Two-step estimation of functional linear models with applications to longitudinal data

Functional linear models are useful in longitudinal data analysis. They include many classical and recently proposed statistical models for longitudinal data and other functional data. Recently, smoothing spline and kernel methods have been proposed for estimating their coefficient functions nonparametrically but these methods are either intensive in computation or inefficient in performance. To overcome these drawbacks, in this paper, a simple and powerful two-step alternative is proposed. In particular, the implementation of the proposed approach via local polynomial smoothing is discussed. Methods for estimating standard deviations of estimated coefficient functions are also proposed. Some asymptotic results for the local polynomial estimators are established. Two longitudinal data sets, one of which involves time-dependent covariates, are used to demonstrate the approach proposed. Simulation studies show that our two-step approach improves the kernel method proposed by Hoover and co-workers in several aspects such as accuracy, computational time and visual appeal of the estimators.     

Joint Mean-Covariance Models with Applications to Longitudinal Data in Partially Linear Model

Semiparametric regression models and estimating covariance functions are very useful in longitudinal study. Unfortunately, challenges arise in estimating the covariance function of longitudinal data collected at irregular time points. In this article, for mean term, a partially linear model is introduced and for covariance structure, a modified Cholesky decomposition approach is proposed to heed the positive-definiteness constraint. We estimate the regression function by using the local linear technique and propose quasi-likelihood estimating equations for both the mean and covariance structures. Moreover, asymptotic normality of the resulting estimators is established. Finally, simulation study and real data analysis are used to illustrate the proposed approach.     

Bootstrap methods for stationary functional time series

Bootstrap methods for estimating the long-run covariance of stationary functional time series are considered. We introduce a versatile bootstrap method that relies on functional principal component analysis, where principal component scores can be bootstrapped by maximum entropy. Two other bootstrap methods resample error functions, after the dependence structure being modeled linearly by a sieve method or nonlinearly by a functional kernel regression. Through a series of Monte-Carlo simulation, we evaluate and compare the finite-sample performances of these three bootstrap methods for estimating the long-run covariance in a functional time series. Using the intraday particulate matter (\(\hbox {PM}_{10}\)) dataset in Graz, the proposed bootstrap methods provide a way of constructing the distribution of estimated long-run covariance for functional time series.     

Marginal semiparametric multivariate accelerated failure time model with generalized estimating equations

The semiparametric accelerated failure time (AFT) model is not as widely used as the Cox relative risk model due to computational difficulties. Recent developments in least squares estimation and induced smoothing estimating equations for censored data provide promising tools to make the AFT models more attractive in practice. For multivariate AFT models, we propose a generalized estimating equations (GEE) approach, extending the GEE to censored data. The consistency of the regression coefficient estimator is robust to misspecification of working covariance, and the efficiency is higher when the working covariance structure is closer to the truth. The marginal error distributions and regression coefficients are allowed to be unique for each margin or partially shared across margins as needed. The initial estimator is a rank-based estimator with Gehan’s weight, but obtained from an induced smoothing approach with computational ease. The resulting estimator is consistent and asymptotically normal, with variance estimated through a multiplier resampling method. In a large scale simulation study, our estimator was up to three times as efficient as the estimateor that ignores the within-cluster dependence, especially when the within-cluster dependence was strong. The methods were applied to the bivariate failure times data from a diabetic retinopathy study.     

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.     

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.     

Function-on-function regression for two-dimensional functional data

ABSTRACT

We present methods for modeling and estimation of a concurrent functional regression when the predictors and responses are two-dimensional functional datasets. The implementations use spline basis functions and model fitting is based on smoothing penalties and mixed model estimation. The proposed methods are implemented in available statistical software, allow the construction of confidence intervals for the bivariate model parameters, and can be applied to completely or sparsely sampled responses. Methods are tested to data in simulations and they show favorable results in practice. The usefulness of the methods is illustrated in an application to environmental data.     

Adaptive varying-coefficient linear models

Summary. Varying-coefficient linear models arise from multivariate nonparametric regression, non-linear time series modelling and forecasting, functional data analysis, longitudinal data analysis and others. It has been a common practice to assume that the varying coefficients are functions of a given variable, which is often called an index . To enlarge the modelling capacity substantially, this paper explores a class of varying-coefficient linear models in which the index is unknown and is estimated as a linear combination of regressors and/or other variables. We search for the index such that the derived varying-coefficient model provides the least squares approximation to the underlying unknown multidimensional regression function. The search is implemented through a newly proposed hybrid backfitting algorithm. The core of the algorithm is the alternating iteration between estimating the index through a one-step scheme and estimating coefficient functions through one-dimensional local linear smoothing. The locally significant variables are selected in terms of a combined use of the t -statistic and the Akaike information criterion. We further extend the algorithm for models with two indices. Simulation shows that the methodology proposed has appreciable flexibility to model complex multivariate non-linear structure and is practically feasible with average modern computers. The methods are further illustrated through the Canadian mink–muskrat data in 1925–1994 and the pound–dollar exchange rates in 1974–1983.     

Fast accelerated failure time modeling for case-cohort data

Semiparametric accelerated failure time (AFT) models directly relate the expected failure times to covariates and are a useful alternative to models that work on the hazard function or the survival function. For case-cohort data, much less development has been done with AFT models. In addition to the missing covariates outside of the sub-cohort in controls, challenges from AFT model inferences with full cohort are retained. The regression parameter estimator is hard to compute because the most widely used rank-based estimating equations are not smooth. Further, its variance depends on the unspecified error distribution, and most methods rely on computationally intensive bootstrap to estimate it. We propose fast rank-based inference procedures for AFT models, applying recent methodological advances to the context of case-cohort data. Parameters are estimated with an induced smoothing approach that smooths the estimating functions and facilitates the numerical solution. Variance estimators are obtained through efficient resampling methods for nonsmooth estimating functions that avoids full blown bootstrap. Simulation studies suggest that the recommended procedure provides fast and valid inferences among several competing procedures. Application to a tumor study demonstrates the utility of the proposed method in routine data analysis.     

Robust estimation for functional coefficient regression models with spatial data

A global smoothing procedure is developed using B-spline function approximation for estimating the unknown functions of a functional coefficient regression model with spatial data. A general formulation is used to treat mean regression, median regression, quantile regression and robust mean regression in one setting. The global convergence rates of the estimators of unknown coefficient functions are established. Various applications of the main results, including estimating conditional quantile coefficient functions and robustifying the mean regression coefficient functions are given. Finite sample properties of our procedures are studied through Monte Carlo simulations. A housing data example is used to illustrate the proposed methodology.     

Smoothing parameter selection for a class of semiparametric linear models

Summary.  Spline-based approaches to non-parametric and semiparametric regression, as well as to regression of scalar outcomes on functional predictors, entail choosing a parameter controlling the extent to which roughness of the fitted function is penalized. We demonstrate that the equations determining two popular methods for smoothing parameter selection, generalized cross-validation and restricted maximum likelihood, share a similar form that allows us to prove several results which are common to both, and to derive a condition under which they yield identical values. These ideas are illustrated by application of functional principal component regression, a method for regressing scalars on functions, to two chemometric data sets.     

Functional quasi-likelihood regression models with smooth random effects

Summary. We propose a class of semiparametric functional regression models to describe the influence of vector-valued covariates on a sample of response curves. Each observed curve is viewed as the realization of a random process, composed of an overall mean function and random components. The finite dimensional covariates influence the random components of the eigenfunction expansion through single-index models that include unknown smooth link and variance functions. The parametric components of the single-index models are estimated via quasi-score estimating equations with link and variance functions being estimated nonparametrically. We obtain several basic asymptotic results. The functional regression models proposed are illustrated with the analysis of a data set consisting of egg laying curves for 1000 female Mediterranean fruit-flies (medflies).     

A regression approach for estimating the parameters of the covariance function of a stationary spatial random process

We consider the problem of estimating the parameters of the covariance function of a stationary spatial random process. In spatial statistics, there are widely used parametric forms for the covariance functions, and various methods for estimating the parameters have been proposed in the literature. We develop a method for estimating the parameters of the covariance function that is based on a regression approach. Our method utilizes pairs of observations whose distances are closest to a value h>0$h>0$ which is chosen in a way that the estimated correlation at distance h is a predetermined value. We demonstrate the effectiveness of our procedure by simulation studies and an application to a water pH data set. Simulation studies show that our method outperforms all well-known least squares-based approaches to the variogram estimation and is comparable to the maximum likelihood estimation of the parameters of the covariance function. We also show that under a mixing condition on the random field, the proposed estimator is consistent for standard one parameter models for stationary correlation functions.     

Theory & Methods: Krige,Smooth, Both or Neither?

Both kriging and non-parametric regression smoothing can model a non-stationary regression function with spatially correlated errors. However comparisons have mainly been based on ordinary kriging and smoothing with uncorrelated errors. Ordinary kriging attributes smoothness of the response to spatial autocorrelation whereas non-parametric regression attributes trends to a smooth regression function. For spatial processes it is reasonable to suppose that the response is due to both trend and autocorrelation. This paper reviews methodology for non-parametric regression with autocorrelated errors which is a natural compromise between the two methods. Re-analysis of the one-dimensional stationary spatial data of Laslett (1994) and a clearly non-stationary time series demonstrates the rather surprising result that for these data, ordinary kriging outperforms more computationally intensive models including both universal kriging and correlated splines for spatial prediction. For estimating the regression function, non-parametric regression provides adaptive estimation, but the autocorrelation must be accounted for in selecting the smoothing parameter.     

INFLUENCE FUNCTIONS IN FUNCTIONAL MEASUREMENT ERROR MODELS WITH REPLICATED DATA

We consider the construction and properties of influence functions in the context of functional measurement error models with replicated data. In these models estimates of the parameters can be affected both by the individual observations and the means of replicated observations. We show that influence function of the means of replicates on the estimate of regression coefficients can be only derived under the assumption that the variances of the errors are known, while one for the individual observations can be only derived simultaneously with their influence function on the estimators of the variances of the errors.     

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.     

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.     

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     

State-space models for multivariate longitudinal data of mixed types

We propose a class of state-space models for multivariate longitudinal data where the components of the response vector may have different distributions. The approach is based on the class of Tweedie exponential dispersion models, which accommodates a wide variety of discrete, continuous and mixed data. The latent process is assumed to be a Markov process, and the observations are conditionally independent given the latent process, over time as well as over the components of the response vector. This provides a fully parametric alternative to the quasilikelihood approach of Liang and Zeger. We estimate the regression parameters for time-varying covariates entering either via the observation model or via the latent process, based on an estimating equation derived from the Kalman smoother. We also consider analysis of residuals from both the observation model and the latent process.     

Local Box–Cox transformation on time-varying parametric models for smoothing estimation of conditional CDF with longitudinal data

Nonparametric estimation and inferences of conditional distribution functions with longitudinal data have important applications in biomedical studies, such as epidemiological studies and longitudinal clinical trials. Estimation approaches without any structural assumptions may lead to inadequate and numerically unstable estimators in practice. We propose in this paper a nonparametric approach based on time-varying parametric models for estimating the conditional distribution functions with a longitudinal sample. Our model assumes that the conditional distribution of the outcome variable at each given time point can be approximated by a parametric model after local Box–Cox transformation. Our estimation is based on a two-step smoothing method, in which we first obtain the raw estimators of the conditional distribution functions at a set of disjoint time points, and then compute the final estimators at any time by smoothing the raw estimators. Applications of our two-step estimation method have been demonstrated through a large epidemiological study of childhood growth and blood pressure. Finite sample properties of our procedures are investigated through a simulation study. Application and simulation results show that smoothing estimation from time-variant parametric models outperforms the existing kernel smoothing estimator by producing narrower pointwise bootstrap confidence band and smaller root mean squared error.