title: Impact of Molecular Diagnostics for Tuberculosis on Patient-Important Outcomes: A Systematic Review of Study Methodologies.
abstract: BACKGROUND
  Several reviews on the accuracy of Tuberculosis (TB) Nucleic Acid Amplification Tests (NAATs) have been performed but the evidence on their impact on patient-important outcomes has not been systematically reviewed. Given the recent increase in research evaluating such outcomes and the growing list of TB NAATs that will reach the market over the coming years, there is a need to bring together the existing evidence on impact, rather than accuracy. We aimed to assess the approaches that have been employed to measure the impact of TB NAATs on patient-important outcomes in adults with possible pulmonary TB and/or drug-resistant TB.
  
  
  METHODS
  We first develop a conceptual framework to clarify through which mechanisms the improved technical performance of a novel TB test may lead to improved patient outcomes and outline which designs may be used to measure them. We then systematically review the literature on studies attempting to assess the impact of molecular TB diagnostics on such outcomes and provide a narrative synthesis of designs used, outcomes assessed and risk of bias across different study designs.
  
  
  RESULTS
  We found 25 eligible studies that assessed a wide range of outcomes and utilized a variety of experimental and observational study designs. Many potentially strong design options have never been used. We found that much of the available evidence on patient-important outcomes comes from a small number of settings with particular epidemiological and operational context and that confounding, time trends and incomplete outcome data receive insufficient attention.
  
  
  CONCLUSIONS
  A broader range of designs should be considered when designing studies to assess the impact of TB diagnostics on patient outcomes and more attention needs to be paid to the analysis as concerns about confounding and selection bias become relevant in addition to those on measurement that are of greatest concern in accuracy studies.
authors.affiliation: McGill University Department of Epidemiology & Biostatistics, Montreal, Canada.|McGill International TB Centre, Montreal, Canada.
authors.forename: Samuel G
authors.initials: SG
authors.lastname: Schumacher
authors.affiliation: McGill University Department of Epidemiology & Biostatistics, Montreal, Canada.|McGill International TB Centre, Montreal, Canada.
authors.forename: Hojoon
authors.initials: H
authors.lastname: Sohn
authors.affiliation: McGill University Department of Epidemiology & Biostatistics, Montreal, Canada.|McGill International TB Centre, Montreal, Canada.
authors.forename: Zhi Zhen
authors.initials: ZZ
authors.lastname: Qin
authors.affiliation: McGill University, Schulich Library of Science and Engineering, Montreal, Canada.
authors.forename: Genevieve
authors.initials: G
authors.lastname: Gore
authors.affiliation: UCSF Pulmonary & Critical Care Medicine, San Francisco, United States of America.
authors.forename: J Lucian
authors.initials: JL
authors.lastname: Davis
authors.affiliation: McGill University Department of Epidemiology & Biostatistics, Montreal, Canada.|McGill International TB Centre, Montreal, Canada.|Beth Israel Deaconess Medical Centre, Division of Infectious Disease, Boston, MA, United States of America.
authors.forename: Claudia M
authors.initials: CM
authors.lastname: Denkinger
authors.affiliation: McGill University Department of Epidemiology & Biostatistics, Montreal, Canada.|McGill International TB Centre, Montreal, Canada.
authors.forename: Madhukar
authors.initials: M
authors.lastname: Pai
mesh_terms: D006801:Humans; D025202:Molecular Diagnostic Techniques; D009169:Mycobacterium tuberculosis / Q000235:genetics*; D021141:Nucleic Acid Amplification Techniques; D017063:Outcome Assessment, Health Care; D017594:Publication Bias; D014376:Tuberculosis / Q000175:diagnosis* / Q000382:microbiology*; D018088:Tuberculosis, Multidrug-Resistant / Q000175:diagnosis / Q000382:microbiology; D014397:Tuberculosis, Pulmonary / Q000175:diagnosis / Q000382:microbiology