title: Handling incomplete correlated continuous and binary outcomes in meta-analysis of individual participant data.
abstract: Meta-analysis of individual participant data (IPD) is increasingly utilised to improve the estimation of treatment effects, particularly among different participant subgroups. An important concern in IPD meta-analysis relates to partially or completely missing outcomes for some studies, a problem exacerbated when interest is on multiple discrete and continuous outcomes. When leveraging information from incomplete correlated outcomes across studies, the fully observed outcomes may provide important information about the incompleteness of the other outcomes. In this paper, we compare two models for handling incomplete continuous and binary outcomes in IPD meta-analysis: a joint hierarchical model and a sequence of full conditional mixed models. We illustrate how these approaches incorporate the correlation across the multiple outcomes and the between-study heterogeneity when addressing the missing data. Simulations characterise the performance of the methods across a range of scenarios which differ according to the proportion and type of missingness, strength of correlation between outcomes and the number of studies. The joint model provided confidence interval coverage consistently closer to nominal levels and lower mean squared error compared with the fully conditional approach across the scenarios considered. Methods are illustrated in a meta-analysis of randomised controlled trials comparing the effectiveness of implantable cardioverter-defibrillator devices alone to implantable cardioverter-defibrillator combined with cardiac resynchronisation therapy for treating patients with chronic heart failure. © 2016 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd.
authors.affiliation: Faculty of Public Health and Policy, London School of Hygiene and Tropical Medicine, London, U.K.
authors.forename: Manuel
authors.initials: M
authors.lastname: Gomes
authors.affiliation: Department of Health Care Policy, Harvard Medical School, Boston, 02115, MA, U.S.A.
authors.forename: Laura
authors.initials: L
authors.lastname: Hatfield
authors.affiliation: Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, 02115, MA, U.S.A.
authors.forename: Sharon-Lise
authors.initials: SL
authors.lastname: Normand
mesh_terms: D001699:Biometry; D000068598:Data Accuracy; D017147:Defibrillators, Implantable; D006801:Humans; D015201:Meta-Analysis as Topic; D016032:Randomized Controlled Trials as Topic
keywords: Bayesian analysis; IPD meta-analysis; fully conditional specification; joint modelling; missing data; multiple imputation