Cost-effectiveness of pharmaceutical strategies to prevent respiratory syncytial virus disease in young children: a decision-support model for use in low-income and middle-income countries

Abstract

Background: Respiratory syncytial virus (RSV) is a leading cause of respiratory disease in young children. A number of mathematical models have been used to assess the cost-effectiveness of RSV prevention strategies, but these have not been designed for ease of use by multidisciplinary teams working in low-income and middle-income countries (LMICs).

Methods: We describe the UNIVAC decision-support model (a proportionate outcomes static cohort model) and its approach to exploring the potential cost-effectiveness of two RSV prevention strategies: a single-dose maternal vaccine and a single-dose long-lasting monoclonal antibody (mAb) for infants. We identified model input parameters for 133 LMICs using evidence from the literature and selected national datasets. We calculated the potential cost-effectiveness of each RSV prevention strategy (compared to nothing and to each other) over the lifetimes of all children born in the year 2025 and compared our results to a separate model published by PATH. We ran sensitivity and scenario analyses to identify the inputs with the largest influence on the cost-effectiveness results.

Results: Our illustrative results assuming base case input assumptions for maternal vaccination ($3.50 per dose, 69% efficacy, 6 months protection) and infant mAb ($3.50 per dose, 77% efficacy, 5 months protection) showed that both interventions were cost-saving compared to status quo in around one-third of 133 LMICs, and had a cost per DALY averted below 0.5 times the national GDP per capita in the remaining LMICs. UNIVAC generated similar results to a separate model published by PATH. Cost-effectiveness results were most sensitive to changes in the price, efficacy and duration of protection of each strategy, and the rate (and cost) of RSV hospital admissions.

Conclusions: Forthcoming RSV interventions (maternal vaccines and infant mAbs) are worth serious consideration in LMICs, but there is a good deal of uncertainty around several influential inputs, including intervention price, efficacy, and duration of protection. The UNIVAC decision-support model provides a framework for country teams to build consensus on data inputs, explore scenarios, and strengthen the local ownership and policy-relevance of results.

Keywords: Economic evaluation; LMICs; Maternal vaccine; Monoclonal antibody; RSV.

Fig. 1

Integration of a decision-support model into a country-led vaccine decision-making process

Fig. 2

Rates of RSV disease events in the recommended setup of UNIVAC (A) and possible pathways underlying these disease event rates (B). Caption: While there are many pathways to RSV death (and therefore different probabilities of dying for different treatment pathways), for simplicity only one rate of RSV mortality is required by the model. Similarly, while many healthcare utilisation pathways (clinic visits and/or hospital admissions) are possible, for simplicity all this activity is captured within a single rate of RSV hospital admissions, and two rates of RSV clinic visits (one for severe RSV and one for non-severe RSV). The model does not include a separate category for emergency room (ER) visits, and since the model will assume the same efficacy and treatment costs for all outcomes that are grouped together, country teams should clarify whether ER visits are included within the estimated rate of clinic visits or hospital admissions. Estimates of the average treatment cost per patient should also be adjusted appropriately to account for the contribution and cost of ER visits

Fig. 3

Percentage of 133 LMICs willing to pay for RSV prevention strategies (compared to no pharmaceutical intervention) at different willingness-to-pay thresholds: base case and alternative efficacy scenarios. Caption: The thick black lines show the base case (scenario 1) assumptions. For maternal vaccination, this assumes efficacy of 69.4% (severe RSV disease) and 51.3% (non-severe RSV disease) for a 6-month period and zero protection thereafter. For mAb this assumes efficacy of 77.3% (severe RSV disease) and 74.5% (non-severe RSV disease) for a 5-month period, and zero protection thereafter. The grey lines show the scenario 2 assumptions. For this scenario, we used previously described methods [53] to fit estimates of instantaneous efficacy (iE) that were consistent with the reported cumulative efficacy (cE) at 3 and 6 months of follow-up (see Additional file 1, page 32, and Fig. S3, for more details). Finally, we applied one additional scenario (scenario 3) for maternal vaccination with efficacy of 81.8% (severe RSV disease) and 57.1% (non-severe RSV disease) for a 3-month period, and zero protection thereafter