Background:

Missing outcome data for trial participants represents a serious potential source of bias, particularly when associated with the likelihood of outcome events. Systematic review authors frequently deal with this problem when conducting meta-analyses.

Objectives:

To review the literature systematically to identify proposed approaches that systematic review authors should use to handle missing participant data (MPD) when conducting a meta-analysis.

Methods:

We searched MEDLINE and the Cochrane Methodology Group Specialised Trials Register. We included papers that devoted at least two paragraphs to discuss a relevant approach for missing dichotomous data. Ten pairs of reviewers selected relevant papers in duplicate and independently. One reviewer (LK) abstracted data in a tabular format from included papers and a second reviewer (EA) verified them. We then prepared narrative summaries of the results

Results:

Of 9138 assessed citations, six proved eligible: three provided general approaches and three addressed specific statistical issues when handling MPD for a dichotomous outcome when conducting a meta-analysis. The Table summarizes the three proposed general approaches. They recommend a complete case analysis as a primary analysis, and additional sensitivity analyses using different imputation methods, including: based on reasons for missingness, relative to risk among followed-up, best-case scenario, and worst-case scenario. Two approaches suggest taking uncertainty into account. Out of the three papers addressing specific statistical issues, one discussed correcting the bias resulting from missing data in a meta-analysis (Yuan 2009), and two discussed statistical methods for allowing for uncertainty due to missing data in meta-analysis (White 2008).

Conclusions:

The results of this study summarize current recommendations regarding when or how systematic reviews authors may handle MPD when conducting a meta-analysis. While these approaches require further testing, they will help in developing specific guidance for Cochrane review authors on how to address missing participant dichotomous data.