Multivariate measurement error models based on Student-t distribution under censored responses

Measurement error models constitute a wide class of models that include linear and nonlinear regression models. They are very useful to model many real-life phenomena, particularly in the medical and biological areas. The great advantage of these models is that, in some sense, they can be represented as mixed effects models, allowing us to implement well-known techniques, like the EM-algorithm for the parameter estimation. In this paper, we consider a class of multivariate measurement error models where the observed response and/or covariate are not fully observed, i.e., the observations are subject to certain threshold values below or above which the measurements are not quantifiable. Consequently, these observations are considered censored. We assume a Student-t distribution for the unobserved true values of the mismeasured covariate and the error term of the model, providing a robust alternative for parameter estimation. Our approach relies on a likelihood-based inference using an EM-type algorithm. The proposed method is illustrated through some simulation studies and the analysis of an AIDS clinical trial dataset.     

Estimation in large cross random-effect models by data augmentation

Estimation in mixed linear models is, in general, computationally demanding, since applied problems may involve extensive data sets and large numbers of random effects. Existing computer algorithms are slow and/or require large amounts of memory. These problems are compounded in generalized linear mixed models for categorical data, since even approximate methods involve fitting of a linear mixed model within steps of an iteratively reweighted least squares algorithm. Only in models in which the random effects are hierarchically nested can the computations for fitting these models to large data sets be carried out rapidly. We describe a data augmentation approach to these computational difficulties in which we repeatedly fit an overlapping series of submodels, incorporating the missing terms in each submodel as 'offsets'. The submodels are chosen so that they have a nested random-effect structure, thus allowing maximum exploitation of the computational efficiency which is available in this case. Examples of the use of the algorithm for both metric and discrete responses are discussed, all calculations being carried out using macros within the MLwiN program.     

A Bayesian conditional model for bivariate mixed ordinal and skew continuous longitudinal responses using quantile regression

In this paper, we develop a conditional model for analyzing mixed bivariate continuous and ordinal longitudinal responses. We propose a quantile regression model with random effects for analyzing continuous responses. For this purpose, an Asymmetric Laplace Distribution (ALD) is allocated for continuous response given random effects. For modeling ordinal responses, a cumulative logit model is used, via specifying a latent variable model, with considering other random effects. Therefore, the intra-association between continuous and ordinal responses is taken into account using their own exclusive random effects. But, the inter-association between two mixed responses is taken into account by adding a continuous response term in the ordinal model. We use a Bayesian approach via Markov chain Monte Carlo method for analyzing the proposed conditional model and to estimate unknown parameters, a Gibbs sampler algorithm is used. Moreover, we illustrate an application of the proposed model using a part of the British Household Panel Survey data set. The results of data analysis show that gender, age, marital status, educational level and the amount of money spent on leisure have significant effects on annual income. Also, the associated parameter is significant in using the best fitting proposed conditional model, thus it should be employed rather than analyzing separate models.     

A heteroscedastic measurement error model based on skew and heavy-tailed distributions with known error variances

In this paper, we study inference in a heteroscedastic measurement error model with known error variances. Instead of the normal distribution for the random components, we develop a model that assumes a skew-t distribution for the true covariate and a centred Student's t distribution for the error terms. The proposed model enables to accommodate skewness and heavy-tailedness in the data, while the degrees of freedom of the distributions can be different. Maximum likelihood estimates are computed via an EM-type algorithm. The behaviour of the estimators is also assessed in a simulation study. Finally, the approach is illustrated with a real data set from a methods comparison study in Analytical Chemistry.     

An Alternative Estimation Approach for the Heterogeneity Linear Mixed Model

In this article, an alternative estimation approach is proposed to fit linear mixed effects models where the random effects follow a finite mixture of normal distributions. This heterogeneity linear mixed model is an interesting tool since it relaxes the classical normality assumption and is also perfectly suitable for classification purposes, based on longitudinal profiles. Instead of fitting directly the heterogeneity linear mixed model, we propose to fit an equivalent mixture of linear mixed models under some restrictions which is computationally simpler. Unlike the former model, the latter can be maximized analytically using an EM-algorithm and the obtained parameter estimates can be easily used to compute the parameter estimates of interest.     

A monte carlo comparison of the smoothing,scoring and em algorithms for dispersion matrix estimation with incomplete growth curve data

Incomplete growth curve data often result from missing or mistimed observations in a repeated measures design. Virtually all methods of analysis rely on the dispersion matrix estimates. A Monte Carlo simulation was used to compare three methods of estimation of dispersion matrices for incomplete growth curve data. The three methods were: 1) maximum likelihood estimation with a smoothing algorithm, which finds the closest positive semidefinite estimate of the pairwise estimated dispersion matrix; 2) a mixed effects model using the EM (estimation maximization) algorithm; and 3) a mixed effects model with the scoring algorithm. The simulation included 5 dispersion structures, 20 or 40 subjects with 4 or 8 observations per subject and 10 or 30% missing data. In all the simulations, the smoothing algorithm was the poorest estimator of the dispersion matrix. In most cases, there were no significant differences between the scoring and EM algorithms. The EM algorithm tended to be better than the scoring algorithm when the variances of the random effects were close to zero, especially for the simulations with 4 observations per subject and two random effects.     

A shared parameter model of longitudinal measurements and survival time with heterogeneous random-effects distribution

Typical joint modeling of longitudinal measurements and time to event data assumes that two models share a common set of random effects with a normal distribution assumption. But, sometimes the underlying population that the sample is extracted from is a heterogeneous population and detecting homogeneous subsamples of it is an important scientific question. In this paper, a finite mixture of normal distributions for the shared random effects is proposed for considering the heterogeneity in the population. For detecting whether the unobserved heterogeneity exits or not, we use a simple graphical exploratory diagnostic tool proposed by Verbeke and Molenberghs [34] to assess whether the traditional normality assumption for the random effects in the mixed model is adequate. In the joint modeling setting, in the case of evidence against normality (homogeneity), a finite mixture of normals is used for the shared random-effects distribution. A Bayesian MCMC procedure is developed for parameter estimation and inference. The methodology is illustrated using some simulation studies. Also, the proposed approach is used for analyzing a real HIV data set, using the heterogeneous joint model for this data set, the individuals are classified into two groups: a group with high risk and a group with moderate risk.     

Maximizing generalized linear mixed model likelihoods with an automated Monte Carlo EM algorithm

Two new implementations of the EM algorithm are proposed for maximum likelihood fitting of generalized linear mixed models. Both methods use random (independent and identically distributed) sampling to construct Monte Carlo approximations at the E-step. One approach involves generating random samples from the exact conditional distribution of the random effects (given the data) by rejection sampling, using the marginal distribution as a candidate. The second method uses a multivariate t importance sampling approximation. In many applications the two methods are complementary. Rejection sampling is more efficient when sample sizes are small, whereas importance sampling is better with larger sample sizes. Monte Carlo approximation using random samples allows the Monte Carlo error at each iteration to be assessed by using standard central limit theory combined with Taylor series methods. Specifically, we construct a sandwich variance estimate for the maximizer at each approximate E-step. This suggests a rule for automatically increasing the Monte Carlo sample size after iterations in which the true EM step is swamped by Monte Carlo error. In contrast, techniques for assessing Monte Carlo error have not been developed for use with alternative implementations of Monte Carlo EM algorithms utilizing Markov chain Monte Carlo E-step approximations. Three different data sets, including the infamous salamander data of McCullagh and Nelder, are used to illustrate the techniques and to compare them with the alternatives. The results show that the methods proposed can be considerably more efficient than those based on Markov chain Monte Carlo algorithms. However, the methods proposed may break down when the intractable integrals in the likelihood function are of high dimension.     

A simultaneous variable selection methodology for linear mixed models

Selecting an appropriate structure for a linear mixed model serves as an appealing problem in a number of applications such as in the modelling of longitudinal or clustered data. In this paper, we propose a variable selection procedure for simultaneously selecting and estimating the fixed and random effects. More specifically, a profile log-likelihood function, along with an adaptive penalty, is utilized for sparse selection. The Newton-Raphson optimization algorithm is performed to complete the parameter estimation. By jointly selecting the fixed and random effects, the proposed approach increases selection accuracy compared with two-stage procedures, and the usage of the profile log-likelihood can improve computational efficiency in one-stage procedures. We prove that the proposed procedure enjoys the model selection consistency. A simulation study and a real data application are conducted for demonstrating the effectiveness of the proposed method.     

Mixture of linear mixed models using multivariate t distribution

Linear mixed models are widely used when multiple correlated measurements are made on each unit of interest. In many applications, the units may form several distinct clusters, and such heterogeneity can be more appropriately modelled by a finite mixture linear mixed model. The classical estimation approach, in which both the random effects and the error parts are assumed to follow normal distribution, is sensitive to outliers, and failure to accommodate outliers may greatly jeopardize the model estimation and inference. We propose a new mixture linear mixed model using multivariate t distribution. For each mixture component, we assume the response and the random effects jointly follow a multivariate t distribution, to conveniently robustify the estimation procedure. An efficient expectation conditional maximization algorithm is developed for conducting maximum likelihood estimation. The degrees of freedom parameters of the t distributions are chosen data adaptively, for achieving flexible trade-off between estimation robustness and efficiency. Simulation studies and an application on analysing lung growth longitudinal data showcase the efficacy of the proposed approach.     

Parametric bootstrap tests for unbalanced nested designs under heteroscedasticity

In this article, we consider the two-factor unbalanced nested design model without the assumption of equal error variance. For the problem of testing ‘main effects’ of both factors, we propose a parametric bootstrap (PB) approach and compare it with the existing generalized F (GF) test. The Type I error rates of the tests are evaluated using Monte Carlo simulation. Our studies show that the PB test performs better than the GF test. The PB test performs very satisfactorily even for small samples while the GF test exhibit poor Type I error properties when the number of factorial combinations or treatments goes up. It is also noted that the same tests can be used to test the significance of the random effect variance component in a two-factor mixed effects nested model under unequal error variances.     

A linear mixed model for analyzing longitudinal skew-normal responses with random dropout

In this paper, a linear mixed effects model is used to fit skewed longitudinal data in the presence of dropout. Two distributional assumptions are considered to produce background for heavy tailed models. One is the linear mixed model with skew-normal random effects and normal errors and the other one is the linear mixed model with skew-normal errors and normal random effects. An ECM algorithm is developed to obtain the parameter estimates. Also an empirical Bayes approach is used for estimating random effects. A simulation study is implemented to investigate the performance of the presented algorithm. Results of an application are also reported where standard errors of estimates are calculated using the Bootstrap approach.     

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.     

Random Effects Modeling and the Zero-Inflated Poisson Distribution

Overdispersion due to a large proportion of zero observations in data sets is a common occurrence in many applications of many fields of research; we consider such scenarios in count panel (longitudinal) data. A well-known and widely implemented technique for handling such data is that of random effects modeling, which addresses the serial correlation inherent in panel data, as well as overdispersion. To deal with the excess zeros, a zero-inflated Poisson distribution has come to be canonical, which relaxes the equal mean-variance specification of a traditional Poisson model and allows for the larger variance characteristic of overdispersed data. A natural proposal then to approach count panel data with overdispersion due to excess zeros is to combine these two methodologies, deriving a likelihood from the resulting conditional probability. In performing simulation studies, we find that this approach in fact poses problems of identifiability. In this article, we construct and explain in full detail why a model obtained from the marriage of two classical and well-established techniques is unidentifiable and provide results of simulation studies demonstrating this effect. A discussion on alternative methodologies to resolve the problem is provided in the conclusion.     

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.     

Modelling growth and decline in lung function in Duchenne's muscular dystrophy with an augmented linear mixed effects model

Summary.  Longitudinal modelling of lung function in Duchenne's muscular dystrophy is complicated by a mixture of both growth and decline in lung function within each subject, an unknown point of separation between these phases and significant heterogeneity between individual trajectories. Linear mixed effects models can be used, assuming a single changepoint for all cases; however, this assumption may be incorrect. The paper describes an extension of linear mixed effects modelling in which random changepoints are integrated into the model as parameters and estimated by using a stochastic EM algorithm. We find that use of this 'mixture modelling' approach improves the fit significantly.     

Monte Carlo approximation of likelihood function in spatial GLMMs through an empirical Bayes method

In spatial generalized linear mixed models (SGLMMs), statistical inference encounters problems, since random effects in the model imply high-dimensional integrals to calculate the marginal likelihood function. In this article, we temporarily treat parameters as random variables and express the marginal likelihood function as a posterior expectation. Hence, the marginal likelihood function is approximated using the obtained samples from the posterior density of the latent variables and parameters given the data. However, in this setting, misspecification of prior distribution of correlation function parameter and problems associated with convergence of Markov chain Monte Carlo (MCMC) methods could have an unpleasant influence on the likelihood approximation. To avoid these challenges, we utilize an empirical Bayes approach to estimate prior hyperparameters. We also use a computationally efficient hybrid algorithm by combining inverse Bayes formula (IBF) and Gibbs sampler procedures. A simulation study is conducted to assess the performance of our method. Finally, we illustrate the method applying a dataset of standard penetration test of soil in an area in south of Iran.     

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.     

Adaptive LASSO for linear mixed model selection via profile log-likelihood

Mixed model selection is quite important in statistical literature. To assist the mixed model selection, we employ the adaptive LASSO penalized term to propose a two-stage selection procedure for the purpose of choosing both the random and fixed effects. In the first stage, we utilize the penalized restricted profile log-likelihood to choose the random effects; in the second stage, after the random effects are determined, we apply the penalized profile log-likelihood to select the fixed effects. In each stage, the Newton–Raphson algorithm is performed to complete the parameter estimation. We prove that the proposed procedure is consistent and possesses the oracle properties. The simulations and a real data application are conducted for demonstrating the effectiveness of the proposed selection procedure.     

Generalized Linear Factor Models: A New Local EM Estimation Algorithm

In this article, a general approach to latent variable models based on an underlying generalized linear model (GLM) with factor analysis observation process is introduced. We call these models Generalized Linear Factor Models (GLFM). The observations are produced from a general model framework that involves observed and latent variables that are assumed to be distributed in the exponential family. More specifically, we concentrate on situations where the observed variables are both discretely measured (e.g., binomial, Poisson) and continuously distributed (e.g., gamma). The common latent factors are assumed to be independent with a standard multivariate normal distribution. Practical details of training such models with a new local expectation-maximization (EM) algorithm, which can be considered as a generalized EM-type algorithm, are also discussed. In conjunction with an approximated version of the Fisher score algorithm (FSA), we show how to calculate maximum likelihood estimates of the model parameters, and to yield inferences about the unobservable path of the common factors. The methodology is illustrated by an extensive Monte Carlo simulation study and the results show promising performance.