbursement dossiers covering a total of 350 pharmaceutical indications in the timeframe. CEAs were conducted for 86 indications, primarily for hospital pharmaceuticals (n = 49), for which assessment became mandatory following the introduction of the lock procedure. Of the 86 indications with CEAs, 27 (31%) were deemed cost-effective and 42 (49%) were not, and cost-effectiveness was classified as unknown for 17 (20%), mostly because these CEAs were judged methodologically insufficient by ZIN. Many cost-ineffective pharmaceutical indications exceeded their reference value substantially. Mean incremental cost-effectiveness ratios (ICERs) reported by ZIN for pharmaceutical indications associated with reference values of €20,000, €50,000, and €80,000 per quality-adjusted life-year (QALY) were €97,300, €81,400, and €278,900 per QALY, respectively. CEA results informed proposed price reductions, by relating the ICER to the relevant reference value. ZIN also frequently based its proposed discount on a more plausible scenario analysis or invoked additional arguments, such as uncertainty in costs or effects, anticipated indication expansions, or ample revenue from earlier indications, to determine a societally acceptable price. CONCLUSIONS: In Dutch pharmaceutical reimbursement decision-making, CEA outcomes directly inform price negotiations, and explicit reference values function primarily as anchors for negotiations rather than as strict cut-off points for reimbursement. Additional considerations, such as uncertainty about long-term effects and anticipated changes in the treatment landscape, were frequently invoked alongside cost-effectiveness to argue for further price reductions.