A model-based economic analysis of pre-pandemic influenza vaccination cost-effectiveness

Abstract

Background: A vaccine matched to a newly emerged pandemic influenza virus would require a production time of at least 6 months with current proven techniques, and so could only be used reactively after the peak of the pandemic. A pre-pandemic vaccine, although probably having lower efficacy, could be produced and used pre-emptively. While several previous studies have investigated the cost effectiveness of pre-emptive vaccination strategies, they have not been directly compared to realistic reactive vaccination strategies.

Methods: An individual-based simulation model of ~30,000 people was used to examine a pre-emptive vaccination strategy, assuming vaccination conducted prior to a pandemic using a low-efficacy vaccine. A reactive vaccination strategy, assuming a 6-month delay between pandemic emergence and availability of a high-efficacy vaccine, was also modelled. Social distancing and antiviral interventions were examined in combination with these alternative vaccination strategies. Moderate and severe pandemics were examined, based on estimates of transmissibility and clinical severity of the 1957 and 1918 pandemics respectively, and the cost effectiveness of each strategy was evaluated.

Results: Provided that a pre-pandemic vaccine achieved at least 30% efficacy, pre-emptive vaccination strategies were found to be more cost effective when compared to reactive vaccination strategies. Reactive vaccination coupled with sustained social distancing and antiviral interventions was found to be as effective at saving lives as pre-emptive vaccination coupled with limited duration social distancing and antiviral use, with both strategies saving approximately 420 life-years per 10,000 population for a moderate pandemic with a basic reproduction number of 1.9 and case fatality rate of 0.25%. Reactive vaccination was however more costly due to larger productivity losses incurred by sustained social distancing, costing $8 million per 10,000 population ($19,074/LYS) versus $6.8 million per 10,000 population ($15,897/LYS) for a pre-emptive vaccination strategy. Similar trends were observed for severe pandemics.

Conclusions: Compared to reactive vaccination, pre-emptive strategies would be more effective and more cost effective, conditional on the pre-pandemic vaccine being able to achieve a certain level of coverage and efficacy. Reactive vaccination strategies exist which are as effective at mortality reduction as pre-emptive strategies, though they are less cost effective.

Figure 1

Synopsis of methodology.

Figure 2

Cost effectiveness plane for intervention strategies for different scenarios. Intervention strategies are labelled as R: Reactive vaccination, P: Pre-emptive vaccination, R + LSD: Reactive vaccination + Limited Social Distancing (8 weeks of SC + CCR) + AV, P + LSD: Pre-emptive vaccination + Limited Social Distancing + AV, R + SSD: Reactive vaccination + Sustained Social Distancing (Sustained SC + CCR) + AV, P + SSD: Pre-emptive vaccination + Sustained Social Distancing + AV, SC – School Closure, CCR – Community Contact Reduction, AV – Antiviral treatment for cases and prophylaxis for their household members, LSD – Limited Social Distancing, SSD – Sustained Social Distancing. All LSD and SSD interventions integrate the use of antivirals (AV).

Figure 3

Cost breakdowns to different costing components. Interventions strategies are labelled as Figure 2.

Figure 4

Impact of vaccination coverage on the cost effectiveness. Interventions strategies are labelled as Figure 2.

Figure 5

Impact of vaccine renewal frequency on the cost effectiveness. Interventions strategies are labelled as Figure 2.

Figure 6

Impact of pandemic frequency on the cost effectiveness. Interventions strategies are labelled as Figure 2.

Figure 7

Impact of pre-pandemic vaccine mismatch on the cost effectiveness. Interventions strategies are labelled as Figure 2.