Non parametric hazard estimation with dependent censoring using penalized likelihood and an assumed copula

This article introduces a novel non parametric penalized likelihood hazard estimation when the censoring time is dependent on the failure time for each subject under observation. More specifically, we model this dependence using a copula, and the method of maximum penalized likelihood (MPL) is adopted to estimate the hazard function. We do not consider covariates in this article. The non negatively constrained MPL hazard estimation is obtained using a multiplicative iterative algorithm. The consistency results and the asymptotic properties of the proposed hazard estimator are derived. The simulation studies show that our MPL estimator under dependent censoring with an assumed copula model provides a better accuracy than the MPL estimator under independent censoring if the sign of dependence is correctly specified in the copula function. The proposed method is applied to a real dataset, with a sensitivity analysis performed over various values of correlation between failure and censoring times.     

Penalized Empirical Likelihood via Bridge Estimator in Cox's Proportional Hazard Model

We propose the penalized empirical likelihood method via bridge estimator in Cox's proportional hazard model for parameter estimation and variable selection. Under reasonable conditions, we show that penalized empirical likelihood in Cox's proportional hazard model has oracle property. A penalized empirical likelihood ratio for the vector of regression coefficients is defined and its limiting distribution is a chi-square distributions. The advantage of penalized empirical likelihood as a nonparametric likelihood approach is illustrated in testing hypothesis and constructing confidence sets. The method is illustrated by extensive simulation studies and a real example.     

Maximum Penalized Likelihood Estimation in a Gamma-Frailty Model

The shared frailty models allow for unobserved heterogeneity or for statistical dependence between observed survival data. The most commonly used estimation procedure in frailty models is the EM algorithm, but this approach yields a discrete estimator of the distribution and consequently does not allow direct estimation of the hazard function. We show how maximum penalized likelihood estimation can be applied to nonparametric estimation of a continuous hazard function in a shared gamma-frailty model with right-censored and left-truncated data. We examine the problem of obtaining variance estimators for regression coefficients, the frailty parameter and baseline hazard functions. Some simulations for the proposed estimation procedure are presented. A prospective cohort (Paquid) with grouped survival data serves to illustrate the method which was used to analyze the relationship between environmental factors and the risk of dementia.     

Penalized pseudo-likelihood hazard estimation: A fast alternative to penalized likelihood

Penalized likelihood method has been developed previously for hazard function estimation using standard left-truncated, right-censored lifetime data with covariates, and the functional ANOVA structures built into the log hazard allows for versatile nonparametric modeling in the setting. The computation of the method can be time-consuming in the presence of continuous covariates; however, due to the repeated numerical integrations involved. Adapting a device developed by Jeon and Lin [An effective method for high dimensional log-density ANOVA estimation, with application to nonparametric graphical model building. Statist. Sinica 16, 353–374] for penalized likelihood density estimation, we explore an alternative approach to hazard estimation where the log likelihood is replaced by some computationally less demanding pseudo-likelihood. An assortment of issues are addressed concerning the practical implementations of the approach including the selection of smoothing parameters, and extensive simulations are presented to assess the inferential efficiency of the “pseudo” method as compared to the “real” one. Also noted is an asymptotic theory concerning the convergence rates of the estimates parallel to that for the original penalized likelihood estimation.     

Sparse Functional Principal Component Analysis via Regularized Basis Expansions and Its Application

This article introduces principal component analysis for multidimensional sparse functional data, utilizing Gaussian basis functions. Our multidimensional model is estimated by maximizing a penalized log-likelihood function, while previous mixed-type models were estimated by maximum likelihood methods for one-dimensional data. The penalized estimation performs well for our multidimensional model, while maximum likelihood methods yield unstable parameter estimates and some of the parameter estimates are infinite. Numerical experiments are conducted to investigate the effectiveness of our method for some types of missing data. The proposed method is applied to handwriting data, which consist of the XY coordinates values in handwritings.     

A Mixed Model Approach for Geoadditive Hazard Regression

Abstract.  Mixed model based approaches for semiparametric regression have gained much interest in recent years, both in theory and application. They provide a unified and modular framework for penalized likelihood and closely related empirical Bayes inference. In this article, we develop mixed model methodology for a broad class of Cox-type hazard regression models where the usual linear predictor is generalized to a geoadditive predictor incorporating non-parametric terms for the (log-)baseline hazard rate, time-varying coefficients and non-linear effects of continuous covariates, a spatial component, and additional cluster-specific frailties. Non-linear and time-varying effects are modelled through penalized splines, while spatial components are treated as correlated random effects following either a Markov random field or a stationary Gaussian random field prior. Generalizing existing mixed model methodology, inference is derived using penalized likelihood for regression coefficients and (approximate) marginal likelihood for smoothing parameters. In a simulation we study the performance of the proposed method, in particular comparing it with its fully Bayesian counterpart using Markov chain Monte Carlo methodology, and complement the results by some asymptotic considerations. As an application, we analyse leukaemia survival data from northwest England.     

Penalized spline joint models for longitudinal and time-to-event data

The joint models for longitudinal data and time-to-event data have recently received numerous attention in clinical and epidemiologic studies. Our interest is in modeling the relationship between event time outcomes and internal time-dependent covariates. In practice, the longitudinal responses often show non linear and fluctuated curves. Therefore, the main aim of this paper is to use penalized splines with a truncated polynomial basis to parameterize the non linear longitudinal process. Then, the linear mixed-effects model is applied to subject-specific curves and to control the smoothing. The association between the dropout process and longitudinal outcomes is modeled through a proportional hazard model. Two types of baseline risk functions are considered, namely a Gompertz distribution and a piecewise constant model. The resulting models are referred to as penalized spline joint models; an extension of the standard joint models. The expectation conditional maximization (ECM) algorithm is applied to estimate the parameters in the proposed models. To validate the proposed algorithm, extensive simulation studies were implemented followed by a case study. In summary, the penalized spline joint models provide a new approach for joint models that have improved the existing standard joint models.     

Estimating the Expectation of the Log-Likelihood with Censored Data for Estimator Selection

A criterion for choosing an estimator in a family of semi-parametric estimators from incomplete data is proposed. This criterion is the expected observed log-likelihood (ELL). Adapted versions of this criterion in case of censored data and in presence of explanatory variables are exhibited. We show that likelihood cross-validation (LCV) is an estimator of ELL and we exhibit three bootstrap estimators. A simulation study considering both families of kernel and penalized likelihood estimators of the hazard function (indexed on a smoothing parameter) demonstrates good results of LCV and a bootstrap estimator called ELL_bboot . We apply the ELL_bboot criterion to compare the kernel and penalized likelihood estimators to estimate the risk of developing dementia for women using data from a large cohort study.     

Penalized empirical likelihood inference for sparse additive hazards regression with a diverging number of covariates

High-dimensional sparse modeling with censored survival data is of great practical importance, as exemplified by applications in high-throughput genomic data analysis. In this paper, we propose a class of regularization methods, integrating both the penalized empirical likelihood and pseudoscore approaches, for variable selection and estimation in sparse and high-dimensional additive hazards regression models. When the number of covariates grows with the sample size, we establish asymptotic properties of the resulting estimator and the oracle property of the proposed method. It is shown that the proposed estimator is more efficient than that obtained from the non-concave penalized likelihood approach in the literature. Based on a penalized empirical likelihood ratio statistic, we further develop a nonparametric likelihood approach for testing the linear hypothesis of regression coefficients and constructing confidence regions consequently. Simulation studies are carried out to evaluate the performance of the proposed methodology and also two real data sets are analyzed.     

A Kernel Smooth Approach for Joint Modeling of Accelerated Failure Time and Longitudinal Data

Joint likelihood approaches have been widely used to handle survival data with time-dependent covariates. In construction of the joint likelihood function for the accelerated failure time (AFT) model, the unspecified baseline hazard function is assumed to be a piecewise constant function in the literature. However, there are usually no close form formulas for the regression parameters, which require numerical methods in the EM iterations. The nonsmooth step function assumption leads to very spiky likelihood function which is very hard to find the globe maximum. Besides, due to nonsmoothness of the likelihood function, direct search methods are conducted for the maximization which are very inefficient and time consuming. To overcome the two disadvantages, we propose a kernel smooth pseudo-likelihood function to replace the nonsmooth step function assumption. The performance of the proposed method is evaluated by simulation studies. A case study of reproductive egg-laying data is provided to demonstrate the usefulness of the new approach.     

Hypothesis Testing of Hazard Ratio Parameters in Marginal Models for Multivariate Failure Time Data

Marginal hazard models for multivariate failure time data have been studied extensively in recent literature. However, standard hypothesis test statistics based on the likelihood method are not exactly appropriate for this kind of model. In this paper, extensions of the three commonly used likelihood hypothesis test statistics are discussed. Generalized Wald, generalized score and generalized likelihood ratio tests for hazard ratio parameters in a marginal hazard model for multivariate failure time data are proposed and their asymptotic distributions examined. The finite sample properties of these statistics are studied through simulations. The proposed method is applied to data from Busselton Population Health Surveys.     

Missing genetic information in case-control family data with general semi-parametric shared frailty model

Case-control family data are now widely used to examine the role of gene-environment interactions in the etiology of complex diseases. In these types of studies, exposure levels are obtained retrospectively and, frequently, information on most risk factors of interest is available on the probands but not on their relatives. In this work we consider correlated failure time data arising from population-based case-control family studies with missing genotypes of relatives. We present a new method for estimating the age-dependent marginalized hazard function. The proposed technique has two major advantages: (1) it is based on the pseudo full likelihood function rather than a pseudo composite likelihood function, which usually suffers from substantial efficiency loss; (2) the cumulative baseline hazard function is estimated using a two-stage estimator instead of an iterative process. We assess the performance of the proposed methodology with simulation studies, and illustrate its utility on a real data example.     

Proportional cause-specific reversed hazards model

The proportional reversed hazards model explains the multiplicative effect of covariates on the baseline reversed hazard rate function of lifetimes. In the present study, we introduce a proportional cause-specific reversed hazards model. The proposed regression model facilitates the analysis of failure time data with multiple causes of failure under left censoring. We estimate the regression parameters using a partial likelihood approach. We provide Breslow's type estimators for the cumulative cause-specific reversed hazard rate functions. Asymptotic properties of the estimators are discussed. Simulation studies are conducted to assess their performance. We illustrate the applicability of the proposed model using a real data set.     

Simplex Mixed‐Effects Models for Longitudinal Proportional Data

Abstract. Continuous proportional outcomes are collected from many practical studies, where responses are confined within the unit interval (0,1). Utilizing Barndorff‐Nielsen and Jørgensen's simplex distribution, we propose a new type of generalized linear mixed‐effects model for longitudinal proportional data, where the expected value of proportion is directly modelled through a logit function of fixed and random effects. We establish statistical inference along the lines of Breslow and Clayton's penalized quasi‐likelihood (PQL) and restricted maximum likelihood (REML) in the proposed model. We derive the PQL/REML using the high‐order multivariate Laplace approximation, which gives satisfactory estimation of the model parameters. The proposed model and inference are illustrated by simulation studies and a data example. The simulation studies conclude that the fourth order approximate PQL/REML performs satisfactorily. The data example shows that Aitchison's technique of the normal linear mixed model for logit‐transformed proportional outcomes is not robust against outliers.     

Markov Poisson regression models for discrete time series. Part 1: Methodology

This paper proposes and investigates a class of Markov Poisson regression models in which Poisson rate functions of covariates are conditional on unobserved states which follow a finite-state Markov chain. Features of the proposed model, estimation, inference, bootstrap confidence intervals, model selection and other implementation issues are discussed. Monte Carlo studies suggest that the proposed estimation method is accurate and reliable for single- and multiple-subject time series data; the choice of starting probabilities for the Markov process has little eff ect on the parameter estimates; and penalized likelihood criteria are reliable for determining the number of states. Part 2 provides applications of the proposed model.     

Penalized Maximum Likelihood Estimator for Normal Mixtures

The estimation of the parameters of a mixture of Gaussian densities is considered, within the framework of maximum likelihood. Due to unboundedness of the likelihood function, the maximum likelihood estimator fails to exist. We adopt a solution to likelihood function degeneracy which consists in penalizing the likelihood function. The resulting penalized likelihood function is then bounded over the parameter space and the existence of the penalized maximum likelihood estimator is granted. As original contribution we provide asymptotic properties, and in particular a consistency proof, for the penalized maximum likelihood estimator. Numerical examples are provided in the finite data case, showing the performances of the penalized estimator compared to the standard one.     

Generalized varying-coefficient single-index model

In this paper, the generalized varying-coefficient single-index model is discussed based on penalized likelihood. All the unknown functions are fitted by penalized spline. The estimates of the unknown parameters and the unknown coefficient functions are obtained and the estimation approach is rapid and computationally stable. Under some mild conditions, the consistency and the asymptotic normality of these resulting estimators are given. Two simulation studies are carried out to illustrate the performance of the estimates. An application of the model to the Hong Kong environmental data further demonstrates the potential of the proposed modelling procedures.     

Hellinger distance as a penalized log likelihood

The present paper studies the minimum Hellinger distance estimator by recasting it as the maximum likelihood estimator in a data driven modification of the model density. In the process, the Hellinger distance itself is expressed as a penalized log likelihood function. The penalty is the sum of the model probabilities over the non-observed values of the sample space. A comparison of the modified model density with the original data provides insights into the robustness of the minimum Hellinger distance estimator. Adjustments of the amount of penalty leads to a class of minimum penalized Hellinger distance estimators, some members of which perform substantially better than the minimum Hellinger distance estimator at the model for small samples, without compromising the robustness properties of the latter.     

Fitting survival data with penalized Poisson regression

Cox’s proportional hazards model is the most common way to analyze survival data. The model can be extended in the presence of collinearity to include a ridge penalty, or in cases where a very large number of coefficients (e.g. with microarray data) has to be estimated. To maximize the penalized likelihood, optimal weights of the ridge penalty have to be obtained. However, there is no definite rule for choosing the penalty weight. One approach suggests maximization of the weights by maximizing the leave-one-out cross validated partial likelihood, however this is time consuming and computationally expensive, especially in large datasets. We suggest modelling survival data through a Poisson model. Using this approach, the log-likelihood of a Poisson model is maximized by standard iterative weighted least squares. We will illustrate this simple approach, which includes smoothing of the hazard function and move on to include a ridge term in the likelihood. We will then maximize the likelihood by considering tools from generalized mixed linear models. We will show that the optimal value of the penalty is found simply by computing the hat matrix of the system of linear equations and dividing its trace by a product of the estimated coefficients.     

Model selection for the localized mixture of experts models

In this paper, we propose a penalized likelihood method to simultaneous select covariate, and mixing component and obtain parameter estimation in the localized mixture of experts models. We develop an expectation maximization algorithm to solve the proposed penalized likelihood procedure, and introduce a data-driven procedure to select the tuning parameters. Extensive numerical studies are carried out to compare the finite sample performances of our proposed method and other existing methods. Finally, we apply the proposed methodology to analyze the Boston housing price data set and the baseball salaries data set.