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

Hierarchical models for semi-competing risks data with application to quality of end-of-life care for pancreatic cancer

Readmission following discharge from an initial hospitalization is a key marker of quality of health care in the United States. For the most part, readmission has been used to study quality of care for patients with acute health conditions, such as pneumonia and heart failure, with analyses typically based on a logistic-Normal generalized linear mixed model. Applying this model to the study readmission among patients with increasingly prevalent advanced health conditions such as pancreatic cancer is problematic, however, because it ignores death as a competing risk. A more appropriate analysis is to imbed such studies within the semi-competing risks framework. To our knowledge, however, no comprehensive statistical methods have been developed for cluster-correlated semi-competing risks data. In this paper we propose a novel hierarchical modeling framework for the analysis of cluster-correlated semi-competing risks data. The framework permits parametric or non-parametric specifications for a range of model components, including baseline hazard functions and distributions for key random effects, giving analysts substantial flexibility as they consider their own analyses. Estimation and inference is performed within the Bayesian paradigm since it facilitates the straightforward characterization of (posterior) uncertainty for all model parameters including hospital-specific random effects. The proposed framework is used to study the risk of readmission among 5,298 Medicare beneficiaries diagnosed with pancreatic cancer at 112 hospitals in the six New England states between 2000-2009, specifically to investigate the role of patient-level risk factors and to characterize variation in risk across hospitals that is not explained by differences in patient case-mix

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

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