Economic implications of novel regimens for tuberculosis treatment in three high-burden countries: a modelling analysis

Abstract

Background: With numerous trials investigating novel drug combinations to treat tuberculosis, we aimed to evaluate the extent to which future improvements in tuberculosis treatment regimens could offset potential increases in drug costs.

Methods: In this modelling analysis, we used an ingredients-based approach to estimate prices at which novel regimens for rifampin-susceptible and rifampin-resistant tuberculosis treatment would be cost-neutral or cost-effective compared with standards of care in India, the Philippines, and South Africa. We modelled regimens meeting targets set in the WHO's 2023 Target Regimen Profiles (TRPs). Our decision-analytical model tracked cohorts of adults initiating rifampin-susceptible or rifampin-resistant tuberculosis treatment, simulating their health outcomes and costs accumulated during and following treatment under standard-of-care and novel regimen scenarios. Price thresholds included short-term cost-neutrality (considering only savings accrued during treatment), medium-term cost-neutrality (additionally considering savings from averted retreatments and secondary cases), and cost-effectiveness (incorporating willingness-to-pay for improved health outcomes).

Findings: Total medium-term costs per person treated using standard-of-care regimens were estimated at US$450 (95% uncertainty interval 310-630) in India, $560 (350-860) in the Philippines, and $730 (530-1090) in South Africa for rifampin-susceptible tuberculosis (current drug costs $46) and $2100 (1590-2810) in India, $2610 (2090-3280) in the Philippines, and $3790 (3090-4630) in South Africa for rifampin-resistant tuberculosis (current drug costs $432). A rifampin-susceptible tuberculosis regimen meeting the optimal targets defined in the TRPs could be cost-neutral in the short term at drug costs of $140 (90-210) per full course in India, $230 (130-380) in the Philippines, and $280 (180-460) in South Africa. For rifampin-resistant tuberculosis, short-term cost-neutral thresholds were higher with $930 (720-1230) in India, $1180 (980-1430) in the Philippines, and $1480 (1230-1780) in South Africa. Medium-term cost-neutral prices were approximately $50-100 higher than short-term cost-neutral prices for rifampin-susceptible tuberculosis and $250-550 higher for rifampin-resistant tuberculosis. Health system cost-neutral prices that excluded patient-borne costs were 45-70% lower (rifampin-susceptible regimens) and 15-50% lower (rifampin-resistant regimens) than the cost-neutral prices that included patient costs. Cost-effective prices were substantially higher. Shorter duration was the most important driver of medium-term savings with novel regimens, followed by ease of adherence.

Interpretation: Improved tuberculosis regimens, particularly shorter regimens or those that facilitate better adherence, could reduce overall costs, potentially offsetting higher prices.

Funding: WHO.

Figure 1

Medium-term societal costs of standard of care and improved tuberculosis treatment regimens Estimated mean medium-term costs per patient with rifampin-susceptible tuberculosis treated with the standard of care (6 months of isoniazid, rifampin, pyrazinamide, and ethambutol for most patients) and with regimens meeting all optimal targets in the 2023 TRPs (A). Estimated mean costs per patient with rifampin-resistant tuberculosis treated with the standard of care (6 months of bedaquiline, pretomanid, linezolid, and moxifloxacin for most patients) and TRP-optimal regimens (B). TRP-optimal regimen costs include the costs of drugs when priced at their estimated medium-term cost-neutral prices (lightest blue), whereas standard-of-care regimen costs include the cost of drugs at their current prices (dark blue). The difference in the heights of the non-drug (non-lightest blue and non-dark blue) bars within each panel thus represent medium-term non-drug cost savings from an optimla TRP regimen. Shading indicates mean costs attributed to different components of treatment and error bars indicate uncertainty intervals (2·5th and 97·5th percentiles across 10 000 parameter set samples) for total cost estimates under the standard of care. The heights of the lightest blue bars (drug costs at cost-neutral prices) for the TRP-optimal regimens differ slightly from the thresholds shown in table 3 (cost-neutral prices) because of wastage and incomplete person-time on treatment. Note the difference in y-axis scales between panels A and B. TRP=Target Regimen Profile.

Figure 2

Influence of five novel tuberculosis-treatment regimen attributes on medium-term cost-neutral price thresholds in India Medium-term cost-neutral price thresholds for novel rifampin-susceptible (A) and rifampin-resistant (B) regimens in India under the societal perspective. Coloured bars show the variation in the price threshold when a single characteristic is varied from its standard-of-care value to its optimal TRP value. The values that the non-varying characteristics take on differ between the three sections of each panel; the bottom sections of both panels (all but one characteristic set to standard of care) show thresholds when all non-varying characteristics are fixed at their standard-of-care values (vertical dashed line), the middle sections of each panel (all but one characteristic set to minimal TRP) show results when all non-varying characteristics are fixed at their minimal target values from the TRPs (table 2), and the top sections of each panel (all but one characteristic set to optimal TRP) show results when all non-varying characteristics are fixed at their optimal values from the TRPs. Colours indicate which characteristic is being varied, and text labels indicate the values of each characteristic (left of the bars, standard-of-care values for each characteristic; right of the bars, TRP-optimal values for each characteristic). Bars are ordered vertically by the effect each characteristic has on the threshold (the vertical distance between each bar is equal and not meaningful). TRP=Target Regimen Profile. UI=uncertainty interval.