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.     

Estimation and testing for semiparametric mixtures of partially linear models

In this paper, we study the estimation and inference for a class of semiparametric mixtures of partially linear models. We prove that the proposed models are identifiable under mild conditions, and then give a PL–EM algorithm estimation procedure based on profile likelihood. The asymptotic properties for the resulting estimators and the ascent property of the PL–EM algorithm are investigated. Furthermore, we develop a test statistic for testing whether the non parametric component has a linear structure. Monte Carlo simulations and a real data application highlight the interest of the proposed procedures.     

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.     

Regression analysis of informative current status data with the semiparametric linear transformation model

Many methods have been developed in the literature for regression analysis of current status data with noninformative censoring and also some approaches have been proposed for semiparametric regression analysis of current status data with informative censoring. However, the existing approaches for the latter situation are mainly on specific models such as the proportional hazards model and the additive hazard model. Corresponding to this, in this paper, we consider a general class of semiparametric linear transformation models and develop a sieve maximum likelihood estimation approach for the inference. In the method, the copula model is employed to describe the informative censoring or relationship between the failure time of interest and the censoring time, and Bernstein polynomials are used to approximate the nonparametric functions involved. The asymptotic consistency and normality of the proposed estimators are established, and an extensive simulation study is conducted and indicates that the proposed approach works well for practical situations. In addition, an illustrative example is provided.     

A class of semiparametric cure models with current status data

Current status data occur in many biomedical studies where we only know whether the event of interest occurs before or after a particular time point. In practice, some subjects may never experience the event of interest, i.e., a certain fraction of the population is cured or is not susceptible to the event of interest. We consider a class of semiparametric transformation cure models for current status data with a survival fraction. This class includes both the proportional hazards and the proportional odds cure models as two special cases. We develop efficient likelihood-based estimation and inference procedures. We show that the maximum likelihood estimators for the regression coefficients are consistent, asymptotically normal, and asymptotically efficient. Simulation studies demonstrate that the proposed methods perform well in finite samples. For illustration, we provide an application of the models to a study on the calcification of the hydrogel intraocular lenses.

     

Semiparametric analysis of mixture regression models with competing risks data

In the analysis of competing risks data, cumulative incidence function is a useful summary of the overall crude risk for a failure type of interest. Mixture regression modeling has served as a natural approach to performing covariate analysis based on this quantity. However, existing mixture regression methods with competing risks data either impose parametric assumptions on the conditional risks or require stringent censoring assumptions. In this article, we propose a new semiparametric regression approach for competing risks data under the usual conditional independent censoring mechanism. We establish the consistency and asymptotic normality of the resulting estimators. A simple resampling method is proposed to approximate the distribution of the estimated parameters and that of the predicted cumulative incidence functions. Simulation studies and an analysis of a breast cancer dataset demonstrate that our method performs well with realistic sample sizes and is appropriate for practical use.     

Marginal Regression Model with Time-Varying Coefficients for Panel Data

In this article, we formulate a class of semiparametric marginal means models with a mixture of time-varying and time-independent parameters for analyzing panel data. For inference about the regression parameters, an estimation procedure is developed and asymptotic properties of the proposed estimators are established. In addition, some tests are presented for investigating whether or not covariate effects vary with time. The finite-sample behavior of the proposed methods is examined in simulation studies, and the data from an AIDS clinical trial study are used to illustrate the methodology.     

Estimation and Inference Procedures for Semiparametric Distribution Models with Varying Linear‐Index

More flexible semiparametric linear‐index regression models are proposed to describe the conditional distribution. Such a model formulation captures varying effects of covariates over the support of a response variable in distribution, offers an alternative perspective on dimension reduction and covers a lot of widely used parametric and semiparameteric regression models. A feasible pseudo likelihood approach, accompanied with a simple and easily implemented algorithm, is further developed for the mixed case with both varying and invariant coefficients. By justifying some theoretical properties on Banach spaces, the uniform consistency and asymptotic Gaussian process of the proposed estimator are also established in this article. In addition, under the monotonicity of distribution in linear‐index, we develop an alternative approach based on maximizing a varying accuracy measure. By virtue of the asymptotic recursion relation for the estimators, some of the achievements in this direction include showing the convergence of the iterative computation procedure and establishing the large sample properties of the resulting estimator. It is noticeable that our theoretical framework is very helpful in constructing confidence bands for the parameters of interest and tests for the hypotheses of various qualitative structures in distribution. Generally, the developed estimation and inference procedures perform quite satisfactorily in the conducted simulations and are demonstrated to be useful in reanalysing data from the Boston house price study and the World Values Survey.     

Correcting for non-compliance in randomized trials using rank preserving structural failure time models

We propose correcting for non-compliance in randomized trials by estimating the parameters of a class of semi-parametric failure time models, the rank preserving structural failure time models, using a class of rank estimators. These models are the structural or strong version of the “accelerated failure time model with time-dependent covariates” of Cox and Oakes (1984). In this paper we develop a large sample theory for these estimators, derive the optimal estimator within this class, and briefly consider the construction of “partially adaptive” estimators whose efficiency may approach that of the optimal estimator. We show that in the absence of censoring the optimal estimator attains the semiparametric efficiency bound for the model.     

Robust quasi-randomization-based estimation with ensemble learning for missing data

Missing data analysis requires assumptions about an outcome model or a response probability model to adjust for potential bias due to nonresponse. Doubly robust (DR) estimators are consistent if at least one of the models is correctly specified. Multiply robust (MR) estimators extend DR estimators by allowing for multiple models for both the outcome and/or response probability models and are consistent if at least one of the multiple models is correctly specified. We propose a robust quasi-randomization-based model approach to bring more protection against model misspecification than the existing DR and MR estimators, where any multiple semiparametric, nonparametric or machine learning models can be used for the outcome variable. The proposed estimator achieves unbiasedness by using a subsampling Rao–Blackwell method, given cell-homogenous response, regardless of any working models for the outcome. An unbiased variance estimation formula is proposed, which does not use any replicate jackknife or bootstrap methods. A simulation study shows that our proposed method outperforms the existing multiply robust estimators.     

Statistical Properties of a Modified Accelerated Design for Phase I Cancer Clinical Trials

We consider the semiparametric profile likelihood inference for the distribution function under doubly censored data. For further developments of the statistical inference based on the profile likelihood ratio and alternative tools such as the score or Wald-type inference, we discuss the structures of the profile likelihood estimators and their derivatives included in the score function and the Fisher function of the profile likelihood, establishing the consistencies of their estimators.     

Covariate adjustment and estimation of mean response in randomised trials

Analyses of randomised trials are often based on regression models which adjust for baseline covariates, in addition to randomised group. Based on such models, one can obtain estimates of the marginal mean outcome for the population under assignment to each treatment, by averaging the model‐based predictions across the empirical distribution of the baseline covariates in the trial. We identify under what conditions such estimates are consistent, and in particular show that for canonical generalised linear models, the resulting estimates are always consistent. We show that a recently proposed variance estimator underestimates the variance of the estimator around the true marginal population mean when the baseline covariates are not fixed in repeated sampling and provide a simple adjustment to remedy this. We also describe an alternative semiparametric estimator, which is consistent even when the outcome regression model used is misspecified. The different estimators are compared through simulations and application to a recently conducted trial in asthma.     

Semiparametric log-linear regression for longitudinal measurements subject to outcome-dependent follow-up

A common problem for longitudinal data analyses is that subjects follow-up is irregular, often related to the past outcome or other factors associated with the outcome measure that are not included in the regression model. Analyses unadjusted for outcome-dependent follow-up yield biased estimates. We propose a longitudinal data analysis that can provide consistent estimates in regression models that are subject to outcome-dependent follow-up. We focus on semiparametric marginal log-link regression with arbitrary unspecified baseline function. Based on estimating equations, the proposed class of estimators are root n consistent and asymptotically normal. We present simulation studies that assess the performance of the estimators under finite samples. We illustrate our approach using data from a health services research study.     

A Class of Weighted Estimating Equations for Semiparametric Transformation Models with Missing Covariates

In survival analysis, covariate measurements often contain missing observations; ignoring this feature can lead to invalid inference. We propose a class of weighted estimating equations for right‐censored data with missing covariates under semiparametric transformation models. Time‐specific and subject‐specific weights are accommodated in the formulation of the weighted estimating equations. We establish unified results for estimating missingness probabilities that cover both parametric and non‐parametric modelling schemes. To improve estimation efficiency, the weighted estimating equations are augmented by a new set of unbiased estimating equations. The resultant estimator has the so‐called ‘double robustness’ property and is optimal within a class of consistent estimators.     

Maximum Likelihood Estimations and EM Algorithms with Length-biased Data

Length-biased sampling has been well recognized in economics, industrial reliability, etiology applications, epidemiological, genetic and cancer screening studies. Length-biased right-censored data have a unique data structure different from traditional survival data. The nonparametric and semiparametric estimations and inference methods for traditional survival data are not directly applicable for length-biased right-censored data. We propose new expectation-maximization algorithms for estimations based on full likelihoods involving infinite dimensional parameters under three settings for length-biased data: estimating nonparametric distribution function, estimating nonparametric hazard function under an increasing failure rate constraint, and jointly estimating baseline hazards function and the covariate coefficients under the Cox proportional hazards model. Extensive empirical simulation studies show that the maximum likelihood estimators perform well with moderate sample sizes and lead to more efficient estimators compared to the estimating equation approaches. The proposed estimates are also more robust to various right-censoring mechanisms. We prove the strong consistency properties of the estimators, and establish the asymptotic normality of the semi-parametric maximum likelihood estimators under the Cox model using modern empirical processes theory. We apply the proposed methods to a prevalent cohort medical study. Supplemental materials are available online.     

Estimation and Inference of Distributional Partial Effects: Theory and Application

This article considers nonparametric and semiparametric estimation and inference of the effects of a covariate, either discrete or continuous, on the conditional distribution of a response outcome. It also proposes various uniform tests following estimation. This type of analysis is useful in situations where the econometrician or policy-maker is interested in knowing the effect of a variable or policy on the whole distribution of the response outcome conditional on covariates and is not willing to make parametric functional form assumptions. Monte Carlo experiments show that the proposed estimators and tests are well-behaved in small samples. The empirical section studies the effect of minimum wage hikes on household labor earnings. It is found that the minimum wage has a heterogenous impact on household earnings in the U.S. and that small hikes in the minimum wage are more effective in improving the household earnings distribution.     

Bayesian Semiparametric Regression for Median Residual Life

Abstract.  With survival data there is often interest not only in the survival time distribution but also in the residual survival time distribution. In fact, regression models to explain residual survival time might be desired. Building upon recent work of Kottas & Gelfand [ J. Amer. Statist. Assoc. 96 (2001) 1458], we formulate a semiparametric median residual life regression model induced by a semiparametric accelerated failure time regression model. We utilize a Bayesian approach which allows full and exact inference. Classical work essentially ignores covariates and is either based upon parametric assumptions or is limited to asymptotic inference in non-parametric settings. No regression modelling of median residual life appears to exist. The Bayesian modelling is developed through Dirichlet process mixing. The models are fitted using Gibbs sampling. Residual life inference is implemented extending the approach of Gelfand & Kottas [ J. Comput. Graph. Statist. 11 (2002) 289]. Finally, we present a fairly detailed analysis of a set of survival times with moderate censoring for patients with small cell lung cancer.     

Semiparametric Mixtures of Generalized Exponential Families

Abstract.  A semiparametric mixture model is characterized by a non-parametric mixing distribution Q (with respect to a parameter θ ) and a structural parameter β common to all components. Much of the literature on mixture models has focused on fixing β and estimating Q . However, this can lead to inconsistent estimation of both Q and the order of the model m . Creating a framework for consistent estimation remains an open problem and is the focus of this article. We formulate a class of generalized exponential family (GEF) models and establish sufficient conditions for the identifiability of finite mixtures formed from a GEF along with sufficient conditions for a nesting structure. Finite identifiability and nesting structure lead to the central result that semiparametric maximum likelihood estimation of Q and β fails. However, consistent estimation is possible if we restrict the class of mixing distributions and employ an information-theoretic approach. This article provides a foundation for inference in semiparametric mixture models, in which GEFs and their structural properties play an instrumental role.     

Estimation of tobit-type models with individual specific effects

The aim of this paper is two-fold. First, we review recent estimators for censored regression and sample selection panel data models with unobservable individual specific effects, and show how the idea behind these estimators can be used to construct estimators for a variety of other Tobit-type models. The estimators presented in this paper are semiparametric, in the sense that they do not require the parametrization of the distribution of the unobservables. The second aim of the paper is to introduce a new class of estimators for the censored regression model. The advantage of the new estimators is that they can be applied under a stationarity assumption on the transitory error terms, which is weaker than the exchangeability assumption that is usually made in this literature. A similar generalization does not seem feasible for the estimators of the other models that are considered.     

Semiparametric estimation and inference for distributional and general treatment effects

Summary.  There is a large literature on methods of analysis for randomized trials with noncompliance which focuses on the effect of treatment on the average outcome. The paper considers evaluating the effect of treatment on the entire distribution and general functions of this effect. For distributional treatment effects, fully non-parametric and fully parametric approaches have been proposed. The fully non-parametric approach could be inefficient but the fully parametric approach is not robust to the violation of distribution assumptions. We develop a semiparametric instrumental variable method based on the empirical likelihood approach. Our method can be applied to general outcomes and general functions of outcome distributions and allows us to predict a subject's latent compliance class on the basis of an observed outcome value in observed assignment and treatment received groups. Asymptotic results for the estimators and likelihood ratio statistic are derived. A simulation study shows that our estimators of various treatment effects are substantially more efficient than the currently used fully non-parametric estimators. The method is illustrated by an analysis of data from a randomized trial of an encouragement intervention to improve adherence to prescribed depression treatments among depressed elderly patients in primary care practices.