Given the higher effectiveness of the HZ/su, but the lower price, greater tolerability, and lack of need for a booster injection with the ZVL, a comprehensive comparison of downstream patient outcomes and the costs associated with each vaccine was necessary to inform payers, providers, and patients on choosing between these alternatives. Within this context, de Boer and colleagues  present an elegant cost-effectiveness analysis of the HZ/su, the ZVL with or without a 10-year booster, and no vaccination, in four cohorts of 50, 60, 70, and 80 years of age, from the perspective of the Netherlands. Specifically, they express their findings as the maximum cost under which the ZVL or HZ/su would be cost-effective compared to no vaccination under willingness-to-pay thresholds of €20,000 per quality-adjusted life year (QALY) and €50,000 per QALY. Input estimates for the incidence of HZ and PHN and associated costs were obtained from Dutch national registries, and health disutilities were extracted from a Dutch prospective study. The authors performed several sensitivity analyses to evaluate the robustness of their results for variations in assumptions and in input parameters.
As expected, the authors found that the HZ/su prevents significantly more cases of HZ than the ZVL, resulting in a higher number of QALYs. For the HZ/su, the number needed to vaccinate to avoid one case of HZ was less than 11 for all age cohorts, whereas for the ZVL it was 22.8, 34.9, and 117.0 for patients of 60, 70, and 80 years of age, respectively. Vaccination with the HZ/su was most cost-effective in the 70-year-old cohort, and the cost-effectiveness of the ZVL was highest for the 60-year-old cohort. Specifically, for the 60-year-old cohort, the HZ/su would be cost-effective compared to no vaccination for costs below €104 (per series), and the ZVL would be cost-effective if priced at €51.40 or below. For the 70-year-old cohort, the HZ/su would be cost-effective compared to no vaccination for costs below €109, and the ZVL would be cost-effective if priced at €27.50 or below. Given the current prices of both vaccines in the Netherlands, neither vaccine was cost-effective in any patient population under the €20,000 per QALY willingness-to-pay threshold. However, many countries or healthcare systems use a higher willingness-to-pay threshold. Under the €50,000 per QALY threshold, the HZ/su vaccine would be cost-effective in some scenarios.
There are several important assumptions in their analysis. First, the base case analysis assumes 100% compliance with both doses of the HZ/su, which is unlikely in real-world clinical practice. To relax this assumption, the authors performed sensitivity analyses in which compliance for the second dose was 90%, 70%, and 50%. Under the 50% compliance scenario, the HZ/su is cost-effective compared to no vaccination in the 70-year-old cohort if priced around €30 less than in the base case scenario. This suggests that the impact of missing the second dose on the cost-effectiveness of the vaccine is considerable, which should support efforts by health systems to improve compliance with the booster injection. Second, because the waning effectiveness rate of the HZ/su is unknown, the authors assumed a 4.1% per year decline over a time horizon of 15 years in patients 70 years or older. Using lower waning rates significantly improved the cost-effectiveness of the vaccine.