Variation in the observed effect of Xpert MTB/RIF testing for tuberculosis on mortality: a systematic review and analysis of trial design considerations

Research output: Contribution to journalArticlepeer-review


  • Eleanor A. Ochodo
  • Nelson Kalema
  • Samuel Schumacher
  • Karen R. Steingart
  • Taryn Young
  • Frank Cobelens
  • Patrick M. Bossuyt
  • Mark P Nicol
  • Adithya Cattamanchi

Colleges, School and Institutes

External organisations

  • Makerere University
  • Foundation for Innovative New Diagnostics
  • Liverpool School of Tropical Medicine
  • University of Stellenbosch
  • Queen Elizabeth Hospital Birmingham
  • Amsterdam University Medical Centers
  • University of Western Australia
  • University of California, San Francisco


Most studies evaluating the effect of Xpert MTB/RIF testing for tuberculosis (TB) concluded that it did not reduce overall mortality compared to usual care. We conducted a systematic review to assess whether key study design and execution features contributed to earlier identification of patients with TB and decreased pre-treatment loss to follow-up, thereby reducing the potential impact of Xpert MTB/RIF testing.

We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and Scopus for literature published from 1 January 2009 to February 2019. We included all primary intervention studies that had evaluated the effect of Xpert MTB/RIF on mortality compared to usual care in participants with presumptive pulmonary TB. We critically reviewed features of included studies across: Study setting and context, Study population, Participant recruitment and enrolment, Study procedures, and Study follow-up.

We included seven randomised and one non-randomised study. All included studies demonstrated relative reductions in overall mortality in the Xpert MTB/RIF arm ranging from 6% to 40%. However, mortality reduction was reported to be statistically significant in two studies. Study features that could explain the lack of observed effect on mortality included: the higher quality of care at study sites; inclusion of patients with a higher pre-test probability of TB leading to higher than expected empirical rates; performance of additional diagnostic testing not done in usual care leading to increased TB diagnosis or empiric treatment initiation; the recruitment of participants likely to return for follow-up; and involvement of study staff in ensuring adherence with care and follow-up.

Most studies of Xpert MTB/RIF were designed and conducted in a manner that resulted in more patients being diagnosed and treated for TB, minimising the potential difference in mortality Xpert MTB/RIF testing could have achieved compared to usual care.


Original languageEnglish
Article number173
Number of pages13
JournalWellcome Open Research
Publication statusPublished - 17 Aug 2020


  • Tuberculosis diagnosis, Methodology, Diagnostic trials, Impact studies

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