Cost-effectiveness of Targeted Next Generation Sequencing for TB drug-resistance testing as an alternative to the standard of care in South Africa

Background South Africa faces emerging resistance to TB drugs like bedaquiline. Phenotypic drug susceptibility testing (DST), the current reference standard for bedaquiline DST, has long turnaround times. Targeted next-generation sequencing (tNGS) offers a comprehensive alternative, potentially delivering faster results. However, these advantages must be weighed against differences in cost and test accuracy. Methods We used a decision tree model to evaluate the cost-effectiveness of tNGS against the standard of care (SOC) in South Africa across different levels of tNGS decentralization. Key outcomes included survival rates, time to a correct resistance profile, infectious time, and disability-adjusted life years (DALYs). Sensitivity analyses assessed the impact of drug resistance prevalence, tNGS sensitivity, and improved DST access on overall cost-effectiveness. Results tNGS averted 408 DALYs and correctly identified 90.7% of resistance profiles as compared to 87.7% with SOC. Based on model assumptions for South Africa, tNGS had a reduced turnaround time and averted 97 years of infectious time. Centralized tNGS was cost-saving relative to SOC, however decentralization of tNGS resulted in higher costs per DALY averted ($671- $2,454). tNGS performance, relative to the SOC, improved at higher bedaquiline resistance and with increased sensitivity. Any increase in DST access through tNGS would improve cost-effectiveness in decentralized scenarios. Conclusions tNGS could be cost-saving (centralized) or cost-effective (decentralized) in South Africa and has the potential to improve patient outcomes by returning a greater number of correct results in a shorter time. This analysis should be replicated across other settings to evaluate the broader feasibility of tNGS for DST.