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Meta-Analysis
. 2021 May 6;5(5):CD012972.
doi: 10.1002/14651858.CD012972.pub2.

Impact of the diagnostic test Xpert MTB/RIF on patient outcomes for tuberculosis

Frederick Haraka  1   2   3   4 , Mwaka Kakolwa  5 , Samuel G Schumacher  6 , Ruvandhi R Nathavitharana  7 , Claudia M Denkinger  6   8 , Sebastien Gagneux  3   4 , Klaus Reither  2   3   4 , Amanda Ross  3   4
Affiliations
Meta-Analysis

Impact of the diagnostic test Xpert MTB/RIF on patient outcomes for tuberculosis

Frederick Haraka et al. Cochrane Database Syst Rev. .

Abstract
in English, Spanish

Background: The World Health Organization (WHO) recommends Xpert MTB/RIF in place of smear microscopy to diagnose tuberculosis (TB), and many countries have adopted it into their diagnostic algorithms. However, it is not clear whether the greater accuracy of the test translates into improved health outcomes.

Objectives: To assess the impact of Xpert MTB/RIF on patient outcomes in people being investigated for tuberculosis.

Search methods: We searched the following databases, without language restriction, from 2007 to 24 July 2020: Cochrane Infectious Disease Group (CIDG) Specialized Register; CENTRAL; MEDLINE OVID; Embase OVID; CINAHL EBSCO; LILACS BIREME; Science Citation Index Expanded (Web of Science), Social Sciences citation index (Web of Science), and Conference Proceedings Citation Index - Social Science & Humanities (Web of Science). We also searched the WHO International Clinical Trials Registry Platform, ClinicalTrials.gov, and the Pan African Clinical Trials Registry for ongoing trials.

Selection criteria: We included individual- and cluster-randomized trials, and before-after studies, in participants being investigated for tuberculosis. We analysed the randomized and non-randomized studies separately. DATA COLLECTION AND ANALYSIS: For each study, two review authors independently extracted data, using a piloted data extraction tool. We assessed the risk of bias using Cochrane and Effective Practice and Organisation of Care (EPOC) tools. We used random effects meta-analysis to allow for heterogeneity between studies in setting and design. The certainty of the evidence in the randomized trials was assessed by GRADE.

Main results: We included 12 studies: eight were randomized controlled trials (RCTs), and four were before-and-after studies. Most included RCTs had a low risk of bias in most domains of the Cochrane 'Risk of bias' tool. There was inconclusive evidence of an effect of Xpert MTB/RIF on all-cause mortality, both overall (risk ratio (RR) 0.89, 95% confidence interval (CI) 0.75 to 1.05; 5 RCTs, 9932 participants, moderate-certainty evidence), and restricted to studies with six-month follow-up (RR 0.98, 95% CI 0.78 to 1.22; 3 RCTs, 8143 participants; moderate-certainty evidence). There was probably a reduction in mortality in participants known to be infected with HIV (odds ratio (OR) 0.80, 95% CI 0.67 to 0.96; 5 RCTs, 5855 participants; moderate-certainty evidence). It is uncertain whether Xpert MTB/RIF has no or a modest effect on the proportion of participants starting tuberculosis treatment who had a successful treatment outcome (OR) 1.10, 95% CI 0.96 to 1.26; 3RCTs, 4802 participants; moderate-certainty evidence). There was also inconclusive evidence of an effect on the proportion of participants who were treated for tuberculosis (RR 1.10, 95% CI 0.98 to 1.23; 5 RCTs, 8793 participants; moderate-certainty evidence). The proportion of participants treated for tuberculosis who had bacteriological confirmation was probably higher in the Xpert MTB/RIF group (RR 1.44, 95% CI 1.29 to 1.61; 6 RCTs, 2068 participants; moderate-certainty evidence). The proportion of participants with bacteriological confirmation who were lost to follow-up pre-treatment was probably reduced (RR 0.59, 95% CI 0.41 to 0.85; 3 RCTs, 1217 participants; moderate-certainty evidence).

Authors' conclusions: We were unable to confidently rule in or rule out the effect on all-cause mortality of using Xpert MTB/RIF rather than smear microscopy. Xpert MTB/RIF probably reduces mortality among participants known to be infected with HIV. We are uncertain whether Xpert MTB/RIF has a modest effect or not on the proportion treated or, among those treated, on the proportion with a successful outcome. It probably does not have a substantial effect on these outcomes. Xpert MTB/RIF probably increases both the proportion of treated participants who had bacteriological confirmation, and the proportion with a laboratory-confirmed diagnosis who were treated. These findings may inform decisions about uptake alongside evidence on cost-effectiveness and implementation.

Antecedentes: La Organización Mundial de la Salud (OMS) recomienda la Xpert MTB/RIF en lugar de la baciloscopia para diagnosticar la tuberculosis (TB) y muchos países la han adoptado en sus algoritmos de diagnóstico. Sin embargo, no está claro si la mayor exactitud de la prueba se traduce en mejores desenlaces de salud.

Objetivos: Evaluar el impacto de la Xpert MTB/RIF en los desenlaces de las personas sometidas a pruebas para la tuberculosis. MÉTODOS DE BÚSQUEDA: Se realizaron búsquedas en las siguientes bases de datos, sin restricción de idioma, desde 2007 hasta el 24 de julio de 2020: Registro especializado del Grupo Cochrane de Enfermedades infecciosas (Cochrane Infectious Disease Group [CIDG]); CENTRAL; MEDLINE OVID; Embase OVID; CINAHL EBSCO; LILACS BIREME; Science Citation Index Expanded (Web of Science), Social Sciences citation index (Web of Science), y Conference Proceedings Citation Index ‐ Social Science & Humanities (Web of Science). También se buscaron ensayos en curso en la Plataforma de registros internacionales de ensayos clínicos de la OMS, en ClinicalTrials.gov y en el Pan African Clinical Trials Registry. CRITERIOS DE SELECCIÓN: Se incluyeron ensayos aleatorizados individuales y por conglomerados, y estudios tipo antes y después (before‐after studie), con participantes sometidos a pruebas para la tuberculosis. Los estudios aleatorizados y no aleatorizados se analizaron por separado. OBTENCIÓN Y ANÁLISIS DE LOS DATOS: Dos autores de la revisión, de forma independiente, extrajeron los datos de cada estudio mediante una herramienta de extracción de datos analizada. El riesgo de sesgo se evaluó mediante las herramientas de Cochrane y del Grupo Cochrane para una Práctica y organización sanitarias efectivas (Effective Practice and Organisation of Care [EPOC]). Se utilizó el metanálisis de efectos aleatorios para considerar la heterogeneidad entre los estudios en cuanto al contexto y el diseño. La certeza de la evidencia en los ensayos aleatorizados se evaluó mediante el método GRADE.

Resultados principales: Se incluyeron 12 estudios: ocho eran ensayos controlados aleatorizados (ECA) y cuatro eran estudios tipo antes y después. La mayoría de los ECA incluidos tenían un bajo riesgo de sesgo en la mayoría de los dominios de la herramienta Cochrane "Risk of bias". Hubo evidencia no concluyente de un efecto de la Xpert MTB/RIF sobre la mortalidad por todas las causas, tanto en general (razón de riesgos [RR] 0,89; intervalo de confianza [IC] del 95%: 0,75 a 1,05; cinco ECA, 9932 participantes, evidencia de certeza moderada), como limitada a los estudios con seguimiento de seis meses (RR 0,98; IC del 95%: 0,78 a 1,22; tres ECA, 8143 participantes; evidencia de certeza moderada). Probablemente hubo una reducción de la mortalidad en los participantes que se sabía que estaban infectados por el VIH (odds ratio [OR] 0,80; IC del 95%: 0,67 a 0,96; cinco ECA, 5855 participantes; evidencia de certeza moderada). No está claro si la Xpert MTB/RIF no tiene efectos o tiene un efecto modesto sobre la proporción de participantes que inician el tratamiento de la tuberculosis y que tienen un desenlace exitoso del tratamiento (OR 1,10; IC del 95%: 0,96 a 1,26; tres ECA, 4802 participantes; evidencia de certeza moderada). También hubo evidencia no concluyente de un efecto sobre el porcentaje de participantes que recibieron tratamiento para la tuberculosis (RR 1,10; IC del 95%: 0,98 a 1,23; cinco ECA, 8793 participantes; evidencia de certeza moderada). Es probable que la proporción de participantes tratados por tuberculosis que tuvieron confirmación bacteriológica fuera mayor en el grupo de Xpert MTB/RIF (RR 1,44; IC del 95%: 1,29 a 1,61; seis ECA, 2068 participantes; evidencia de certeza moderada). Es probable que se redujera la proporción de participantes con confirmación bacteriológica que se perdió durante el seguimiento previo al tratamiento (RR 0,59; IC del 95%: 0,41 a 0,85; tres ECA, 1217 participantes; evidencia de certeza moderada).

Conclusiones de los autores: No fue posible descartar con seguridad el efecto sobre la mortalidad por todas las causas del uso de Xpert MTB/RIF en lugar de la baciloscopia. La Xpert MTB/RIF probablemente reduce la mortalidad en los participantes que se sabe que están infectados por el VIH. No hay certeza con respecto a si la Xpert MTB/RIF tiene un efecto modesto o no en la proporción tratada o, entre los tratados, en la proporción con un desenlace exitoso. Probablemente no tenga un efecto importante sobre estos desenlaces. La Xpert MTB/RIF probablemente aumenta la proporción de participantes tratados que tenían confirmación bacteriológica, así como la de aquellos con un diagnóstico confirmado por el laboratorio que fueron tratados. Estos hallazgos podrían servir de base para las decisiones sobre la adopción de la prueba, junto con la evidencia sobre la coste‐efectividad y la aplicación.

PubMed Disclaimer

Conflict of interest statement

FH has no known conflict of interest.

RRN has no known conflict of interest.

SGS is employed by the Foundation for Innovative New Diagnostics (FIND). FIND has conducted studies and published on Xpert MTB/RIF as part of a collaborative project between FIND, a Swiss non‐profit, Cepheid, a US company, and academic partners. The product developed through this partnership was developed under a contract that obligated FIND to pay for development costs and trial costs, and Cepheid to make the test available at preferential pricing to the public sector in developing countries. In addition, FIND conducted studies for the Xpert MTB/RIF Ultra assay, which have also been published.

MK has no known conflict of interest.

CMD was also employed by FIND during this review.

SG has no known conflict of interest.

KR is a board member of the Trial Safety Board, iM4TB, Lausanne, CH for a tuberculosis drug trial unrelated to the submitted work.

AR has no known conflict of interest.

Figures

1
1
Flow diagram of included studies
2
2
Summary of risk of bias for all included studies
3
3
1.1 All‐cause mortality
4
4
1.4 Proportion of participants starting tuberculosis treatment who had successful treatment outcomes
5
5
1.6 Proportion of participants treated for tuberculosis who were microbiologically confirmed
6
6
1.7 Proportion of participants with microbiological confirmation who had pre‐treatment loss to follow‐up
1.1
1.1. Analysis
Comparison 1: Xpert MTB/RIF vs smear microscopy, Outcome 1: All‐cause mortality
1.2
1.2. Analysis
Comparison 1: Xpert MTB/RIF vs smear microscopy, Outcome 2: All‐cause mortality in the subgroup assessed at six months
1.3
1.3. Analysis
Comparison 1: Xpert MTB/RIF vs smear microscopy, Outcome 3: All‐cause mortality: subgroup analysis by HIV status
1.4
1.4. Analysis
Comparison 1: Xpert MTB/RIF vs smear microscopy, Outcome 4: Proportion of participants starting tuberculosis treatment who had a successful treatment outcome
1.5
1.5. Analysis
Comparison 1: Xpert MTB/RIF vs smear microscopy, Outcome 5: Proportion of participants treated for tuberculosis
1.6
1.6. Analysis
Comparison 1: Xpert MTB/RIF vs smear microscopy, Outcome 6: Proportion of participants treated for tuberculosis who were microbiologically confirmed
1.7
1.7. Analysis
Comparison 1: Xpert MTB/RIF vs smear microscopy, Outcome 7: Proportion of participants with microbiological confirmation, who had pre‐treatment loss to follow‐up
See this image and copyright information in PMC

Update of

  • doi: 10.1002/14651858.CD012972

References

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