REPLACING PHENOTYPIC TESTING WITH RAPID MOLECULAR DIAGNOSTICS FOR DRUG-RESISTANT TB IN HIGH-BURDEN SETTINGS: A COST-EFFECTIVENESS ANALYSIS
Author(s)
Ginenus Fekadu, PhD1, Tadesse Tolossa, PhD2, Tesfaye Regassa Feyissa, PhD2, Martin Siegel, PhD3, Wai-kit Ming, PhD, MD1.
1City University of Hong Kong, Hong Kong, Hong Kong, 2Deakin University, Melbourne, Australia, 3University of Greifswald, Greifswald, Germany.
1City University of Hong Kong, Hong Kong, Hong Kong, 2Deakin University, Melbourne, Australia, 3University of Greifswald, Greifswald, Germany.
OBJECTIVES: The World Health Organization conditionally recommends rapid molecular tests when concurrent phenotypic drug susceptibility testing (pDST) is not feasible. However, real‑world economic evidence to guide such replacement decisions is lacking in high‑burden settings. This study evaluates the cost‑effectiveness of replacing pDST with rapid molecular assays for detecting rifampicin, isoniazid, and fluoroquinolone resistance from the South African healthcare provider perspective.
METHODS: A decision‑analytic model simulated diagnostic and treatment pathways for a cohort of microbiologically confirmed TB patients. Five strategies were compared: pDST alone, line probe assays, Xpert MTB/RIF followed by Xpert MTB/XDR, Xpert Ultra followed by Xpert XDR, and targeted next‑generation sequencing (tNGS). Outcomes included early treatment rates, mortality, direct medical costs, disability‑adjusted life‑years (DALYs), and incremental cost‑effectiveness ratios (ICERs). A willingness‑to‑pay (WTP) threshold of South Africa’s GDP per capita (USD 6,767) was applied, with one‑way and probabilistic sensitivity analyses (10,000 Monte Carlo simulations).
RESULTS: In the base‑case analysis, all four rapid molecular strategies were either cost‑saving or cost‑effective compared to pDST. tNGS was the preferred cost‑effective alternative, yielding the greatest health benefits: lowest DALYs (2.0185), highest early treatment rate (995.54/1,000 tested), and lowest mortality (91.72/1,000 tested)—with an ICER of USD 1,712/DALY averted, well below the WTP threshold. Xpert followed by Xpert XDR was a less costly, highly effective option (ICER vs. pDST: cost‑saving). One‑way sensitivity analysis showed tNGS remained cost‑effective unless the hazard ratio for late treatment fell below 1.19. Probabilistic analysis showed tNGS was cost‑effective in 80.9% of simulations compared to pDST at a WTP of USD 6,767, and the most likely cost‑effective strategy when WTP exceeded USD 3,400/DALY.
CONCLUSIONS: Where pDST is unavailable, tNGS is a cost‑effective replacement for drug-resistant TB diagnosis in South Africa. Xpert‑based algorithms remain a robust, lower‑cost alternative. These findings directly support WHO’s conditional recommendation and provide actionable evidence for policymakers in resource‑constrained, high‑burden settings.
METHODS: A decision‑analytic model simulated diagnostic and treatment pathways for a cohort of microbiologically confirmed TB patients. Five strategies were compared: pDST alone, line probe assays, Xpert MTB/RIF followed by Xpert MTB/XDR, Xpert Ultra followed by Xpert XDR, and targeted next‑generation sequencing (tNGS). Outcomes included early treatment rates, mortality, direct medical costs, disability‑adjusted life‑years (DALYs), and incremental cost‑effectiveness ratios (ICERs). A willingness‑to‑pay (WTP) threshold of South Africa’s GDP per capita (USD 6,767) was applied, with one‑way and probabilistic sensitivity analyses (10,000 Monte Carlo simulations).
RESULTS: In the base‑case analysis, all four rapid molecular strategies were either cost‑saving or cost‑effective compared to pDST. tNGS was the preferred cost‑effective alternative, yielding the greatest health benefits: lowest DALYs (2.0185), highest early treatment rate (995.54/1,000 tested), and lowest mortality (91.72/1,000 tested)—with an ICER of USD 1,712/DALY averted, well below the WTP threshold. Xpert followed by Xpert XDR was a less costly, highly effective option (ICER vs. pDST: cost‑saving). One‑way sensitivity analysis showed tNGS remained cost‑effective unless the hazard ratio for late treatment fell below 1.19. Probabilistic analysis showed tNGS was cost‑effective in 80.9% of simulations compared to pDST at a WTP of USD 6,767, and the most likely cost‑effective strategy when WTP exceeded USD 3,400/DALY.
CONCLUSIONS: Where pDST is unavailable, tNGS is a cost‑effective replacement for drug-resistant TB diagnosis in South Africa. Xpert‑based algorithms remain a robust, lower‑cost alternative. These findings directly support WHO’s conditional recommendation and provide actionable evidence for policymakers in resource‑constrained, high‑burden settings.
Conference/Value in Health Info
2026-11, ISPOR Europe 2026, Vienna, Austria
Value in Health, Volume 29, Issue 12S
Code
EE185
Topic
Economic Evaluation, Health Technology Assessment, Methodological & Statistical Research
Disease
Infectious Disease (non-vaccine), Respiratory-Related Disorders (Allergy, Asthma, Smoking, Other Respiratory)