Locally Efficient Semiparametric Estimators for Proportional Hazards Models with Measurement Error

We propose a new class of semiparametric estimators for proportional hazards models in the presence of measurement error in the covariates, where the baseline hazard function, the hazard function for the censoring time, and the distribution of the true covariates are considered as unknown infinite dimensional parameters. We estimate the model components by solving estimating equations based on the semiparametric efficient scores under a sequence of restricted models where the logarithm of the hazard functions are approximated by reduced rank regression splines. The proposed estimators are locally efficient in the sense that the estimators are semiparametrically efficient if the distribution of the error‐prone covariates is specified correctly and are still consistent and asymptotically normal if the distribution is misspecified. Our simulation studies show that the proposed estimators have smaller biases and variances than competing methods. We further illustrate the new method with a real application in an HIV clinical trial.     

A Bayesian semiparametric accelerated failure time model for arbitrarily censored data with covariates subject to measurement error

A flexible Bayesian semiparametric accelerated failure time (AFT) model is proposed for analyzing arbitrarily censored survival data with covariates subject to measurement error. Specifically, the baseline error distribution in the AFT model is nonparametrically modeled as a Dirichlet process mixture of normals. Classical measurement error models are imposed for covariates subject to measurement error. An efficient and easy-to-implement Gibbs sampler, based on the stick-breaking formulation of the Dirichlet process combined with the techniques of retrospective and slice sampling, is developed for the posterior calculation. An extensive simulation study is conducted to illustrate the advantages of our approach.     

Bayesian semiparametric inference for the accelerated failure-time model

Bayesian semiparametric inference is considered for a loglinear model. This model consists of a parametric component for the regression coefficients and a nonparametric component for the unknown error distribution. Bayesian analysis is studied for the case of a parametric prior on the regression coefficients and a mixture-of-Dirichlet-processes prior on the unknown error distribution. A Markov-chain Monte Carlo (MCMC) method is developed to compute the features of the posterior distribution. A model selection method for obtaining a more parsimonious set of predictors is studied. The method adds indicator variables to the regression equation. The set of indicator variables represents all the possible subsets to be considered. A MCMC method is developed to search stochastically for the best subset. These procedures are applied to two examples, one with censored data.     

A Semiparametric Approach for Accelerated Failure Time Models with Covariates Subject to Measurement Error

There are relatively few discussions about measurement error in the accelerated failure time (AFT) model, particularly for the semiparametric AFT model. In this article, we propose an adjusted estimation procedure for the semiparametric AFT model with covariates subject to measurement error, based on the profile likelihood approach and simulation and exploration (SIMEX) method. The simulation studies show that the proposed semiparametric SIMEX approach performs well. The proposed approach is applied to a coronary heart disease dataset from the Busselton Health study for illustration.     

Local and omnibus goodness-of-fit tests in classical measurement error models

We consider functional measurement error models, i.e. models where covariates are measured with error and yet no distributional assumptions are made about the mismeasured variable. We propose and study a score-type local test and an orthogonal series-based, omnibus goodness-of-fit test in this context, where no likelihood function is available or calculated-i.e. all the tests are proposed in the semiparametric model framework. We demonstrate that our tests have optimality properties and computational advantages that are similar to those of the classical score tests in the parametric model framework. The test procedures are applicable to several semiparametric extensions of measurement error models, including when the measurement error distribution is estimated non-parametrically as well as for generalized partially linear models. The performance of the local score-type and omnibus goodness-of-fit tests is demonstrated through simulation studies and analysis of a nutrition data set.     

Bayesian Semiparametric Modelling in Quantile Regression

Abstract. We propose a Bayesian semiparametric methodology for quantile regression modelling. In particular, working with parametric quantile regression functions, we develop Dirichlet process mixture models for the error distribution in an additive quantile regression formulation. The proposed non‐parametric prior probability models allow the shape of the error density to adapt to the data and thus provide more reliable predictive inference than models based on parametric error distributions. We consider extensions to quantile regression for data sets that include censored observations. Moreover, we employ dependent Dirichlet processes to develop quantile regression models that allow the error distribution to change non‐parametrically with the covariates. Posterior inference is implemented using Markov chain Monte Carlo methods. We assess and compare the performance of our models using both simulated and real data sets.     

Semiparametric errors-in-variables models A Bayesian approach

Regression models incorporating measurement error have received much attention in the recent literature. Measurement error can arise both in the explanatory variables and in the response. We introduce a fairly general model which permits both types of errors. The model naturally arises as a hierarchical structure involving three distinct regressions. For each regression, a semiparametric generalized linear model is introduced utilizing an unknown monotonic function. By transformation, such a function can be viewed as a c.d.f. We model an unknown c.d.f. using mixtures of Beta c.d.f.'s, noting that such mixtures are dense within the class of all continuous distributions on [0,1]. Thus, the overall model incorporates nonparametric links or calibration curves along with customary regression coefficients clarifying its semiparametric nature. Fully Bayesian fitting of such a model using sampling-based methods is proposed. We indicate numerous attractive advantages which our model and its fitting provide. A simulation example demonstrates quantitatively the potential benefit.     

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.     

SEMIPARAMETRIC ESTIMATION OF THE ERROR DISTRIBUTION IN MULTIVARIATE REGRESSION USING COPULAS

A semiparametric method is developed to estimate the dependence parameter and the joint distribution of the error term in the multivariate linear regression model. The nonparametric part of the method treats the marginal distributions of the error term as unknown, and estimates them using suitable empirical distribution functions. Then the dependence parameter is estimated by either maximizing a pseudolikelihood or solving an estimating equation. It is shown that this estimator is asymptotically normal, and a consistent estimator of its large sample variance is given. A simulation study shows that the proposed semiparametric method is better than the parametric ones available when the error distribution is unknown, which is almost always the case in practice. It turns out that there is no loss of asymptotic efficiency as a result of the estimation of regression parameters. An empirical example on portfolio management is used to illustrate the method.     

Parametric and semiparametric hypotheses in the linear model

The independent additive errors linear model consists of a structure for the mean and a separate structure for the error distribution. The error structure may be parametric or it may be semiparametric. Under alternative values of the mean structure, the best fitting additive errors model has an error distribution which can be represented as the convolution of the actual error distribution and the marginal distribution of a misspecification term. The model misspecification term results from the covariates' distribution. Conditions are developed to distinguish when the semiparametric model yields sharper inference than the parametric model and vice versa. The main conditions concern the actual error distribution and the covariates' distribution. The theoretical results explain a paradoxical finding in semiparametric Bayesian modelling, where the posterior distribution under a semiparametric model is found to be more concentrated than is the posterior distribution under a corresponding parametric model. The paradox is illustrated on a set of allometric data. The Canadian Journal of Statistics 39: 165–180; 2011 ©2011 Statistical Society of Canada     

On semiparametric pivotal bayesian inference for quantiles

In semiparametric inference we distinguish between the parameter of interest which may be a location parameter, and a nuisance parameter that determines the remaining shape of the sampling distribution. As was pointed out by Diaconis and Freedman the main problem in semiparametric Bayesian inference is to obtain a consistent posterior distribution for the parameter of interest. The present paper considers a semiparametric Bayesian method based on a pivotal likelihood function. It is shown that when the parameter of interest is the median, this method produces a consistent posterior distribution and is easily implemented, Numerical comparisons with classical methods and with Bayesian methods based on a Dirichlet prior are provided. It is also shown that in the case of symmetric intervals, the classical confidence coefficients have a Bayesian interpretation as the limiting posterior probability of the interval based on the Dirichlet prior with a parameter that converges to zero.     

Cox regression for mixed case interval-censored data with covariate errors

Covariate measurement error problems have been extensively studied in the context of right-censored data but less so for interval-censored data. Motivated by the AIDS Clinical Trial Group 175 study, where the occurrence time of AIDS was examined only at intermittent clinic visits and the baseline covariate CD4 count was measured with error, we describe a semiparametric maximum likelihood method for analyzing mixed case interval-censored data with mismeasured covariates under the proportional hazards model. We show that the estimator of the regression coefficient is asymptotically normal and efficient and provide a very stable and efficient algorithm for computing the estimators. We evaluate the method through simulation studies and illustrate it with AIDS data.     

Generalized linear models with covariate measurement error and unknown link function

Generalized linear models (GLMs) with error-in-covariates are useful in epidemiological research due to the ubiquity of non-normal response variables and inaccurate measurements. The link function in GLMs is chosen by the user depending on the type of response variable, frequently the canonical link function. When covariates are measured with error, incorrect inference can be made, compounded by incorrect choice of link function. In this article we propose three flexible approaches for handling error-in-covariates and estimating an unknown link simultaneously. The first approach uses a fully Bayesian (FB) hierarchical framework, treating the unobserved covariate as a latent variable to be integrated over. The second and third are approximate Bayesian approach which use a Laplace approximation to marginalize the variables measured with error out of the likelihood. Our simulation results show support that the FB approach is often a better choice than the approximate Bayesian approaches for adjusting for measurement error, particularly when the measurement error distribution is misspecified. These approaches are demonstrated on an application with binary response.     

Hierarchical Generalized Linear Models and Frailty Models with Bayesian Nonparametric Mixing

This paper proposes Bayesian nonparametric mixing for some well-known and popular models. The distribution of the observations is assumed to contain an unknown mixed effects term which includes a fixed effects term, a function of the observed covariates, and an additive or multiplicative random effects term. Typically these random effects are assumed to be independent of the observed covariates and independent and identically distributed from a distribution from some known parametric family. This assumption may be suspect if either there is interaction between observed covariates and unobserved covariates or the fixed effects predictor of observed covariates is misspecified. Another cause for concern might be simply that the covariates affect more than just the location of the mixed effects distribution. As a consequence the distribution of the random effects could be highly irregular in modality and skewness leaving parametric families unable to model the distribution adequately. This paper therefore proposes a Bayesian nonparametric prior for the random effects to capture possible deviances in modality and skewness and to explore the observed covariates' effect on the distribution of the mixed effects.     

Bayesian Survival Analysis in Proportional Hazard Models with Logistic Relative Risk

Abstract.  The traditional Cox proportional hazards regression model uses an exponential relative risk function. We argue that under various plausible scenarios, the relative risk part of the model should be bounded, suggesting also that the traditional model often might overdramatize the hazard rate assessment for individuals with unusual covariates. This motivates our working with proportional hazards models where the relative risk function takes a logistic form. We provide frequentist methods, based on the partial likelihood, and then go on to semiparametric Bayesian constructions. These involve a Beta process for the cumulative baseline hazard function and any prior with a density, for example that dictated by a Jeffreys-type argument, for the regression coefficients. The posterior is derived using machinery for Lévy processes, and a simulation recipe is devised for sampling from the posterior distribution of any quantity. Our methods are illustrated on real data. A Bernshtĕn–von Mises theorem is reached for our class of semiparametric priors, guaranteeing asymptotic normality of the posterior processes.     

Bayesian inference for generalized additive mixed models based on Markov random field priors

Most regression problems in practice require flexible semiparametric forms of the predictor for modelling the dependence of responses on covariates. Moreover, it is often necessary to add random effects accounting for overdispersion caused by unobserved heterogeneity or for correlation in longitudinal or spatial data. We present a unified approach for Bayesian inference via Markov chain Monte Carlo simulation in generalized additive and semiparametric mixed models. Different types of covariates, such as the usual covariates with fixed effects, metrical covariates with non-linear effects, unstructured random effects, trend and seasonal components in longitudinal data and spatial covariates, are all treated within the same general framework by assigning appropriate Markov random field priors with different forms and degrees of smoothness. We applied the approach in several case-studies and consulting cases, showing that the methods are also computationally feasible in problems with many covariates and large data sets. In this paper, we choose two typical applications.     

Bayesian Nonparametric Instrumental Variables Regression Based on Penalized Splines and Dirichlet Process Mixtures

We propose a Bayesian nonparametric instrumental variable approach under additive separability that allows us to correct for endogeneity bias in regression models where the covariate effects enter with unknown functional form. Bias correction relies on a simultaneous equations specification with flexible modeling of the joint error distribution implemented via a Dirichlet process mixture prior. Both the structural and instrumental variable equation are specified in terms of additive predictors comprising penalized splines for nonlinear effects of continuous covariates. Inference is fully Bayesian, employing efficient Markov chain Monte Carlo simulation techniques. The resulting posterior samples do not only provide us with point estimates, but allow us to construct simultaneous credible bands for the nonparametric effects, including data-driven smoothing parameter selection. In addition, improved robustness properties are achieved due to the flexible error distribution specification. Both these features are challenging in the classical framework, making the Bayesian one advantageous. In simulations, we investigate small sample properties and an investigation of the effect of class size on student performance in Israel provides an illustration of the proposed approach which is implemented in an R package bayesIV. Supplementary materials for this article are available online.     

Semiparametric methods for response-selective and missing data problems in regression

Suppose that data are generated according to the model f ( y | x ; θ ) g ( x ), where y is a response and x are covariates. We derive and compare semiparametric likelihood and pseudolikelihood methods for estimating θ for situations in which units generated are not fully observed and in which it is impossible or undesirable to model the covariate distribution. The probability that a unit is fully observed may depend on y , and there may be a subset of covariates which is observed only for a subsample of individuals. Our key assumptions are that the probability that a unit has missing data depends only on which of a finite number of strata that ( y , x ) belongs to and that the stratum membership is observed for every unit. Applications include case–control studies in epidemiology, field reliability studies and broad classes of missing data and measurement error problems. Our results make fully efficient estimation of θ feasible, and they generalize and provide insight into a variety of methods that have been proposed for specific problems.     

Bayesian Semiparametric Cure Rate Model with an Unknown Threshold

Abstract.  We propose a Bayesian semiparametric model for survival data with a cure fraction. We explicitly consider a finite cure time in the model, which allows us to separate the cured and the uncured populations. We take a mixture prior of a Markov gamma process and a point mass at zero to model the baseline hazard rate function of the entire population. We focus on estimating the cure threshold after which subjects are considered cured. We can incorporate covariates through a structure similar to the proportional hazards model and allow the cure threshold also to depend on the covariates. For illustration, we undertake simulation studies and a full Bayesian analysis of a bone marrow transplant data set.     

Cox regression for current status data with mismeasured covariates

Covariate measurement error problems have been extensively studied in the context of right‐censored data but less so for current status data. Motivated by the zebrafish basal cell carcinoma (BCC) study, where the occurrence time of BCC was only known to lie before or after a sacrifice time and where the covariate (Sonic hedgehog expression) was measured with error, the authors describe a semiparametric maximum likelihood method for analyzing current status data with mismeasured covariates under the proportional hazards model. They show that the estimator of the regression coefficient is asymptotically normal and efficient and that the profile likelihood ratio test is asymptotically Chi‐squared. They also provide an easily implemented algorithm for computing the estimators. They evaluate their method through simulation studies, and illustrate it with a real data example. The Canadian Journal of Statistics 39: 73–88; 2011 © 2011 Statistical Society of Canada