Joint mean–covariance model in generalized partially linear varying coefficient models for longitudinal data

In longitudinal data analysis, efficient estimation of regression coefficients requires a correct specification of certain covariance structure, and efficient estimation of covariance matrix requires a correct specification of mean regression model. In this article, we propose a general semiparametric model for the mean and the covariance simultaneously using the modified Cholesky decomposition. A regression spline-based approach within the framework of generalized estimating equations is proposed to estimate the parameters in the mean and the covariance. Under regularity conditions, asymptotic properties of the resulting estimators are established. Extensive simulation is conducted to investigate the performance of the proposed estimator and in the end a real data set is analysed using the proposed approach.     

Estimated estimating equations: semiparametric inference for clustered and longitudinal data

Summary.  We introduce a flexible marginal modelling approach for statistical inference for clustered and longitudinal data under minimal assumptions. This estimated estimating equations approach is semiparametric and the proposed models are fitted by quasi-likelihood regression, where the unknown marginal means are a function of the fixed effects linear predictor with unknown smooth link, and variance–covariance is an unknown smooth function of the marginal means. We propose to estimate the nonparametric link and variance–covariance functions via smoothing methods, whereas the regression parameters are obtained via the estimated estimating equations. These are score equations that contain nonparametric function estimates. The proposed estimated estimating equations approach is motivated by its flexibility and easy implementation. Moreover, if data follow a generalized linear mixed model, with either a specified or an unspecified distribution of random effects and link function, the model proposed emerges as the corresponding marginal (population-average) version and can be used to obtain inference for the fixed effects in the underlying generalized linear mixed model, without the need to specify any other components of this generalized linear mixed model. Among marginal models, the estimated estimating equations approach provides a flexible alternative to modelling with generalized estimating equations. Applications of estimated estimating equations include diagnostics and link selection. The asymptotic distribution of the proposed estimators for the model parameters is derived, enabling statistical inference. Practical illustrations include Poisson modelling of repeated epileptic seizure counts and simulations for clustered binomial responses.     

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.     

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.     

Weighted composite quantile regression method via empirical likelihood for non linear models

In this paper, we investigate empirical likelihood (EL) inferences via weighted composite quantile regression for non linear models. Under regularity conditions, we establish that the proposed empirical log-likelihood ratio is asymptotically chi-squared, and then the confidence intervals for the regression coefficients are constructed. The proposed method avoids estimating the unknown error density function involved in the asymptotic covariance matrix of the estimators. Simulations suggest that the proposed EL procedure is more efficient and robust, and a real data analysis is used to illustrate the performance.     

Efficient estimation in partially linear single‐index models for longitudinal data

In this paper, we consider the estimation of both the parameters and the nonparametric link function in partially linear single‐index models for longitudinal data that may be unbalanced. In particular, a new three‐stage approach is proposed to estimate the nonparametric link function using marginal kernel regression and the parametric components with generalized estimating equations. The resulting estimators properly account for the within‐subject correlation. We show that the parameter estimators are asymptotically semiparametrically efficient. We also show that the asymptotic variance of the link function estimator is minimized when the working error covariance matrices are correctly specified. The new estimators are more efficient than estimators in the existing literature. These asymptotic results are obtained without assuming normality. The finite‐sample performance of the proposed method is demonstrated by simulation studies. In addition, two real‐data examples are analyzed to illustrate the methodology.     

Empirical likelihood for quantile regression models with longitudinal data

We develop two empirical likelihood-based inference procedures for longitudinal data under the framework of quantile regression. The proposed methods avoid estimating the unknown error density function and the intra-subject correlation involved in the asymptotic covariance matrix of the quantile estimators. By appropriately smoothing the quantile score function, the empirical likelihood approach is shown to have a higher-order accuracy through the Bartlett correction. The proposed methods exhibit finite-sample advantages over the normal approximation-based and bootstrap methods in a simulation study and the analysis of a longitudinal ophthalmology data set.     

Rank Regression Analysis of Multivariate Failure Time Data Based on Marginal Linear Models

Abstract.  Multivariate failure time data arises when each study subject can potentially ex-perience several types of failures or recurrences of a certain phenomenon, or when failure times are sampled in clusters. We formulate the marginal distributions of such multivariate data with semiparametric accelerated failure time models (i.e. linear regression models for log-transformed failure times with arbitrary error distributions) while leaving the dependence structures for related failure times completely unspecified. We develop rank-based monotone estimating functions for the regression parameters of these marginal models based on right-censored observations. The estimating equations can be easily solved via linear programming. The resultant estimators are consistent and asymptotically normal. The limiting covariance matrices can be readily estimated by a novel resampling approach, which does not involve non-parametric density estimation or evaluation of numerical derivatives. The proposed estimators represent consistent roots to the potentially non-monotone estimating equations based on weighted log-rank statistics. Simulation studies show that the new inference procedures perform well in small samples. Illustrations with real medical data are provided.     

On repeated measures analysis with misspecified covariance structure

In recent years various sophisticated methods have been developed for the analysis of repeated measures, or longitudinal data. The more traditional approach, based on a normal likelihood function, has been shown to be unsatisfactory, in the sense of yielding asymptotically biased estimates when the covariance structure is misspecified. More recent methodology, based on generalized linear models and quasi-likelihood estimation, has gained widespread acceptance as 'generalized estimating equations'. However, this also has theoretical problems. In this paper a suggestion is made for improving the asymptotic behaviour of estimators by using the older approach, implemented via Gaussian estimation. The resulting estimating equations include the quasi-score function as one component, so the methodology proposed can be viewed as a combination of Gaussian estimation and generalized estimating equations which has a firmer asymptotic basis than either alone has.     

Optimal estimation in functional linear regression for sparse noise‐contaminated data

In this article, we propose a novel approach to fit a functional linear regression in which both the response and the predictor are functions. We consider the case where the response and the predictor processes are both sparsely sampled at random time points and are contaminated with random errors. In addition, the random times are allowed to be different for the measurements of the predictor and the response functions. The aforementioned situation often occurs in longitudinal data settings. To estimate the covariance and the cross‐covariance functions, we use a regularization method over a reproducing kernel Hilbert space. The estimate of the cross‐covariance function is used to obtain estimates of the regression coefficient function and of the functional singular components. We derive the convergence rates of the proposed cross‐covariance, the regression coefficient, and the singular component function estimators. Furthermore, we show that, under some regularity conditions, the estimator of the coefficient function has a minimax optimal rate. We conduct a simulation study and demonstrate merits of the proposed method by comparing it to some other existing methods in the literature. We illustrate the method by an example of an application to a real‐world air quality dataset. The Canadian Journal of Statistics 47: 524–559; 2019 © 2019 Statistical Society of Canada     

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.     

Bayesian modelling of the mean and covariance matrix in normal nonlinear models

An important problem in statistics is the study of longitudinal data taking into account the effect of other explanatory variables such as treatments and time. In this paper, a new Bayesian approach for analysing longitudinal data is proposed. This innovative approach takes into account the possibility of having nonlinear regression structures on the mean and linear regression structures on the variance–covariance matrix of normal observations, and it is based on the modelling strategy suggested by Pourahmadi [M. Pourahmadi, Joint mean-covariance models with applications to longitudinal data: Unconstrained parameterizations, Biometrika, 87 (1999), pp. 667–690.]. We initially extend the classical methodology to accommodate the fitting of nonlinear mean models then we propose our Bayesian approach based on a generalization of the Metropolis–Hastings algorithm of Cepeda [E.C. Cepeda, Variability modeling in generalized linear models, Unpublished Ph.D. Thesis, Mathematics Institute, Universidade Federal do Rio de Janeiro, 2001]. Finally, we illustrate the proposed methodology by analysing one example, the cattle data set, that is used to study cattle growth.     

Marginal Regression of Multivariate Event Times Based on Linear Transformation Models

Multivariate event time data are common in medical studies and have received much attention recently. In such data, each study subject may potentially experience several types of events or recurrences of the same type of event, or event times may be clustered. Marginal distributions are specified for the multivariate event times in multiple events and clustered events data, and for the gap times in recurrent events data, using the semiparametric linear transformation models while leaving the dependence structures for related events unspecified. We propose several estimating equations for simultaneous estimation of the regression parameters and the transformation function. It is shown that the resulting regression estimators are asymptotically normal, with variance–covariance matrix that has a closed form and can be consistently estimated by the usual plug-in method. Simulation studies show that the proposed approach is appropriate for practical use. An application to the well-known bladder cancer tumor recurrences data is also given to illustrate the methodology.     

An additive–multiplicative mean model for panel count data with dependent observation and dropout processes

This paper discusses regression analysis of panel count data with dependent observation and dropout processes. For the problem, a general mean model is presented that can allow both additive and multiplicative effects of covariates on the underlying point process. In addition, the proportional rates model and the accelerated failure time model are employed to describe possible covariate effects on the observation process and the dropout or follow‐up process, respectively. For estimation of regression parameters, some estimating equation‐based procedures are developed and the asymptotic properties of the proposed estimators are established. In addition, a resampling approach is proposed for estimating a covariance matrix of the proposed estimator and a model checking procedure is also provided. Results from an extensive simulation study indicate that the proposed methodology works well for practical situations, and it is applied to a motivating set of real data.     

Model selection and model averaging for semiparametric partially linear models with missing data

We study model selection and model averaging in semiparametric partially linear models with missing responses. An imputation method is used to estimate the linear regression coefficients and the nonparametric function. We show that the corresponding estimators of the linear regression coefficients are asymptotically normal. Then a focused information criterion and frequentist model average estimators are proposed and their theoretical properties are established. Simulation studies are performed to demonstrate the superiority of the proposed methods over the existing strategies in terms of mean squared error and coverage probability. Finally, the approach is applied to a real data case.     

Estimation of the Variance Function in Heteroscedastic Linear Regression Models

Heteroscedasticity generally exists when a linear regression model is applied to analyzing some real-world problems. Therefore, how to accurately estimate the variance functions of the error term in a heteroscedastic linear regression model is of great importance for obtaining efficient estimates of the regression parameters and making valid statistical inferences. A method for estimating the variance function of heteroscedastic linear regression models is proposed in this article based on the variance-reduced local linear smoothing technique. Some simulations and comparisons with other method are conducted to assess the performance of the proposed method. The results demonstrate that the proposed method can accurately estimate the variance functions and therefore produce more efficient estimates of the regression parameters.     

Robust testing with generalized partial linear models for longitudinal data

By approximating the nonparametric component using a regression spline in generalized partial linear models (GPLM), robust generalized estimating equations (GEE), involving bounded score function and leverage-based weighting function, can be used to estimate the regression parameters in GPLM robustly for longitudinal data or clustered data. In this paper, score test statistics are proposed for testing the regression parameters with robustness, and their asymptotic distributions under the null hypothesis and a class of local alternative hypotheses are studied. The proposed score tests reply on the estimation of a smaller model without the testing parameters involved, and perform well in the simulation studies and real data analysis conducted in this paper.     

Estimation of patterned covariance in the multivariate linear models: an outer product least-squares approach

In this article, we present a framework of estimating patterned covariance of interest in the multivariate linear models. The main idea in it is to estimate a patterned covariance by minimizing a trace distance function between outer product of residuals and its expected value. The proposed framework can provide us explicit estimators, called outer product least-squares estimators, for parameters in the patterned covariance of the multivariate linear model without or with restrictions on regression coefficients. The outer product least-squares estimators enjoy the desired properties in finite and large samples, including unbiasedness, invariance, consistency and asymptotic normality. We still apply the framework to three special situations where their patterned covariances are the uniform correlation, a generalized uniform correlation and a general q-dependence structure, respectively. Simulation studies for three special cases illustrate that the proposed method is a competent alternative of the maximum likelihood method in finite size samples.     

Semiparametric statistical inferences for longitudinal data with nonparametric covariance modelling

In this paper, semiparametric modelling for longitudinal data with an unstructured error process is considered. We propose a partially linear additive regression model for longitudinal data in which within-subject variances and covariances of the error process are described by unknown univariate and bivariate functions, respectively. We provide an estimating approach in which polynomial splines are used to approximate the additive nonparametric components and the within-subject variance and covariance functions are estimated nonparametrically. Both the asymptotic normality of the resulting parametric component estimators and optimal convergence rate of the resulting nonparametric component estimators are established. In addition, we develop a variable selection procedure to identify significant parametric and nonparametric components simultaneously. We show that the proposed SCAD penalty-based estimators of non-zero components have an oracle property. Some simulation studies are conducted to examine the finite-sample performance of the proposed estimation and variable selection procedures. A real data set is also analysed to demonstrate the usefulness of the proposed method.     

Population-averaged and subjectspecific approaches for clustered categorical data

Modeling clustered categorical data based on extensions of generalized linear model theory has received much attention in recent years. The rapidly increasing number of approaches suitable for categorical data in which clusters are uncorrelated, but correlations exist within a cluster, has caused uncertainty among applied scientists as to their respective merits and demerits. Upon centering estimation around solving an unbiased estimating function for mean parameters and estimation of covariance parameters describing within-cluster or among-cluster heterogeneity, many approaches can easily be related. This contribution describes a series of algorithms and their implementation in detail, based on a classification of inferential procedures for clustered data.