Targeted rotavirus vaccination of high-risk infants; a low cost and highly cost-effective alternative to universal vaccination

Abstract

Background: The cost-effectiveness of universal rotavirus (RV) vaccination is controversial in developed countries. As a result, RV vaccination programs do not currently exist in most European countries. Hospitalization is the main driver of RV disease costs, and prematurity, low birth weight (LBW) and underlying medical conditions have been associated with RV hospitalization and complications. We investigated the cost-effectiveness of targeted RV vaccination of high-risk infants and universal RV vaccination versus no vaccination.

Methods: Disease burden, mortality and healthcare costs of RV hospitalization for children with and without prematurity, LBW and congenital pathology were quantified in two hospital-based observational studies in the Netherlands. Cost-effectiveness analysis was based on an age-structured stochastic multi-cohort model of the Dutch population comparing universal RV vaccination and targeted vaccination of high-risk infants to no vaccination. The primary endpoint was the incremental cost-effectiveness ratio (ICER), with a threshold of €35,000/quality-adjusted life year (QALY) from the healthcare provider perspective. Sensitivity analyses included vaccine price and coverage, herd-immunity and QALY losses.

Results: A total of 936 children with RV infection were included. Prematurity, LBW and congenital pathology were associated with increased risks of RV hospitalization (relative risks (RR) ranging from 1.6 to 4.4), ICU admission (RR ranging from 4.2 to 7.9), prolonged hospital stay (1.5 to 3.0 excess days) and higher healthcare costs (€648 to €1,533 excess costs). Seven children succumbed due to RV complications, all belonging to the high-risk population. Targeted RV vaccination was highly cost-effective and potentially cost-saving from the healthcare provider perspective with ICERs below €20,000/QALY in all scenarios with total (undiscounted) annual healthcare costs between -€0.1 and €0.5 million/year. Results were most sensitive to mortality rates, but targeted vaccination remained highly cost-effective up to reductions of 90% compared to observed mortality. Universal RV vaccination was not considered cost-effective (mean ICER: €60,200/QALY) unless herd-immunity and caretaker QALY losses were included and vaccine prices were €60 at most (mean ICER: €21,309/QALY).

Conclusion: We recommend targeted RV vaccination for high-risk infants in developed countries.

Figure 1

Comparison of annual net healthcare costs for RV vaccination strategies. Net undiscounted annual healthcare costs for universal (A) and targeted RV vaccination (B) compared to no vaccination under different assumptions and corresponding 95% CI. ‘Basecase’ represents results when the vaccine price per course is €75 per child, coverage is 88%, and no herd immunity is present. ‘Vaccine price low’ and ‘high’ represent results for a vaccine price per course of €60 and €95 per vaccinated child, respectively. ‘Herd immunity’ includes protection of unvaccinated children. A scenario with herd immunity effects was not included for targeted vaccination. ‘Best case’ represents results from a low vaccine price, coverage of 97% and presence of herd immunity. ‘Worst case’ represents a high vaccine price, coverage of 65% and no herd immunity. ‘Vaccine Free Market Price’ shows results when the current listed vaccine price is used without any tender effects. CI:confidence interval; RV: rotavirus.

Figure 2

Comparison of cost-effectiveness of RV vaccination strategies. Cost per QALY gained (mean and 95% CI) for universal (A) and targeted RV vaccination (B), using a healthcare provider perspective and a discount rate of 3% for both costs and effects, under different assumptions. ‘Basecase’ represents results when the vaccine price per course is €75 per child, coverage is 88%, and no herd immunity is present. ‘Vaccine price low’ and ‘high’ represent results for vaccine price per course of €60 and €95 per vaccinated child, respectively, for universal RV vaccination and vaccine price per course of €80 and €120 for targeted RV vaccination. ‘Herd immunity’ includes protection of unvaccinated children (only used in universal RV vaccination). ‘QALY2’ represents results when QALY loss of caretakers is taken into account. ‘Best case’ represents results from a low vaccine price, coverage of 97%, including caretaker QALY’s and presence of herd immunity. ‘Worst case’ represents a high vaccine price, coverage of 65%, no caretaker QALY’s included and no herd immunity. ‘Vaccine Free Market Price’ shows results when the current listed vaccine price is used without any tender effects under base-case assumptions. CI: confidence interval; QALY: quality-adjested life year; RV: rotavirus.

Figure 3

Mean cost per QALY gained by universal (grey line) and targeted (black line) RV vaccination, using a healthcare provider perspective and a discount rate of 3% for both costs and effects, as a function of change in mortality rate between 0% and −100% (that is, no mortality at all) compared to baseline. QALY: quality-adjusted life year; RV: rotavirus.

Figure 4

Probability of willingness-to-pay at different thresholds for universal and targeted RV vaccination versus no vaccination under base-case assumptions showing results for both healthcare provider (HP) and societal perspective (SP). RV: rotavirus.