Rapid, point-of-care diagnosis of tuberculosis with novel Truenat assay: Cost-effectiveness analysis for India's public sector

Abstract

Background: Truenat is a novel molecular assay that rapidly detects tuberculosis (TB) and rifampicin-resistance. Due to the portability of its battery-powered testing platform, it may be valuable in peripheral healthcare settings in India.

Methods: Using a microsimulation model, we compared four TB diagnostic strategies for HIV-negative adults with presumptive TB: (1) sputum smear microscopy in designated microscopy centers (DMCs) (SSM); (2) Xpert MTB/RIF in DMCs (Xpert); (3) Truenat in DMCs (Truenat DMC); and (4) Truenat for point-of-care testing in primary healthcare facilities (Truenat POC). We projected life expectancy, costs, incremental cost-effectiveness ratios (ICERs), and 5-year budget impact of deploying Truenat POC in India's public sector. We defined a strategy "cost-effective" if its ICER was <US$990/year-of-life saved (YLS). Model inputs included: TB prevalence, 15% (among those not previously treated for TB) and 27% (among those previously treated for TB); sensitivity for TB detection, 89% (Xpert) and 86% (Truenat); per test cost, $12.63 (Xpert) and $13.20 (Truenat); and linkage-to-care after diagnosis, 84% (DMC) and 95% (POC). We varied these parameters in sensitivity analyses.

Results: Compared to SSM, Truenat POC increased life expectancy by 0.39 years and was cost-effective (ICER $210/YLS). Compared to Xpert, Truenat POC increased life expectancy by 0.08 years due to improved linkage-to-care and was cost-effective (ICER $120/YLS). In sensitivity analysis, the cost-effectiveness of Truenat POC, relative to Xpert, depended on the diagnostic sensitivity of Truenat and linkage-to-care with Truenat. Deploying Truenat POC instead of Xpert increased 5-year expenditures by $270 million, due mostly to treatment costs. Limitations of our study include uncertainty in Truenat's sensitivity for TB and not accounting for the "start-up" costs of implementing Truenat in the field.

Conclusions: Used at the point-of-care in India, Truenat for TB diagnosis should improve linkage-to-care, increase life expectancy, and be cost-effective compared with smear microscopy or Xpert.

Fig 1. One-way sensitivity analyses of key model parameters, comparing Truenat POC to SSM, at lifetime horizon.

TB: tuberculosis. MDR-TB: multidrug-resistant tuberculosis. RIF: rifampicin. C&DST: culture and drug-susceptibility test. yr: year. POC: point-of-care. “previously treated”: previously treated for TB. GDP: gross domestic product. ICER: incremental cost-effectiveness ratio. USD: United States dollars. YLS: year-of-life saved. Horizontal bars represent ranges of ICERs when varying each model parameter across its plausible range. The vertical dashed line represents 50% of the GDP per capita of India in 2017 ($990), which we consider the cost-effectiveness threshold (see Methods). ICERs less than $990/YLS (left of dashed line) are considered cost-effective.

Fig 2. Sensitivity analysis of Truenat sensitivity for TB, comparing Truenat POC to Xpert at 5-year horizon.

TB: tuberculosis. POC: point-of-care. ICER: incremental cost-effectiveness ratio. YLS: year-of-life saved. USD: United States dollars. This plot shows the differences in life expectancy and costs between Truenat POC and Xpert at a 5-year horizon when varying the sensitivity of Truenat for TB detection. The horizontal axis is the sensitivity of Truenat for TB detection. The blue line corresponds to the left vertical axis, which is the difference in life expectancy between Truenat POC and Xpert. The red line corresponds to the right vertical axis, which is the difference in per-person lifetime costs between Truenat POC and Xpert. The ICER (i.e., the difference in costs divided by the difference in life expectancy) is provided at regular intervals of test sensitivity values. For integer values of test sensitivity ≥78% (green panel), Truenat POC is cost-effective compared to Xpert (ICER <$990/YLS). For integer values <78% (red panel), Xpert is more efficient than Truenat POC. ^a“Xpert is more efficient than Truenat POC”: For Truenat sensitivity values <75%, Xpert was cost-effective compared to Truenat POC (ICER <$990/YLS). At Truenat sensitivity of 75–76%, Xpert was cost-saving (lower cost, higher clinical benefit [more life-years accrued]) compared to Truenat POC. At Truenat sensitivity of 77%, Xpert was decrementally cost-effective (lower cost and lower clinical benefit but with ICER >$990/year-of-life lost [YLL]—that is, at least $990 saved per year-of-life-lost) compared to Truenat POC.

Fig 3. Two-way sensitivity and scenario analysis heat maps, comparing Truenat POC to Xpert at 5-year horizon.

TB: tuberculosis. POC: point-of-care. YLS: year-of-life saved. YLL: year-of- lost. These heat maps evaluate the incremental cost-effectiveness ratio of Truenat POC strategy relative to Xpert at a 5-year time horizon for different values of Truenat sensitivity for TB detection and linkage-to-care. Each panel displays different costs of Truenat, including the scenario (B), in which the price of the Truenat chip is negotiated to 60% of its current estimate for the public sector (S1 Appendix). Sensitivity of Truenat for TB detection increases from left to right on the horizontal axes. The probability of linking to care upon receiving a positive TB test result with Truenat increases up the vertical axes. ^a“Decrementally cost-effective”: Truenat POC results in lower cost and lower clinical benefit compared to Xpert, but with ICER >$990/year-of-life lost (YLL)—that is, at least $990 is saved per year-of-life lost. ^b“Xpert is more efficient than Truenat POC”: Xpert is either cost-effective (ICER <$990/YLS), cost-saving (lower cost, higher clinical benefit [more life-years accrued]), or decrementally cost-effective (ICER >$990/YLL), compared to Truenat POC.

Fig 4. Budget impact analysis over 2 and 5 years.

TB: tuberculosis. ds-TB: drug-susceptible tuberculosis. MDR-TB: multidrug-resistant tuberculosis. SSM: sputum smear microscopy. POC: point-of-care. mill: million. bill: billion. Budget impact analysis of full public sector implementation of sputum smear microscopy (SSM), Xpert, and Truenat POC strategies over 2- and 5-year time horizons. Cumulative TB-related costs (2017 USD, billions) are on the vertical axis. This analysis assumes that 7.9 million adults in India are tested each year for symptoms suggestive of TB (S1 Appendix) [4]. All calculations were made using exact numbers before rounding to the nearest $10 million (for costs) and 1% (for percentages). ^aEach treatment regimen is associated with a frequency of clinic visits and rate of hospitalization during the course of TB treatment, as reported by published guidelines and/or epidemiological data (S1 Appendix). These clinical costs are incorporated into the budget impact projection for each category.