Targeted Next-Generation Sequencing for Diagnosing Pre-Extensively and Extensively Drug-Resistant Tuberculosis-Cost-Effectiveness Analysis in India
Author(s)
Ginenus Fekadu, PhD1, Tadesse Tolossa, MPH2, Tesfaye Regassa Feyissa, PhD3, Martin Siegel, PhD4, Wai-kit Ming, PhD, MD1.
1Department of Infectious Diseases and Public Health, City University of Hong Kong, Kowloon, Hong Kong, 2Deakin Health Economics, School of Health and Social Development, Deakin University, Victoria, Australia, 3Deakin Rural Health, School of Medicine, Deakin University, Victoria, Australia, 4Department of Empirical Health Economics, Technische Universität Berlin, Berlin, Germany.
1Department of Infectious Diseases and Public Health, City University of Hong Kong, Kowloon, Hong Kong, 2Deakin Health Economics, School of Health and Social Development, Deakin University, Victoria, Australia, 3Deakin Rural Health, School of Medicine, Deakin University, Victoria, Australia, 4Department of Empirical Health Economics, Technische Universität Berlin, Berlin, Germany.
OBJECTIVES: Pre-extensively and extensively drug-resistant tuberculosis (pre-XDR/XDR-TB) remains a major public health challenge in India. Although phenotypic drug susceptibility testing (pDST) is the gold standard, it faces limitations such as slow turnaround times and operational barriers. Targeted next-generation sequencing (tNGS) provides faster, culture-free detection of resistance-conferring mutations but lacks evidence on cost-effectiveness in resource-limited settings. This study evaluated tNGS for diagnosing pre-XDR/XDR-TB from the healthcare provider’s perspective in India.
METHODS: A decision-analytic model combining a short-term decision tree and a 10-year Markov cohort compared three diagnostic strategies: pDST, tNGS, and tNGS+pDST. Outcomes included direct medical costs, quality-adjusted life years (QALYs), early treatment initiation, and mortality. Model parameters were derived from published literature and public data. Incremental cost-effectiveness ratios (ICERs) were assessed against India’s GDP-based willingness-to-pay (WTP) threshold ($2,485/QALY). Sensitivity analyses tested the robustness of the findings.
RESULTS: In the base-case analysis, the tNGS and tNGS+pDST strategies yielded superior health outcomes compared to pDST, including higher early treatment initiation (995.55 vs. 805.20 per 1,000 tested) and lower mortality (25.67-27.02 vs. 30.13 deaths per 1,000 cases). However, neither tNGS (ICER: $4,453/QALY) nor tNGS+pDST (ICER: $6,198/QALY) was cost-effective at India’s WTP threshold. One-way sensitivity analysis identified the hazard ratio for mortality associated with delayed treatment (base-case: 1.5) as the most influential parameter. The maximum price threshold for tNGS to achieve cost neutrality was $116. Probabilistic sensitivity analysis with 10,000 Monte Carlo simulations indicated that pDST was the preferred strategy below a WTP of $6,240/QALY.
CONCLUSIONS: Although tNGS-based strategies offer superior health benefits, they are not cost-effective under India’s current GDP-based WTP threshold. However, viability could be achieved through higher WTP thresholds or by reducing tNGS costs to the $116 price ceiling. These findings highlight the need for tailored economic evaluations and strategic investments to enhance TB diagnostic approaches in high-burden settings like India.
METHODS: A decision-analytic model combining a short-term decision tree and a 10-year Markov cohort compared three diagnostic strategies: pDST, tNGS, and tNGS+pDST. Outcomes included direct medical costs, quality-adjusted life years (QALYs), early treatment initiation, and mortality. Model parameters were derived from published literature and public data. Incremental cost-effectiveness ratios (ICERs) were assessed against India’s GDP-based willingness-to-pay (WTP) threshold ($2,485/QALY). Sensitivity analyses tested the robustness of the findings.
RESULTS: In the base-case analysis, the tNGS and tNGS+pDST strategies yielded superior health outcomes compared to pDST, including higher early treatment initiation (995.55 vs. 805.20 per 1,000 tested) and lower mortality (25.67-27.02 vs. 30.13 deaths per 1,000 cases). However, neither tNGS (ICER: $4,453/QALY) nor tNGS+pDST (ICER: $6,198/QALY) was cost-effective at India’s WTP threshold. One-way sensitivity analysis identified the hazard ratio for mortality associated with delayed treatment (base-case: 1.5) as the most influential parameter. The maximum price threshold for tNGS to achieve cost neutrality was $116. Probabilistic sensitivity analysis with 10,000 Monte Carlo simulations indicated that pDST was the preferred strategy below a WTP of $6,240/QALY.
CONCLUSIONS: Although tNGS-based strategies offer superior health benefits, they are not cost-effective under India’s current GDP-based WTP threshold. However, viability could be achieved through higher WTP thresholds or by reducing tNGS costs to the $116 price ceiling. These findings highlight the need for tailored economic evaluations and strategic investments to enhance TB diagnostic approaches in high-burden settings like India.
Conference/Value in Health Info
2025-09, ISPOR Real-World Evidence Summit 2025, Tokyo, Japan
Value in Health Regional, Volume 49S (September 2025)
Code
RWD3
Topic Subcategory
Data Protection, Integrity, & Quality Assurance
Disease
SDC: Infectious Disease (non-vaccine)