The Use and Reporting of the Cross-Over Study Design in Clinical Trials and Systematic Reviews: A Systematic Assessment

PLoS One. 2016 Jul 13;11(7):e0159014. doi: 10.1371/journal.pone.0159014. eCollection 2016.


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.

Methodology: We performed data extraction of methodology and reporting in reviews, trials identified and trials included within reviews.

Principal findings: 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.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Clinical Trials as Topic / methods*
  • Cross-Over Studies
  • Cystic Fibrosis / genetics
  • Humans

Grant support

The time of SJN and KD was partly supported by the National Institute for Health Research, via Cochrane Infrastructure funding to the Cochrane Cystic Fibrosis and Genetic Disorders Group [], []. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. IH received no specific funding for this work.