Modelling Survival Events with Longitudinal Covariates Measured with Error

In survival analysis, time-dependent covariates are usually present as longitudinal data collected periodically and measured with error. The longitudinal data can be assumed to follow a linear mixed effect model and Cox regression models may be used for modelling of survival events. The hazard rate of survival times depends on the underlying time-dependent covariate measured with error, which may be described by random effects. Most existing methods proposed for such models assume a parametric distribution assumption on the random effects and specify a normally distributed error term for the linear mixed effect model. These assumptions may not be always valid in practice. In this article, we propose a new likelihood method for Cox regression models with error-contaminated time-dependent covariates. The proposed method does not require any parametric distribution assumption on random effects and random errors. Asymptotic properties for parameter estimators are provided. Simulation results show that under certain situations the proposed methods are more efficient than the existing methods.     

A Semiparametric Bayesian Approach to Multivariate Longitudinal Data

We extend the standard multivariate mixed model by incorporating a smooth time effect and relaxing distributional assumptions. We propose a semiparametric Bayesian approach to multivariate longitudinal data using a mixture of Polya trees prior distribution. Usually, the distribution of random effects in a longitudinal data model is assumed to be Gaussian. However, the normality assumption may be suspect, particularly if the estimated longitudinal trajectory parameters exhibit multimodality and skewness. In this paper we propose a mixture of Polya trees prior density to address the limitations of the parametric random effects distribution. We illustrate the methodology by analyzing data from a recent HIV-AIDS study.     

A Bayesian approach of joint models for clustered zero-inflated count data with skewness and measurement errors

Count data with excess zeros are widely encountered in the fields of biomedical, medical, public health and social survey, etc. Zero-inflated Poisson (ZIP) regression models with mixed effects are useful tools for analyzing such data, in which covariates are usually incorporated in the model to explain inter-subject variation and normal distribution is assumed for both random effects and random errors. However, in many practical applications, such assumptions may be violated as the data often exhibit skewness and some covariates may be measured with measurement errors. In this paper, we deal with these issues simultaneously by developing a Bayesian joint hierarchical modeling approach. Specifically, by treating intercepts and slopes in logistic and Poisson regression as random, a flexible two-level ZIP regression model is proposed, where a covariate process with measurement errors is established and a skew-t-distribution is considered for both random errors and random effects. Under the Bayesian framework, model selection is carried out using deviance information criterion (DIC) and a goodness-of-fit statistics is also developed for assessing the plausibility of the posited model. The main advantage of our method is that it allows for more robustness and correctness for investigating heterogeneity from different levels, while accommodating the skewness and measurement errors simultaneously. An application to Shanghai Youth Fitness Survey is used as an illustrate example. Through this real example, it is showed that our approach is of interest and usefulness for applications.     

Augmented mixed beta regression models with skew-normal independent distributions: Bayesian analysis of labor force data

Abstract

Augmented mixed beta regression models are suitable choices for modeling continuous response variables on the closed interval [0, 1]. The random eeceeects in these models are typically assumed to be normally distributed, but this assumption is frequently violated in some applied studies. In this paper, an augmented mixed beta regression model with skew-normal independent distribution for random effects are used. Next, we adopt a Bayesian approach for parameter estimation using the MCMC algorithm. The methods are then evaluated using some intensive simulation studies. Finally, the proposed models have applied to analyze a dataset from an Iranian Labor Force Survey.     

A flexible semiparametric regression model for bimodal,asymmetric and censored data

In this paper, we propose a new semiparametric heteroscedastic regression model allowing for positive and negative skewness and bimodal shapes using the B-spline basis for nonlinear effects. The proposed distribution is based on the generalized additive models for location, scale and shape framework in order to model any or all parameters of the distribution using parametric linear and/or nonparametric smooth functions of explanatory variables. We motivate the new model by means of Monte Carlo simulations, thus ignoring the skewness and bimodality of the random errors in semiparametric regression models, which may introduce biases on the parameter estimates and/or on the estimation of the associated variability measures. An iterative estimation process and some diagnostic methods are investigated. Applications to two real data sets are presented and the method is compared to the usual regression methods.     

Prediction of transplant-free survival in idiopathic pulmonary fibrosis patients using joint models for event times and mixed multivariate longitudinal data

We implement a joint model for mixed multivariate longitudinal measurements, applied to the prediction of time until lung transplant or death in idiopathic pulmonary fibrosis. Specifically, we formulate a unified Bayesian joint model for the mixed longitudinal responses and time-to-event outcomes. For the longitudinal model of continuous and binary responses, we investigate multivariate generalized linear mixed models using shared random effects. Longitudinal and time-to-event data are assumed to be independent conditional on available covariates and shared parameters. A Markov chain Monte Carlo algorithm, implemented in OpenBUGS, is used for parameter estimation. To illustrate practical considerations in choosing a final model, we fit 37 different candidate models using all possible combinations of random effects and employ a deviance information criterion to select a best-fitting model. We demonstrate the prediction of future event probabilities within a fixed time interval for patients utilizing baseline data, post-baseline longitudinal responses, and the time-to-event outcome. The performance of our joint model is also evaluated in simulation studies.     

Inference in generalized additive mixed modelsby using smoothing splines

Generalized additive mixed models are proposed for overdispersed and correlated data, which arise frequently in studies involving clustered, hierarchical and spatial designs. This class of models allows flexible functional dependence of an outcome variable on covariates by using nonparametric regression, while accounting for correlation between observations by using random effects. We estimate nonparametric functions by using smoothing splines and jointly estimate smoothing parameters and variance components by using marginal quasi-likelihood. Because numerical integration is often required by maximizing the objective functions, double penalized quasi-likelihood is proposed to make approximate inference. Frequentist and Bayesian inferences are compared. A key feature of the method proposed is that it allows us to make systematic inference on all model components within a unified parametric mixed model framework and can be easily implemented by fitting a working generalized linear mixed model by using existing statistical software. A bias correction procedure is also proposed to improve the performance of double penalized quasi-likelihood for sparse data. We illustrate the method with an application to infectious disease data and we evaluate its performance through simulation.     

A unified approach to rank tests for mixed models

The nonparametric version of the classical mixed model is considered and the common hypotheses of (parametric) main effects and interactions are reformulated in a nonparametric setup. To test these nonparametric hypotheses, the asymptotic distributions of quadratic forms of rank statistics are derived in a general framework which enables the derivation of the statistics for the nonparametric hypotheses of the fixed treatment effects and interactions in an arbitrary mixed model. The procedures given here are not restricted to semiparametric models or models with additive effects. Moreover, they are robust to outliers since only the ranks of the observations are needed. They are also applicable to pure ordinal data and since no continuity of the distribution functions is assumed, they can also be applied to data with ties. Some approximations for small sample sizes are suggested and analyzed in a simulation study. The application of the statistics and the interpretation of the results is demonstrated in several worked-out examples where some data sets given in the literature are re-analyzed.     

A Case Study for Modelling Cancer Incidence Using Bayesian Spatio‐Temporal Models

Researchers familiar with spatial models are aware of the challenge of choosing the level of spatial aggregation. Few studies have been published on the investigation of temporal aggregation and its impact on inferences regarding disease outcome in space–time analyses. We perform a case study for modelling individual disease outcomes using several Bayesian hierarchical spatio‐temporal models, while taking into account the possible impact of spatial and temporal aggregation. Using longitudinal breast cancer data from South East Queensland, Australia, we consider both parametric and non‐parametric formulations for temporal effects at various levels of aggregation. Two temporal smoothness priors are considered separately; each is modelled with fixed effects for the covariates and an intrinsic conditional autoregressive prior for the spatial random effects. Our case study reveals that different model formulations produce considerably different model performances. For this particular dataset, a classical parametric formulation that assumes a linear time trend produces the best fit among the five models considered. Different aggregation levels of temporal random effects were found to have little impact on model goodness‐of‐fit and estimation of fixed effects.     

Optimal Estimator for Logistic Model with Distribution‐free Random Intercept

Logistic models with a random intercept are prevalent in medical and social research where clustered and longitudinal data are often collected. Traditionally, the random intercept in these models is assumed to follow some parametric distribution such as the normal distribution. However, such an assumption inevitably raises concerns about model misspecification and misleading inference conclusions, especially when there is dependence between the random intercept and model covariates. To protect against such issues, we use a semiparametric approach to develop a computationally simple and consistent estimator where the random intercept is distribution‐free. The estimator is revealed to be optimal and achieve the efficiency bound without the need to postulate or estimate any latent variable distributions. We further characterize other general mixed models where such an optimal estimator exists.     

Semiparametric ARCH Models

This article introduces a semiparametric autoregressive conditional heteroscedasticity (ARCH) model that has conditional first and second moments given by autoregressive moving average and ARCH parametric formulations but a conditional density that is assumed only to be sufficiently smooth to be approximated by a nonparametric density estimator. For several particular conditional densities, the relative efficiency of the quasi-maximum likelihood estimator is compared with maximum likelihood under correct specification. These potential efficiency gains for a fully adaptive procedure are compared in a Monte Carlo experiment with the observed gains from using the proposed semiparametric procedure, and it is found that the estimator captures a substantial proportion of the potential. The estimator is applied to daily stock returns from small firms that are found to exhibit conditional skewness and kurtosis and to the British pound to dollar exchange rate.     

Evaluation of Bayesian multiple stage estimation under spatial CAR model variants

In this study, an evaluation of Bayesian hierarchical models is made based on simulation scenarios to compare single-stage and multi-stage Bayesian estimations. Simulated datasets of lung cancer disease counts for men aged 65 and older across 44 wards in the London Health Authority were analysed using a range of spatially structured random effect components. The goals of this study are to determine which of these single-stage models perform best given a certain simulating model, how estimation methods (single- vs. multi-stage) compare in yielding posterior estimates of fixed effects in the presence of spatially structured random effects, and finally which of two spatial prior models – the Leroux or ICAR model, perform best in a multi-stage context under different assumptions concerning spatial correlation. Among the fitted single-stage models without covariates, we found that when there is low amount of variability in the distribution of disease counts, the BYM model is relatively robust to misspecification in terms of DIC, while the Leroux model is the least robust to misspecification. When these models were fit to data generated from models with covariates, we found that when there was one set of covariates – either spatially correlated or non-spatially correlated, changing the values of the fixed coefficients affected the ability of either the Leroux or ICAR model to fit the data well in terms of DIC. When there were multiple sets of spatially correlated covariates in the simulating model, however, we could not distinguish the goodness of fit to the data between these single-stage models. We found that the multi-stage modelling process via the Leroux and ICAR models generally reduced the variance of the posterior estimated fixed effects for data generated from models with covariates and a UH term compared to analogous single-stage models. Finally, we found the multi-stage Leroux model compares favourably to the multi-stage ICAR model in terms of DIC. We conclude that the mutli-stage Leroux model should be seriously considered in applications of Bayesian disease mapping when an investigator desires to fit a model with both fixed effects and spatially structured random effects to Poisson count data.     

Bayesian Methods for Missing Covariates in Cure Rate Models

We propose methods for Bayesian inference for missing covariate data with a novel class of semi-parametric survival models with a cure fraction. We allow the missing covariates to be either categorical or continuous and specify a parametric distribution for the covariates that is written as a sequence of one dimensional conditional distributions. We assume that the missing covariates are missing at random (MAR) throughout. We propose an informative class of joint prior distributions for the regression coefficients and the parameters arising from the covariate distributions. The proposed class of priors are shown to be useful in recovering information on the missing covariates especially in situations where the missing data fraction is large. Properties of the proposed prior and resulting posterior distributions are examined. Also, model checking techniques are proposed for sensitivity analyses and for checking the goodness of fit of a particular model. Specifically, we extend the Conditional Predictive Ordinate (CPO) statistic to assess goodness of fit in the presence of missing covariate data. Computational techniques using the Gibbs sampler are implemented. A real data set involving a melanoma cancer clinical trial is examined to demonstrate the methodology.     

Lack-of-Fit Tests for Generalized Linear Models via Splines

Cubic B-splines are used to estimate the nonparametric component of a semiparametric generalized linear model. A penalized log-likelihood ratio test statistic is constructed for the null hypothesis of the linearity of the nonparametric function. When the number of knots is fixed, its limiting null distribution is the distribution of a linear combination of independent chi-squared random variables, each with one df. The smoothing parameter is determined by giving a specified value for its asymptotically expected value under the null hypothesis. A simulation study is conducted to evaluate its power performance; a real-life dataset is used to illustrate its practical use.     

Fourth-order kernel method for simple linear degradation model

Degradation analysis is a useful technique when life tests result in few or even no failures. The degradation measurements are recorded over time and the estimation of time-to-failure distribution plays a vital role in degradation analysis. The parametric method to estimate the time-to-failure distribution assumed a specific parametric model with known shape for the random effects parameter. To avoid any assumption about the model shape, a nonparametric method can be used. In this paper, we suggest to use the nonparametric fourth-order kernel method to estimate the time-to-failure distribution and its percentiles for the simple linear degradation model. The performances of the proposed method are investigated and compared with the classical kernel; maximum likelihood and ordinary least squares methods via simulation technique. The numerical results show the good performance of the fourth-order kernel method and demonstrate its superiority over the parametric method when there is no information about the shape of the random effect parameter distribution.     

Posterior consistency of random effects models for binary data

In longitudinal studies or clustered designs, observations for each subject or cluster are dependent and exhibit intra-correlation. To account for this dependency, we consider Bayesian analysis for conditionally specified models, so-called generalized linear mixed model. In nonlinear mixed models, the maximum likelihood estimator of the regression coefficients is typically a function of the distribution of random effects, and so the misspecified choice of the distribution of random effects can cause bias in the estimator. To avoid the problem of the misspecification of the distribution of random effects, one can resort in nonparametric approaches. We give sufficient conditions for posterior consistency of the distribution of random effects as well as regression coefficients.     

A Bayesian random effects model for analyzing mixed negative binomial and continuous longitudinal responses

ABSTRACT

A general Bayesian random effects model for analyzing longitudinal mixed correlated continuous and negative binomial responses with and without missing data is presented. This Bayesian model, given some random effects, uses a normal distribution for the continuous response and a negative binomial distribution for the count response. A Markov Chain Monte Carlo sampling algorithm is described for estimating the posterior distribution of the parameters. This Bayesian model is illustrated by a simulation study. For sensitivity analysis to investigate the change of parameter estimates with respect to the perturbation from missing at random to not missing at random assumption, the use of posterior curvature is proposed. The model is applied to a medical data, obtained from an observational study on women, where the correlated responses are the negative binomial response of joint damage and continuous response of body mass index. The simultaneous effects of some covariates on both responses are also investigated.     

Restricted Estimation in Partially Linear Errors-in-Variables Models

As a compromise between parametric regression and nonparametric regression, partially linear models are frequently used in statistical modelling. This article considers statistical inference for this semiparametric model when the linear covariate is measured with additive error and some additional linear restrictions on the parametric component are assumed to hold. We propose a restricted corrected profile least-squares estimator for the parametric component, and study the asymptotic normality of the estimator. To test hypothesis on the parametric component, we construct a Wald test statistic and obtain its limiting distribution. Some simulation studies are conducted to illustrate our approaches.     

Estimation of regression vectors in linear mixed models with Dirichlet process random effects

The Dirichlet process has been used extensively in Bayesian non parametric modeling, and has proven to be very useful. In particular, mixed models with Dirichlet process random effects have been used in modeling many types of data and can often outperform their normal random effect counterparts. Here we examine the linear mixed model with Dirichlet process random effects from a classical view, and derive the best linear unbiased estimator (BLUE) of the fixed effects. We are also able to calculate the resulting covariance matrix and find that the covariance is directly related to the precision parameter of the Dirichlet process, giving a new interpretation of this parameter. We also characterize the relationship between the BLUE and the ordinary least-squares (OLS) estimator and show how confidence intervals can be approximated.     

Random partition models with regression on covariates

Many recent applications of nonparametric Bayesian inference use random partition models, i.e. probability models for clustering a set of experimental units. We review the popular basic constructions. We then focus on an interesting extension of such models. In many applications covariates are available that could be used to a priori inform the clustering. This leads to random clustering models indexed by covariates, i.e., regression models with the outcome being a partition of the experimental units. We discuss some alternative approaches that have been used in the recent literature to implement such models, with an emphasis on a recently proposed extension of product partition models. Several of the reviewed approaches were not originally intended as covariate-based random partition models, but can be used for such inference.