title: Multiple imputation methods for bivariate outcomes in cluster randomised trials.
abstract: Missing observations are common in cluster randomised trials. The problem is exacerbated when modelling bivariate outcomes jointly, as the proportion of complete cases is often considerably smaller than the proportion having either of the outcomes fully observed. Approaches taken to handling such missing data include the following: complete case analysis, single-level multiple imputation that ignores the clustering, multiple imputation with a fixed effect for each cluster and multilevel multiple imputation. We contrasted the alternative approaches to handling missing data in a cost-effectiveness analysis that uses data from a cluster randomised trial to evaluate an exercise intervention for care home residents. We then conducted a simulation study to assess the performance of these approaches on bivariate continuous outcomes, in terms of confidence interval coverage and empirical bias in the estimated treatment effects. Missing-at-random clustered data scenarios were simulated following a full-factorial design. Across all the missing data mechanisms considered, the multiple imputation methods provided estimators with negligible bias, while complete case analysis resulted in biased treatment effect estimates in scenarios where the randomised treatment arm was associated with missingness. Confidence interval coverage was generally in excess of nominal levels (up to 99.8%) following fixed-effects multiple imputation and too low following single-level multiple imputation. Multilevel multiple imputation led to coverage levels of approximately 95% throughout. © 2016 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd.
authors.affiliation: Department of Medical Statistics, London School of Hygiene and Tropical Medicine, Keppel Street, London, W1C 7HT, U.K.
authors.forename: K
authors.initials: K
authors.lastname: DiazOrdaz
authors.affiliation: Department of Medical Statistics, London School of Hygiene and Tropical Medicine, Keppel Street, London, W1C 7HT, U.K.
authors.forename: M G
authors.identifier: 0000-0003-0808-4192
authors.initials: MG
authors.lastname: Kenward
authors.affiliation: Department of Health Services Research and Policy, London School of Hygiene and Tropical Medicine, 15-17 Tavistock Place, London, WC1H 9SH, U.K.
authors.forename: M
authors.initials: M
authors.lastname: Gomes
authors.affiliation: Department of Health Services Research and Policy, London School of Hygiene and Tropical Medicine, 15-17 Tavistock Place, London, WC1H 9SH, U.K.
authors.forename: R
authors.initials: R
authors.lastname: Grieve
mesh_terms: D015982:Bias; D016000:Cluster Analysis; D003362:Cost-Benefit Analysis; D003627:Data Interpretation, Statistical; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D012107:Research Design
keywords: bivariate outcomes; cluster randomised trials; missing data; multiple imputation