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. 2013 Dec 18;8(12):e82786.
doi: 10.1371/journal.pone.0082786. eCollection 2013.

Optimal triage test characteristics to improve the cost-effectiveness of the Xpert MTB/RIF assay for TB diagnosis: a decision analysis

Anna H van't Hoog  1 , Frank Cobelens  1 , Anna Vassall  2 , Sanne van Kampen  3 , Susan E Dorman  4 , David Alland  5 , Jerrold Ellner  6
Affiliations

Optimal triage test characteristics to improve the cost-effectiveness of the Xpert MTB/RIF assay for TB diagnosis: a decision analysis

Anna H van't Hoog et al. PLoS One. .

Abstract

Background: High 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.

Methods: In 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.

Findings: A 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.

Conclusions: A 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.

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Conflict of interest statement

Competing Interests: The authors AvH, AV, SvK, SD and JE have declared that no competing interests exist. The authors have read the journal's policy and declare possible conflicts for the authors DA and FC: DA receives royalties from licensing fees from the UMDNJ molecular beacon patent pool. Cepheid, which manufactures the Xpert test pays UMDNJ licensing fees for the molecular beacons used in the test. This conflict has been managed as follows: DA has irrevocably limited the amount of money that he can personally receive from Cepheid license payments to $4,999 per year. DA served as an ad-hoc unpaid member of the Cepheid advisory board in 2010. Cepheid did not pay for any expenses, including no payment for travel, meals, honorarium etc to DA or his laboratory. DA's laboratory received a $20,000 research grant from Cepheid in 2010 to perform a blinded study of clinical samples using the Xpert assay. DA no longer accepts research grants from Cepheid. FC serves as a consultant for the Foundation of Innovative New Diagnostics (FIND) and the Bill and Melinda Gates Foundation. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials.

Figures

Figure 1
Figure 1. Simplified schematic presentation of the two pathways in the model.
Figure 2
Figure 2. Combinations of cost and specificity of a triage test with 100% relative sensitivity.
These combinations result in equal or reduced diagnostic cost of a triage pathway, compared to Xpert on all persons with presumptive TB. Panel 2A shows the Uganda setting, 2B the India setting and 2C the South African setting.
Figure 3
Figure 3. Incremental Cost-Effectiveness Ratios (ICERs) of Xpert on all persons with presumptive TB compared to triage algorithms for various sensitivity, specificity and cost combinations of a triage test.
The figure shows the Uganda setting.
Figure 4
Figure 4. Sensitivity analyses.
The effect of varying the prevalence of TB among persons with presumptive TB on the Incremental Cost-Effectiveness ratios (ICERs) for Xpert compared to triage pathways, with triage tests examples with sensitivity and specificity of 95%/75% and 85%/85% respectively, for the Uganda (4A), India (4B) and South Africa (4C) setting.
See this image and copyright information in PMC

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