Optimal Triage Test Characteristics to Improve the Cost-Effectiveness of the Xpert MTB/RIF Assay for TB Diagnosis: A Decision Analysis

Abstract

BackgroundHigh costs are a limitation to scaling up the Xpert MTB/RIF assay (Xpert) for the diagnosis of tuberculosis in resource-constrained settings. A triaging strategy in which a sensitive but not necessarily highly specific rapid test is used to select patients for Xpert may result in a more affordable diagnostic algorithm. To inform the selection and development of particular diagnostics as a triage test we explored combinations of sensitivity, specificity and cost at which a hypothetical triage test will improve affordability of the Xpert assay.MethodsIn a decision analytical model parameterized for Uganda, India and South Africa, we compared a diagnostic algorithm in which a cohort of patients with presumptive TB received Xpert to a triage algorithm whereby only those with a positive triage test were tested by Xpert.FindingsA triage test with sensitivity equal to Xpert, 75% specificity, and costs of US$5 per patient tested reduced total diagnostic costs by 42% in the Uganda setting, and by 34% and 39% respectively in the India and South Africa settings. When exploring triage algorithms with lower sensitivity, the use of an example triage test with 95% sensitivity relative to Xpert, 75% specificity and test costs $5 resulted in similar cost reduction, and was cost-effective by the WHO willingness-to-pay threshold compared to Xpert for all in Uganda, but not in India and South Africa. The gain in affordability of the examined triage algorithms increased with decreasing prevalence of tuberculosis among the cohort.ConclusionsA triage test strategy could potentially improve the affordability of Xpert for TB diagnosis, particularly in low-income countries and with enhanced case-finding. Tests and markers with lower accuracy than desired of a diagnostic test may fall within the ranges of sensitivity, specificity and cost required for triage tests and be developed as such.

Microscopic observation drug‐susceptibility assay vs. Xpert®MTB/RIF for the diagnosis of tuberculosis in a rural African setting: a cost–utility analysis

“…Our results reinforce the WHO conditional recommendation of using Xpert ® MTB/RIF as a first‐line test for every pulmonary TB suspect in rural Sub‐Saharan Africa with a long‐term utility‐based evaluation. The ICER found in our study is within the same range of those found in other studies in other settings, namely South Africa, India and Uganda . Whether Xpert ® MTB/RIF is such a huge step forward in TB diagnostics that it should replace the 125‐year‐old SM as the first TB diagnostic test remains controversial .…”

Diagnostic performance of smear microscopy and incremental yield of Xpert in detection of pulmonary tuberculosis in Rwanda

“…Although the cost per test and compulsory required maintenance of Xpert machine (annual calibration, replacement of modules, good and constant power supply) may be not affordable by many poor resource settings given the limited heath budgets [20], the savings from increased case detection and timely initiation of treatment due to early diagnosis, may be more cost effective in terms of supplies savings as well as patient savings from repeat facility visits. In addition, early diagnosis may reduce the risk of TB transmission.…”

Performance of a Novel Algorithm Using Automated Digital Microscopy for Diagnosing Tuberculosis

“…One of the primary reasons for incomplete uptake of GXP is its cost ($9.98 per cartridge under concessional pricing) (7), which in most settings is several fold higher than that of microscopy (6) on a per-test basis and well beyond the existing TB budgets of most high-burden countries (8). Diagnostic "triage" algorithms that can reduce the number of GXP tests conducted without substantially lowering diagnostic performance are now an important priority (9).…”