Least squares estimation of varying‐coefficient hazard regression with application to breast cancer dose‐intensity data

To enhance modeling flexibility, the authors propose a nonparametric hazard regression model, for which the ordinary and weighted least squares estimation and inference procedures are studied. The proposed model does not assume any parametric specifications on the covariate effects, which is suitable for exploring the nonlinear interactions between covariates, time and some exposure variable. The authors propose the local ordinary and weighted least squares estimators for the varying‐coefficient functions and establish the corresponding asymptotic normality properties. Simulation studies are conducted to empirically examine the finite‐sample performance of the new methods, and a real data example from a recent breast cancer study is used as an illustration. The Canadian Journal of Statistics 37: 659–674; 2009 © 2009 Statistical Society of Canada     

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     

A semiparametric approach for modelling multivariate nonlinear time series

In this article, a semiparametric time‐varying nonlinear vector autoregressive (NVAR) model is proposed to model nonlinear vector time series data. We consider a combination of parametric and nonparametric estimation approaches to estimate the NVAR function for both independent and dependent errors. We use the multivariate Taylor series expansion of the link function up to the second order which has a parametric framework as a representation of the nonlinear vector regression function. After the unknown parameters are estimated by the maximum likelihood estimation procedure, the obtained NVAR function is adjusted by a nonparametric diagonal matrix, where the proposed adjusted matrix is estimated by the nonparametric kernel estimator. The asymptotic consistency properties of the proposed estimators are established. Simulation studies are conducted to evaluate the performance of the proposed semiparametric method. A real data example on short‐run interest rates and long‐run interest rates of United States Treasury securities is analyzed to demonstrate the application of the proposed approach. The Canadian Journal of Statistics 47: 668–687; 2019 © 2019 Statistical Society of Canada     

NEW EFFICIENT ESTIMATION AND VARIABLE SELECTION METHODS FOR SEMIPARAMETRIC VARYING-COEFFICIENT PARTIALLY LINEAR MODELS

The complexity of semiparametric models poses new challenges to statistical inference and model selection that frequently arise from real applications. In this work, we propose new estimation and variable selection procedures for the semiparametric varying-coefficient partially linear model. We first study quantile regression estimates for the nonparametric varying-coefficient functions and the parametric regression coefficients. To achieve nice efficiency properties, we further develop a semiparametric composite quantile regression procedure. We establish the asymptotic normality of proposed estimators for both the parametric and nonparametric parts and show that the estimators achieve the best convergence rate. Moreover, we show that the proposed method is much more efficient than the least-squares-based method for many non-normal errors and that it only loses a small amount of efficiency for normal errors. In addition, it is shown that the loss in efficiency is at most 11.1% for estimating varying coefficient functions and is no greater than 13.6% for estimating parametric components. To achieve sparsity with high-dimensional covariates, we propose adaptive penalization methods for variable selection in the semiparametric varying-coefficient partially linear model and prove that the methods possess the oracle property. Extensive Monte Carlo simulation studies are conducted to examine the finite-sample performance of the proposed procedures. Finally, we apply the new methods to analyze the plasma beta-carotene level data.     

Semiparametric Time-Varying Coefficients Regression Model for Longitudinal Data

Abstract.  In this paper, we consider a semiparametric time-varying coefficients regression model where the influences of some covariates vary non-parametrically with time while the effects of the remaining covariates follow certain parametric functions of time. The weighted least squares type estimators for the unknown parameters of the parametric coefficient functions as well as the estimators for the non-parametric coefficient functions are developed. We show that the kernel smoothing that avoids modelling of the sampling times is asymptotically more efficient than a single nearest neighbour smoothing that depends on the estimation of the sampling model. The asymptotic optimal bandwidth is also derived. A hypothesis testing procedure is proposed to test whether some covariate effects follow certain parametric forms. Simulation studies are conducted to compare the finite sample performances of the kernel neighbourhood smoothing and the single nearest neighbour smoothing and to check the empirical sizes and powers of the proposed testing procedures. An application to a data set from an AIDS clinical trial study is provided for illustration.     

Evaluating functional covariate‐environment interactions in the Cox regression model

Children exposed to mixtures of endocrine disrupting compounds such as phthalates are at high risk of experiencing significant friction in their growth and sexual maturation. This article is primarily motivated by a study that aims to assess the toxicants‐modified effects of risk factors related to the hazards of early or delayed onset of puberty among children living in Mexico City. To address the hypothesis of potential nonlinear modification of covariate effects, we propose a new Cox regression model with multiple functional covariate‐environment interactions, which allows covariate effects to be altered nonlinearly by mixtures of exposed toxicants. This new class of models is rather flexible and includes many existing semiparametric Cox models as special cases. To achieve efficient estimation, we develop the global partial likelihood method of inference, in which we establish key large‐sample results, including estimation consistency, asymptotic normality, semiparametric efficiency and the generalized likelihood ratio test for both parameters and nonparametric functions. The proposed methodology is examined via simulation studies and applied to the analysis of the motivating data, where maternal exposures to phthalates during the third trimester of pregnancy are found to be important risk modifiers for the age of attaining the first stage of puberty. The Canadian Journal of Statistics 47: 204–221; 2019 © 2019 Statistical Society of Canada     

A Semiparametric Regression Model for Longitudinal Data with Non‐stationary Errors

Motivated by the need to analyze the National Longitudinal Surveys data, we propose a new semiparametric longitudinal mean‐covariance model in which the effects on dependent variable of some explanatory variables are linear and others are non‐linear, while the within‐subject correlations are modelled by a non‐stationary autoregressive error structure. We develop an estimation machinery based on least squares technique by approximating non‐parametric functions via B‐spline expansions and establish the asymptotic normality of parametric estimators as well as the rate of convergence for the non‐parametric estimators. We further advocate a new model selection strategy in the varying‐coefficient model framework, for distinguishing whether a component is significant and subsequently whether it is linear or non‐linear. Besides, the proposed method can also be employed for identifying the true order of lagged terms consistently. Monte Carlo studies are conducted to examine the finite sample performance of our approach, and an application of real data is also illustrated.     

Estimation for semiparametric varying coefficient models with different smoothing variables under random right censoring

In this paper we study a semiparametric varying coefficient model when the response is subject to random right censoring. The model gives an easy interpretation due to its direct connectivity to the classical linear model and is very flexible since nonparametric functions which accommodates various nonlinear interaction effects between covariates are admitted in the model. We propose estimators for this model using mean-preserving transformation and establish their asymptotic properties. The estimation procedure is based on the profiling and the smooth backfitting techniques. A simulation study is presented to show the reliability of the proposed estimators and an automatic bandwidth selector is given in a data-driven way.     

Quantile regression for robust estimation and variable selection in partially linear varying-coefficient models

In this paper, we develop a new estimation procedure based on quantile regression for semiparametric partially linear varying-coefficient models. The proposed estimation approach is empirically shown to be much more efficient than the popular least squares estimation method for non-normal error distributions, and almost not lose any efficiency for normal errors. Asymptotic normalities of the proposed estimators for both the parametric and nonparametric parts are established. To achieve sparsity when there exist irrelevant variables in the model, two variable selection procedures based on adaptive penalty are developed to select important parametric covariates as well as significant nonparametric functions. Moreover, both these two variable selection procedures are demonstrated to enjoy the oracle property under some regularity conditions. Some Monte Carlo simulations are conducted to assess the finite sample performance of the proposed estimators, and a real-data example is used to illustrate the application of the proposed methods.     

Estimation and Inference of Distributional Partial Effects: Theory and Application

This article considers nonparametric and semiparametric estimation and inference of the effects of a covariate, either discrete or continuous, on the conditional distribution of a response outcome. It also proposes various uniform tests following estimation. This type of analysis is useful in situations where the econometrician or policy-maker is interested in knowing the effect of a variable or policy on the whole distribution of the response outcome conditional on covariates and is not willing to make parametric functional form assumptions. Monte Carlo experiments show that the proposed estimators and tests are well-behaved in small samples. The empirical section studies the effect of minimum wage hikes on household labor earnings. It is found that the minimum wage has a heterogenous impact on household earnings in the U.S. and that small hikes in the minimum wage are more effective in improving the household earnings distribution.     

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.     

Variable selection for semiparametric varying coefficient partially linear model based on modal regression with missing data

Abstract

In this article, we focus on the variable selection for semiparametric varying coefficient partially linear model with response missing at random. Variable selection is proposed based on modal regression, where the non parametric functions are approximated by B-spline basis. The proposed procedure uses SCAD penalty to realize variable selection of parametric and nonparametric components simultaneously. Furthermore, we establish the consistency, the sparse property and asymptotic normality of the resulting estimators. The penalty estimation parameters value of the proposed method is calculated by EM algorithm. Simulation studies are carried out to assess the finite sample performance of the proposed variable selection procedure.     

An Additive–Multiplicative Restricted Mean Residual Life Model

The mean residual life measures the expected remaining life of a subject who has survived up to a particular time. When survival time distribution is highly skewed or heavy tailed, the restricted mean residual life must be considered. In this paper, we propose an additive–multiplicative restricted mean residual life model to study the association between the restricted mean residual life function and potential regression covariates in the presence of right censoring. This model extends the proportional mean residual life model using an additive model as its covariate dependent baseline. For the suggested model, some covariate effects are allowed to be time‐varying. To estimate the model parameters, martingale estimating equations are developed, and the large sample properties of the resulting estimators are established. In addition, to assess the adequacy of the model, we investigate a goodness of fit test that is asymptotically justified. The proposed methodology is evaluated via simulation studies and further applied to a kidney cancer data set collected from a clinical trial.     

Dimension reduced kernel estimation for distribution function with incomplete data

This work focuses on the estimation of distribution functions with incomplete data, where the variable of interest Y has ignorable missingness but the covariate X is always observed. When X is high dimensional, parametric approaches to incorporate X—information is encumbered by the risk of model misspecification and nonparametric approaches by the curse of dimensionality. We propose a semiparametric approach, which is developed under a nonparametric kernel regression framework, but with a parametric working index to condense the high dimensional X—information for reduced dimension. This kernel dimension reduction estimator has double robustness to model misspecification and is most efficient if the working index adequately conveys the X—information about the distribution of Y. Numerical studies indicate better performance of the semiparametric estimator over its parametric and nonparametric counterparts. We apply the kernel dimension reduction estimation to an HIV study for the effect of antiretroviral therapy on HIV virologic suppression.     

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.     

Analysis of longitudinal health-related quality of life data with terminal events

Longitudinal health-related quality of life data arise naturally from studies of progressive and neurodegenerative diseases. In such studies, patients’ mental and physical conditions are measured over their follow-up periods and the resulting data are often complicated by subject-specific measurement times and possible terminal events associated with outcome variables. Motivated by the “Predictor’s Cohort” study on patients with advanced Alzheimer disease, we propose in this paper a semiparametric modeling approach to longitudinal health-related quality of life data. It builds upon and extends some recent developments for longitudinal data with irregular observation times. The new approach handles possibly dependent terminal events. It allows one to examine time-dependent covariate effects on the evolution of outcome variable and to assess nonparametrically change of outcome measurement that is due to factors not incorporated in the covariates. The usual large-sample properties for parameter estimation are established. In particular, it is shown that relevant parameter estimators are asymptotically normal and the asymptotic variances can be estimated consistently by the simple plug-in method. A general procedure for testing a specific parametric form in the nonparametric component is also developed. Simulation studies show that the proposed approach performs well for practical settings. The method is applied to the motivating example.     

Estimation for varying coefficient partially nonlinear models with distorted measurement errors

In this paper, we propose a new varying coefficient partially nonlinear model where both the response and predictors are not directly observed, but are observed by unknown distorting functions of a commonly observable covariate. Because of the complexity of the model, existing estimation methods cannot be directly employed. For this, we propose using an efficient nonparametric regression to estimate the unknown distortion functions concerning the covariates and response on the distorting variable, and further, we obtain the profile nonlinear least squares estimators for the parameters and the coefficient functions using the calibrated variables. Furthermore, we establish the asymptotic properties of the resulting estimators. To illustrate our proposed methodology, we carry out some simulated and real examples.     

Semiparametric inference for open populations using the Jolly–Seber model: a penalized spline approach

When there are frequent capture occasions, both semiparametric and nonparametric estimators for the size of an open population have been proposed using kernel smoothing methods. While kernel smoothing methods are mathematically tractable, fitting them to data is computationally intensive. Here, we use smoothing splines in the form of P-splines to provide an alternate less computationally intensive method of fitting these models to capture–recapture data from open populations with frequent capture occasions. We fit the model to capture data collected over 64 occasions and model the population size as a function of time, seasonal effects and an environmental covariate. A small simulation study is also conducted to examine the performance of the estimators and their standard errors.     

A Semiparametrically Efficient Estimator of the Time‐Varying Effects for Survival Data with Time‐Dependent Treatment

The timing of a time‐dependent treatment—for example, when to perform a kidney transplantation—is an important factor for evaluating treatment efficacy. A naïve comparison between the treated and untreated groups, while ignoring the timing of treatment, typically yields biased results that might favour the treated group because only patients who survive long enough will get treated. On the other hand, studying the effect of a time‐dependent treatment is often complex, as it involves modelling treatment history and accounting for the possible time‐varying nature of the treatment effect. We propose a varying‐coefficient Cox model that investigates the efficacy of a time‐dependent treatment by utilizing a global partial likelihood, which renders appealing statistical properties, including consistency, asymptotic normality and semiparametric efficiency. Extensive simulations verify the finite sample performance, and we apply the proposed method to study the efficacy of kidney transplantation for end‐stage renal disease patients in the US Scientific Registry of Transplant Recipients.     

Nonparametric Shrinkage Estimation for Aalen's Additive Hazards Model

Aalen's nonparametric additive model in which the regression coefficients are assumed to be unspecified functions of time is a flexible alternative to Cox's proportional hazards model when the proportionality assumption is in doubt. In this paper, we incorporate a general linear hypothesis into the estimation of the time‐varying regression coefficients. We combine unrestricted least squares estimators and estimators that are restricted by the linear hypothesis and produce James‐Stein‐type shrinkage estimators of the regression coefficients. We develop the asymptotic joint distribution of such restricted and unrestricted estimators and use this to study the relative performance of the proposed estimators via their integrated asymptotic distributional risks. We conduct Monte Carlo simulations to examine the relative performance of the estimators in terms of their integrated mean square errors. We also compare the performance of the proposed estimators with a recently devised LASSO estimator as well as with ridge‐type estimators both via simulations and data on the survival of primary billiary cirhosis patients.