Influential drivers of the cost-effectiveness of respiratory syncytial virus vaccination in European older adults: a multi-country analysis

Background: We aimed to identify influential drivers of the cost-effectiveness of older adult respiratory syncytial virus (RSV) vaccination in Denmark, Finland, the Netherlands and Valencia-Spain. Methods: A static multi-cohort model was parameterised using country- and age-specific hospitalisations using three approaches: (A) the International Classification of Diseases (ICD)-coded hospitalisations, (B) laboratory RSV-confirmed hospitalisations and (C) time-series modelling (TSM). Plausible hypothetical RSV vaccine characteristics were derived from two protein subunit vaccines for adults aged ≥60 years. A full incremental analysis was conducted by comparing three RSV vaccination strategies: (1) in adults aged ≥60 years (“60y+”); (2) in adults aged ≥65 years (“65y+”); (3) in adults aged ≥75 years (“75y+”) to “no intervention” and to each other. Both costs and quality-adjusted life-years (QALYs) were discounted at country-specific discount rates and the analysis was conducted from both the healthcare payers’ and societal perspectives. Value of information, probabilistic sensitivity and scenario analyses identified influential drivers. Results: Besides vaccine price, the hospitalisation estimates were most influential: (A) Using adjusted RSV-ICD-coded hospitalisations at a vaccine price of €150 per dose, no intervention was cost-effective up to willingness-to-pay (WTP) values of €150,000 per QALY gained in Denmark and the Netherlands, and up to €124,000 per QALY gained in Finland. (B) Using the adjusted RSV-confirmed dataset, the findings were consistent in Denmark and comparable in Finland. In Spain-Valencia, the 75y+ strategy became cost-effective at WTP >€55,000. (C) Using TSM-based estimates, the 75y+ strategy was cost-effective at WTP >€45,000, >€101,000, >€41,000 and >€114,000 in Denmark, Finland, the Netherlands and Spain-Valencia, respectively. Sensitivity analyses showed that the (in-hospital) case fatality ratio and the specification of its age dependency were both influential. Duration of protection was found more influential than a variety of plausible waning patterns over the duration of protection. Conclusions: Data gaps and uncertainties on the RSV-related burden in older adults persist and influence the cost-effectiveness of RSV vaccination. More refined age- and country-specific data on the RSV attributable burden are crucial to aid decision making.