Estimation of the health impact and cost-effectiveness of influenza vaccination with enhanced effectiveness in Canada

Abstract

Introduction: The propensity for influenza viruses to mutate and recombine makes them both a familiar threat and a prototype emerging infectious disease. Emerging evidence suggests that the use of MF59-adjuvanted vaccines in older adults and young children enhances protection against influenza infection and reduces adverse influenza-attributable outcomes compared to unadjuvanted vaccines. The health and economic impact of such vaccines in the Canadian population are uncertain.

Methods: We constructed an age-structured compartmental model simulating the transmission of influenza in the Canadian population over a ten-year period. We compared projected health outcomes (quality-adjusted life years (QALY) lost), costs, and incremental cost-effectiveness ratios (ICERs) for three strategies: (i) current use of unadjuvanted trivalent influenza vaccine; (ii) use of MF59-adjuvanted influenza vaccine adults ≥65 in the Canadian population, and (iii) adjuvanted vaccine used in both older adults and children aged < 6.

Results: In the base case analysis, use of adjuvanted vaccine in older adults was highly cost-effective (ICER = $2111/QALY gained), but such a program was "dominated" by a program that extended the use of adjuvanted vaccine to include young children (ICER = $1612/QALY). Results were similar whether or not a universal influenza immunization program was used in other age groups; projections were robust in the face of wide-ranging sensitivity analyses.

Interpretation: Based on the best available data, it is projected that replacement of traditional trivalent influenza vaccines with MF59-adjuvanted vaccines would confer substantial benefits to vaccinated and unvaccinated individuals, and would be economically attractive relative to other widely-used preventive interventions.

Figure 1. Outline of model structure, showing population flows between compartments.

Each compartment is further stratified by age category.

Figure 2. Projected health benefits of using adjuvanted influenza vaccine.

Health benefits are estimated for a strategy in which adults >65 or adults ≥65 and children <6 years are vaccinated with adjuvanted influenza vaccine. Projected number of infections, hospitalizations, and deaths averted, by age, over a 10-year period were calculated relative to the use of unadjuvanted trivalent influenza vaccine in the entire population over this time period.

Figure 3. Tornado diagram comparing the relative importance of model parameters on estimated cost-effectiveness.

Incremental cost-effectiveness ratios (ICER) are calculated relative to the use of unadjuvanted vaccine in the entire population when adjuvanted vaccine is used in (a) older adults and (b) older adults and young children. The vertical line corresponds to the base case value for each parameter, with the width of the bars indicating the uncertainty associated with each parameter. The blue segments of the bars correspond to parameter values that result in decreased estimates of cost effectiveness (with negative values corresponding to projected cost savings), while red segments indicate values that increase the base case cost effectiveness. The range of parameters considered in the analysis is described in Table 2 and File S1 .

Figure 4. Vaccine efficacy values above which use of adjuvanted vaccine is no longer the preferred strategy.

Thresholds were determined for different assumed unadjuvanted vaccine efficacies in (a) older adults and (b) young children, assuming different willingness-to-pay thresholds. Unadjuvanted vaccine efficacy used in base case scenarios is indicated by a dotted line.