Flexible linear mixed models with improper priors for longitudinal and survival data

We propose a Bayesian approach using improper priors for hierarchical linear mixed models with flexible random effects and residual error distributions. The error distribution is modelled using scale mixtures of normals, which can capture tails heavier than those of the normal distribution. This generalisation is useful to produce models that are robust to the presence of outliers. The case of asymmetric residual errors is also studied. We present general results for the propriety of the posterior that also cover cases with censored observations, allowing for the use of these models in the contexts of popular longitudinal and survival analyses. We consider the use of copulas with flexible marginals for modelling the dependence between the random effects, but our results cover the use of any random effects distribution. Thus, our paper provides a formal justification for Bayesian inference in a very wide class of models (covering virtually all of the literature) under attractive prior structures that limit the amount of required user elicitation

Bayesian semiparametric multi-state models

Multi-state models provide a unified framework for the description of the evolution of discrete phenomena in continuous time. One particular example is Markov processes which can be characterised by a set of time-constant transition intensities between the states. In this paper, we will extend such parametric approaches to semiparametric models with flexible transition intensities based on Bayesian versions of penalised splines. The transition intensities will be modelled as smooth functions of time and can further be related to parametric as well as nonparametric covariate effects. Covariates with time-varying effects and frailty terms can be included in addition. Inference will be conducted either fully Bayesian (using Markov chain Monte Carlo simulation techniques) or empirically Bayesian (based on a mixed model representation). A counting process representation of semiparametric multi-state models provides the likelihood formula and also forms the basis for model validation via martingale residual processes. As an application, we will consider human sleep data with a discrete set of sleep states such as REM and non-REM phases. In this case, simple parametric approaches are inappropriate since the dynamics underlying human sleep are strongly varying throughout the night and individual specific variation has to be accounted for using covariate information and frailty terms

Generalized structured additive regression based on Bayesian P-splines

Generalized additive models (GAM) for modelling nonlinear effects of continuous covariates are now well established tools for the applied statistician. In this paper we develop Bayesian GAM's and extensions to generalized structured additive regression based on one or two dimensional P-splines as the main building block. The approach extends previous work by Lang und Brezger (2003) for Gaussian responses. Inference relies on Markov chain Monte Carlo (MCMC) simulation techniques, and is either based on iteratively weighted least squares (IWLS) proposals or on latent utility representations of (multi)categorical regression models. Our approach covers the most common univariate response distributions, e.g. the Binomial, Poisson or Gamma distribution, as well as multicategorical responses. For the first time, we present Bayesian semiparametric inference for the widely used multinomial logit models. As we will demonstrate through two applications on the forest health status of trees and a space-time analysis of health insurance data, the approach allows realistic modelling of complex problems. We consider the enormous flexibility and extendability of our approach as a main advantage of Bayesian inference based on MCMC techniques compared to more traditional approaches. Software for the methodology presented in the paper is provided within the public domain package BayesX

Bayesian P-Splines to investigate the impact of covariates on Multiple Sclerosis clinical course

This paper aims at proposing suitable statistical tools to address heterogeneity in repeated measures, within a Multiple Sclerosis (MS) longitudinal study. Indeed, due to unobservable sources of heterogeneity, modelling the effect of covariates on MS severity evolves as a very difficult feature. Bayesian P-Splines are suggested for modelling non linear smooth effects of covariates within generalized additive models. Thus, based on a pooled MS data set, we show how extending Bayesian P-splines to mixed effects models (Lang and Brezger, 2001), represents an attractive statistical approach to investigate the role of prognostic factors in affecting individual change in disability

A mixed model approach for structured hazard regression

The classical Cox proportional hazards model is a benchmark approach to analyze continuous survival times in the presence of covariate information. In a number of applications, there is a need to relax one or more of its inherent assumptions, such as linearity of the predictor or the proportional hazards property. Also, one is often interested in jointly estimating the baseline hazard together with covariate effects or one may wish to add a spatial component for spatially correlated survival data. We propose an extended Cox model, where the (log-)baseline hazard is weakly parameterized using penalized splines and the usual linear predictor is replaced by a structured additive predictor incorporating nonlinear effects of continuous covariates and further time scales, spatial effects, frailty components, and more complex interactions. Inclusion of time-varying coefficients leads to models that relax the proportional hazards assumption. Nonlinear and time-varying effects are modelled through penalized splines, and spatial components are treated as correlated random effects following either a Markov random field or a stationary Gaussian random field. All model components, including smoothing parameters, are specified within a unified framework and are estimated simultaneously based on mixed model methodology. The estimation procedure for such general mixed hazard regression models is derived using penalized likelihood for regression coefficients and (approximate) marginal likelihood for smoothing parameters. Performance of the proposed method is studied through simulation and an application to leukemia survival data in Northwest England

Bayesian Semiparametric Multi-State Models

Multi-state models provide a unified framework for the description of the evolution of discrete phenomena in continuous time. One particular example are Markov processes which can be characterised by a set of time-constant transition intensities between the states. In this paper, we will extend such parametric approaches to semiparametric models with flexible transition intensities based on Bayesian versions of penalised splines. The transition intensities will be modelled as smooth functions of time and can further be related to parametric as well as nonparametric covariate effects. Covariates with time-varying effects and frailty terms can be included in addition. Inference will be conducted either fully Bayesian using Markov chain Monte Carlo simulation techniques or empirically Bayesian based on a mixed model representation. A counting process representation of semiparametric multi-state models provides the likelihood formula and also forms the basis for model validation via martingale residual processes. As an application, we will consider human sleep data with a discrete set of sleep states such as REM and Non-REM phases. In this case, simple parametric approaches are inappropriate since the dynamics underlying human sleep are strongly varying throughout the night and individual-specific variation has to be accounted for using covariate information and frailty terms

Bayesian Semiparametric Multi-State Models

Multi-state models provide a unified framework for the description of the evolution of discrete phenomena in continuous time. One particular example are Markov processes which can be characterised by a set of time-constant transition intensities between the states. In this paper, we will extend such parametric approaches to semiparametric models with flexible transition intensities based on Bayesian versions of penalised splines. The transition intensities will be modelled as smooth functions of time and can further be related to parametric as well as nonparametric covariate effects. Covariates with time-varying effects and frailty terms can be included in addition. Inference will be conducted either fully Bayesian using Markov chain Monte Carlo simulation techniques or empirically Bayesian based on a mixed model representation. A counting process representation of semiparametric multi-state models provides the likelihood formula and also forms the basis for model validation via martingale residual processes. As an application, we will consider human sleep data with a discrete set of sleep states such as REM and Non-REM phases. In this case, simple parametric approaches are inappropriate since the dynamics underlying human sleep are strongly varying throughout the night and individual-specific variation has to be accounted for using covariate information and frailty terms

Structured additive regression for multicategorical space-time data: A mixed model approach

In many practical situations, simple regression models suffer from the fact that the dependence of responses on covariates can not be sufficiently described by a purely parametric predictor. For example effects of continuous covariates may be nonlinear or complex interactions between covariates may be present. A specific problem of space-time data is that observations are in general spatially and/or temporally correlated. Moreover, unobserved heterogeneity between individuals or units may be present. While, in recent years, there has been a lot of work in this area dealing with univariate response models, only limited attention has been given to models for multicategorical space-time data. We propose a general class of structured additive regression models (STAR) for multicategorical responses, allowing for a flexible semiparametric predictor. This class includes models for multinomial responses with unordered categories as well as models for ordinal responses. Non-linear effects of continuous covariates, time trends and interactions between continuous covariates are modelled through Bayesian versions of penalized splines and flexible seasonal components. Spatial effects can be estimated based on Markov random fields, stationary Gaussian random fields or two-dimensional penalized splines. We present our approach from a Bayesian perspective, allowing to treat all functions and effects within a unified general framework by assigning appropriate priors with different forms and degrees of smoothness. Inference is performed on the basis of a multicategorical linear mixed model representation. This can be viewed as posterior mode estimation and is closely related to penalized likelihood estimation in a frequentist setting. Variance components, corresponding to inverse smoothing parameters, are then estimated by using restricted maximum likelihood. Numerically efficient algorithms allow computations even for fairly large data sets. As a typical example we present results on an analysis of data from a forest health survey