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.     

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.     

Bayesian local influence analysis of skew-normal spatial dynamic panel data models

The existing studies on spatial dynamic panel data model (SDPDM) mainly focus on the normality assumption of response variables and random effects. This assumption may be inappropriate in some applications. This paper proposes a new SDPDM by assuming that response variables and random effects follow the multivariate skew-normal distribution. A Markov chain Monte Carlo algorithm is developed to evaluate Bayesian estimates of unknown parameters and random effects in skew-normal SDPDM by combining the Gibbs sampler and the Metropolis–Hastings algorithm. A Bayesian local influence analysis method is developed to simultaneously assess the effect of minor perturbations to the data, priors and sampling distributions. Simulation studies are conducted to investigate the finite-sample performance of the proposed methodologies. An example is illustrated by the proposed methodologies.     

Bayesian analysis of multivariate t linear mixed models with missing responses at random

The multivariate t linear mixed model (MtLMM) has been recently proposed as a robust tool for analysing multivariate longitudinal data with atypical observations. Missing outcomes frequently occur in longitudinal research even in well controlled situations. As a powerful alternative to the traditional expectation maximization based algorithm employing single imputation, we consider a Bayesian analysis of the MtLMM to account for the uncertainties of model parameters and missing outcomes through multiple imputation. An inverse Bayes formulas sampler coupled with Metropolis-within-Gibbs scheme is used to effectively draw the posterior distributions of latent data and model parameters. The techniques for multiple imputation of missing values, estimation of random effects, prediction of future responses, and diagnostics of potential outliers are investigated as well. The proposed methodology is illustrated through a simulation study and an application to AIDS/HIV data.     

Bayesian analysis of multivariate survival data using Monte Carlo methods

This paper deals with the analysis of multivariate survival data from a Bayesian perspective using Markov-chain Monte Carlo methods. The Metropolis along with the Gibbs algorithm is used to calculate some of the marginal posterior distributions. A multivariate survival model is proposed, since survival times within the same group are correlated as a consequence of a frailty random block effect. The conditional proportional-hazards model of Clayton and Cuzick is used with a martingale structured prior process (Arjas and Gasbarra) for the discretized baseline hazard. Besides the calculation of the marginal posterior distributions of the parameters of interest, this paper presents some Bayesian EDA diagnostic techniques to detect model adequacy. The methodology is exemplified with kidney infection data where the times to infections within the same patients are expected to be correlated.     

A NONPARAMETRIC MIXED‐EFFECTS MODEL FOR CANCER MORTALITY

There are several ways to handle within‐subject correlations with a longitudinal discrete outcome, such as mortality. The most frequently used models are either marginal or random‐effects types. This paper deals with a random‐effects‐based approach. We propose a nonparametric regression model having time‐varying mixed effects for longitudinal cancer mortality data. The time‐varying mixed effects in the proposed model are estimated by combining kernel‐smoothing techniques and a growth‐curve model. As an illustration based on real data, we apply the proposed method to a set of prefecture‐specific data on mortality from large‐bowel cancer in Japan.     

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, non-parametric 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 penalized 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 Jeffreys 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.     

On familial Poisson mixed models with multi-dimensional random effects

When a generalized linear mixed model with multiple (two or more) sources of random effects is considered, the inferences may vary depending on the nature of the random effects. In this paper, we consider a familial Poisson mixed model where each of the count responses of a family are influenced by two independent unobservable familial random effects with two distinct components of dispersion. A generalized quasilikelihood (GQL) approach is discussed for the estimation of the dispersion components as well as the regression effects of the model. A simulation study is conducted to examine the relative performance of the GQL approach as opposed to a simpler method of moments. Furthermore, the GQL estimation methodology is illustrated by using health care utilization data that follow a Poisson mixed model with one component of dispersion and by using simulated asthma data that follow a Poisson mixed model with two sources of random effects with two distinct components of dispersion.     

Structural learning with time-varying components: tracking the cross-section of financial time series

Summary.  When modelling multivariate financial data, the problem of structural learning is compounded by the fact that the covariance structure changes with time. Previous work has focused on modelling those changes by using multivariate stochastic volatility models. We present an alternative to these models that focuses instead on the latent graphical structure that is related to the precision matrix. We develop a graphical model for sequences of Gaussian random vectors when changes in the underlying graph occur at random times, and a new block of data is created with the addition or deletion of an edge. We show how a Bayesian hierarchical model incorporates both the uncertainty about that graph and the time variation thereof.     

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.     

COMPOSITIONAL TIME SERIES ANALYSIS OF MORTALITY PROPORTIONS

Compositional time series are multivariate time series which at each time point are proportions that sum to a constant. Accurate inference for such series which occur in several disciplines such as geology, economics and ecology is important in practice. Usual multivariate statistical procedures ignore the inherent constrained nature of these observations as parts of a whole and may lead to inaccurate estimation and prediction. In this article, a regression model with vector autoregressive moving average (VARMA) errors is fit to the compositional time series after an additive log ratio (ALR) transformation. Inference is carried out in a hierarchical Bayesian framework using Markov chain Monte Carlo techniques. The approach is illustrated on compositional time series of mortality events in Los Angeles in order to investigate dependence of different categories of mortality on air quality.     

Gamma shared frailty model based on reversed hazard rate

Abstract

Frailty models are used in survival analysis to account for unobserved heterogeneity in individual risks to disease and death. To analyze bivariate data on related survival times (e.g., matched pairs experiments, twin, or family data), shared frailty models were suggested. Shared frailty models are frequently used to model heterogeneity in survival analysis. The most common shared frailty model is a model in which hazard function is a product of random factor(frailty) and baseline hazard function which is common to all individuals. There are certain assumptions about the baseline distribution and distribution of frailty. In this paper, we introduce shared gamma frailty models with reversed hazard rate. We introduce Bayesian estimation procedure using Markov Chain Monte Carlo (MCMC) technique to estimate the parameters involved in the model. We present a simulation study to compare the true values of the parameters with the estimated values. Also, we apply the proposed model to the Australian twin data set.     

On the clustering term in ecological analysis: how do different prior specifications affect results?

We study how different prior assumptions on the spatially structured heterogeneity term of the convolution hierarchical Bayesian model for spatial disease data could affect the results of an ecological analysis when response and exposure exhibit a strong spatial pattern. We show that in this case the estimate of the regression parameter could be strongly biased, both by analyzing the association between lung cancer mortality and education level on a real dataset and by a simulation experiment. The analysis is based on a hierarchical Bayesian model with a time dependent covariate in which we allow for a latency period between exposure and mortality, with time and space random terms and misaligned exposure-disease data.     

Bayesian Analysis of Nonlinear Reproductive Dispersion Mixed Models for Longitudinal Data with Nonignorable Missing Covariates

This article proposes a Bayesian approach, which can simultaneously obtain the Bayesian estimates of unknown parameters and random effects, to analyze nonlinear reproductive dispersion mixed models (NRDMMs) for longitudinal data with nonignorable missing covariates and responses. The logistic regression model is employed to model the missing data mechanisms for missing covariates and responses. A hybrid sampling procedure combining the Gibber sampler and the Metropolis-Hastings algorithm is presented to draw observations from the conditional distributions. Because missing data mechanism is not testable, we develop the logarithm of the pseudo-marginal likelihood, deviance information criterion, the Bayes factor, and the pseudo-Bayes factor to compare several competing missing data mechanism models in the current considered NRDMMs with nonignorable missing covaraites and responses. Three simulation studies and a real example taken from the paediatric AIDS clinical trial group ACTG are used to illustrate the proposed methodologies. Empirical results show that our proposed methods are effective in selecting missing data mechanism models.     

A general joint model for longitudinal measurements and competing risks survival data with heterogeneous random effects

This article studies a general joint model for longitudinal measurements and competing risks survival data. The model consists of a linear mixed effects sub-model for the longitudinal outcome, a proportional cause-specific hazards frailty sub-model for the competing risks survival data, and a regression sub-model for the variance–covariance matrix of the multivariate latent random effects based on a modified Cholesky decomposition. The model provides a useful approach to adjust for non-ignorable missing data due to dropout for the longitudinal outcome, enables analysis of the survival outcome with informative censoring and intermittently measured time-dependent covariates, as well as joint analysis of the longitudinal and survival outcomes. Unlike previously studied joint models, our model allows for heterogeneous random covariance matrices. It also offers a framework to assess the homogeneous covariance assumption of existing joint models. A Bayesian MCMC procedure is developed for parameter estimation and inference. Its performances and frequentist properties are investigated using simulations. A real data example is used to illustrate the usefulness of the approach.     

Estimation of Median in Two-Phase Sampling Using Two Auxiliary Variables

In recent years, zero-inflated count data models, such as zero-inflated Poisson (ZIP) models, are widely used as the count data with extra zeros are very common in many practical problems. In order to model the correlated count data which are either clustered or repeated and to assess the effects of continuous covariates or of time scales in a flexible way, a class of semiparametric mixed-effects models for zero-inflated count data is considered. In this article, we propose a fully Bayesian inference for such models based on a data augmentation scheme that reflects both random effects of covariates and mixture of zero-inflated distribution. A computational efficient MCMC method which combines the Gibbs sampler and M-H algorithm is implemented to obtain the estimate of the model parameters. Finally, a simulation study and a real example are used to illustrate the proposed methodologies.     

On efficient inferences in familial-longitudinal binary models with two variance components

When a generalized linear mixed model (GLMM) with multiple (two or more) sources of random effects is considered, the inferences may vary depending on the nature of the random effects. For example, the inference in GLMMs with two independent random effects with two distinct components of dispersion will be different from the inference in GLMMs with two random effects in a two factor factorial design set-up. In this paper, we consider a familial-longitudinal model for repeated binary data where the binary response of an individual member of a family at a given time point is assumed to be influenced by the past responses of the member as well as two but independent sources of random family effects. For the estimation of the parameters of the proposed model, we discuss the well-known maximum-likelihood (ML) method as well as a generalized quasi-likelihood (GQL) approach. The main objective of the paper is to examine the relative asymptotic efficiency performance of the ML and GQL estimators for the regression effects, dynamic (longitudinal) dependence and variance parameters of the random family effects from two sources.     

Modelling Trends and Inequality in Small Area Mortality

This paper considers the modelling of mortality rates classified by age, time, and small area with a view to developing life table parameters relevant to assessing trends in inequalities in life chances. In particular, using a fully Bayes perspective, one may assess the stochastic variation in small area life table parameters, such as life expectancies, and also formally assess whether trends in indices of inequality in mortality are significant. Modelling questions include choice between random walk priors for age and time effects as against non-linear regression functions, questions of identifiability when several random effects are present in the death rates model, and the choice of model when both within and out-of-sample performance may be important. A case study application involves 44 small areas in North East London and mortality in five sub-periods (1986-88, 1989-91, 1992-94, 1995-97, 1998-2000) between 1986 and 2000, with the final period used for assessing out-of-sample performance.     

Computation aspects of the parameter estimates of linear mixed effects model in multivariate repeated measures set-up

The number of parameters mushrooms in a linear mixed effects (LME) model in the case of multivariate repeated measures data. Computation of these parameters is a real problem with the increase in the number of response variables or with the increase in the number of time points. The problem becomes more intricate and involved with the addition of additional random effects. A multivariate analysis is not possible in a small sample setting. We propose a method to estimate these many parameters in bits and pieces from baby models, by taking a subset of response variables at a time, and finally using these bits and pieces at the end to get the parameter estimates for the mother model, with all variables taken together. Applying this method one can calculate the fixed effects, the best linear unbiased predictions (BLUPs) for the random effects in the model, and also the BLUPs at each time of observation for each response variable, to monitor the effectiveness of the treatment for each subject. The proposed method is illustrated with an example of multiple response variables measured over multiple time points arising from a clinical trial in osteoporosis.