Penalized Spline Estimation for Varying-Coefficient Models

Varying-coefficient models are useful extensions of classical linear models. They arise from multivariate nonparametric regression, nonlinear time series modeling and forecasting, longitudinal data analysis, and others. This article proposes the penalized spline estimation for the varying-coefficient models. Assuming a fixed but potentially large number of knots, the penalized spline estimators are shown to be strong consistency and asymptotic normality. A systematic optimization algorithm for the selection of multiple smoothing parameters is developed. One of the advantages of the penalized spline estimation is that it can accommodate varying degrees of smoothness among coefficient functions due to multiple smoothing parameters being used. Some simulation studies are presented to illustrate the proposed methods.     

Local Influence Analysis for Penalized Gaussian Likelihood Estimators in Partially Linear Models

Abstract. Partially linear models are extensions of linear models to include a non-parametric function of some covariate. They have been found to be useful in both cross-sectional and longitudinal studies. This paper provides a convenient means to extend Cook's local influence analysis to the penalized Gaussian likelihood estimator that uses a smoothing spline as a solution to its non-parametric component. Insight is also provided into the interplay of the influence or leverage measures between the linear and the non-parametric components in the model. The diagnostics are applied to a mouthwash data set and a longitudinal hormone study with informative results.     

Variable selection for longitudinal data with high-dimensional covariates and dropouts

A new variable selection approach utilizing penalized estimating equations is developed for high-dimensional longitudinal data with dropouts under a missing at random (MAR) mechanism. The proposed method is based on the best linear approximation of efficient scores from the full dataset and does not need to specify a separate model for the missing or imputation process. The coordinate descent algorithm is adopted to implement the proposed method and is computational feasible and stable. The oracle property is established and extensive simulation studies show that the performance of the proposed variable selection method is much better than that of penalized estimating equations dealing with complete data which do not account for the MAR mechanism. In the end, the proposed method is applied to a Lifestyle Education for Activity and Nutrition study and the interaction effect between intervention and time is identified, which is consistent with previous findings.     

Self‐modelling regression for longitudinal data with time‐invariant covariates

The authors propose the use of self‐modelling regression to analyze longitudinal data with time invariant covariates. They model the population time curve with a penalized regression spline and use a linear mixed model for transformation of the time and response scales to fit the individual curves. Fitting is done by an iterative algorithm using off‐the‐shelf linear and nonlinear mixed model software. Their method is demonstrated in a simulation study and in the analysis of tree swallow nestling growth from an experiment that includes an experimentally controlled treatment, an observational covariate and multi‐level sampling.     

Prediction of transplant-free survival in idiopathic pulmonary fibrosis patients using joint models for event times and mixed multivariate longitudinal data

We implement a joint model for mixed multivariate longitudinal measurements, applied to the prediction of time until lung transplant or death in idiopathic pulmonary fibrosis. Specifically, we formulate a unified Bayesian joint model for the mixed longitudinal responses and time-to-event outcomes. For the longitudinal model of continuous and binary responses, we investigate multivariate generalized linear mixed models using shared random effects. Longitudinal and time-to-event data are assumed to be independent conditional on available covariates and shared parameters. A Markov chain Monte Carlo algorithm, implemented in OpenBUGS, is used for parameter estimation. To illustrate practical considerations in choosing a final model, we fit 37 different candidate models using all possible combinations of random effects and employ a deviance information criterion to select a best-fitting model. We demonstrate the prediction of future event probabilities within a fixed time interval for patients utilizing baseline data, post-baseline longitudinal responses, and the time-to-event outcome. The performance of our joint model is also evaluated in simulation studies.     

S-estimator in partially linear regression models

In this paper, a robust estimator is proposed for partially linear regression models. We first estimate the nonparametric component using the penalized regression spline, then we construct an estimator of parametric component by using robust S-estimator. We propose an iterative algorithm to solve the proposed optimization problem, and introduce a robust generalized cross-validation to select the penalized parameter. Simulation studies and a real data analysis illustrate that the our proposed method is robust against outliers in the dataset or errors with heavy tails.     

Jointly modeling longitudinal proportional data and survival times with an application to the quality of life data in a breast cancer trial

Motivated by the joint analysis of longitudinal quality of life data and recurrence free survival times from a cancer clinical trial, we present in this paper two approaches to jointly model the longitudinal proportional measurements, which are confined in a finite interval, and survival data. Both approaches assume a proportional hazards model for the survival times. For the longitudinal component, the first approach applies the classical linear mixed model to logit transformed responses, while the second approach directly models the responses using a simplex distribution. A semiparametric method based on a penalized joint likelihood generated by the Laplace approximation is derived to fit the joint model defined by the second approach. The proposed procedures are evaluated in a simulation study and applied to the analysis of breast cancer data motivated this research.     

Robust estimation for partially linear single-index model

In this article, we investigate a new estimation approach for the partially linear single-index model based on modal regression method, where the non parametric function is estimated by penalized spline method. Moreover, we develop an expection maximum (EM)-type algorithm and establish the large sample properties of the proposed estimation method. A distinguishing characteristic of the newly proposed estimation is robust against outliers through introducing an additional tuning parameter which can be automatically selected using the observed data. Simulation studies and real data example are used to evaluate the finite-sample performance, and the results show that the newly proposed method works very well.     

Component Selection in the Additive Regression Model

Abstract. Similar to variable selection in the linear model, selecting significant components in the additive model is of great interest. However, such components are unknown, unobservable functions of independent variables. Some approximation is needed. We suggest a combination of penalized regression spline approximation and group variable selection, called the group‐bridge‐type spline method (GBSM), to handle this component selection problem with a diverging number of correlated variables in each group. The proposed method can select significant components and estimate non‐parametric additive function components simultaneously. To make the GBSM stable in computation and adaptive to the level of smoothness of the component functions, weighted power spline bases and projected weighted power spline bases are proposed. Their performance is examined by simulation studies. The proposed method is extended to a partial linear regression model analysis with real data, and gives reliable results.     

Partial Linear Models for Longitudinal Data Based on Quadratic Inference Functions

In this paper, we consider improved estimating equations for semiparametric partial linear models (PLM) for longitudinal data, or clustered data in general. We approximate the non‐parametric function in the PLM by a regression spline, and utilize quadratic inference functions (QIF) in the estimating equations to achieve a more efficient estimation of the parametric part in the model, even when the correlation structure is misspecified. Moreover, we construct a test which is an analogue to the likelihood ratio inference function for inferring the parametric component in the model. The proposed methods perform well in simulation studies and real data analysis conducted in this paper.     

Functional approach of flexibly modelling generalized longitudinal data and survival time

We propose a flexible functional approach for modelling generalized longitudinal data and survival time using principal components. In the proposed model the longitudinal observations can be continuous or categorical data, such as Gaussian, binomial or Poisson outcomes. We generalize the traditional joint models that treat categorical data as continuous data by using some transformations, such as CD4 counts. The proposed model is data-adaptive, which does not require pre-specified functional forms for longitudinal trajectories and automatically detects characteristic patterns. The longitudinal trajectories observed with measurement error or random error are represented by flexible basis functions through a possibly nonlinear link function, combining dimension reduction techniques resulting from functional principal component (FPC) analysis. The relationship between the longitudinal process and event history is assessed using a Cox regression model. Although the proposed model inherits the flexibility of non-parametric methods, the estimation procedure based on the EM algorithm is still parametric in computation, and thus simple and easy to implement. The computation is simplified by dimension reduction for random coefficients or FPC scores. An iterative selection procedure based on Akaike information criterion (AIC) is proposed to choose the tuning parameters, such as the knots of spline basis and the number of FPCs, so that appropriate degree of smoothness and fluctuation can be addressed. The effectiveness of the proposed approach is illustrated through a simulation study, followed by an application to longitudinal CD4 counts and survival data which were collected in a recent clinical trial to compare the efficiency and safety of two antiretroviral drugs.     

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.     

Nonconcave penalized estimation for partially linear models with longitudinal data

A nonconcave penalized estimation method is proposed for partially linear models with longitudinal data when the number of parameters diverges with the sample size. The proposed procedure can simultaneously estimate the parameters and select the important variables. Under some regularity conditions, the rate of convergence and asymptotic normality of the resulting estimators are established. In addition, an iterative algorithm is proposed to implement the proposed estimators. To improve efficiency for regression coefficients, the estimation of the covariance function is integrated in the iterative algorithm. Simulation studies are carried out to demonstrate that the proposed method performs well, and a real data example is analysed to illustrate the proposed procedure.     

Analysis of growth curve data by using cubic smoothing splines

Longitudinal data frequently arises in various fields of applied sciences where individuals are measured according to some ordered variable, e.g. time. A common approach used to model such data is based on the mixed models for repeated measures. This model provides an eminently flexible approach to modeling of a wide range of mean and covariance structures. However, such models are forced into a rigidly defined class of mathematical formulas which may not be well supported by the data within the whole sequence of observations. A possible non-parametric alternative is a cubic smoothing spline, which is highly flexible and has useful smoothing properties. It can be shown that under normality assumption, the solution of the penalized log-likelihood equation is the cubic smoothing spline, and this solution can be further expressed as a solution of the linear mixed model. It is shown here how cubic smoothing splines can be easily used in the analysis of complete and balanced data. Analysis can be greatly simplified by using the unweighted estimator studied in the paper. It is shown that if the covariance structure of random errors belong to certain class of matrices, the unweighted estimator is the solution to the penalized log-likelihood function. This result is new in smoothing spline context and it is not only confined to growth curve settings. The connection to mixed models is used in developing a rough testing of group profiles. Numerical examples are presented to illustrate the techniques proposed.     

Bivariate modelling of longitudinal measurements of two human immunodeficiency type 1 disease progression markers in the presence of informative drop-outs

Summary.  The main statistical problem in many epidemiological studies which involve repeated measurements of surrogate markers is the frequent occurrence of missing data. Standard likelihood-based approaches like the linear random-effects model fail to give unbiased estimates when data are non-ignorably missing. In human immunodeficiency virus (HIV) type 1 infection, two markers which have been widely used to track progression of the disease are CD4 cell counts and HIV–ribonucleic acid (RNA) viral load levels. Repeated measurements of these markers tend to be informatively censored, which is a special case of non-ignorable missingness. In such cases, we need to apply methods that jointly model the observed data and the missingness process. Despite their high correlation, longitudinal data of these markers have been analysed independently by using mainly random-effects models. Touloumi and co-workers have proposed a model termed the joint multivariate random-effects model which combines a linear random-effects model for the underlying pattern of the marker with a log-normal survival model for the drop-out process. We extend the joint multivariate random-effects model to model simultaneously the CD4 cell and viral load data while adjusting for informative drop-outs due to disease progression or death. Estimates of all the model's parameters are obtained by using the restricted iterative generalized least squares method or a modified version of it using the EM algorithm as a nested algorithm in the case of censored survival data taking also into account non-linearity in the HIV–RNA trend. The method proposed is evaluated and compared with simpler approaches in a simulation study. Finally the method is applied to a subset of the data from the 'Concerted action on seroconversion to AIDS and death in Europe' study.     

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     

Unsupervised learning of regression mixture models with unknown number of components

ABSTRACT

We propose a new unsupervised learning algorithm to fit regression mixture models with unknown number of components. The developed approach consists in a penalized maximum likelihood estimation carried out by a robust expectation–maximization (EM)-like algorithm. We derive it for polynomial, spline, and B-spline regression mixtures. The proposed learning approach is unsupervised: (i) it simultaneously infers the model parameters and the optimal number of the regression mixture components from the data as the learning proceeds, rather than in a two-fold scheme as in standard model-based clustering using afterward model selection criteria, and (ii) it does not require accurate initialization unlike the standard EM for regression mixtures. The developed approach is applied to curve clustering problems. Numerical experiments on simulated and real data show that the proposed algorithm performs well and provides accurate clustering results, and confirm its benefit for practical applications.     

Reference priors for linear models with general covariance structures

We develop a new class of reference priors for linear models with general covariance structures. A general Markov chain Monte Carlo algorithm is also proposed for implementing the computation. We present several examples to demonstrate the results: Bayesian penalized spline smoothing, a Bayesian approach to bivariate smoothing for a spatial model, and prior specification for structural equation models.     

Fast covariance estimation for sparse functional data

Smoothing of noisy sample covariances is an important component in functional data analysis. We propose a novel covariance smoothing method based on penalized splines and associated software. The proposed method is a bivariate spline smoother that is designed for covariance smoothing and can be used for sparse functional or longitudinal data. We propose a fast algorithm for covariance smoothing using leave-one-subject-out cross-validation. Our simulations show that the proposed method compares favorably against several commonly used methods. The method is applied to a study of child growth led by one of coauthors and to a public dataset of longitudinal CD4 counts.     

Influence diagnostics and outlier tests for semiparametric mixed models

Summary. Semiparametric mixed models are useful in biometric and econometric applications, especially for longitudinal data. Maximum penalized likelihood estimators (MPLEs) have been shown to work well by Zhang and co-workers for both linear coefficients and nonparametric functions. This paper considers the role of influence diagnostics in the MPLE by extending the case deletion and subject deletion analysis of linear models to accommodate the inclusion of a nonparametric component. We focus on influence measures for the fixed effects and provide formulae that are analogous to those for simpler models and readily computable with the MPLE algorithm. We also establish an equivalence between the case or subject deletion model and a mean shift outlier model from which we derive tests for outliers. The influence diagnostics proposed are illustrated through a longitudinal hormone study on progesterone and a simulated example.