General partially linear additive transformation model with right-censored data

We propose a class of general partially linear additive transformation models (GPLATM) with right-censored survival data in this work. The class of models are flexible enough to cover many commonly used parametric and nonparametric survival analysis models as its special cases. Based on the B spline interpolation technique, we estimate the unknown regression parameters and functions by the maximum marginal likelihood estimation method. One important feature of the estimation procedure is that it does not need the baseline and censoring cumulative density distributions. Some numerical studies illustrate that this procedure can work very well for the moderate sample size.     

Local maximum likelihood estimation and inference

Local maximum likelihood estimation is a nonparametric counterpart of the widely used parametric maximum likelihood technique. It extends the scope of the parametric maximum likelihood method to a much wider class of parametric spaces. Associated with this nonparametric estimation scheme is the issue of bandwidth selection and bias and variance assessment. This paper provides a unified approach to selecting a bandwidth and constructing confidence intervals in local maximum likelihood estimation. The approach is then applied to least squares nonparametric regression and to nonparametric logistic regression. Our experiences in these two settings show that the general idea outlined here is powerful and encouraging.     

LASSO-type estimators for semiparametric nonlinear mixed-effects models estimation

Parametric nonlinear mixed effects models (NLMEs) are now widely used in biometrical studies, especially in pharmacokinetics research and HIV dynamics models, due to, among other aspects, the computational advances achieved during the last years. However, this kind of models may not be flexible enough for complex longitudinal data analysis. Semiparametric NLMEs (SNMMs) have been proposed as an extension of NLMEs. These models are a good compromise and retain nice features of both parametric and nonparametric models resulting in more flexible models than standard parametric NLMEs. However, SNMMs are complex models for which estimation still remains a challenge. Previous estimation procedures are based on a combination of log-likelihood approximation methods for parametric estimation and smoothing splines techniques for nonparametric estimation. In this work, we propose new estimation strategies in SNMMs. On the one hand, we use the Stochastic Approximation version of EM algorithm (SAEM) to obtain exact ML and REML estimates of the fixed effects and variance components. On the other hand, we propose a LASSO-type method to estimate the unknown nonlinear function. We derive oracle inequalities for this nonparametric estimator. We combine the two approaches in a general estimation procedure that we illustrate with simulations and through the analysis of a real data set of price evolution in on-line auctions.     

Flexible estimates of tumour incidence for intermediately lethal tumours in a typical long-term animal bioassay

The estimation of the incidence of tumours in an animal carcinogenicity study is complicated by the occult nature of the tumours involved (i.e. tumours are not observable before an animal's death). Also, the lethality of tumours is generally unknown, making the tumour incidence function non-identifiable without interim sacrifices, cause-of-death data or modelling assumptions. Although Kaplan–Meier curves for overall survival are typically displayed, obtaining analogous plots for tumour incidence generally requires fairly elaborate model fitting. We present a case-study of tetrafluoroethylene to illustrate a simple method for estimating the incidence of tumours as a function of more easily estimable components. One of the components, tumour prevalence, is modelled by using a generalized additive model, which leads to estimates that are more flexible than those derived under the usual parametric models. A multiplicative assumption for tumour lethality allows for the incorporation of concomitant information, such as the size of tumours. Our approach requires only terminal sacrifice data although additional sacrifice data are easily accommodated. Simulations are used to illustrate the estimator proposed and to evaluate its properties. The method also yields a simple summary measure of tumour lethality, which can be helpful in interpreting the results of a 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     

Quantile regression estimation of partially linear additive models

In this paper, we consider the estimation of partially linear additive quantile regression models where the conditional quantile function comprises a linear parametric component and a nonparametric additive component. We propose a two-step estimation approach: in the first step, we approximate the conditional quantile function using a series estimation method. In the second step, the nonparametric additive component is recovered using either a local polynomial estimator or a weighted Nadaraya–Watson estimator. Both consistency and asymptotic normality of the proposed estimators are established. Particularly, we show that the first-stage estimator for the finite-dimensional parameters attains the semiparametric efficiency bound under homoskedasticity, and that the second-stage estimators for the nonparametric additive component have an oracle efficiency property. Monte Carlo experiments are conducted to assess the finite sample performance of the proposed estimators. An application to a real data set is also illustrated.     

A gradient-based algorithm for semiparametric models with missing covariates

In the parametric regression model, the covariate missing problem under missing at random is considered. It is often desirable to use flexible parametric or semiparametric models for the covariate distribution, which can reduce a potential misspecification problem. Recently, a completely nonparametric approach was developed by [H.Y. Chen, Nonparametric and semiparametric models for missing covariates in parameter regression, J. Amer. Statist. Assoc. 99 (2004), pp. 1176–1189; Z. Zhang and H.E. Rockette, On maximum likelihood estimation in parametric regression with missing covariates, J. Statist. Plann. Inference 47 (2005), pp. 206–223]. Although it does not require a model for the covariate distribution or the missing data mechanism, the proposed method assumes that the covariate distribution is supported only by observed values. Consequently, their estimator is a restricted maximum likelihood estimator (MLE) rather than the global MLE. In this article, we show the restricted semiparametric MLE could be very misleading in some cases. We discuss why this problem occurs and suggest an algorithm to obtain the global MLE. Then, we assess the performance of the proposed method via some simulation experiments.     

Empirical likelihood inferences for varying coefficient partially nonlinear models

In this article, empirical likelihood inferences for the varying coefficient partially nonlinear models are investigated. An empirical log-likelihood ratio function for the unknown parameter vector in the nonlinear function part and a residual-adjusted empirical log-likelihood ratio function for the nonparametric component are proposed. The corresponding Wilks phenomena are proved and the confidence regions for parametric component and nonparametric component are constructed. Simulation studies indicate that, in terms of coverage probabilities and average areas of the confidence regions, the empirical likelihood method performs better than the normal approximation-based method. Furthermore, a real data set application is also provided to illustrate the proposed empirical likelihood estimation technique.     

Estimation and inference for generalized semi-varying coefficient models

This paper is concerned with the estimation and inference in generalized semi-varying coefficient models. An orthogonal projection local quasi-likelihood estimation is investigated, which can easily be used to estimate the model parametric and nonparametric parts. Then an empirical likelihood logarithmic approach to construct the confidence regions/intervals of the nonparametric parts is developed. Under some mild conditions, the asymptotic properties of the resulting estimators are studied explicitly, respectively. Some simulation studies are carried out to examine the finite sample performance of the proposed methods. Finally, the methodologies are illustrated by a real data set.     

Direct parametric inference for the cumulative incidence function

Summary.  In survival data that are collected from phase III clinical trials on breast cancer, a patient may experience more than one event, including recurrence of the original cancer, new primary cancer and death. Radiation oncologists are often interested in comparing patterns of local or regional recurrences alone as first events to identify a subgroup of patients who need to be treated by radiation therapy after surgery. The cumulative incidence function provides estimates of the cumulative probability of locoregional recurrences in the presence of other competing events. A simple version of the Gompertz distribution is proposed to parameterize the cumulative incidence function directly. The model interpretation for the cumulative incidence function is more natural than it is with the usual cause-specific hazard parameterization. Maximum likelihood analysis is used to estimate simultaneously parametric models for cumulative incidence functions of all causes. The parametric cumulative incidence approach is applied to a data set from the National Surgical Adjuvant Breast and Bowel Project and compared with analyses that are based on parametric cause-specific hazard models and nonparametric cumulative incidence estimation.     

Estimating herd-specific force of infection by using random-effects models for clustered binary data and monotone fractional polynomials

Summary.  In veterinary epidemiology, we are often confronted with hierarchical or clustered data. Typically animals are grouped within herds, and consequently we cannot ignore the possibility of animals within herds being more alike than between herds. Based on a serological survey of bovine herpes virus type 1 in cattle, we describe a method for the estimation of herd-specific rates at which susceptible animals acquire the infection at different ages. In contrast with the population-averaged force of infection, this method allows us to model the herd-specific force of infection, allowing investigation of the variability between herds. A random-effects approach is used to account for the correlation in the data, allowing us to study both population-averaged and herd-specific force of infection. In contrast, generalized estimating equations can be used when interest is only in the population-averaged force of infection. Further, a flexible predictor model is needed to describe the dependence of covariates appropriately. Fractional polynomials as proposed by Royston and Altman offer such flexibility. However, the flexibility of this model should be restricted, since only positive forces of infection have a meaningful interpretation.     

Nonparametric empirical Bayes for the Dirichlet process mixture model

The Dirichlet process prior allows flexible nonparametric mixture modeling. The number of mixture components is not specified in advance and can grow as new data arrive. However, analyses based on the Dirichlet process prior are sensitive to the choice of the parameters, including an infinite-dimensional distributional parameter G ₀. Most previous applications have either fixed G ₀ as a member of a parametric family or treated G ₀ in a Bayesian fashion, using parametric prior specifications. In contrast, we have developed an adaptive nonparametric method for constructing smooth estimates of G ₀. We combine this method with a technique for estimating α, the other Dirichlet process parameter, that is inspired by an existing characterization of its maximum-likelihood estimator. Together, these estimation procedures yield a flexible empirical Bayes treatment of Dirichlet process mixtures. Such a treatment is useful in situations where smooth point estimates of G ₀ are of intrinsic interest, or where the structure of G ₀ cannot be conveniently modeled with the usual parametric prior families. Analysis of simulated and real-world datasets illustrates the robustness of this approach.     

Testing the Significance of Categorical Predictor Variables in Nonparametric Regression Models

In this paper we propose a test for the significance of categorical predictors in nonparametric regression models. The test is fully data-driven and employs cross-validated smoothing parameter selection while the null distribution of the test is obtained via bootstrapping. The proposed approach allows applied researchers to test hypotheses concerning categorical variables in a fully nonparametric and robust framework, thereby deflecting potential criticism that a particular finding is driven by an arbitrary parametric specification. Simulations reveal that the test performs well, having significantly better power than a conventional frequency-based nonparametric test. The test is applied to determine whether OECD and non-OECD countries follow the same growth rate model or not. Our test suggests that OECD and non-OECD countries follow different growth rate models, while the tests based on a popular parametric specification and the conventional frequency-based nonparametric estimation method fail to detect any significant difference.     

Outlier Resistant Estimation in Difference-Based Semiparametric Partially Linear Models

Partially linear models are extensions of linear models that include a nonparametric function of some covariate allowing an adequate and more flexible handling of explanatory variables than in linear models. The difference-based estimation in partially linear models is an approach designed to estimate parametric component by using the ordinary least squares estimator after removing the nonparametric component from the model by differencing. However, it is known that least squares estimates do not provide useful information for the majority of data when the error distribution is not normal, particularly when the errors are heavy-tailed and when outliers are present in the dataset. This paper aims to find an outlier-resistant fit that represents the information in the majority of the data by robustly estimating the parametric and the nonparametric components of the partially linear model. Simulations and a real data example are used to illustrate the feasibility of the proposed methodology and to compare it with the classical difference-based estimator when outliers exist.     

Estimating curves and derivatives with parametric penalized spline smoothing

Accurate estimation of an underlying function and its derivatives is one of the central problems in statistics. Parametric forms are often proposed based on the expert opinion or prior knowledge of the underlying function. However, these strict parametric assumptions may result in biased estimates when they are not completely accurate. Meanwhile, nonparametric smoothing methods, which do not impose any parametric form, are quite flexible. We propose a parametric penalized spline smoothing method, which has the same flexibility as the nonparametric smoothing methods. It also uses the prior knowledge of the underlying function by defining an additional penalty term using the distance of the fitted function to the assumed parametric function. Our simulation studies show that the parametric penalized spline smoothing method can obtain more accurate estimates of the function and its derivatives than the penalized spline smoothing method. The parametric penalized spline smoothing method is also demonstrated by estimating the human height function and its derivatives from the real data.     

Decriminalization and Marijuana Smoking Prevalence: Evidence From Australia

This article uses the 2001 National Drug Strategy Household Survey to assess the impact of marijuana decriminalization policy on marijuana smoking prevalence in Australia. Both parametric and nonparametric methods are used. The parametric approach includes endogenous probit switching, two-part, sample selection, and standard dummy variable models, while the nonparametric approach uses propensity score stratification matching. Specification analyses are also conducted. A nonparametric kernel-based test is constructed to select between parametric and nonparametric models, and the likelihood ratio test is used to choose among parametric models. Our analyses favor the endogenous switching model where decriminalization increases the probability of smoking by 16.2%.     

Semiparametric Analysis of Truncated Data

Randomly truncated data are frequently encountered in many studies where truncation arises as a result of the sampling design. In the literature, nonparametric and semiparametric methods have been proposed to estimate parameters in one-sample models. This paper considers a semiparametric model and develops an efficient method for the estimation of unknown parameters. The model assumes that K populations have a common probability distribution but the populations are observed subject to different truncation mechanisms. Semiparametric likelihood estimation is studied and the corresponding inferences are derived for both parametric and nonparametric components in the model. The method can also be applied to two-sample problems to test the difference of lifetime distributions. Simulation results and a real data analysis are presented to illustrate the methods.     

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.     

Monotone Nonparametric Regression and Confidence Intervals

Several variations of monotone nonparametric regression have been developed over the past 30 years. One approach is to first apply nonparametric regression to data and then monotone smooth the initial estimates to “iron out” violations to the assumed order. Here, such estimators are considered, where local polynomial regression is first used, followed by either least squares isotonic regression or a monotone method using simple averages. The primary focus of this work is to evaluate different types of confidence intervals for these monotone nonparametric regression estimators through Monte Carlo simulation. Most of the confidence intervals use bootstrap or jackknife procedures. Estimation of a response variable as a function of two continuous predictor variables is considered, where the estimation is performed at the observed values of the predictors (instead of on a grid). The methods are then applied to data involving subjects that worked at plants that use beryllium metal who have developed chronic beryllium disease.     

Nonparametric density estimation for censored survival data: Regression-spline approach

A method for nonparametric estimation of density based on a randomly censored sample is presented. The density is expressed as a linear combination of cubic M -splines, and the coefficients are determined by pseudo-maximum-likelihood estimation (likelihood is maximized conditionally on data-dependent knots). By using regression splines (small number of knots) it is possible to reduce the estimation problem to a space of low dimension while preserving flexibility, thus striking a compromise between parametric approaches and ordinary nonparametric approaches based on spline smoothing. The number of knots is determined by the minimum AIC. Examples of simulated and real data are presented. Asymptotic theory and the bootstrap indicate that the precision and the accuracy of the estimates are satisfactory.