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.     

Comparing crossing hazard rate functions by joint modelling of survival and longitudinal data

Abstract

It is one of the important issues in survival analysis to compare two hazard rate functions to evaluate treatment effect. It is quite common that the two hazard rate functions cross each other at one or more unknown time points, representing temporal changes of the treatment effect. In certain applications, besides survival data, we also have related longitudinal data available regarding some time-dependent covariates. In such cases, a joint model that accommodates both types of data can allow us to infer the association between the survival and longitudinal data and to assess the treatment effect better. In this paper, we propose a modelling approach for comparing two crossing hazard rate functions by joint modelling survival and longitudinal data. Maximum likelihood estimation is used in estimating the parameters of the proposed joint model using the EM algorithm. Asymptotic properties of the maximum likelihood estimators are studied. To illustrate the virtues of the proposed method, we compare the performance of the proposed method with several existing methods in a simulation study. Our proposed method is also demonstrated using a real dataset obtained from an HIV clinical trial.     

Semiparametric Regression Analysis of Longitudinal Skewed Data

In this paper, we develop a semiparametric regression model for longitudinal skewed data. In the new model, we allow the transformation function and the baseline function to be unknown. The proposed model can provide a much broader class of models than the existing additive and multiplicative models. Our estimators for regression parameters, transformation function and baseline function are asymptotically normal. Particularly, the estimator for the transformation function converges to its true value at the rate n ^{? 1 ∕ 2}, the convergence rate that one could expect for a parametric model. In simulation studies, we demonstrate that the proposed semiparametric method is robust with little loss of efficiency. Finally, we apply the new method to a study on longitudinal health care costs.     

Adaptive robust estimation in joint mean–covariance regression model for bivariate longitudinal data

The estimation of the covariance matrix is important in the analysis of bivariate longitudinal data. A good estimator for the covariance matrix can improve the efficiency of the estimators of the mean regression coefficients. Furthermore, the covariance estimation itself is also of interest, but it is a challenging job to model the covariance matrix of bivariate longitudinal data due to the complex structure and positive definite constraint. In addition, most of existing approaches are based on the maximum likelihood, which is very sensitive to outliers or heavy-tail error distributions. In this article, an adaptive robust estimation method is proposed for bivariate longitudinal data. Unlike the existing likelihood-based methods, the proposed method can adapt to different error distributions. Specifically, at first, we utilize the modified Cholesky block decomposition to parameterize the covariance matrices. Secondly, we apply the bounded Huber's score function to develop a set of robust generalized estimating equations to estimate the parameters both in the mean and the covariance models simultaneously. A data-driven approach is presented to select the parameter c in the Huber's score function, which can ensure that the proposed method is robust and efficient. A simulation study and a real data analysis are conducted to illustrate the robustness and efficiency of the proposed approach.     

A practical extension of the generalized estimating equation approach for longitudinal data

Liang and Zeger (1986) proposed an extension of generalized linear models to the analysis of longitudinal data. In their formulation, a common dispersion parameter assumption across observation times is required. However, this assumption is not expected to hold in most situations. Park (1993) proposed a simple extension of Liang and Zeger's formulation to allow for different dispersion parameters for each time point. The proposed model is easy to apply without heavy computations and useful to handle the cases when variations in over-dispersion over time exist. In this paper, we focus on evaluating the effect of additional dispersion parameters on the estimators of model parameters. Through a Monte Carlo simulation study, efficiency of Park's method is compared with the Liang and Zeger's method.     

Marginal Projected Multivariate Linear Models for Clustered Angular Data

Among the diverse frameworks that have been proposed for regression analysis of angular data, the projected multivariate linear model provides a particularly appealing and tractable methodology. In this model, the observed directional responses are assumed to correspond to the angles formed by latent bivariate normal random vectors that are assumed to depend upon covariates through a linear model. This implies an angular normal distribution for the observed angles, and incorporates a regression structure through a familiar and convenient relationship. In this paper we extend this methodology to accommodate clustered data (e.g., longitudinal or repeated measures data) by formulating a marginal version of the model and basing estimation on an EM‐like algorithm in which correlation among within‐cluster responses is taken into account by incorporating a working correlation matrix into the M step. A sandwich estimator is used for the parameter estimates’ covariance matrix. The methodology is motivated and illustrated using an example involving clustered measurements of microbril angle on loblolly pine (Pinus taeda L.) Simulation studies are presented that evaluate the finite sample properties of the proposed fitting method. In addition, the relationship between within‐cluster correlation on the latent Euclidean vectors and the corresponding correlation structure for the observed angles is explored.     

Robust estimation of covariance parameters in partial linear model for longitudinal data

For longitudinal data, the within-subject dependence structure and covariance parameters may be of practical and theoretical interests. The estimation of covariance parameters has received much attention and been studied mainly in the framework of generalized estimating equations (GEEs). The GEEs method, however, is sensitive to outliers. In this paper, an alternative set of robust generalized estimating equations for both the mean and covariance parameters are proposed in the partial linear model for longitudinal data. The asymptotic properties of the proposed estimators of regression parameters, non-parametric function and covariance parameters are obtained. Simulation studies are conducted to evaluate the performance of the proposed estimators under different contaminations. The proposed method is illustrated with a real data analysis.     

Jointly modeling skew longitudinal survival data with missingness and mismeasured covariates

Jointly modeling longitudinal and survival data has been an active research area. Most researches focus on improving the estimating efficiency but ignore many data features frequently encountered in practice. In the current study, we develop the joint models that concurrently accounting for longitudinal and survival data with multiple features. Specifically, the proposed model handles skewness, missingness and measurement errors in covariates which are typically observed in the collection of longitudinal survival data from many studies. We employ a Bayesian inferential method to make inference on the proposed model. We applied the proposed model to an real data study. A few alternative models under different conditions are compared. We conduct extensive simulations in order to evaluate how the method works.     

A protective estimator for longitudinal binary data subject to non-ignorable non-monotone missingness

Summary.  In longitudinal studies missing data are the rule not the exception. We consider the analysis of longitudinal binary data with non-monotone missingness that is thought to be non-ignorable. In this setting a full likelihood approach is complicated algebraically and can be computationally prohibitive when there are many measurement occasions. We propose a 'protective' estimator that assumes that the probability that a response is missing at any occasion depends, in a completely unspecified way, on the value of that variable alone. Relying on this 'protectiveness' assumption, we describe a pseudolikelihood estimator of the regression parameters under non-ignorable missingness, without having to model the missing data mechanism directly. The method proposed is applied to CD4 cell count data from two longitudinal clinical trials of patients infected with the human immunodeficiency virus.     

Data-driven sensitivity analysis to detect missing data mechanism with applications to structural equation modelling

Missing data are a common problem in almost all areas of empirical research. Ignoring the missing data mechanism, especially when data are missing not at random (MNAR), can result in biased and/or inefficient inference. Because MNAR mechanism is not verifiable based on the observed data, sensitivity analysis is often used to assess it. Current sensitivity analysis methods primarily assume a model for the response mechanism in conjunction with a measurement model and examine sensitivity to missing data mechanism via the parameters of the response model. Recently, Jamshidian and Mata (Post-modelling sensitivity analysis to detect the effect of missing data mechanism, Multivariate Behav. Res. 43 (2008), pp. 432–452) introduced a new method of sensitivity analysis that does not require the difficult task of modelling the missing data mechanism. In this method, a single measurement model is fitted to all of the data and to a sub-sample of the data. Discrepancy in the parameter estimates obtained from the the two data sets is used as a measure of sensitivity to missing data mechanism. Jamshidian and Mata describe their method mainly in the context of detecting data that are missing completely at random (MCAR). They used a bootstrap type method, that relies on heuristic input from the researcher, to test for the discrepancy of the parameter estimates. Instead of using bootstrap, the current article obtains confidence interval for parameter differences on two samples based on an asymptotic approximation. Because it does not use bootstrap, the developed procedure avoids likely convergence problems with the bootstrap methods. It does not require heuristic input from the researcher and can be readily implemented in statistical software. The article also discusses methods of obtaining sub-samples that may be used to test missing at random in addition to MCAR. An application of the developed procedure to a real data set, from the first wave of an ongoing longitudinal study on aging, is presented. Simulation studies are performed as well, using two methods of missing data generation, which show promise for the proposed sensitivity method. One method of missing data generation is also new and interesting in its own right.     

Penalized spline joint models for longitudinal and time-to-event data

The joint models for longitudinal data and time-to-event data have recently received numerous attention in clinical and epidemiologic studies. Our interest is in modeling the relationship between event time outcomes and internal time-dependent covariates. In practice, the longitudinal responses often show non linear and fluctuated curves. Therefore, the main aim of this paper is to use penalized splines with a truncated polynomial basis to parameterize the non linear longitudinal process. Then, the linear mixed-effects model is applied to subject-specific curves and to control the smoothing. The association between the dropout process and longitudinal outcomes is modeled through a proportional hazard model. Two types of baseline risk functions are considered, namely a Gompertz distribution and a piecewise constant model. The resulting models are referred to as penalized spline joint models; an extension of the standard joint models. The expectation conditional maximization (ECM) algorithm is applied to estimate the parameters in the proposed models. To validate the proposed algorithm, extensive simulation studies were implemented followed by a case study. In summary, the penalized spline joint models provide a new approach for joint models that have improved the existing standard joint models.     

Weak Instrumental Variables Models for Longitudinal Data

This article considers the estimation and testing of a within-group two-stage least squares (TSLS) estimator for instruments with varying degrees of weakness in a longitudinal (panel) data model. We show that adding the repeated cross-sectional information into a regression model can improve the estimation in weak instruments. Moreover, the consistency and limiting distribution of the TSLS estimator are established when both N and T tend to infinity. Some asymptotically pivotal tests are extended to a longitudinal data model and their asymptotic properties are examined. A Monte Carlo experiment is conducted to evaluate the finite sample performance of the proposed estimators.     

COVARIATE-ADJUSTED REGRESSION FOR LONGITUDINAL DATA INCORPORATING CORRELATION BETWEEN REPEATED MEASUREMENTS

We propose an estimation method that incorporates the correlation/covariance structure between repeated measurements in covariate-adjusted regression models for distorted longitudinal data. In this distorted data setting, neither the longitudinal response nor (possibly time-varying) predictors are directly observable. The unobserved response and predictors are assumed to be distorted/contaminated by unknown functions of a common observable confounder. The proposed estimation methodology adjusts for the distortion effects both in estimation of the covariance structure and in the regression parameters using generalized least squares. The finite-sample performance of the proposed estimators is studied numerically by means of simulations. The consistency and convergence rates of the proposed estimators are also established. The proposed method is illustrated with an application to data from a longitudinal study of cognitive and social development in children.     

A semiparametric stochastic mixed effects model for bivariate cyclic longitudinal data

We propose a flexible semiparametric stochastic mixed effects model for bivariate cyclic longitudinal data. The model can handle either single cycle or, more generally, multiple consecutive cycle data. The approach models the mean of responses by parametric fixed effects and a smooth nonparametric function for the underlying time effects, and the relationship across the bivariate responses by a bivariate Gaussian random field and a joint distribution of random effects. The proposed model not only can model complicated individual profiles, but also allows for more flexible within-subject and between-response correlations. The fixed effects regression coefficients and the nonparametric time functions are estimated using maximum penalized likelihood, where the resulting estimator for the nonparametric time function is a cubic smoothing spline. The smoothing parameters and variance components are estimated simultaneously using restricted maximum likelihood. Simulation results show that the parameter estimates are close to the true values. The fit of the proposed model on a real bivariate longitudinal dataset of pre-menopausal women also performs well, both for a single cycle analysis and for a multiple consecutive cycle analysis. The Canadian Journal of Statistics 48: 471–498; 2020 © 2020 Statistical Society of Canada     

Regression Analysis of Longitudinal Data with Time‐Dependent Covariates and Informative Observation Times

Abstract. Longitudinal data frequently occur in many studies, and longitudinal responses may be correlated with observation times. In this paper, we propose a new joint modelling for the analysis of longitudinal data with time‐dependent covariates and possibly informative observation times via two latent variables. For inference about regression parameters, estimating equation approaches are developed and asymptotic properties of the proposed estimators are established. In addition, a lack‐of‐fit test is presented for assessing the adequacy of the model. The proposed method performs well in finite‐sample simulation studies, and an application to a bladder tumour study is provided.     

A generalized Q–Q plot for longitudinal data

Most biomedical research is carried out using longitudinal studies. The method of generalized estimating equations (GEEs) introduced by Liang and Zeger [Longitudinal data analysis using generalized linear models, Biometrika 73 (1986), pp. 13–22] and Zeger and Liang [Longitudinal data analysis for discrete and continuous outcomes, Biometrics 42 (1986), pp. 121–130] has become a standard method for analyzing non-normal longitudinal data. Since then, a large variety of GEEs have been proposed. However, the model diagnostic problem has not been explored intensively. Oh et al. [Modeldiagnostic plots for repeated measures data using the generalized estimating equations approach, Comput. Statist. Data Anal. 53 (2008), pp. 222–232] proposed residual plots based on the quantile–quantile (Q–Q) plots of the χ²-distribution for repeated-measures data using the GEE methodology. They considered the Pearson, Anscombe and deviance residuals. In this work, we propose to extend this graphical diagnostic using a generalized residual. A simulation study is presented as well as two examples illustrating the proposed generalized Q–Q plots.     

Bayesian Lasso-mixed quantile regression

In this paper, we discuss the regularization in linear-mixed quantile regression. A hierarchical Bayesian model is used to shrink the fixed and random effects towards the common population values by introducing an l₁ penalty in the mixed quantile regression check function. A Gibbs sampler is developed to simulate the parameters from the posterior distributions. Through simulation studies and analysis of an age-related macular degeneration (ARMD) data, we assess the performance of the proposed method. The simulation studies and the ARMD data analysis indicate that the proposed method performs well in comparison with the other approaches.     

Semiparametric Analysis of Truncated Data

Randomly truncated data are frequently encountered in many studies where truncation arises as a result of the sampling design. In the literature, nonparametric and semiparametric methods have been proposed to estimate parameters in one-sample models. This paper considers a semiparametric model and develops an efficient method for the estimation of unknown parameters. The model assumes that K populations have a common probability distribution but the populations are observed subject to different truncation mechanisms. Semiparametric likelihood estimation is studied and the corresponding inferences are derived for both parametric and nonparametric components in the model. The method can also be applied to two-sample problems to test the difference of lifetime distributions. Simulation results and a real data analysis are presented to illustrate the methods.     

A modified two-stage approach for joint modelling of longitudinal and time-to-event data

Joint models for longitudinal and time-to-event data have been applied in many different fields of statistics and clinical studies. However, the main difficulty these models have to face with is the computational problem. The requirement for numerical integration becomes severe when the dimension of random effects increases. In this paper, a modified two-stage approach has been proposed to estimate the parameters in joint models. In particular, in the first stage, the linear mixed-effects models and best linear unbiased predictorsare applied to estimate parameters in the longitudinal submodel. In the second stage, an approximation of the fully joint log-likelihood is proposed using the estimated the values of these parameters from the longitudinal submodel. Survival parameters are estimated bymaximizing the approximation of the fully joint log-likelihood. Simulation studies show that the approach performs well, especially when the dimension of random effects increases. Finally, we implement this approach on AIDS data.     

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.