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


METHODS
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.


CONCLUSIONS
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.
Gamble
Carrol
C
Centre for Medical Statistics and Health Evaluation, Shelleys Cottage, University of Liverpool, Merseyside, UK. c.gamble@liverpool.ac.uk
Hollis
Sally
S
D000962:Antimalarials / Q000627:therapeutic use; D003627:Data Interpretation, Statistical; D006801:Humans; D015201:Meta-Analysis as Topic; D016032:Randomized Controlled Trials as Topic; D012196:Review Literature as Topic; D016896:Treatment Outcome; D035501:Uncertainty
D000962:Antimalarials