Effect of Xpert MTB/RIF on clinical outcomes in routine care settings: individual patient data meta-analysis

Gian Luca Di Tanna, Ali Raza Khaki, Grant Theron, Kerrigan McCarthy, Helen Cox, Lucy Mupfumi, Anete Trajman, Lynn Sodai Zijenah, Peter Mason, Tsitsi Bandason, Betina Durovni, Wilbert Bara, Michael Hoelscher, Petra Clowes, Chacha Mangu, Duncan Chanda, Alexander Pym, Peter Mwaba, Frank Cobelens, Mark P. Nicol & 4 others Keertan Dheda, Gavin Churchyard, Katherine Fielding, John Z. Metcalfe

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Background: Xpert MTB/RIF, the most widely used automated nucleic acid amplification test for tuberculosis, is available in more than 130 countries. Although diagnostic accuracy is well documented, anticipated improvements in patient outcomes have not been clearly identified. We performed an individual patient data meta-analysis to examine improvements in patient outcomes associated with Xpert MTB/RIF. Methods: We searched PubMed, Embase, ClinicalTrials.gov, and the Pan African Clinical Trials Registry from inception to Feb 1, 2018, for randomised controlled trials (RCTs) comparing the use of Xpert MTB/RIF with sputum smear microscopy as tests for tuberculosis diagnosis in adults (aged 18 years or older). We excluded studies of patients with extrapulmonary tuberculosis, and studies in which mortality was not assessed. We used a two-stage approach for our primary analysis and a one-stage approach for the sensitivity analysis. To assess the primary outcome of cumulative 6-month all-cause mortality, we first performed logistic regression models (random effects for cluster randomised trials, with robust SEs for multicentre studies) for each trial, and then pooled the odds ratio (OR) estimates by a fixed-effects (inverse variance) or random-effects (Der Simonian Laird) meta-analysis. We adjusted for age and gender, and stratified by HIV status and previous tuberculosis-treatment history. The study protocol has been registered with PROSPERO, number CRD42014013394. Findings: Our search identified 387 studies, of which five RCTs were eligible for analysis. 8567 adult clinic attendees (4490 [63·5%] of 7074 participants for whom data were available were HIV-positive) were tested for tuberculosis with Xpert MTB/RIF (Xpert group) versus sputum smear microscopy (sputum smear group), across five low-income and middle-income countries (South Africa, Brazil, Zimbabwe, Zambia, and Tanzania). The primary outcome (reported in three studies) occurred in 182 (4·5%) of 4050 patients in the Xpert group and 217 (5·3%) of 4093 patients in the smear group (pooled adjusted OR 0·88, 95% CI 0·68–1·14 [p=0·34]; for HIV-positive individuals OR 0·83, 0·65–1·05 [p=0·12]). Kaplan-Meier estimates showed a lower rate of death (12·73 per 100 person-years in the Xpert group vs 16·38 per 100 person-years in the sputum smear group) for HIV-positive patients (hazard ratio 0·76, 95% CI 0·60–0·97; p=0·03). The risk of bias was assessed as reasonable and the statistical heterogeneity across studies was low (I2<20% for the primary outcome). Interpretation: Despite individual patient data analysis from five RCTs, we were unable to confidently rule in nor rule out an Xpert MTB/RIF-associated reduction in mortality among outpatients tested for tuberculosis. Reduction in mortality among HIV-positive patients in a secondary analysis suggests the possibility of population-level impact. Funding: US National Institutes of Health.

Original languageEnglish
Pages (from-to)e191-e199
JournalThe Lancet Global Health
Volume7
Issue number2
DOIs
Publication statusPublished - 1 Feb 2019
Externally publishedYes

Fingerprint

Meta-Analysis
Tuberculosis
Sputum
HIV
Mortality
Randomized Controlled Trials
Odds Ratio
Microscopy
Logistic Models
Nucleic Acid Amplification Techniques
Zambia
Zimbabwe
Tanzania
National Institutes of Health (U.S.)
Kaplan-Meier Estimate
South Africa
PubMed
Multicenter Studies
Brazil
Registries

Cite this

Di Tanna, G. L., Raza Khaki, A., Theron, G., McCarthy, K., Cox, H., Mupfumi, L., ... Metcalfe, J. Z. (2019). Effect of Xpert MTB/RIF on clinical outcomes in routine care settings: individual patient data meta-analysis. The Lancet Global Health, 7(2), e191-e199. https://doi.org/10.1016/S2214-109X(18)30458-3
Di Tanna, Gian Luca ; Raza Khaki, Ali ; Theron, Grant ; McCarthy, Kerrigan ; Cox, Helen ; Mupfumi, Lucy ; Trajman, Anete ; Sodai Zijenah, Lynn ; Mason, Peter ; Bandason, Tsitsi ; Durovni, Betina ; Bara, Wilbert ; Hoelscher, Michael ; Clowes, Petra ; Mangu, Chacha ; Chanda, Duncan ; Pym, Alexander ; Mwaba, Peter ; Cobelens, Frank ; Nicol, Mark P. ; Dheda, Keertan ; Churchyard, Gavin ; Fielding, Katherine ; Metcalfe, John Z. / Effect of Xpert MTB/RIF on clinical outcomes in routine care settings : individual patient data meta-analysis. In: The Lancet Global Health. 2019 ; Vol. 7, No. 2. pp. e191-e199.
@article{cce7a76ff8044b1a90d9937050ffa6bf,
title = "Effect of Xpert MTB/RIF on clinical outcomes in routine care settings: individual patient data meta-analysis",
abstract = "Background: Xpert MTB/RIF, the most widely used automated nucleic acid amplification test for tuberculosis, is available in more than 130 countries. Although diagnostic accuracy is well documented, anticipated improvements in patient outcomes have not been clearly identified. We performed an individual patient data meta-analysis to examine improvements in patient outcomes associated with Xpert MTB/RIF. Methods: We searched PubMed, Embase, ClinicalTrials.gov, and the Pan African Clinical Trials Registry from inception to Feb 1, 2018, for randomised controlled trials (RCTs) comparing the use of Xpert MTB/RIF with sputum smear microscopy as tests for tuberculosis diagnosis in adults (aged 18 years or older). We excluded studies of patients with extrapulmonary tuberculosis, and studies in which mortality was not assessed. We used a two-stage approach for our primary analysis and a one-stage approach for the sensitivity analysis. To assess the primary outcome of cumulative 6-month all-cause mortality, we first performed logistic regression models (random effects for cluster randomised trials, with robust SEs for multicentre studies) for each trial, and then pooled the odds ratio (OR) estimates by a fixed-effects (inverse variance) or random-effects (Der Simonian Laird) meta-analysis. We adjusted for age and gender, and stratified by HIV status and previous tuberculosis-treatment history. The study protocol has been registered with PROSPERO, number CRD42014013394. Findings: Our search identified 387 studies, of which five RCTs were eligible for analysis. 8567 adult clinic attendees (4490 [63·5{\%}] of 7074 participants for whom data were available were HIV-positive) were tested for tuberculosis with Xpert MTB/RIF (Xpert group) versus sputum smear microscopy (sputum smear group), across five low-income and middle-income countries (South Africa, Brazil, Zimbabwe, Zambia, and Tanzania). The primary outcome (reported in three studies) occurred in 182 (4·5{\%}) of 4050 patients in the Xpert group and 217 (5·3{\%}) of 4093 patients in the smear group (pooled adjusted OR 0·88, 95{\%} CI 0·68–1·14 [p=0·34]; for HIV-positive individuals OR 0·83, 0·65–1·05 [p=0·12]). Kaplan-Meier estimates showed a lower rate of death (12·73 per 100 person-years in the Xpert group vs 16·38 per 100 person-years in the sputum smear group) for HIV-positive patients (hazard ratio 0·76, 95{\%} CI 0·60–0·97; p=0·03). The risk of bias was assessed as reasonable and the statistical heterogeneity across studies was low (I2<20{\%} for the primary outcome). Interpretation: Despite individual patient data analysis from five RCTs, we were unable to confidently rule in nor rule out an Xpert MTB/RIF-associated reduction in mortality among outpatients tested for tuberculosis. Reduction in mortality among HIV-positive patients in a secondary analysis suggests the possibility of population-level impact. Funding: US National Institutes of Health.",
author = "{Di Tanna}, {Gian Luca} and {Raza Khaki}, Ali and Grant Theron and Kerrigan McCarthy and Helen Cox and Lucy Mupfumi and Anete Trajman and {Sodai Zijenah}, Lynn and Peter Mason and Tsitsi Bandason and Betina Durovni and Wilbert Bara and Michael Hoelscher and Petra Clowes and Chacha Mangu and Duncan Chanda and Alexander Pym and Peter Mwaba and Frank Cobelens and Nicol, {Mark P.} and Keertan Dheda and Gavin Churchyard and Katherine Fielding and Metcalfe, {John Z.}",
year = "2019",
month = "2",
day = "1",
doi = "10.1016/S2214-109X(18)30458-3",
language = "English",
volume = "7",
pages = "e191--e199",
journal = "The Lancet Global Health",
issn = "2214-109X",
publisher = "Elsevier",
number = "2",

}

Di Tanna, GL, Raza Khaki, A, Theron, G, McCarthy, K, Cox, H, Mupfumi, L, Trajman, A, Sodai Zijenah, L, Mason, P, Bandason, T, Durovni, B, Bara, W, Hoelscher, M, Clowes, P, Mangu, C, Chanda, D, Pym, A, Mwaba, P, Cobelens, F, Nicol, MP, Dheda, K, Churchyard, G, Fielding, K & Metcalfe, JZ 2019, 'Effect of Xpert MTB/RIF on clinical outcomes in routine care settings: individual patient data meta-analysis' The Lancet Global Health, vol. 7, no. 2, pp. e191-e199. https://doi.org/10.1016/S2214-109X(18)30458-3

Effect of Xpert MTB/RIF on clinical outcomes in routine care settings : individual patient data meta-analysis. / Di Tanna, Gian Luca; Raza Khaki, Ali; Theron, Grant; McCarthy, Kerrigan; Cox, Helen; Mupfumi, Lucy; Trajman, Anete; Sodai Zijenah, Lynn; Mason, Peter; Bandason, Tsitsi; Durovni, Betina; Bara, Wilbert; Hoelscher, Michael; Clowes, Petra; Mangu, Chacha; Chanda, Duncan; Pym, Alexander; Mwaba, Peter; Cobelens, Frank; Nicol, Mark P.; Dheda, Keertan; Churchyard, Gavin; Fielding, Katherine; Metcalfe, John Z.

In: The Lancet Global Health, Vol. 7, No. 2, 01.02.2019, p. e191-e199.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Effect of Xpert MTB/RIF on clinical outcomes in routine care settings

T2 - individual patient data meta-analysis

AU - Di Tanna, Gian Luca

AU - Raza Khaki, Ali

AU - Theron, Grant

AU - McCarthy, Kerrigan

AU - Cox, Helen

AU - Mupfumi, Lucy

AU - Trajman, Anete

AU - Sodai Zijenah, Lynn

AU - Mason, Peter

AU - Bandason, Tsitsi

AU - Durovni, Betina

AU - Bara, Wilbert

AU - Hoelscher, Michael

AU - Clowes, Petra

AU - Mangu, Chacha

AU - Chanda, Duncan

AU - Pym, Alexander

AU - Mwaba, Peter

AU - Cobelens, Frank

AU - Nicol, Mark P.

AU - Dheda, Keertan

AU - Churchyard, Gavin

AU - Fielding, Katherine

AU - Metcalfe, John Z.

PY - 2019/2/1

Y1 - 2019/2/1

N2 - Background: Xpert MTB/RIF, the most widely used automated nucleic acid amplification test for tuberculosis, is available in more than 130 countries. Although diagnostic accuracy is well documented, anticipated improvements in patient outcomes have not been clearly identified. We performed an individual patient data meta-analysis to examine improvements in patient outcomes associated with Xpert MTB/RIF. Methods: We searched PubMed, Embase, ClinicalTrials.gov, and the Pan African Clinical Trials Registry from inception to Feb 1, 2018, for randomised controlled trials (RCTs) comparing the use of Xpert MTB/RIF with sputum smear microscopy as tests for tuberculosis diagnosis in adults (aged 18 years or older). We excluded studies of patients with extrapulmonary tuberculosis, and studies in which mortality was not assessed. We used a two-stage approach for our primary analysis and a one-stage approach for the sensitivity analysis. To assess the primary outcome of cumulative 6-month all-cause mortality, we first performed logistic regression models (random effects for cluster randomised trials, with robust SEs for multicentre studies) for each trial, and then pooled the odds ratio (OR) estimates by a fixed-effects (inverse variance) or random-effects (Der Simonian Laird) meta-analysis. We adjusted for age and gender, and stratified by HIV status and previous tuberculosis-treatment history. The study protocol has been registered with PROSPERO, number CRD42014013394. Findings: Our search identified 387 studies, of which five RCTs were eligible for analysis. 8567 adult clinic attendees (4490 [63·5%] of 7074 participants for whom data were available were HIV-positive) were tested for tuberculosis with Xpert MTB/RIF (Xpert group) versus sputum smear microscopy (sputum smear group), across five low-income and middle-income countries (South Africa, Brazil, Zimbabwe, Zambia, and Tanzania). The primary outcome (reported in three studies) occurred in 182 (4·5%) of 4050 patients in the Xpert group and 217 (5·3%) of 4093 patients in the smear group (pooled adjusted OR 0·88, 95% CI 0·68–1·14 [p=0·34]; for HIV-positive individuals OR 0·83, 0·65–1·05 [p=0·12]). Kaplan-Meier estimates showed a lower rate of death (12·73 per 100 person-years in the Xpert group vs 16·38 per 100 person-years in the sputum smear group) for HIV-positive patients (hazard ratio 0·76, 95% CI 0·60–0·97; p=0·03). The risk of bias was assessed as reasonable and the statistical heterogeneity across studies was low (I2<20% for the primary outcome). Interpretation: Despite individual patient data analysis from five RCTs, we were unable to confidently rule in nor rule out an Xpert MTB/RIF-associated reduction in mortality among outpatients tested for tuberculosis. Reduction in mortality among HIV-positive patients in a secondary analysis suggests the possibility of population-level impact. Funding: US National Institutes of Health.

AB - Background: Xpert MTB/RIF, the most widely used automated nucleic acid amplification test for tuberculosis, is available in more than 130 countries. Although diagnostic accuracy is well documented, anticipated improvements in patient outcomes have not been clearly identified. We performed an individual patient data meta-analysis to examine improvements in patient outcomes associated with Xpert MTB/RIF. Methods: We searched PubMed, Embase, ClinicalTrials.gov, and the Pan African Clinical Trials Registry from inception to Feb 1, 2018, for randomised controlled trials (RCTs) comparing the use of Xpert MTB/RIF with sputum smear microscopy as tests for tuberculosis diagnosis in adults (aged 18 years or older). We excluded studies of patients with extrapulmonary tuberculosis, and studies in which mortality was not assessed. We used a two-stage approach for our primary analysis and a one-stage approach for the sensitivity analysis. To assess the primary outcome of cumulative 6-month all-cause mortality, we first performed logistic regression models (random effects for cluster randomised trials, with robust SEs for multicentre studies) for each trial, and then pooled the odds ratio (OR) estimates by a fixed-effects (inverse variance) or random-effects (Der Simonian Laird) meta-analysis. We adjusted for age and gender, and stratified by HIV status and previous tuberculosis-treatment history. The study protocol has been registered with PROSPERO, number CRD42014013394. Findings: Our search identified 387 studies, of which five RCTs were eligible for analysis. 8567 adult clinic attendees (4490 [63·5%] of 7074 participants for whom data were available were HIV-positive) were tested for tuberculosis with Xpert MTB/RIF (Xpert group) versus sputum smear microscopy (sputum smear group), across five low-income and middle-income countries (South Africa, Brazil, Zimbabwe, Zambia, and Tanzania). The primary outcome (reported in three studies) occurred in 182 (4·5%) of 4050 patients in the Xpert group and 217 (5·3%) of 4093 patients in the smear group (pooled adjusted OR 0·88, 95% CI 0·68–1·14 [p=0·34]; for HIV-positive individuals OR 0·83, 0·65–1·05 [p=0·12]). Kaplan-Meier estimates showed a lower rate of death (12·73 per 100 person-years in the Xpert group vs 16·38 per 100 person-years in the sputum smear group) for HIV-positive patients (hazard ratio 0·76, 95% CI 0·60–0·97; p=0·03). The risk of bias was assessed as reasonable and the statistical heterogeneity across studies was low (I2<20% for the primary outcome). Interpretation: Despite individual patient data analysis from five RCTs, we were unable to confidently rule in nor rule out an Xpert MTB/RIF-associated reduction in mortality among outpatients tested for tuberculosis. Reduction in mortality among HIV-positive patients in a secondary analysis suggests the possibility of population-level impact. Funding: US National Institutes of Health.

UR - http://www.scopus.com/inward/record.url?scp=85060306634&partnerID=8YFLogxK

U2 - 10.1016/S2214-109X(18)30458-3

DO - 10.1016/S2214-109X(18)30458-3

M3 - Article

VL - 7

SP - e191-e199

JO - The Lancet Global Health

JF - The Lancet Global Health

SN - 2214-109X

IS - 2

ER -