Uncertainty method improved on best–worst case analysis in a binary meta-analysis

Abstract 

Background

Most systematic reviewers aim to perform an intention-to-treat meta-analysis, including all randomized participants from each trial. This is not straightforward in practice: reviewers must decide how to handle missing outcome data in the contributing trials.

Objective

To investigate methods of allowing for uncertainty due to missing data in a meta-analysis.

Study Design and Setting

The Cochrane Library was surveyed to assess current use of imputation methods. We developed a methodology for incorporating uncertainty, with weights assigned to trials based on uncertainty interval widths. The uncertainty interval for a trial incorporates both sampling error and the potential impact of missing data. We evaluated the performance of this method using simulated data.

Results

The survey showed that complete-case analysis is commonly considered alongside best–worst case analysis. Best–worst case analysis gives an interval for the treatment effect that includes all of the uncertainty due to missing data. Unless there are few missing data, this interval is very wide. Simulations show that the uncertainty method consistently has better power and narrower interval widths than best–worst case analysis.

Conclusion

The uncertainty method performs consistently better than best–worst case imputation and should be considered along with complete-case analysis whenever missing data are a concern.

Keywords: Meta-analysis, Missing data, Intention to treat, Imputation, Uncertainty, Randomized controlled trials