Josephine van Dongen

3 Updated cost-effectiveness and risk-benefit analysis 71 Discussion Our results show that, in a high-income and relatively low rotavirus endemic setting, targeted rotavirus vaccination of infants with medical risk conditions is a cost-saving strategy and has the most favorable risk-benefit ratio.This finding remains robust in all of our sensitivity analyses.This strategy would also nearly eliminate rotavirus-related mor tality in high-income settings, where fatal rotavirus cases among otherwise healthy children are extremely rare. Yet, the impact of targeted vaccination on the rotavirus disease burden in the pediatric population is limited, with only a 3.4% reduction in AGE episodes and a 14.7% reduction in hospitalizations ( Table 2 ). Universal rotavirus vaccination has the potential to reduce the population rotavirus disease burden in children by >50% and aver t nearly 75% of hospitalizations ( Table 2 ). However, in a low-endemic setting and at assumed vaccine costs of €75 per child, the ICER for universal rotavirus vaccination at €51,280/QALY for the societal perspective and at €72,021/QALY for the healthcare perspective is not considered a cost-effective intervention according to most internationally accepted willingness-to-pay thresholds 40,41,42 . Fur ther reductions in vaccine prices are therefore needed to improve cost-effectiveness. Universal vaccination could become cost-saving when vaccine costs are reduced to €32 per child or less. Impor tantly, even in a low-endemic setting, the risk-benefit ratio for healthy children vaccinated under a universal vaccination strategy can still be considered favorable at 571 aver ted hospitalizations for every vaccine-induced case of IS. Our analysis also showed that the alternative universal vaccination scenario, i.e., no publicly funded program but vaccines individually purchased, is the least favorable strategy due to higher vaccine costs per child (no price reductions generated through tender processes) and absence of herd protection because of moderate vaccine uptake.Yet, this or comparable strategies are currently in use in several high- or middle-income countries 43 . Health authorities may therefore wish to reconsider one of the alternative, more cost-effective vaccination strategies. Healthcare budget restrictions and prioritization may be an impor tant reason why a publicly funded universal vaccination program is unfeasible. In this situation, a publicly funded targeted vaccination program can form a suitable alternative, as it results in cost savings both from the societal and healthcare payer perspective,while protecting the most vulnerable infants.Concerns about vaccine safety of the currently licensed vaccines and public acceptance may be another reason for not implementing universal vaccination. For instance, in France several repor ts on severe and even fatal IS cases following rotavirus vaccination resulted in public concern and the decision by health authorities to withdraw the recommendation for routine infant rotavirus vaccination 44 . A recommendation for targeted vaccination could offer an acceptable solution because of the more favorable risk-benefit ratio.