title: Xpert MTB/RIF - why the lack of morbidity and mortality impact in intervention trials?
abstract: Compared with smear microscopy, the Xpert MTB/RIF assay (Xpert), with superior accuracy and capacity to diagnose rifampicin resistance, has advanced TB diagnostic capability. However, recent trials of Xpert impact have not demonstrated reductions in patient morbidity and mortality. We conducted a narrative review of Xpert impact trials to summarize which patient-relevant outcomes Xpert has improved and explore reasons for no observed morbidity or mortality reductions. We searched PubMed, Google Scholar, Cochrane Library and Embase and identified eight trials meeting inclusion criteria: three individually randomized, three cluster-randomized, and two pre-post trials. In six trials Xpert increased diagnostic yield of bacteriologically-confirmed TB from sputa and in four trials Xpert shortened time to TB treatment. However, all-cause mortality was similar between arms in all six trials reporting this outcome, and the only trial to assess Xpert impact on morbidity reported no impact. Trial characteristics that might explain lack of observed impact on morbidity and mortality include: higher rates of empiric TB treatment in microscopy compared with Xpert arms, enrollment of study populations not comprised exclusively of populations most likely to benefit from Xpert, and health system weaknesses. So far as equipoise exists, future trials that address past limitations are needed to inform Xpert use in resource-limited settings.
authors.affiliation: Division of Global HIV & Tuberculosis, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, 30333, USA aauld@cdc.gov.
authors.forename: Andrew F
authors.initials: AF
authors.lastname: Auld
authors.affiliation: Department of Clinical Research, Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, Keppel Street, London WC1E7HT, UK.
authors.forename: Katherine L
authors.initials: KL
authors.lastname: Fielding
authors.affiliation: Department of Clinical Research, Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, Keppel Street, London WC1E7HT, UK.
authors.forename: Ankur
authors.initials: A
authors.lastname: Gupta-Wright
authors.affiliation: Department of Clinical Research, Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, Keppel Street, London WC1E7HT, UK The Desmond Tutu HIV Centre, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa Department of Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Lawn
mesh_terms: D000995:Antitubercular Agents / Q000494:pharmacology / Q000627:therapeutic use; D015373:Bacterial Typing Techniques; D024881:Drug Resistance, Bacterial; D015658:HIV Infections / Q000150:complications / Q000401:mortality; D006801:Humans; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000235:genetics; D018579:Patient Selection; D016133:Polymerase Chain Reaction; D012293:Rifampin / Q000494:pharmacology / Q000627:therapeutic use; D013183:Sputum / Q000382:microbiology; D016896:Treatment Outcome; D018088:Tuberculosis, Multidrug-Resistant / Q000175:diagnosis* / Q000188:drug therapy / Q000382:microbiology / Q000401:mortality; D014397:Tuberculosis, Pulmonary / Q000175:diagnosis* / Q000188:drug therapy / Q000382:microbiology / Q000401:mortality
chemical_list: D000995:Antitubercular Agents; D012293:Rifampin
keywords: Clinical trials; Health system weaknesses; Impact; Limitations; Study design; Xpert MTB/RIF