Review 3: "The Potential Health and Economic Impacts of New Tuberculosis Vaccines under Varying Delivery Strategies in Delhi and Gujarat, India: A Modelling Study"

Edina Sinanovic

doi:doi:10.1162/2e3983f5.7270f794

The potential health and economic impacts of new tuberculosis vaccines under varying delivery strategies in Delhi and Gujarat, India: a modelling study

by Rebecca A Clark, Allison Portnoy, Chathika K Weerasuriya, Tom Sumner, Roel Bakker, Rebecca C Harris, Kirankumar Rade, Sanjay Kumar Mattoo, Dheeraj Tumu, Nicolas A Menzies, and Richard G White

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Published on Sep 27, 2023
www.medrxiv.org

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Abstract Background India has the largest tuberculosis burden globally, but this burden varies nationwide. All-age tuberculosis prevalence in 2021 ranged from 747/100,000 in Delhi to 137/100,000 in Gujarat. Previous modelling has demonstrated the benefits and costs of introducing novel tuberculosis vaccines in India overall. However, no studies have compared the potential impact of tuberculosis vaccines in regions within India with differing tuberculosis disease and infection prevalence. We used mathematical modelling to investigate how the health and economic impact of two potential tuberculosis vaccines, M72/AS01E and BCG-revaccination, could differ in Delhi and Gujarat under varying delivery strategies.Methods We applied a compartmental tuberculosis model separately for Delhi (higher disease and infection prevalence) and Gujarat (lower disease and infection prevalence), and projected epidemiological trends to 2050 assuming no new vaccine introduction. We simulated M72/AS01E and BCG-revaccination scenarios varying target ages and vaccine characteristics. We estimated cumulative cases, deaths, and disability-adjusted life years averted between 2025–2050 compared to the no-new-vaccine scenario and compared incremental cost-effectiveness ratios to three cost-effectiveness thresholds.Results M72/AS01E averted a higher proportion of tuberculosis cases than BCG-revaccination in both regions (Delhi: 16.0% vs 8.3%, Gujarat: 8.5% vs 5.1%) and had higher vaccination costs (Delhi: USD$118 million vs USD$27 million, Gujarat: US$366 million vs US$97 million). M72/AS01E in Delhi could be cost-effective, or even cost-saving, for all modelled vaccine characteristics. M72/AS01E could be cost-effective in Gujarat, unless efficacy was assumed only for those with current infection at vaccination. BCG-revaccination could be cost-effective, or cost-saving, in both regions for all modelled vaccine scenarios.Discussion M72/AS01E and BCG-revaccination could be impactful and cost-effective in Delhi and Gujarat. Differences in impact, costs, and cost-effectiveness between vaccines and regions, were determined partly by differences in disease and infection prevalence, and demography. Age-specific regional estimates of infection prevalence could help to inform delivery strategies for vaccines that may only be effective in people with a particular infection status. Evidence on the mechanism of effect of M72/AS01E and its effectiveness in uninfected individuals, which were important drivers of impact and cost-effectiveness, particularly in Gujarat, are also key to improve estimates of population-level impact.

RR:C19 Evidence Scale rating by reviewer:

Strong. The main study claims are very well-justified by the data and analytic methods used. There is little room for doubt that the study produced has very similar results and conclusions as compared with the hypothetical ideal study. The study’s main claims should be considered conclusive and actionable without reservation.

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Review:

This preprint claims that both M72/AS01E and BCG-revaccination could potentially have a significant impact and be cost-effective in Delhi and Gujarat. It also claims that there is a need for age-specific regional estimates of infection prevalence to help determine if vaccines only work in uninfected individuals or in those who are infected.

This is a well conceptualized and clearly written study that used mathematical modelling to estimate the potential health and economic impact of two vaccines for TB infection and disease in two regions in India. The study design is clear and valid, and methods are relevant. Figures, tables and references are appropriate. The study conclusions are supported by the data. It is a relevant manuscript that could be useful to decision makers.

The methods used in the study are appropriate for the question asked. Mathematical modelling is often used to estimate future costs and benefits of a new health technology such as novel vaccines. Models are a simplification of reality and often the best way of evaluating an intervention that might become available in the near future.

The study listed and discussed in detail the relevant limitations. The conclusions are appropriate and the identified directions for future research stem from the study findings.

In summary, this preprint claims that both vaccines are likely to be cost-effective in Delhi and Gujarat (unless efficacy was restricted to those with current infection). As there were no region-specific TB prevalence and mortality data, model calibration was not possible and, therefore, there is uncertainty around trends in mortality and vaccine impact.

Review 3: "The Potential Health and Economic Impacts of New Tuberculosis Vaccines under Varying Delivery Strategies in Delhi and Gujarat, India: A Modelling Study"

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