title: Impact of a novel molecular TB diagnostic system in patients at high risk of TB mortality in rural South Africa (Uchwepheshe): study protocol for a cluster randomised trial.
abstract: BACKGROUND
  Tuberculosis control in sub-Saharan Africa has long been hampered by poor diagnostics and weak health systems. New molecular diagnostics, such as the Xpert® MTB/RIF assay, have the potential to improve patient outcomes. We present a cluster randomised trial designed to evaluate whether the positioning of this diagnostic system within the health system has an impact on important patient-level outcomes.
  
  
  METHODS
  This pragmatic cluster randomised clinical trial compared two positioning strategies for the Xpert MTB/RIF system: centralised laboratory versus primary health care clinic. The cluster (unit of randomisation) is a 2-week time block at the trial clinic. Adult pulmonary tuberculosis suspects with confirmed human immunodeficiency virus infection and/or at high risk of multidrug-resistant tuberculosis are enrolled from the primary health care clinic. The primary outcome measure is the proportion of culture-confirmed pulmonary tuberculosis cases initiated on appropriate treatment within 30 days of initial clinic visit. Univariate logistic regression will be performed as the primary analysis using generalised estimating equations with a binomial distribution function and a logit link.
  
  
  CONCLUSIONS
  Diagnostic research tends to focus only on performance of diagnostic tests rather than on patient-important outcomes. This trial has been designed to improve the quality of evidence around diagnostic strategies and to inform the scale-up of new tuberculosis diagnostics within public health systems in high-burden settings.
  
  
  BACKGROUND
  Current Controlled Trials ISRCTN18642314; South African National Clinical Trials Registry DOH-27-0711-3568.
authors.affiliation: Department of Clinical Research, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK. richard.lessells@lshtm.ac.uk
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Lessells
authors.forename: Graham S
authors.initials: GS
authors.lastname: Cooke
authors.forename: Nuala
authors.initials: N
authors.lastname: McGrath
authors.forename: Mark P
authors.initials: MP
authors.lastname: Nicol
authors.forename: Marie-Louise
authors.initials: ML
authors.lastname: Newell
authors.forename: Peter
authors.initials: P
authors.lastname: Godfrey-Faussett
mesh_terms: D000554:Ambulatory Care Facilities; D000995:Antitubercular Agents / Q000627:therapeutic use; D001431:Bacteriological Techniques; D002985:Clinical Protocols; D060085:Coinfection; D015658:HIV Infections / Q000401:mortality; D006801:Humans; D007753:Laboratories; D016015:Logistic Models; D025202:Molecular Diagnostic Techniques; D009169:Mycobacterium tuberculosis / Q000254:growth & development / Q000302:isolation & purification*; D019095:Point-of-Care Systems; D011237:Predictive Value of Tests; D011320:Primary Health Care; D012107:Research Design; D018570:Risk Assessment; D012307:Risk Factors; D019035:Rural Health Services; D013019:South Africa / Q000453:epidemiology; D013183:Sputum / Q000382:microbiology; D013997:Time Factors; 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