The cost and cost-effectiveness of novel tuberculosis vaccines in low- and middle-income countries: A modeling study

Abstract

Background Tuberculosis (TB) is preventable and curable but eliminating it has proven challenging. Safe and effective TB vaccines that can rapidly reduce disease burden are essential for achieving TB elimination. We assessed future costs, cost-savings, and cost-effectiveness of introducing novel TB vaccines in low- and middle-income countries (LMICs) for a range of product characteristics and delivery strategies. Methods and findings We developed a system of epidemiological and economic models, calibrated to demographic, epidemiological, and health service data in 105 LMICs. For each country, we assessed the likely future course of TB-related outcomes under several vaccine introduction scenarios, compared to a “no-new-vaccine” counterfactual. Vaccine scenarios considered 2 vaccine product profiles (1 targeted at infants, 1 at adolescents/adults), both assumed to prevent progression to active TB. Key economic inputs were derived from the Global Health Cost Consortium, World Health Organization (WHO) patient cost surveys, and the published literature. We estimated the incremental impact of vaccine introduction for a range of health and economic outcomes. In the base-case, we assumed a vaccine price of $4.60 and used a 1× per-capita gross domestic product (GDP) cost-effectiveness threshold (both varied in sensitivity analyses). Vaccine introduction was estimated to require substantial near-term resources, offset by future cost-savings from averted TB burden. From a health system perspective, adolescent/adult vaccination was cost-effective in 64 of 105 LMICs. From a societal perspective (including productivity gains and averted patient costs), adolescent/adult vaccination was projected to be cost-effective in 73 of 105 LMICs and cost-saving in 58 of 105 LMICs, including 96% of countries with higher TB burden. When considering the monetized value of health gains, we estimated that introduction of an adolescent/adult vaccine could produce $283 to 474 billion in economic benefits by 2050. Limited data availability required assumptions and extrapolations that may omit important country-level heterogeneity in epidemiology and costs. Conclusions TB vaccination would be highly impactful and cost-effective in most LMICs. Further efforts are needed for future development, adoption, and implementation of novel TB vaccines.

New tuberculosis vaccines in India: Modelling the potential health and economic impacts of adolescent/adult vaccination with M72/AS01Eand BCG-revaccination

“…Our analyses demonstrated that both vaccines could be cost-effective, aligning with previous cost-effectiveness analyses of tuberculosis vaccines. 6,29 While vaccination could have a substantial budget impact, costs could be partially offset with diagnostic and treatment savings.…”

“…4 The National Strategic Plan also calls for further development in tuberculosis vaccines, which has been a high priority for global organisations such as the World Health Organization (WHO). A recently completed WHO-commissioned study assessing the full value of tuberculosis vaccines made a strong case from the health and economic perspectives for continued investment, [5][6][7][8][9] and previous work has demonstrated that novel vaccines or vaccination strategies will be needed to eliminate tuberculosis. 10,11 Currently, sixteen candidates are in various phases throughout the vaccine pipeline, being trialled in a variety of ages and spanning prevention of disease, infection, and recurrence endpoints.…”

Is neglect of self-clearance biassing TB vaccine impact estimates?

“…Mathematical models have been used extensively to estimate the potential impact and cost-effectiveness of tuberculosis vaccines with different specifications [6]. Models have, for example, provided age indications for TB vaccines, by demonstrating the greater and more rapid impact before 2050 of targeting adolescents and adults instead of infants in low and middle income countries [7], [8], and older adults only in settings such as China [9].…”

“…Since the efficacy of new tuberculosis vaccines may depend on the host infection status, self-clearance also has the potential to affect the impact of new vaccines. While a number of more recent vaccine models have included a simple representation of self-clearance ( [6], [8]), none have investigated its effects on vaccine impact, or have explored the effects of the large amounts of uncertainty that exists around the properties of self-clearance. No earlier vaccine models included self-clearance at all ([10], [15]).…”

Planning to introduce novel tuberculosis vaccines in high burden settings: how could this be done?

“…The same group also published a cost-effectiveness model for the same LMICs, estimating a saving of US$283 billion to $474 billion by 2050, especially in countries with high tuberculosis burdens. 8 …”