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Published on: April 9, 2012
Cost-Effectiveness of Targeted Next-Generation Sequencing for Diagnosing Pre-XDR and XDR Tuberculosis in
Ginenus Fekadu1, Tadesse Tolossa2, Busha Gamachu Labata3
1Department of Infectious Diseases and Public Health, Jockey Club College of Veterinary Medicine and Life Sciences, City University of Hong Kong, Hong Kong; School of Pharmacy, Institute of Health Sciences, Wollega University, Nekemte, Ethiopia.
Objectives:
To evaluate whether targeted next-generation sequencing (tNGS)-alone or in combination with phenotypic drug susceptibility testing (pDST)-is cost-effective for diagnosing pre-extensively drug-resistant and extensively drug-resistant tuberculosis (pre-XDR/XDR-TB) in rifampicin-resistant tuberculosis (RR-TB) patients across South Africa, India, and Georgia, and to quantify mortality reduction from earlier treatment initiation enabled by rapid molecular diagnostics.
Methods:
We developed a decision-analytic model combining a short-term decision tree with a 10-year Markov model to simulate outcomes in a hypothetical RR-TB cohort. Three diagnostic strategies were compared: pDST, tNGS, and tNGS+pDST. Outcomes included costs, quality-adjusted life years (QALYs), early treatment initiation, TB-related mortality, and incremental cost-effectiveness ratios (ICERs). Cost-effectiveness was assessed against country-specific willingness-to-pay (WTP) thresholds. Sensitivity analyses were conducted to characterize uncertainty.
Results:
Tngs-based strategies improved early treatment initiation (South Africa: +9.8%; India: +19.1%; Georgia: +29.6%) and reduced mortality across all settings. In South Africa, tNGS was cost-effective (ICER, $2805/QALY). In Georgia, the combination strategy was cost-effective (ICER, $6361/QALY). In India, neither tNGS (ICER, $4453/QALY) nor the combination strategy (ICER, $6198/QALY) met the WTP threshold; tNGS would require cost reduction to ≤$116/test. The HR, for delayed treatment and tNGS cost were primary ICER drivers. Probabilistic analysis confirmed robustness, with tNGS cost-effective in 58% of simulations in South Africa and the combination strategy in 42% in Georgia.
Conclusions:
Tngs is cost-effective in South Africa and Georgia when the survival benefit of earlier treatment initiation is accounted for. In India, tNGS pricing exceeds affordability thresholds, necessitating cost reductions and targeted deployment. These findings provide context-specific guidance for national TB programs.
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