A method for combining inference across related nonparametric Bayesian models

Summary.  We consider the problem of combining inference in related nonparametric Bayes models. Analogous to parametric hierarchical models, the hierarchical extension formalizes borrowing strength across the related submodels. In the nonparametric context, modelling is complicated by the fact that the random quantities over which we define the hierarchy are infinite dimensional. We discuss a formal definition of such a hierarchical model. The approach includes a regression at the level of the nonparametric model. For the special case of Dirichlet process mixtures, we develop a Markov chain Monte Carlo scheme to allow efficient implementation of full posterior inference in the given model.     

Semiparametric Bayesian classification with longitudinal markers

Summary.  We analyse data from a study involving 173 pregnant women. The data are observed values of the β human chorionic gonadotropin hormone measured during the first 80 days of gestational age, including from one up to six longitudinal responses for each woman. The main objective in this study is to predict normal versus abnormal pregnancy outcomes from data that are available at the early stages of pregnancy. We achieve the desired classification with a semiparametric hierarchical model. Specifically, we consider a Dirichlet process mixture prior for the distribution of the random effects in each group. The unknown random-effects distributions are allowed to vary across groups but are made dependent by using a design vector to select different features of a single underlying random probability measure. The resulting model is an extension of the dependent Dirichlet process model, with an additional probability model for group classification. The model is shown to perform better than an alternative model which is based on independent Dirichlet processes for the groups. Relevant posterior distributions are summarized by using Markov chain Monte Carlo methods.     

Semiparametric Bayesian hierarchical models for heterogeneous population in nonlinear mixed effect model: application to gastric emptying studies

Gastric emptying studies are frequently used in medical research, both human and animal, when evaluating the effectiveness and determining the unintended side-effects of new and existing medications, diets, and procedures or interventions. It is essential that gastric emptying data be appropriately summarized before making comparisons between study groups of interest and to allow study the comparisons. Since gastric emptying data have a nonlinear emptying curve and are longitudinal data, nonlinear mixed effect (NLME) models can accommodate both the variation among measurements within individuals and the individual-to-individual variation. However, the NLME model requires strong assumptions that are often not satisfied in real applications that involve a relatively small number of subjects, have heterogeneous measurement errors, or have large variation among subjects. Therefore, we propose three semiparametric Bayesian NLMEs constructed with Dirichlet process priors, which automatically cluster sub-populations and estimate heterogeneous measurement errors. To compare three semiparametric models with the parametric model we propose a penalized posterior Bayes factor. We compare the performance of our semiparametric hierarchical Bayesian approaches with that of the parametric Bayesian hierarchical approach. Simulation results suggest that our semiparametric approaches are more robust and flexible. Our gastric emptying studies from equine medicine are used to demonstrate the advantage of our approaches.     

A class of semiparametric transformation models for survival data with a cured proportion

We propose a new class of semiparametric regression models based on a multiplicative frailty assumption with a discrete frailty, which may account for cured subgroup in population. The cure model framework is then recast as a problem with a transformation model. The proposed models can explain a broad range of nonproportional hazards structures along with a cured proportion. An efficient and simple algorithm based on the martingale process is developed to locate the nonparametric maximum likelihood estimator. Unlike existing expectation-maximization based methods, our approach directly maximizes a nonparametric likelihood function, and the calculation of consistent variance estimates is immediate. The proposed method is useful for resolving identifiability features embedded in semiparametric cure models. Simulation studies are presented to demonstrate the finite sample properties of the proposed method. A case study of stage III soft-tissue sarcoma is given as an illustration.     

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.     

Semiparametric Estimation with Profile Algorithm for Longitudinal Binary Data

This article considers analyzing longitudinal binary data semiparametrically and proposing GEE-Smoothing spline in the estimation of parametric and nonparametric components. The method is an extension of the parametric generalized estimating equation to semiparametric. The nonparametric component is estimated by smoothing spline approach, i.e., natural cubic spline. We use profile algorithm in the estimation of both parametric and nonparametric components. Properties of the estimators are evaluated by simulation.     

Flexible clustering via hidden hierarchical Dirichlet priors

The Bayesian approach to inference stands out for naturally allowing borrowing information across heterogeneous populations, with different samples possibly sharing the same distribution. A popular Bayesian nonparametric model for clustering probability distributions is the nested Dirichlet process, which however has the drawback of grouping distributions in a single cluster when ties are observed across samples. With the goal of achieving a flexible and effective clustering method for both samples and observations, we investigate a nonparametric prior that arises as the composition of two different discrete random structures and derive a closed-form expression for the induced distribution of the random partition, the fundamental tool regulating the clustering behavior of the model. On the one hand, this allows to gain a deeper insight into the theoretical properties of the model and, on the other hand, it yields an MCMC algorithm for evaluating Bayesian inferences of interest. Moreover, we single out limitations of this algorithm when working with more than two populations and, consequently, devise an alternative more efficient sampling scheme, which as a by-product, allows testing homogeneity between different populations. Finally, we perform a comparison with the nested Dirichlet process and provide illustrative examples of both synthetic and real data.     

Estimation in semiparametric models using an auxiliary model

Two classes of semiparametric and nonparametric mixture models are defined to represent general kinds of prior information. For these models the nonparametric maximum likelihood estimator (NPMLE) of an unknown probability distribution is derived and is shown to be consistent and relative efficient. Linear functionals are used for the estimation of parameters. Their consistency is proved, the gain of efficiency is derived and asymptotical distributions are given.     

Nonparametric and semiparametric estimation of the three way receiver operating characteristic surface

In many situations the diagnostic decision is not limited to a binary choice. Binary statistical tools such as receiver operating characteristic (ROC) curve and area under the ROC curve (AUC) need to be expanded to address three-category classification problem. Previous authors have suggest various ways to model the extension of AUC but not the ROC surface. Only simple parametric approaches are proposed for modeling the ROC measure under the assumption that test results all follow normal distributions. We study the estimation methods of three-dimensional ROC surfaces with nonparametric and semiparametric estimators. Asymptotical results are provided as a basis for statistical inference. Simulation studies are performed to assess the validity of our proposed methods in finite samples. We consider an Alzheimer's disease example from a clinical study in the US as an illustration. The nonparametric and semiparametric modelling approaches for the three way ROC analysis can be readily generalized to diagnostic problems with more than three classes.     

Semiparametric model average prediction in panel data analysis

Forecasting in economic data analysis is dominated by linear prediction methods where the predicted values are calculated from a fitted linear regression model. With multiple predictor variables, multivariate nonparametric models were proposed in the literature. However, empirical studies indicate the prediction performance of multi-dimensional nonparametric models may be unsatisfactory. We propose a new semiparametric model average prediction (SMAP) approach to analyse panel data and investigate its prediction performance with numerical examples. Estimation of individual covariate effect only requires univariate smoothing and thus may be more stable than previous multivariate smoothing approaches. The estimation of optimal weight parameters incorporates the longitudinal correlation and the asymptotic properties of the estimated results are carefully studied in this paper.     

Case-cohort analysis with semiparametric transformation models

Semiparametric transformation models provide flexible regression models for survival analysis, including the Cox proportional hazards and the proportional odds models as special cases. We consider the application of semiparametric transformation models in case-cohort studies, where the covariate data are observed only on cases and on a subcohort randomly sampled from the full cohort. We first propose an approximate profile likelihood approach with full-cohort data, which amounts to the pseudo-partial likelihood approach of Zucker [2005. A pseudo-partial likelihood method for semiparametric survival regression with covariate errors. J. Amer. Statist. Assoc. 100, 1264–1277]. Simulation results show that our proposal is almost as efficient as the nonparametric maximum likelihood estimator. We then extend this approach to the case-cohort design, applying the Horvitz–Thompson weighting method to the estimating equations from the approximated profile likelihood. Two levels of weights can be utilized to achieve unbiasedness and to gain efficiency. The resulting estimator has a closed-form asymptotic covariance matrix, and is found in simulations to be substantially more efficient than the estimator based on martingale estimating equations. The extension to left-truncated data will be discussed. We illustrate the proposed method on data from a cardiovascular risk factor study conducted in Taiwan.     

Influence Diagnostics of Semiparametric Nonlinear Reproductive Dispersion Models

This article proposes a semiparametric nonlinear reproductive dispersion model (SNRDM) which is an extension of nonlinear reproductive dispersion model and semiparametric regression model. Maximum penalized likelihood estimators (MPLEs) of unknown parameters and nonparametric functions in SNRDMs are presented. Some novel diagnostic statistics such as Cook distance and difference deviance for parametric and nonparametric parts are developed to identify influence observations in SNRDMs on the basis of case-deletion method, and some formulae readily computed with the MPLEs algorithm for diagnostic measures are given. The equivalency of case-deletion models and mean-shift outlier models in SNRDM is investigated. A simulation study and a real example are used to illustrate the proposed diagnostic measures.     

Robust exchangeability designs for early phase clinical trials with multiple strata

Clinical trials with multiple strata are increasingly used in drug development. They may sometimes be the only option to study a new treatment, for example in small populations and rare diseases. In early phase trials, where data are often sparse, good statistical inference and subsequent decision‐making can be challenging. Inferences from simple pooling or stratification are known to be inferior to hierarchical modeling methods, which build on exchangeable strata parameters and allow borrowing information across strata. However, the standard exchangeability (EX) assumption bears the risk of too much shrinkage and excessive borrowing for extreme strata. We propose the exchangeability–nonexchangeability (EXNEX) approach as a robust mixture extension of the standard EX approach. It allows each stratum‐specific parameter to be exchangeable with other similar strata parameters or nonexchangeable with any of them. While EXNEX computations can be performed easily with standard Bayesian software, model specifications and prior distributions are more demanding and require a good understanding of the context. Two case studies from phases I and II (with three and four strata) show promising results for EXNEX. Data scenarios reveal tempered degrees of borrowing for extreme strata, and frequentist operating characteristics perform well for estimation (bias, mean‐squared error) and testing (less type‐I error inflation). Copyright © 2015 John Wiley & Sons, Ltd.     

Estimation of finite mixtures with symmetric components

It may sometimes be clear from background knowledge that a population under investigation proportionally consists of a known number of subpopulations, whose distributions belong to the same, yet unknown, family. While a parametric family is commonly used in practice, one can also consider some nonparametric families to avoid distributional misspecification. In this article, we propose a solution using a mixture-based nonparametric family for the component distribution in a finite mixture model as opposed to some recent research that utilizes a kernel-based approach. In particular, we present a semiparametric maximum likelihood estimation procedure for the model parameters and tackle the bandwidth parameter selection problem via some popular means for model selection. Empirical comparisons through simulation studies and three real data sets suggest that estimators based on our mixture-based approach are more efficient than those based on the kernel-based approach, in terms of both parameter estimation and overall density estimation.     

Empirical Likelihood Inferences for Semiparametric Varying-Coefficient Partially Linear Models with Longitudinal Data

In this article, empirical likelihood inferences for semiparametric varying-coefficient partially linear models with longitudinal data are investigated. We propose a groupwise empirical likelihood procedure to handle the inter-series dependence of the longitudinal data. By using residual-adjustment, an empirical likelihood ratio function for the nonparametric component is constructed, and a nonparametric version Wilks' phenomenons is proved. Compared with methods based on normal approximations, the empirical likelihood does not require consistent estimators for the asymptotic variance and bias. A simulation study is undertaken to assess the finite sample performance of the proposed confidence regions.     

Regression splines in the quasi-likelihood analysis of recurrent event data

In many longitudinal studies of recurrent events there is an interest in assessing how recurrences vary over time and across treatments or strata in the population. Usual analyses of such data assume a parametric form for the distribution of the recurrences over time. Here, we consider a semiparametric model for the analysis of such longitudinal studies where data are collected as panel counts. The model is a non-homogeneous Poisson process with a multiplicative intensity incorporating covariates through a proportionality assumption. Heterogeneity is accounted for in the model through subject-specific random effects. The key feature of the model is the use of regression splines to model the distribution of recurrences over time. This provides a flexible and robust method of relaxing parametric assumptions. In addition, quasi-likelihood methods are proposed for estimation, requiring only first and second moment assumptions to obtain consistent estimates. Simulations demonstrate that the method produces estimators of the rate with low bias and whose standardized distributions are well approximated by the normal. The usefulness of this approach, especially as an exploratory tool, is illustrated by analyzing a study designed to assess the effectiveness of a pheromone treatment in disturbing the mating habits of the Cherry Bark Tortrix moth.     

A shared parameter model of longitudinal measurements and survival time with heterogeneous random-effects distribution

Typical joint modeling of longitudinal measurements and time to event data assumes that two models share a common set of random effects with a normal distribution assumption. But, sometimes the underlying population that the sample is extracted from is a heterogeneous population and detecting homogeneous subsamples of it is an important scientific question. In this paper, a finite mixture of normal distributions for the shared random effects is proposed for considering the heterogeneity in the population. For detecting whether the unobserved heterogeneity exits or not, we use a simple graphical exploratory diagnostic tool proposed by Verbeke and Molenberghs [34] to assess whether the traditional normality assumption for the random effects in the mixed model is adequate. In the joint modeling setting, in the case of evidence against normality (homogeneity), a finite mixture of normals is used for the shared random-effects distribution. A Bayesian MCMC procedure is developed for parameter estimation and inference. The methodology is illustrated using some simulation studies. Also, the proposed approach is used for analyzing a real HIV data set, using the heterogeneous joint model for this data set, the individuals are classified into two groups: a group with high risk and a group with moderate risk.     

Nonlinear semiparametric autoregressive model with finite mixtures of scale mixtures of skew normal innovations

We propose data generating structures which can be represented as the nonlinear autoregressive models with single and finite mixtures of scale mixtures of skew normal innovations. This class of models covers symmetric/asymmetric and light/heavy-tailed distributions, so provide a useful generalization of the symmetrical nonlinear autoregressive models. As semiparametric and nonparametric curve estimation are the approaches for exploring the structure of a nonlinear time series data set, in this article the semiparametric estimator for estimating the nonlinear function of the model is investigated based on the conditional least square method and nonparametric kernel approach. Also, an Expectation–Maximization-type algorithm to perform the maximum likelihood (ML) inference of unknown parameters of the model is proposed. Furthermore, some strong and weak consistency of the semiparametric estimator in this class of models are presented. Finally, to illustrate the usefulness of the proposed model, some simulation studies and an application to real data set are considered.     

Bayesian spectral analysis models for quantile regression with Dirichlet process mixtures

This paper presents a Bayesian analysis of partially linear additive models for quantile regression. We develop a semiparametric Bayesian approach to quantile regression models using a spectral representation of the nonparametric regression functions and the Dirichlet process (DP) mixture for error distribution. We also consider Bayesian variable selection procedures for both parametric and nonparametric components in a partially linear additive model structure based on the Bayesian shrinkage priors via a stochastic search algorithm. Based on the proposed Bayesian semiparametric additive quantile regression model referred to as BSAQ, the Bayesian inference is considered for estimation and model selection. For the posterior computation, we design a simple and efficient Gibbs sampler based on a location-scale mixture of exponential and normal distributions for an asymmetric Laplace distribution, which facilitates the commonly used collapsed Gibbs sampling algorithms for the DP mixture models. Additionally, we discuss the asymptotic property of the sempiparametric quantile regression model in terms of consistency of posterior distribution. Simulation studies and real data application examples illustrate the proposed method and compare it with Bayesian quantile regression methods in the literature.     

Nonparametric estimation with recurrent competing risks data

Nonparametric estimators of component and system life distributions are developed and presented for situations where recurrent competing risks data from series systems are available. The use of recurrences of components’ failures leads to improved efficiencies in statistical inference, thereby leading to resource-efficient experimental or study designs or improved inferences about the distributions governing the event times. Finite and asymptotic properties of the estimators are obtained through simulation studies and analytically. The detrimental impact of parametric model misspecification is also vividly demonstrated, lending credence to the virtue of adopting nonparametric or semiparametric models, especially in biomedical settings. The estimators are illustrated by applying them to a data set pertaining to car repairs for vehicles that were under warranty.