Cost-effectiveness of rapid susceptibility testing against second-line drugs for tuberculosis

BACKGROUND: Drug susceptibility testing (DST) against second-line tuberculosis drugs (SLDs) is essential for improving outcomes among multidrug-resistant (MDR-) and extensively drug-resistant tuberculosis (XDR-TB) cases. OBJECTIVE: To evaluate the potential cost-effectiveness of rapid DST for SLDs. DESIGN: We constructed a decision analysis model of Xpert® MTB/RIF-based TB diagnosis in East and South-East Asia to compare culture-based DST vs. a hypothetical rapid SLD DST system for specimens resistant to rifampin. Our primary outcomes were the effectiveness and incremental cost-effectiveness of a rapid SLD DST assay relative to culture-based DST. RESULTS: For rapid SLD DST to be more effective than culture-based DST, treating individuals with pre-XDR/XDR-TB with a standardized MDR-TB regimen while awaiting culture-based DST must incur at least 30% excess XDR-TB mortality (100% = treatment with first-line drugs); rapid SLD DST should attain an aggregate sensitivity and specificity for all pre-XDR/XDR mutations of 88% and 96%, respectively. The unit cost of the rapid SLD DST assay must approach that of culture to achieve common thresholds for cost-effectiveness in low-income countries. CONCLUSION: Rapid SLD DST has the potential to be cost-effective, but must meet stringent criteria for accuracy and costs, and requires that standardized second-line treatment for pre-XDR/XDR-TB incur substantial excess mortality before the return of culture results.