Full title: Update of the cost-effectiveness of routine childhood vaccination against invasive meningococcal disease caused by serogroups A, C, W and Y in children aged 4 and 12 months
Authors: Valcárcel-Nazco C, Manzano-Armas KJ, Herrera-Ramos E, Hernández-Yumar A, Cazaña-Pérez V, García-Pérez L
Contact Person: Cristina Valcárcel Nazco (cristina.valcarcelnazco@sescs.es)
RESUMEN
Introduction
Invasive meningococcal disease (IMD) is a rare but very severe infection caused by the bacterium Neisseria meningitidis. It mainly presents as meningitis or sepsis, conditions that can progress rapidly and lead to permanent neurological, auditory or motor sequelae, or even death. Although multiple serogroups exist, serogroups A, C, W and Y account for a significant proportion of severe cases and are preventable through vaccination.
In Europe, the overall incidence of IMD has fluctuated in recent years, with a marked decline during the COVID-19 pandemic followed by a rebound associated with the recovery of respiratory pathogen circulation. In Spain, incidence remains low, although higher rates are observed in infants under one year of age and in children aged 1–4 years. In 2023, 265 confirmed cases were reported, with a case-fatality rate of 13%. Serogroup distribution showed predominance of serogroup B, followed by W, Y and, to a lesser extent, C.
Currently, the national immunisation schedule of the Spanish National Health System (SNS) includes vaccination against MenC at 4 and 12 months of age and a dose of MenACWY at 12 years of age. However, several autonomous communities have expanded infant protection by introducing MenACWY at 12 months or by replacing MenC with MenACWY at 4 and 12 months. This has resulted in territorial heterogeneity in access to vaccination against serogroups A, C, W and Y.
In 2023, the Health Technology Assessment Service of the Canary Islands Health Service (SESCS) published an HTA report on routine infant vaccination with MenACWY at 12 months, concluding that it was not a cost-effective strategy in Spain compared with MenC vaccination. Given the time elapsed, changes in epidemiology, regional expansion of vaccination programmes, and variations in costs and coverage, the Ministry of Health requested an update of the economic analysis for 2025.
Objective
The main objective of this report is to update the economic evaluation of routine infant vaccination against invasive meningococcal disease caused by serogroups A, C, W and Y in Spain, through a review of the most recent evidence on cost-effectiveness and the update of the previously developed economic model, in order to compare different MenACWY vaccination strategies with MenC vaccination from the perspective of the National Health System.
Methodology
Systematic review of cost-effectiveness
An update of the systematic review (SR) of economic evaluations included in the previous SESCS report was conducted. Full economic evaluations (model-based or alongside primary studies) comparing universal infant vaccination with MenACWY versus MenC vaccination or no vaccination were sought.
Eligible studies included infant populations aged ≤12 months and assessed vaccination strategies in terms of costs and outcomes, reporting quality-adjusted life years (QALYs), life years gained (LYG) and incremental cost-effectiveness ratios (ICERs). Studies focusing on adolescents, risk groups, vaccines not authorised in Spain or non-routine vaccination strategies were excluded.
Methodological quality was assessed using Drummond’s criteria. Study selection and data extraction were performed independently by two reviewers, and evidence was synthesised narratively and in tables.
Economic analysis
The static economic model developed in the 2023 SESCS report was updated, incorporating the most recent epidemiological, clinical and economic evidence. Three strategies were compared: (1) routine vaccination against MenC (current practice); (2) routine vaccination with MenACWY at 12 months of age (partial replacement); and (3) routine vaccination with MenACWY at 4 and 12 months of age (full replacement). All three strategies assume the continuation of the current adolescent MenACWY vaccination strategy.
The model adopted the perspective of the National Health System (SNS), with an additional complementary analysis from a societal perspective. Direct healthcare costs were included (vaccines, administration, hospital and outpatient care, and long-term sequelae). Health outcomes were measured in life-years gained (LYG) and quality-adjusted life-years (QALYs). Costs were expressed in 2025 euros, and an annual discount rate of 3% was applied to both costs and health outcomes.
Deterministic sensitivity analyses were conducted on key parameters (vaccine price, incidence, effectiveness, and coverage), together with a probabilistic sensitivity analysis to assess overall uncertainty. The resulting incremental cost-effectiveness ratios (ICERs) were compared with the estimated opportunity cost of a QALY in Spain, ranging between €27,000 and €34,000 per QALY.
Budget impact analysis
Based on the base-case cost-effectiveness analysis, a 5-year budget impact analysis (BIA) (2025–2030) was conducted from the perspective of the National Health System (NHS). The total cost of implementing systematic vaccination with MenACWY compared with the current scenario was estimated, taking into account the annual number of births, vaccination coverage rates, unit vaccine prices, and the costs avoided due to prevented cases.
Results
Systematic review of cost-effectiveness
The updated systematic review of the literature identified a single new economic evaluation that met the inclusion criteria, conducted in Germany. This study assessed different vaccination strategies against invasive meningococcal disease (IMD) caused by serogroups A, C, W, and Y, including the replacement of MenC vaccination with a single dose of MenACWY at 12 months of age. The results showed that, within the German epidemiological context, replacing MenC with MenACWY at 12 months is associated with improved health outcomes and a favorable cost-effectiveness profile. This finding is mainly attributable to a higher incidence of serogroups W and Y and to specific features of the German vaccination programme. However, epidemiological and organizational differences between Germany and Spain limit the direct transferability of these results to the Spanish National Health System (SNS), where the incidence of serogroups covered by MenACWY is lower.
Results of the economic evaluation
The updated economic evaluation, conducted from the perspective of the SNS and complemented by a social perspective analysis, compared three systematic childhood vaccination strategies:
- MenC vaccination at 4 and 12 months (current strategy);
- Partial replacement (MenC at 4 months plus MenACWY at 12 months); and
- Complete replacement with MenACWY at 4 and 12 months.
Base-case results show that strategies incorporating MenACWY yield marginal gains in quality-adjusted life years (QALYs) compared with the current MenC strategy. However, these gains are accompanied by cost increases that result in incremental cost-effectiveness ratios (ICERs) exceeding the opportunity cost of a QALY in Spain (27,000–34,000 €/QALY), from both the SNS and the social perspectives.
The probabilistic sensitivity analysis confirms these findings, showing a low probability that MenACWY-based strategies are cost-effective at willingness-to-pay thresholds below 34,000 €/QALY. Deterministic and scenario sensitivity analyses indicate that vaccine price and IMD incidence are the main drivers of the results. Under scenarios involving a reduction in the price of MenACWY or a substantial and sustained increase in disease incidence, MenACWY-based strategies could become cost-effective.
Results of the budget impact analysis
The budget impact analysis indicates that introducing a systematic childhood vaccination programme with MenACWY in place of MenC would result in an increase in expenditure of up to €2,663,117 in the fifth year following national implementation, assuming high vaccination coverage and a homogeneous distribution of prevented IMD cases across autonomous communities. This impact corresponds to €1,242,528 in the case of partial replacement (MenC at 4 months + MenACWY at 12 months).
Conclusions
Based on the systematic review of cost-effectiveness, the economic evaluation, and the budget impact analysis conducted for this HTA report, the following conclusions can be drawn:
- The recent evidence available on the cost-effectiveness of systematic childhood vaccination with MenACWY in children under 12 months of age remains limited.
- The updated systematic review identified a single new cost-effectiveness study conducted in Germany. This study concludes that replacing MenC vaccination with a dose of MenACWY at 12 months of age could be cost-effective in that context, mainly due to a higher incidence of serogroups W and Y and to differences in vaccine prices and the organisation of the vaccination programme. However, epidemiological differences between Germany and Spain limit the direct transferability of these findings to the context of the Spanish National Health System.
- The results of the updated economic model show that both the partial replacement strategy (MenC at 4 months plus MenACWY at 12 months) and the complete replacement strategy with MenACWY (4 and 12 months) are not cost-effective alternatives in Spain. This conclusion could change if substantial and sustained increases in disease incidence or reductions in the vaccine price considered in the present analysis were to occur.
- The budget impact analysis estimates that the introduction of a systematic MenACWY vaccination strategy in children up to 12 months of age could result in an additional expenditure of approximately €2.66 million in the fifth year following its implementation within the SNS, assuming a homogeneous distribution of prevented IMD cases across the national territory. In the case of partial replacement (MenC at 4 months + MenACWY at 12 months), the budget impact would decrease to €1,242,528.
Keywords: Invasive meningococcal disease; Childhood vaccination; MenACWY; Systematic review; Economic evaluation; Cost-effectiveness.
