The Method Quality of Cross-Over Studies Involved in Cochrane Systematic Reviews

Background: It is possible that cross-over studies included in current systematic reviews are being inadequately assessed, because the current risk of bias tools do not consider possible biases specific to cross-over design. We performed this study to evaluate whether this was being done in cross-over studies included in Cochrane Systematic Reviews (CSRs). Methods: We searched the Cochrane Library (up to 2013 issue 5) for CSRs that included at least one cross-over trial. Two authors independently undertook the study selection and data extraction. A random sample of the CSRs was selected and we evaluated whether the cross-over trials in these CSRs were assessed according to criteria suggested by the Cochrane handbook. In addition we reassessed the risk of bias of these cross-over trials by a checklist developed form the Cochrane handbook. Results: We identified 688 CSRs that included one or more cross-over studies. We chose a random sample of 60 CSRs and these included 139 cross-over studies. None of these CSRs undertook a risk of bias assessment specific for cross-over studies. In fact items specific for cross-over studies were seldom considered anywhere in quality assessment of these CSRs. When we reassessed the risk of bias, including the 3 items specific to cross-over trials, of these 139 studies, a low risk of bias was judged for appropriate cross-over design in 110(79%), carry-over effects in 48(34%) and for reporting data in all stages of the trial in 114(82%).Assessment of biases in cross-over trials could affect the GRADE assessment of a review’s findings. Conclusion: The current Cochrane risk of bias tool is not adequate to assess cross-over studies. Items specific to cross-over trials leading to potential risk of bias are generally neglected in CSRs. A proposed check list for the evaluation of cross-over trials is provided.