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Missing outcome data are commonly encountered in randomized controlled trials and hence may need to be addressed in a meta-analysis of multiple trials. A common and simple approach to deal with missing data is to restrict analysis to individuals for whom the outcome was obtained (complete case analysis). However, estimated treatment effects from complete case analyses are potentially biased if informative missing data are ignored. We develop methods for estimating meta-analytic summary treatment effects for continuous outcomes in the presence of missing data for some of the individuals within the trials. We build on a method previously developed for binary outcomes, which quantifies the degree of departure from a missing at random assumption via the informative missingness odds ratio. Our new model quantifies the degree of departure from missing at random using either an informative missingness difference of means or an informative missingness ratio of means, both of which relate the mean value of the missing outcome data to that of the observed data. We propose estimating the treatment effects, adjusted for informative missingness, and their standard errors by a Taylor series approximation and by a Monte Carlo method. We apply the methodology to examples of both pairwise and network meta-analysis with multi-arm trials.

Original publication

DOI

10.1002/sim.6365

Type

Journal article

Journal

Stat Med

Publication Date

28/02/2015

Volume

34

Pages

721 - 741

Keywords

informative missing, mixed treatment comparison, sensitivity analysis, Bias, Biostatistics, Humans, Intention to Treat Analysis, Meta-Analysis as Topic, Models, Statistical, Monte Carlo Method, Patient Dropouts, Randomized Controlled Trials as Topic, Software, Uncertainty