Empirical likelihood for varying-coefficient semiparametric mixed-effects errors-in-variables models with longitudinal data

In this paper, the empirical likelihood inferences for varying-coefficient semiparametric mixed-effects errors-in-variables models with longitudinal data are investigated. We construct the empirical log-likelihood ratio function for the fixed-effects parameters and the mean parameters of random-effects. The empirical log-likelihood ratio at the true parameters is proven to be asymptotically $\chi ^2_{q+r}$ , where $q$ and $r$ are dimensions of the fixed and random effects respectively, and the corresponding confidence regions for them are then constructed. We also obtain the maximum empirical likelihood estimator of the parameters of interest, and prove it is the asymptotically normal under some suitable conditions. A simulation study and a real data application are undertaken to assess the finite sample performance of the proposed method.     

Two-step and likelihood methods for joint models of longitudinal and survival data

We compare the commonly used two-step methods and joint likelihood method for joint models of longitudinal and survival data via extensive simulations. The longitudinal models include LME, GLMM, and NLME models, and the survival models include Cox models and AFT models. We find that the full likelihood method outperforms the two-step methods for various joint models, but it can be computationally challenging when the dimension of the random effects in the longitudinal model is not small. We thus propose an approximate joint likelihood method which is computationally efficient. We find that the proposed approximation method performs well in the joint model context, and it performs better for more “continuous” longitudinal data. Finally, a real AIDS data example shows that patients with higher initial viral load or lower initial CD4 are more likely to drop out earlier during an anti-HIV treatment.     

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.     

Weighted empirical likelihood for generalized linear models with longitudinal data

In this paper, we introduce the empirical likelihood (EL) method to longitudinal studies. By considering the dependence within subjects in the auxiliary random vectors, we propose a new weighted empirical likelihood (WEL) inference for generalized linear models with longitudinal data. We show that the weighted empirical likelihood ratio always follows an asymptotically standard chi-squared distribution no matter which working weight matrix that we have chosen, but a well chosen working weight matrix can improve the efficiency of statistical inference. Simulations are conducted to demonstrate the accuracy and efficiency of our proposed WEL method, and a real data set is used to illustrate the proposed method.     

Modification of GEE1 and linear mixed-effects models for heteroscedastic longitudinal Gaussian data

A characterization of GLMs is given. Modification of the Gaussian GEE1, modified GEE1, was applied to heteroscedastic longitudinal data, to which linear mixed-effects models are usually applied. The modified GEE1 models scale multivariate data to homoscedastic data maintaining the correlation structure and apply usual GEE1 to homoscedastic data, which needs no-diagnostics for diagonal variances. Relationships among multivariate linear regression methods, ordinary/generalized LS, naïve/modified GEE1, and linear mixed-effects models were discussed. An application showed modified GEE1 gave most efficient parameter estimation. Correct specification of the main diagonals of heteroscedastic data variance appears to be more important for efficient mean parameter estimation.     

Profile maximal likelihood estimation for non linear mixed models with longitudinal data

In this article, the profile maximal likelihood estimate (PMLE) is proposed for non linear mixed models (NLMMs) with longitudinal data where the variance components are estimated by the expectation-maximization (EM) algorithm. Strong consistency and the asymptotic normality of the estimators are derived. A simulation study is conducted where the performance of the PLME and the Fishing scoring estimate (FSE) in literatures are compared. Moreover, a real data is also analyzed to investigate the empirical performance of the procedure.     

Bayesian estimation and influence diagnostics of generalized partially linear mixed-effects models for longitudinal data

This paper develops a Bayesian approach to obtain the joint estimates of unknown parameters, nonparametric functions and random effects in generalized partially linear mixed models (GPLMMs), and presents three case deletion influence measures to identify influential observations based on the φ-divergence, Cook's posterior mean distance and Cook's posterior mode distance of parameters. Fisher's iterative scoring algorithm is developed to evaluate the posterior modes of parameters in GPLMMs. The first-order approximation to Cook's posterior mode distance is presented. The computationally feasible formulae for the φ-divergence diagnostic and Cook's posterior mean distance are given. Several simulation studies and an example are presented to illustrate our proposed methodologies.     

Quantile regression-based Bayesian semiparametric mixed-effects models for longitudinal data with non-normal,missing and mismeasured covariate

Quantile regression (QR) models have received increasing attention recently for longitudinal data analysis. When continuous responses appear non-centrality due to outliers and/or heavy-tails, commonly used mean regression models may fail to produce efficient estimators, whereas QR models may perform satisfactorily. In addition, longitudinal outcomes are often measured with non-normality, substantial errors and non-ignorable missing values. When carrying out statistical inference in such data setting, it is important to account for the simultaneous treatment of these data features; otherwise, erroneous or even misleading results may be produced. In the literature, there has been considerable interest in accommodating either one or some of these data features. However, there is relatively little work concerning all of them simultaneously. There is a need to fill up this gap as longitudinal data do often have these characteristics. Inferential procedure can be complicated dramatically when these data features arise in longitudinal response and covariate outcomes. In this article, our objective is to develop QR-based Bayesian semiparametric mixed-effects models to address the simultaneous impact of these multiple data features. The proposed models and method are applied to analyse a longitudinal data set arising from an AIDS clinical study. Simulation studies are conducted to assess the performance of the proposed method under various scenarios.     

The nonparametric maximum likelihood estimator for middle-censored data

In this note, we consider data subjected to middle censoring where the variable of interest becomes unobservable when it falls within an interval of censorship. We demonstrate that the nonparametric maximum likelihood estimator (NPMLE) of distribution function can be obtained by using Turnbull's (1976) EM algorithm or self-consistent estimating equation (Jammalamadaka and Mangalam, 2003) with an initial estimator which puts mass only on the innermost intervals. The consistency of the NPMLE can be established based on the asymptotic properties of self-consistent estimators (SCE) with mixed interval-censored data ( [Yu et al., 2000] and [Yu et al., 2001]).     

Efficient estimation of variance components in nonparametric mixed-effects models with large samples

Linear mixed-effects (LME) regression models are a popular approach for analyzing correlated data. Nonparametric extensions of the LME regression model have been proposed, but the heavy computational cost makes these extensions impractical for analyzing large samples. In particular, simultaneous estimation of the variance components and smoothing parameters poses a computational challenge when working with large samples. To overcome this computational burden, we propose a two-stage estimation procedure for fitting nonparametric mixed-effects regression models. Our results reveal that, compared to currently popular approaches, our two-stage approach produces more accurate estimates that can be computed in a fraction of the time.     

Selection of linear mixed-effects models for clustered data

We consider model selection for linear mixed-effects models with clustered structure, where conditional Kullback–Leibler (CKL) loss is applied to measure the efficiency of the selection. We estimate the CKL loss by substituting the empirical best linear unbiased predictors (EBLUPs) into random effects with model parameters estimated by maximum likelihood. Although the BLUP approach is commonly used in predicting random effects and future observations, selecting random effects to achieve asymptotic loss efficiency concerning CKL loss is challenging and has not been well studied. In this paper, we propose addressing this difficulty using a conditional generalized information criterion (CGIC) with two tuning parameters. We further consider a challenging but practically relevant situation where the number, $m$, of clusters does not go to infinity with the sample size. Hence the random-effects variances are not consistently estimable. We show that via a novel decomposition of the CKL risk, the CGIC achieves consistency and asymptotic loss efficiency, whether $m$ is fixed or increases to infinity with the sample size. We also conduct numerical experiments to illustrate the theoretical findings.     

Semiparametric mixed-effects models for clustered doubly censored data

The Cox proportional frailty model with a random effect has been proposed for the analysis of right-censored data which consist of a large number of small clusters of correlated failure time observations. For right-censored data, Cai et al. [3] proposed a class of semiparametric mixed-effects models which provides useful alternatives to the Cox model. We demonstrate that the approach of Cai et al. [3] can be used to analyze clustered doubly censored data when both left- and right-censoring variables are always observed. The asymptotic properties of the proposed estimator are derived. A simulation study is conducted to investigate the performance of the proposed estimator.     

Hybrid pairwise‐likelihood estimation methods for incomplete longitudinal binary data

In longitudinal data, missing observations occur commonly with incomplete responses and covariates. Missing data can have a ‘missing not at random’ mechanism, a non‐monotone missing pattern, and moreover response and covariates can be missing not simultaneously. To avoid complexities in both modelling and computation, a two‐stage estimation method and a pairwise‐likelihood method are proposed. The two‐stage estimation method enjoys simplicities in computation, but incurs more severe efficiency loss. On the other hand, the pairwise approach leads to estimators with better efficiency, but can be cumbersome in computation. In this paper, we develop a compromise method using a hybrid pairwise‐likelihood framework. Our proposed approach has better efficiency than the two‐stage method, but its computational cost is still reasonable compared to the pairwise approach. The performance of the methods is evaluated empirically by means of simulation studies. Our methods are used to analyse longitudinal data obtained from the National Population Health Study.     

Empirical likelihood confidence intervals for nonparametric functional data analysis

We consider the problem of constructing confidence intervals for nonparametric functional data analysis using empirical likelihood. In this doubly infinite-dimensional context, we demonstrate the Wilk's phenomenon and propose a bias-corrected construction that requires neither undersmoothing nor direct bias estimation. We also extend our results to partially linear regression models involving functional data. Our numerical results demonstrate improved performance of the empirical likelihood methods over normal approximation-based methods.     

Empirical likelihood inference in mixture of semiparametric varying-coefficient models for longitudinal data with non-ignorable dropout

In this paper, empirical likelihood inference in mixture of semiparametric varying-coefficient models for longitudinal data with non-ignorable dropout is investigated. We estimate the non-parametric function based on the estimating equations and the local linear profile-kernel method. An empirical log-likelihood ratio statistic for parametric components is proposed to construct confidence regions and is shown to be an asymptotically chi-squared distribution. The non-parametric version of Wilk's theorem is also derived. A simulation study is undertaken to illustrate the finite sample performance of the proposed method.     

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.     

Some asymptotic results for semiparametric nonlinear mixed-effects models with incomplete data

In modeling complex longitudinal data, semiparametric nonlinear mixed-effects (SNLME) models are very flexible and useful. Covariates are often introduced in the models to partially explain the inter-individual variations. In practice, data are often incomplete in the sense that there are often measurement errors and missing data in longitudinal studies. The likelihood method is a standard approach for inference for these models but it can be computationally very challenging, so computationally efficient approximate methods are quite valuable. However, the performance of these approximate methods is often based on limited simulation studies, and theoretical results are unavailable for many approximate methods. In this article, we consider a computationally efficient approximate method for a class of SNLME models with incomplete data and investigate its theoretical properties. We show that the estimates based on the approximate method are consistent and asymptotically normally distributed.     

Two-step and likelihood methods for HIV viral dynamic models with covariate measurement errors and missing data

HIV viral dynamic models have received much attention in the literature. Long-term viral dynamics may be modelled by semiparametric nonlinear mixed-effect models, which incorporate large variation between subjects and autocorrelation within subjects and are flexible in modelling complex viral load trajectories. Time-dependent covariates may be introduced in the dynamic models to partially explain the between-individual variations. In the presence of measurement errors and missing data in time-dependent covariates, we show that the commonly used two-step method may give approximately unbiased estimates but may under-estimate standard errors. We propose a two-stage bootstrap method to adjust the standard errors in the two-step method and a likelihood method.     

Inference methods for saturated models in longitudinal clinical trials with incomplete binary data

In the longitudinal studies with binary response, it is often of interest to estimate the percentage of positive responses at each time point and the percentage of having at least one positive response by each time point. When missing data exist, the conventional method based on observed percentages could result in erroneous estimates. This study demonstrates two methods of using expectation-maximization (EM) and data augmentation (DA) algorithms in the estimation of the marginal and cumulative probabilities for incomplete longitudinal binary response data. Both methods provide unbiased estimates when the missingness mechanism is missing at random (MAR) assumption. Sensitivity analyses have been performed for cases when the MAR assumption is in question.