Influence diagnostics for Student-t censored linear regression models

In this paper, we extend the censored linear regression model with normal errors to Student-t errors. A simple EM-type algorithm for iteratively computing maximum-likelihood estimates of the parameters is presented. To examine the performance of the proposed model, case-deletion and local influence techniques are developed to show its robust aspect against outlying and influential observations. This is done by the analysis of the sensitivity of the EM estimates under some usual perturbation schemes in the model or data and by inspecting some proposed diagnostic graphics. The efficacy of the method is verified through the analysis of simulated data sets and modelling a real data set first analysed under normal errors. The proposed algorithm and methods are implemented in the R package CensRegMod.     

Bayesian analysis of generalized elliptical semi-parametric models

In this paper, we study the statistical inference based on the Bayesian approach for regression models with the assumption that independent additive errors follow normal, Student-t, slash, contaminated normal, Laplace or symmetric hyperbolic distribution, where both location and dispersion parameters of the response variable distribution include nonparametric additive components approximated by B-splines. This class of models provides a rich set of symmetric distributions for the model error. Some of these distributions have heavier or lighter tails than the normal as well as different levels of kurtosis. In order to draw samples of the posterior distribution of the interest parameters, we propose an efficient Markov Chain Monte Carlo (MCMC) algorithm, which combines Gibbs sampler and Metropolis–Hastings algorithms. The performance of the proposed MCMC algorithm is assessed through simulation experiments. We apply the proposed methodology to a real data set. The proposed methodology is implemented in the R package BayesGESM using the function gesm().     

A stochastic approximation algorithm for maximum-likelihood estimation with incomplete data

We propose a new stochastic approximation (SA) algorithm for maximum-likelihood estimation (MLE) in the incomplete-data setting. This algorithm is most useful for problems when the EM algorithm is not possible due to an intractable E-step or M-step. Compared to other algorithm that have been proposed for intractable EM problems, such as the MCEM algorithm of Wei and Tanner (1990), our proposed algorithm appears more generally applicable and efficient. The approach we adopt is inspired by the Robbins-Monro (1951) stochastic approximation procedure, and we show that the proposed algorithm can be used to solve some of the long-standing problems in computing an MLE with incomplete data. We prove that in general O(n) simulation steps are required in computing the MLE with the SA algorithm and O(n log n) simulation steps are required in computing the MLE using the MCEM and/or the MCNR algorithm, where n is the sample size of the observations. Examples include computing the MLE in the nonlinear error-in-variable model and nonlinear regression model with random effects.     

Joint analysis of nonlinear heterogeneous longitudinal data and binary outcome: an application to AIDS clinical studies

Finite mixture models are currently used to analyze heterogeneous longitudinal data. By releasing the homogeneity restriction of nonlinear mixed-effects (NLME) models, finite mixture models not only can estimate model parameters but also cluster individuals into one of the pre-specified classes with class membership probabilities. This clustering may have clinical significance, which might be associated with a clinically important binary outcome. This article develops a joint modeling of a finite mixture of NLME models for longitudinal data in the presence of covariate measurement errors and a logistic regression for a binary outcome, linked by individual latent class indicators, under a Bayesian framework. Simulation studies are conducted to assess the performance of the proposed joint model and a naive two-step model, in which finite mixture model and logistic regression are fitted separately, followed by an application to a real data set from an AIDS clinical trial, in which the viral dynamics and dichotomized time to the first decline of CD4/CD8 ratio are analyzed jointly.     

Bayesian adaptive Lasso for quantile regression models with nonignorably missing response data

Abstract

Handling data with the nonignorably missing mechanism is still a challenging problem in statistics. In this paper, we develop a fully Bayesian adaptive Lasso approach for quantile regression models with nonignorably missing response data, where the nonignorable missingness mechanism is specified by a logistic regression model. The proposed method extends the Bayesian Lasso by allowing different penalization parameters for different regression coefficients. Furthermore, a hybrid algorithm that combined the Gibbs sampler and Metropolis-Hastings algorithm is implemented to simulate the parameters from posterior distributions, mainly including regression coefficients, shrinkage coefficients, parameters in the non-ignorable missing models. Finally, some simulation studies and a real example are used to illustrate the proposed methodology.     

Mixtures of general location model with factor analyzer covariance structure for clustering mixed type data

Cluster analysis is one of the most widely used method in statistical analyses, in which homogeneous subgroups are identified in a heterogeneous population. Due to the existence of the continuous and discrete mixed data in many applications, so far, some ordinary clustering methods such as, hierarchical methods, k-means and model-based methods have been extended for analysis of mixed data. However, in the available model-based clustering methods, by increasing the number of continuous variables, the number of parameters increases and identifying as well as fitting an appropriate model may be difficult. In this paper, to reduce the number of the parameters, for the model-based clustering mixed data of continuous (normal) and nominal data, a set of parsimonious models is introduced. Models in this set are extended, using the general location model approach, for modeling distribution of mixed variables and applying factor analyzer structure for covariance matrices. The ECM algorithm is used for estimating the parameters of these models. In order to show the performance of the proposed models for clustering, results from some simulation studies and analyzing two real data sets are presented.     

Joint models for multiple longitudinal processes and time-to-event outcome

ABSTRACT

Joint models are statistical tools for estimating the association between time-to-event and longitudinal outcomes. One challenge to the application of joint models is its computational complexity. Common estimation methods for joint models include a two-stage method, Bayesian and maximum-likelihood methods. In this work, we consider joint models of a time-to-event outcome and multiple longitudinal processes and develop a maximum-likelihood estimation method using the expectation–maximization algorithm. We assess the performance of the proposed method via simulations and apply the methodology to a data set to determine the association between longitudinal systolic and diastolic blood pressure measures and time to coronary artery disease.     

Segmental modeling of changing immunologic response for CD4 data with skewness,missingness and dropout

In clinical practice, the profile of each subject's CD4 response from a longitudinal study may follow a ‘broken stick’ like trajectory, indicating multiple phases of increase and/or decline in response. Such multiple phases (changepoints) may be important indicators to help quantify treatment effect and improve management of patient care. Although it is a common practice to analyze complex AIDS longitudinal data using nonlinear mixed-effects (NLME) or nonparametric mixed-effects (NPME) models in the literature, NLME or NPME models become a challenge to estimate changepoint due to complicated structures of model formulations. In this paper, we propose a changepoint mixed-effects model with random subject-specific parameters, including the changepoint for the analysis of longitudinal CD4 cell counts for HIV infected subjects following highly active antiretroviral treatment. The longitudinal CD4 data in this study may exhibit departures from symmetry, may encounter missing observations due to various reasons, which are likely to be non-ignorable in the sense that missingness may be related to the missing values, and may be censored at the time of the subject going off study-treatment, which is a potentially informative dropout mechanism. Inferential procedures can be complicated dramatically when longitudinal CD4 data with asymmetry (skewness), incompleteness and informative dropout are observed in conjunction with an unknown changepoint. Our objective is to address the simultaneous impact of skewness, missingness and informative censoring by jointly modeling the CD4 response and dropout time processes under a Bayesian framework. The method is illustrated using a real AIDS data set to compare potential models with various scenarios, and some interested results are presented.     

Parameter estimation for mixtures of skew Laplace normal distributions and application in mixture regression modeling

In this article, we propose mixtures of skew Laplace normal (SLN) distributions to model both skewness and heavy-tailedness in the neous data set as an alternative to mixtures of skew Student-t-normal (STN) distributions. We give the expectation–maximization (EM) algorithm to obtain the maximum likelihood (ML) estimators for the parameters of interest. We also analyze the mixture regression model based on the SLN distribution and provide the ML estimators of the parameters using the EM algorithm. The performance of the proposed mixture model is illustrated by a simulation study and two real data examples.     

Influence diagnostics in heteroscedastic and/or autoregressive nonlinear elliptical models for correlated data

In this paper, we propose nonlinear elliptical models for correlated data with heteroscedastic and/or autoregressive structures. Our aim is to extend the models proposed by Russo et al. 22 by considering a more sophisticated scale structure to deal with variations in data dispersion and/or a possible autocorrelation among measurements taken throughout the same experimental unit. Moreover, to avoid the possible influence of outlying observations or to take into account the non-normal symmetric tails of the data, we assume elliptical contours for the joint distribution of random effects and errors, which allows us to attribute different weights to the observations. We propose an iterative algorithm to obtain the maximum-likelihood estimates for the parameters and derive the local influence curvatures for some specific perturbation schemes. The motivation for this work comes from a pharmacokinetic indomethacin data set, which was analysed previously by Bocheng and Xuping 1 under normality.     

Robust variable selection in finite mixture of regression models using the t distribution

Abstract

Variable selection in finite mixture of regression (FMR) models is frequently used in statistical modeling. The majority of applications of variable selection in FMR models use a normal distribution for regression error. Such assumptions are unsuitable for a set of data containing a group or groups of observations with heavy tails and outliers. In this paper, we introduce a robust variable selection procedure for FMR models using the t distribution. With appropriate selection of the tuning parameters, the consistency and the oracle property of the regularized estimators are established. To estimate the parameters of the model, we develop an EM algorithm for numerical computations and a method for selecting tuning parameters adaptively. The parameter estimation performance of the proposed model is evaluated through simulation studies. The application of the proposed model is illustrated by analyzing a real data set.     

On Computing Maximum-Likelihood Estimates of the Unbalanced Two-Way Random-Effects Model

This article applies the ECME algorithm to derive an easily implemented iterative feasible generalized least squares procedure for calculating maximum-likelihood estimates of the parameters of the unbalanced two-way random-effects model. The algorithm increases the log-likelihood monotonically and the fitted variance components are guaranteed to be non negative. This article applies the algorithm in an example.     

Fitting finite mixture models using iterative Monte Carlo classification

Parameters of a finite mixture model are often estimated by the expectation–maximization (EM) algorithm where the observed data log-likelihood function is maximized. This paper proposes an alternative approach for fitting finite mixture models. Our method, called the iterative Monte Carlo classification (IMCC), is also an iterative fitting procedure. Within each iteration, it first estimates the membership probabilities for each data point, namely the conditional probability of a data point belonging to a particular mixing component given that the data point value is obtained, it then classifies each data point into a component distribution using the estimated conditional probabilities and the Monte Carlo method. It finally updates the parameters of each component distribution based on the classified data. Simulation studies were conducted to compare IMCC with some other algorithms for fitting mixture normal, and mixture t, densities.     

Joint model-based clustering of nonlinear longitudinal trajectories and associated time-to-event data analysis,linked by latent class membership: with application to AIDS clinical studies

Longitudinal and time-to-event data are often observed together. Finite mixture models are currently used to analyze nonlinear heterogeneous longitudinal data, which, by releasing the homogeneity restriction of nonlinear mixed-effects (NLME) models, can cluster individuals into one of the pre-specified classes with class membership probabilities. This clustering may have clinical significance, and be associated with clinically important time-to-event data. This article develops a joint modeling approach to a finite mixture of NLME models for longitudinal data and proportional hazard Cox model for time-to-event data, linked by individual latent class indicators, under a Bayesian framework. The proposed joint models and method are applied to a real AIDS clinical trial data set, followed by simulation studies to assess the performance of the proposed joint model and a naive two-step model, in which finite mixture model and Cox model are fitted separately.     

Gaussian Scale Mixture Models for Robust Linear Multivariate Regression with Missing Data

We present an algorithm for multivariate robust Bayesian linear regression with missing data. The iterative algorithm computes an approximative posterior for the model parameters based on the variational Bayes (VB) method. Compared to the EM algorithm, the VB method has the advantage that the variance for the model parameters is also computed directly by the algorithm. We consider three families of Gaussian scale mixture models for the measurements, which include as special cases the multivariate t distribution, the multivariate Laplace distribution, and the contaminated normal model. The observations can contain missing values, assuming that the missing data mechanism can be ignored. A Matlab/Octave implementation of the algorithm is presented and applied to solve three reference examples from the literature.     

Bias reduction of the maximum-likelihood estimator for a conditional Gaussian MA(1) model

In this paper, we consider an estimation for the unknown parameters of a conditional Gaussian MA(1) model. In the majority of cases, a maximum-likelihood estimator is chosen because the estimator is consistent. However, for small sample sizes the error is large, because the estimator has a bias of O(n^{? 1}). Therefore, we provide a bias of O(n^{? 1}) for the maximum-likelihood estimator for the conditional Gaussian MA(1) model. Moreover, we propose new estimators for the unknown parameters of the conditional Gaussian MA(1) model based on the bias of O(n^{? 1}). We investigate the properties of the bias, as well as the asymptotical variance of the maximum-likelihood estimators for the unknown parameters, by performing some simulations. Finally, we demonstrate the validity of the new estimators through this simulation study.     

A novel quantification of information for longitudinal data analyzed by mixed‐effects modeling

Nonlinear mixed‐effects (NLME) modeling is one of the most powerful tools for analyzing longitudinal data especially under the sparse sampling design. The determinant of the Fisher information matrix is a commonly used global metric of the information that can be provided by the data under a given model. However, in clinical studies, it is also important to measure how much information the data provide for a certain parameter of interest under the assumed model, for example, the clearance in population pharmacokinetic models. This paper proposes a new, easy‐to‐interpret information metric, the “relative information” (RI), which is designed for specific parameters of a model and takes a value between 0% and 100%. We establish the relationship between interindividual variability for a specific parameter and the variance of the associated parameter estimator, demonstrating that, under a “perfect” experiment (eg, infinite samples or/and minimum experimental error), the RI and the variance of the model parameter estimator converge, respectively, to 100% and the ratio of the interindividual variability for that parameter and the number of subjects. Extensive simulation experiments and analyses of three real datasets show that our proposed RI metric can accurately characterize the information for parameters of interest for NLME models. The new information metric can be readily used to facilitate study designs and model diagnosis.     

Some bootstrap methods in nonlinear mixed-effect models

Nonlinear mixed-effect (NLME) models arise in many applied fields including pharmacokinetics. Several bootstrap methods are considered for estimating standard errors of parameter (both fixed and random effects) estimates in these models. Keeping in mind the issues that make the NLME different from the simple linear model, modifications of the classical bootstrap methods are suggested. Although the current work specifically relates to the models proposed by Lindstrom and Bayes (1990), and Vonesh and Carter (1992), the described methods should work as well in most other NLME models. Limited data analysis has been performed implementing some of the proposed bootstrap methodologies.     

Influence diagnostics for censored regression models with autoregressive errors

Observations collected over time are often autocorrelated rather than independent, and sometimes include observations below or above detection limits (i.e. censored values reported as less or more than a level of detection) and/or missing data. Practitioners commonly disregard censored data cases or replace these observations with some function of the limit of detection, which often results in biased estimates. Moreover, parameter estimation can be greatly affected by the presence of influential observations in the data. In this paper we derive local influence diagnostic measures for censored regression models with autoregressive errors of order p (hereafter, AR(p)‐CR models) on the basis of the Q‐function under three useful perturbation schemes. In order to account for censoring in a likelihood‐based estimation procedure for AR(p)‐CR models, we used a stochastic approximation version of the expectation‐maximisation algorithm. The accuracy of the local influence diagnostic measure in detecting influential observations is explored through the analysis of empirical studies. The proposed methods are illustrated using data, from a study of total phosphorus concentration, that contain left‐censored observations. These methods are implemented in the R package ARCensReg.     

A generalized Bayesian nonlinear mixed‐effects regression model for zero‐inflated longitudinal count data in tuberculosis trials

In this paper, we investigate Bayesian generalized nonlinear mixed‐effects (NLME) regression models for zero‐inflated longitudinal count data. The methodology is motivated by and applied to colony forming unit (CFU) counts in extended bactericidal activity tuberculosis (TB) trials. Furthermore, for model comparisons, we present a generalized method for calculating the marginal likelihoods required to determine Bayes factors. A simulation study shows that the proposed zero‐inflated negative binomial regression model has good accuracy, precision, and credibility interval coverage. In contrast, conventional normal NLME regression models applied to log‐transformed count data, which handle zero counts as left censored values, may yield credibility intervals that undercover the true bactericidal activity of anti‐TB drugs. We therefore recommend that zero‐inflated NLME regression models should be fitted to CFU count on the original scale, as an alternative to conventional normal NLME regression models on the logarithmic scale.