Geoadditive hazard regression for interval censored survival times

The Cox proportional hazards model is the most commonly used method when analyzing the impact of covariates on continuous survival times. In its classical form, the Cox model was introduced in the setting of right-censored observations. However, in practice other sampling schemes are frequently encountered and therefore extensions allowing for interval and left censoring or left truncation are clearly desired. Furthermore, many applications require a more flexible modeling of covariate information than the usual linear predictor. For example, effects of continuous covariates are likely to be of nonlinear form or spatial information is to be included appropriately. Further extensions should allow for time-varying effects of covariates or covariates that are themselves time-varying. Such models relax the assumption of proportional hazards. We propose a regression model for the hazard rate that combines and extends the above-mentioned features on the basis of a unifying Bayesian model formulation. Nonlinear and time-varying effects as well as the baseline hazard rate are modeled by penalized splines. Spatial effects can be included based on either Markov random fields or stationary Gaussian random fields. The model allows for arbitrary combinations of left, right and interval censoring as well as left truncation. Estimation is based on a reparameterisation of the model as a variance components mixed model. The variance parameters corresponding to inverse smoothing parameters can then be estimated based on an approximate marginal likelihood approach. As an application we present an analysis on childhood mortality in Nigeria, where the interval censoring framework also allows to deal with the problem of heaped survival times caused by memory effects. In a simulation study we investigate the effect of ignoring the impact of interval censored observations

Introduction to the Special Volume on "Ecology and Ecological Modeling in R"

The third special volume in the "Foometrics in R" series of the Journal of Statistical Software collects a number of contributions describing statistical methodology and corresponding implementations related to ecology and ecological modelling. The scope of the papers ranges from theoretical ecology and ecological modelling to statistical methodology relevant for data analyses in ecological applications.

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

Locally Adaptive Bayesian P-Splines with a Normal-Exponential-Gamma Prior

The necessity to replace smoothing approaches with a global amount of smoothing arises in a variety of situations such as effects with highly varying curvature or effects with discontinuities. We present an implementation of locally adaptive spline smoothing using a class of heavy-tailed shrinkage priors. These priors utilize scale mixtures of normals with locally varying exponential-gamma distributed variances for the differences of the P-spline coefficients. A fully Bayesian hierarchical structure is derived with inference about the posterior being based on Markov Chain Monte Carlo techniques. Three increasingly flexible and automatic approaches are introduced to estimate the spatially varying structure of the variances. In an extensive simulation study, the performance of our approach on a number of benchmark functions is shown to be at least equivalent, but mostly better than previous approaches and fits both functions of smoothly varying complexity and discontinuous functions well. Results from two applications also reflecting these two situations support the simulation results

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

Propriety of Posteriors in Structured Additive Regression Models: Theory and Empirical Evidence

Structured additive regression comprises many semiparametric regression models such as generalized additive (mixed) models, geoadditive models, and hazard regression models within a unified framework. In a Bayesian formulation, nonparametric functions, spatial effects and further model components are specified in terms of multivariate Gaussian priors for high-dimensional vectors of regression coefficients. For several model terms, such as penalised splines or Markov random fields, these Gaussian prior distributions involve rank-deficient precision matrices, yielding partially improper priors. Moreover, hyperpriors for the variances (corresponding to inverse smoothing parameters) may also be specified as improper, e.g. corresponding to Jeffery's prior or a flat prior for the standard deviation. Hence, propriety of the joint posterior is a crucial issue for full Bayesian inference in particular if based on Markov chain Monte Carlo simulations. We establish theoretical results providing sufficient (and sometimes necessary) conditions for propriety and provide empirical evidence through several accompanying simulation studies

Supplement to "Structured additive regression for categorical space-time data: A mixed model approach"

This technical report acts as a supplement to the paper "Structured additive regression for categorical space-time data: A mixed model approach" (Kneib and Fahrmeir, Biometrics, 2005, to appear). Details on several specific models for categorical responses are given as well as a description on how to construct design matrices in structured additive regression models. Furthermore some technical information on inferential issues and additional results from the simulation studies are provided. To ease orientation, sections in the supplement are named in analogy to the sections in the original paper. Also, formulas are presented with the same numbers

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

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

Variable Selection and Model Choice in Structured Survival Models

In many situations, medical applications ask for flexible survival models that allow to extend the classical Cox-model via the inclusion of time-varying and nonparametric effects. These structured survival models are very flexible but additional difficulties arise when model choice and variable selection is desired. In particular, it has to be decided which covariates should be assigned time-varying effects or whether parametric modeling is sufficient for a given covariate. Component-wise boosting provides a means of likelihood-based model fitting that enables simultaneous variable selection and model choice. We introduce a component-wise likelihood-based boosting algorithm for survival data that permits the inclusion of both parametric and nonparametric time-varying effects as well as nonparametric effects of continuous covariates utilizing penalized splines as the main modeling technique. Its properties and performance are investigated in simulation studies. The new modeling approach is used to build a flexible survival model for intensive care patients suffering from severe sepsis. A software implementation is available to the interested reader