title: The Use and Reporting of the Cross-Over Study Design in Clinical Trials and Systematic Reviews: A Systematic Assessment.
abstract: BACKGROUND
  Systematic reviews of treatment interventions in stable or chronic conditions often require the synthesis of clinical trials with a cross-over design. Previous work has indicated that methodology for analysing cross-over data is inadequate in trial reports and in systematic reviews assessing trials with this design.
  
  
  OBJECTIVE
  We assessed systematic review methodology for synthesising cross-over trials among Cochrane Cystic Fibrosis and Genetic Disorders Group reviews published to July 2015, and assessed the quality of reporting among the cross-over trials included in these reviews.
  
  
  METHODS
  We performed data extraction of methodology and reporting in reviews, trials identified and trials included within reviews.
  
  
  RESULTS
  We reviewed a total of 142 Cochrane systematic reviews including 53 reviews which synthesised evidence from 218 cross-over trials. Thirty-three (63%) Cochrane reviews described a clear and appropriate method for the inclusion of cross-over data, and of these 19 (56%) used the same method to analyse results. 145 cross-over trials were described narratively or treated as parallel trials in reviews but in 30 (21%) of these trials data existed in the trial reports to account for the cross-over design. At the trial level, the analysis and presentation of results were often inappropriate or unclear, with only 69 (32%) trials presenting results that could be included in meta-analysis.
  
  
  CONCLUSIONS
  Despite development of accessible, technical guidance and training for Cochrane systematic reviewers, statistical analysis and reporting of cross-over data is inadequate at both the systematic review and the trial level. Plain language and practical guidance for the inclusion of cross-over data in meta-analysis would benefit systematic reviewers, who come from a wide range of health specialties. Minimum reporting standards for cross-over trials are needed.
authors.affiliation: Department of Biostatistics, University of Liverpool, Liverpool, United Kingdom.|Cochrane Cystic Fibrosis and Genetic Disorders Group, Liverpool, United Kingdom.
authors.forename: Sarah Jane
authors.identifier: http://orcid.org/0000-0001-9988-2709
authors.initials: SJ
authors.lastname: Nolan
authors.affiliation: Cochrane Cystic Fibrosis and Genetic Disorders Group, Liverpool, United Kingdom.|Chronic Disease Research Centre, The University of the West Indies, Barbados, West Indies.
authors.forename: Ian
authors.initials: I
authors.lastname: Hambleton
authors.affiliation: Cochrane Editorial Unit, London, United Kingdom.
authors.forename: Kerry
authors.initials: K
authors.lastname: Dwan
mesh_terms: D002986:Clinical Trials as Topic / Q000379:methods*; D018592:Cross-Over Studies; D003550:Cystic Fibrosis / Q000235:genetics; D006801:Humans