title: A flexible joint modeling framework for longitudinal and time-to-event data with overdispersion.
abstract: We combine conjugate and normal random effects in a joint model for outcomes, at least one of which is non-Gaussian, with particular emphasis on cases in which one of the outcomes is of survival type. Conjugate random effects are used to relax the often-restrictive mean-variance prescription in the non-Gaussian outcome, while normal random effects account for not only the correlation induced by repeated measurements from the same subject but also the association between the different outcomes. Using a case study in chronic heart failure, we show that model fit can be improved, even resulting in impact on significance tests, by switching to our extended framework. By first taking advantage of the ease of analytical integration over conjugate random effects, we easily estimate our framework, by maximum likelihood, in standard software.
authors.affiliation: I-BioStat, Universiteit Hasselt, Diepenbeek, Belgium edmund.njagi@uhasselt.be.
authors.forename: Edmund N
authors.initials: EN
authors.lastname: Njagi
authors.affiliation: I-BioStat, Universiteit Hasselt, Diepenbeek, Belgium I-BioStat, Katholieke Universiteit Leuven, Leuven, Belgium.
authors.forename: Geert
authors.initials: G
authors.lastname: Molenberghs
authors.affiliation: Department of Biostatistics, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Dimitris
authors.initials: D
authors.lastname: Rizopoulos
authors.affiliation: I-BioStat, Universiteit Hasselt, Diepenbeek, Belgium I-BioStat, Katholieke Universiteit Leuven, Leuven, Belgium.
authors.forename: Geert
authors.initials: G
authors.lastname: Verbeke
authors.affiliation: Medical Statistics Unit, London School of Hygiene and Tropical Medicine, London, UK.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Kenward
authors.affiliation: Faculty of Medicine, Hasselt University, Diepenbeek, Belgium Jessa Hospital, Heart Centre Hasselt, Hasselt, Belgium.
authors.forename: Paul
authors.initials: P
authors.lastname: Dendale
authors.affiliation: Faculty of Medicine, Katholieke Universiteit Leuven, Leuven, Belgium.
authors.forename: Koen
authors.initials: K
authors.lastname: Willekens
mesh_terms: D006333:Heart Failure; D006801:Humans; D016013:Likelihood Functions; D012984:Software
keywords: Poisson-gamma-normal model; Weibull-gamma-normal model; partial marginalization; probit-beta-normal model