A NONPARAMETRIC MIXED‐EFFECTS MODEL FOR CANCER MORTALITY

There are several ways to handle within‐subject correlations with a longitudinal discrete outcome, such as mortality. The most frequently used models are either marginal or random‐effects types. This paper deals with a random‐effects‐based approach. We propose a nonparametric regression model having time‐varying mixed effects for longitudinal cancer mortality data. The time‐varying mixed effects in the proposed model are estimated by combining kernel‐smoothing techniques and a growth‐curve model. As an illustration based on real data, we apply the proposed method to a set of prefecture‐specific data on mortality from large‐bowel cancer in Japan.     

A new orthogonality-based estimation for varying-coefficient partially linear models

Varying coefficient partially linear models are usually used for longitudinal data analysis, and an interest is mainly to improve efficiency of regression coefficients. By the orthogonality estimation technology and the quadratic inference function method, we propose a new orthogonality-based estimation method to estimate parameter and nonparametric components in varying coefficient partially linear models with longitudinal data. The proposed procedure can separately estimate the parametric and nonparametric components, and the resulting estimators do not affect each other. Under some mild conditions, we establish some asymptotic properties of the resulting estimators. Furthermore, the finite sample performance of the proposed procedure is assessed by some simulation experiments.     

纵向部分线性变系数EV模型的估计

纵向数据是随着时间变化对个体进行重复观测而得到的一种相关性数据,广泛出现在诸多科学研究领域。在对个体进行观测时,测量误差不可避免,忽略测量误差往往会导致有偏估计。本文利用二次推断函数方法研究关于纵向数据的参数部分和非参数部分协变量均含有测量误差的部分线性变系数测量误差(errors-in-variables, EV)模型的估计问题。利用B样条逼近模型中的未知系数函数,构造关于回归参数和B样条系数的偏差修正的二次推断函数以处理个体内相关性和测量误差,得到回归参数和变系数的偏差修正的二次推断函数估计,然后证明了估计方法和结果的渐近性质。数值模拟和实例数据分析结果显示本文提出的方法具有一定的实用价值。     

Robust estimation and model identification for longitudinal data varying-coefficient model

It is well known that M-estimation is a widely used method for robust statistical inference and the varying coefficient models have been widely applied in many scientific areas. In this paper, we consider M-estimation and model identification of bivariate varying coefficient models for longitudinal data. We make use of bivariate tensor-product B-splines as an approximation of the function and consider M-type regression splines by minimizing the objective convex function. Mean and median regressions are included in this class. Moreover, with a double smoothly clipped absolute deviation (SCAD) penalization, we study the problem of simultaneous structure identification and estimation. Under approximate conditions, we show that the proposed procedure possesses the oracle property in the sense that it is as efficient as the estimator when the true model is known prior to statistical analysis. Simulation studies are carried out to demonstrate the methodological power of the proposed methods with finite samples. The proposed methodology is illustrated with an analysis of a real data example.     

Functional Modelling and Classification of Longitudinal Data*

Abstract. We review and extend some statistical tools that have proved useful for analysing functional data. Functional data analysis primarily is designed for the analysis of random trajectories and infinite‐dimensional data, and there exists a need for the development of adequate statistical estimation and inference techniques. While this field is in flux, some methods have proven useful. These include warping methods, functional principal component analysis, and conditioning under Gaussian assumptions for the case of sparse data. The latter is a recent development that may provide a bridge between functional and more classical longitudinal data analysis. Besides presenting a brief review of functional principal components and functional regression, we develop some concepts for estimating functional principal component scores in the sparse situation. An extension of the so‐called generalized functional linear model to the case of sparse longitudinal predictors is proposed. This extension includes functional binary regression models for longitudinal data and is illustrated with data on primary biliary cirrhosis.     

Recent History Functional Linear Models for Sparse Longitudinal Data

We consider the recent history functional linear models, relating a longitudinal response to a longitudinal predictor where the predictor process only in a sliding window into the recent past has an effect on the response value at the current time. We propose an estimation procedure for recent history functional linear models that is geared towards sparse longitudinal data, where the observation times across subjects are irregular and total number of measurements per subject is small. The proposed estimation procedure builds upon recent developments in literature for estimation of functional linear models with sparse data and utilizes connections between the recent history functional linear models and varying coefficient models. We establish uniform consistency of the proposed estimators, propose prediction of the response trajectories and derive their asymptotic distribution leading to asymptotic point-wise confidence bands. We include a real data application and simulation studies to demonstrate the efficacy of the proposed methodology.     

Analysis of generalized semiparametric mixed varying‐coefficients models for longitudinal data

The generalized semiparametric mixed varying‐coefficient effects model for longitudinal data can accommodate a variety of link functions and flexibly model different types of covariate effects, including time‐constant, time‐varying and covariate‐varying effects. The time‐varying effects are unspecified functions of time and the covariate‐varying effects are nonparametric functions of a possibly time‐dependent exposure variable. A semiparametric estimation procedure is developed that uses local linear smoothing and profile weighted least squares, which requires smoothing in the two different and yet connected domains of time and the time‐dependent exposure variable. The asymptotic properties of the estimators of both nonparametric and parametric effects are investigated. In addition, hypothesis testing procedures are developed to examine the covariate effects. The finite‐sample properties of the proposed estimators and testing procedures are examined through simulations, indicating satisfactory performances. The proposed methods are applied to analyze the AIDS Clinical Trial Group 244 clinical trial to investigate the effects of antiretroviral treatment switching in HIV‐infected patients before and after developing the T215Y antiretroviral drug resistance mutation. The Canadian Journal of Statistics 47: 352–373; 2019 © 2019 Statistical Society of Canada     

Robust transformation mixed‐effects models for longitudinal continuous proportional data

The authors propose a robust transformation linear mixed‐effects model for longitudinal continuous proportional data when some of the subjects exhibit outlying trajectories over time. It becomes troublesome when including or excluding such subjects in the data analysis results in different statistical conclusions. To robustify the longitudinal analysis using the mixed‐effects model, they utilize the multivariate t distribution for random effects or/and error terms. Estimation and inference in the proposed model are established and illustrated by a real data example from an ophthalmology study. Simulation studies show a substantial robustness gain by the proposed model in comparison to the mixed‐effects model based on Aitchison's logit‐normal approach. As a result, the data analysis benefits from the robustness of making consistent conclusions in the presence of influential outliers. The Canadian Journal of Statistics © 2009 Statistical Society of Canada     

Statistical Inference and Applications of Mixture of Varying Coefficient Models

In this paper, we consider a new mixture of varying coefficient models, in which each mixture component follows a varying coefficient model and the mixing proportions and dispersion parameters are also allowed to be unknown smooth functions. We systematically study the identifiability, estimation and inference for the new mixture model. The proposed new mixture model is rather general, encompassing many mixture models as its special cases such as mixtures of linear regression models, mixtures of generalized linear models, mixtures of partially linear models and mixtures of generalized additive models, some of which are new mixture models by themselves and have not been investigated before. The new mixture of varying coefficient model is shown to be identifiable under mild conditions. We develop a local likelihood procedure and a modified expectation–maximization algorithm for the estimation of the unknown non‐parametric functions. Asymptotic normality is established for the proposed estimator. A generalized likelihood ratio test is further developed for testing whether some of the unknown functions are constants. We derive the asymptotic distribution of the proposed generalized likelihood ratio test statistics and prove that the Wilks phenomenon holds. The proposed methodology is illustrated by Monte Carlo simulations and an analysis of a CO₂‐GDP data set.     

Varying coefficient transformation cure models for failure time data

This article discusses regression analysis of right-censored failure time data where there may exist a cured subgroup, and also covariate effects may be varying with time, a phenomena that often occurs in many medical studies. To address the problem, we discuss a class of varying coefficient transformation models along with a logistic model for the cured subgroup. For inference, a sieve maximum likelihood approach is developed with the use of spline functions, and the asymptotic properties of the proposed estimators are established. The proposed method can be easily implemented, and the conducted simulation study suggests that the proposed method works well in practical situations. An illustrative example is provided.

     

Inference in Semi‐Parametric Dynamic Models for Repeated Count Data

This paper deals with a longitudinal semi‐parametric regression model in a generalised linear model setup for repeated count data collected from a large number of independent individuals. To accommodate the longitudinal correlations, we consider a dynamic model for repeated counts which has decaying auto‐correlations as the time lag increases between the repeated responses. The semi‐parametric regression function involved in the model contains a specified regression function in some suitable time‐dependent covariates and a non‐parametric function in some other time‐dependent covariates. As far as the inference is concerned, because the non‐parametric function is of secondary interest, we estimate this function consistently using the independence assumption‐based well‐known quasi‐likelihood approach. Next, the proposed longitudinal correlation structure and the estimate of the non‐parametric function are used to develop a semi‐parametric generalised quasi‐likelihood approach for consistent and efficient estimation of the regression effects in the parametric regression function. The finite sample performance of the proposed estimation approach is examined through an intensive simulation study based on both large and small samples. Both balanced and unbalanced cluster sizes are incorporated in the simulation study. The asymptotic performances of the estimators are given. The estimation methodology is illustrated by reanalysing the well‐known health care utilisation data consisting of counts of yearly visits to a physician by 180 individuals for four years and several important primary and secondary covariates.     

Skew-normal semiparametric varying coefficient model and score test

In this paper, we consider inference aspects of skew-normal semiparametric varying coefficient models which provide a useful extension of the normal regression models. The maximum likelihood estimation based on B-spline is proposed. Further, we discuss the score test for homogeneity of the variance in skew-normal semiparametric varying coefficient models. Their asymptotical properties are investigated. Some simulated examples are used to examine our proposed methods.     

Estimation methods for time‐dependent AUC models with survival data

The performance of clinical tests for disease screening is often evaluated using the area under the receiver‐operating characteristic (ROC) curve (AUC). Recent developments have extended the traditional setting to the AUC with binary time‐varying failure status. Without considering covariates, our first theme is to propose a simple and easily computed nonparametric estimator for the time‐dependent AUC. Moreover, we use generalized linear models with time‐varying coefficients to characterize the time‐dependent AUC as a function of covariate values. The corresponding estimation procedures are proposed to estimate the parameter functions of interest. The derived limiting Gaussian processes and the estimated asymptotic variances enable us to construct the approximated confidence regions for the AUCs. The finite sample properties of our proposed estimators and inference procedures are examined through extensive simulations. An analysis of the AIDS Clinical Trials Group (ACTG) 175 data is further presented to show the applicability of the proposed methods. The Canadian Journal of Statistics 38:8–26; 2010 © 2009 Statistical Society of Canada     

Structural identification and variable selection in high-dimensional varying-coefficient models

Varying-coefficient models have been widely used to investigate the possible time-dependent effects of covariates when the response variable comes from normal distribution. Much progress has been made for inference and variable selection in the framework of such models. However, the identification of model structure, that is how to identify which covariates have time-varying effects and which have fixed effects, remains a challenging and unsolved problem especially when the dimension of covariates is much larger than the sample size. In this article, we consider the structural identification and variable selection problems in varying-coefficient models for high-dimensional data. Using a modified basis expansion approach and group variable selection methods, we propose a unified procedure to simultaneously identify the model structure, select important variables and estimate the coefficient curves. The unique feature of the proposed approach is that we do not have to specify the model structure in advance, therefore, it is more realistic and appropriate for real data analysis. Asymptotic properties of the proposed estimators have been derived under regular conditions. Furthermore, we evaluate the finite sample performance of the proposed methods with Monte Carlo simulation studies and a real data analysis.     

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.     

Simultaneous structure estimation and variable selection in partial linear varying coefficient models for longitudinal data

Partial linear varying coefficient models (PLVCM) are often considered for analysing longitudinal data for a good balance between flexibility and parsimony. The existing estimation and variable selection methods for this model are mainly built upon which subset of variables have linear or varying effect on the response is known in advance, or say, model structure is determined. However, in application, this is unreasonable. In this work, we propose a simultaneous structure estimation and variable selection method, which can do simultaneous coefficient estimation and three types of selections: varying and constant effects selection, relevant variable selection. It can be easily implemented in one step by employing a penalized M-type regression, which uses a general loss function to treat mean, median, quantile and robust mean regressions in a unified framework. Consistency in the three types of selections and oracle property in estimation are established as well. Simulation studies and real data analysis also confirm our method.     

Global kernel estimator and test of varying‐coefficient autoregressive model

We propose a varying‐coefficient autoregressive model that contains additive models, varying‐ coefficient models, partially linear models and low‐dimensional interaction models as special cases. A global kernel backfitting method is proposed for the estimation and inference of parameters and unknown functions in this model. Key large‐sample results are established, including estimation consistency, asymptotic normality and the generalized likelihood ratio test for parameters and non‐parametric functions. The proposed methodology is examined by simulation studies and applied to examine the relationship between suicide news reports in the three leading newspapers and the daily number of suicides in Taiwan. The relationship between the media reporting and suicide incidence has been established and explored. The Canadian Journal of Statistics 47: 487–519; 2019 © 2019 Statistical Society of Canada     

Testing for constancy in varying coefficient models

We consider varying coefficient models, which are an extension of the classical linear regression models in the sense that the regression coefficients are replaced by functions in certain variables (for example, time), the covariates are also allowed to depend on other variables. Varying coefficient models are popular in longitudinal data and panel data studies, and have been applied in fields such as finance and health sciences. We consider longitudinal data and estimate the coefficient functions by the flexible B-spline technique. An important question in a varying coefficient model is whether an estimated coefficient function is statistically different from a constant (or zero). We develop testing procedures based on the estimated B-spline coefficients by making use of nice properties of a B-spline basis. Our method allows longitudinal data where repeated measurements for an individual can be correlated. We obtain the asymptotic null distribution of the test statistic. The power of the proposed testing procedures are illustrated on simulated data where we highlight the importance of including the correlation structure of the response variable and on real data.     

Marginalized transition random effect models for multivariate longitudinal binary data

Generalized linear models with random effects and/or serial dependence are commonly used to analyze longitudinal data. However, the computation and interpretation of marginal covariate effects can be difficult. This led Heagerty (1999, 2002) to propose models for longitudinal binary data in which a logistic regression is first used to explain the average marginal response. The model is then completed by introducing a conditional regression that allows for the longitudinal, within‐subject, dependence, either via random effects or regressing on previous responses. In this paper, the authors extend the work of Heagerty to handle multivariate longitudinal binary response data using a triple of regression models that directly model the marginal mean response while taking into account dependence across time and across responses. Markov Chain Monte Carlo methods are used for inference. Data from the Iowa Youth and Families Project are used to illustrate the methods.     

Nonlinear mixed‐effects models with misspecified random‐effects distribution

Nonlinear mixed‐effects models are being widely used for the analysis of longitudinal data, especially from pharmaceutical research. They use random effects which are latent and unobservable variables so the random‐effects distribution is subject to misspecification in practice. In this paper, we first study the consequences of misspecifying the random‐effects distribution in nonlinear mixed‐effects models. Our study is focused on Gauss‐Hermite quadrature, which is now the routine method for calculation of the marginal likelihood in mixed models. We then present a formal diagnostic test to check the appropriateness of the assumed random‐effects distribution in nonlinear mixed‐effects models, which is very useful for real data analysis. Our findings show that the estimates of fixed‐effects parameters in nonlinear mixed‐effects models are generally robust to deviations from normality of the random‐effects distribution, but the estimates of variance components are very sensitive to the distributional assumption of random effects. Furthermore, a misspecified random‐effects distribution will either overestimate or underestimate the predictions of random effects. We illustrate the results using a real data application from an intensive pharmacokinetic study.