Design, Analysis, and Reporting of Crossover Trials for Inclusion in a Meta-Analysis

PLoS One. 2015 Aug 18;10(8):e0133023. doi: 10.1371/journal.pone.0133023. eCollection 2015.


Objective: To evaluate the characteristics of the design, analysis, and reporting of crossover trials for inclusion in a meta-analysis of treatment for primary open-angle glaucoma and to provide empirical evidence to inform the development of tools to assess the validity of the results from crossover trials and reporting guidelines.

Methods: We searched MEDLINE, EMBASE, and Cochrane's CENTRAL register for randomized crossover trials for a systematic review and network meta-analysis we are conducting. Two individuals independently screened the search results for eligibility and abstracted data from each included report.

Results: We identified 83 crossover trials eligible for inclusion. Issues affecting the risk of bias in crossover trials, such as carryover, period effects and missing data, were often ignored. Some trials failed to accommodate the within-individual differences in the analysis. For a large proportion of the trials, the authors tabulated the results as if they arose from a parallel design. Precision estimates properly accounting for the paired nature of the design were often unavailable from the study reports; consequently, to include trial findings in a meta-analysis would require further manipulation and assumptions.

Conclusions: The high proportion of poorly reported analyses and results has the potential to affect whether crossover data should or can be included in a meta-analysis. There is pressing need for reporting guidelines for crossover trials.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Cross-Over Studies
  • Glaucoma, Open-Angle / drug therapy
  • Humans
  • Meta-Analysis as Topic*
  • Randomized Controlled Trials as Topic / methods
  • Research Design / standards*