Estimation of conditional cumulative incidence functions under generalized semiparametric regression models with missing covariates,with application to analysis of biomarker correlates in vaccine trials

This article presents generalized semiparametric regression models for conditional cumulative incidence functions with competing risks data when covariates are missing by sampling design or happenstance. A doubly robust augmented inverse probability weighted (AIPW) complete-case approach to estimation and inference is investigated. This approach modifies IPW complete-case estimating equations by exploiting the key features in the relationship between the missing covariates and the phase-one data to improve efficiency. An iterative numerical procedure is derived to solve the nonlinear estimating equations. The asymptotic properties of the proposed estimators are established. A simulation study examining the finite-sample performances of the proposed estimators shows that the AIPW estimators are more efficient than the IPW estimators. The developed method is applied to the RV144 HIV-1 vaccine efficacy trial to investigate vaccine-induced IgG binding antibodies to HIV-1 as correlates of acquisition of HIV-1 infection while taking account of whether the HIV-1 sequences are near or far from the HIV-1 sequences represented in the vaccine construct.     

Empirical likelihood for nonlinear regression models with nonignorable missing responses

This article develops three empirical likelihood (EL) approaches to estimate parameters in nonlinear regression models in the presence of nonignorable missing responses. These are based on the inverse probability weighted (IPW) method, the augmented IPW (AIPW) method and the imputation technique. A logistic regression model is adopted to specify the propensity score. Maximum likelihood estimation is used to estimate parameters in the propensity score by combining the idea of importance sampling and imputing estimating equations. Under some regularity conditions, we obtain the asymptotic properties of the maximum EL estimators of these unknown parameters. Simulation studies are conducted to investigate the finite sample performance of our proposed estimation procedures. Empirical results provide evidence that the AIPW procedure exhibits better performance than the other two procedures. Data from a survey conducted in 2002 are used to illustrate the proposed estimation procedure. The Canadian Journal of Statistics 48: 386–416; 2020 © 2020 Statistical Society of Canada     

Inverse Probability Weighting with Missing Predictors of Treatment Assignment or Missingness

Inverse probability weighting (IPW) can deal with confounding in non randomized studies. The inverse weights are probabilities of treatment assignment (propensity scores), estimated by regressing assignment on predictors. Problems arise if predictors can be missing. Solutions previously proposed include assuming assignment depends only on observed predictors and multiple imputation (MI) of missing predictors. For the MI approach, it was recommended that missingness indicators be used with the other predictors. We determine when the two MI approaches, (with/without missingness indicators) yield consistent estimators and compare their efficiencies.We find that, although including indicators can reduce bias when predictors are missing not at random, it can induce bias when they are missing at random. We propose a consistent variance estimator and investigate performance of the simpler Rubin’s Rules variance estimator. In simulations we find both estimators perform well. IPW is also used to correct bias when an analysis model is fitted to incomplete data by restricting to complete cases. Here, weights are inverse probabilities of being a complete case. We explain how the same MI methods can be used in this situation to deal with missing predictors in the weight model, and illustrate this approach using data from the National Child Development Survey.     

Estimation and inference of combining quantile and least-square regressions with missing data

In this paper, we consider how to incorporate quantile information to improve estimator efficiency for regression model with missing covariates. We combine the quantile information with least-squares normal equations and construct an unbiased estimating equations (EEs). The lack of smoothness of the objective EEs is overcome by replacing them with smooth approximations. The maximum smoothed empirical likelihood (MSEL) estimators are established based on inverse probability weighted (IPW) smoothed EEs and their asymptotic properties are studied under some regular conditions. Moreover, we develop two novel testing procedures for the underlying model. The finite-sample performance of the proposed methodology is examined by simulation studies. A real example is used to illustrate our methods.     

Estimation of the joint survival function for successive duration times

In incident cohort studies, survival data often include subjects who have experienced an initiate event but have not experienced a subsequent event at the calendar time of recruitment. During the follow-up periods, subjects may undergo a series of successive events. Since the second/third duration process becomes observable only if the first/second event has occurred, the data are subject to left-truncation and dependent censoring. In this article, using the inverse-probability-weighted (IPW) approach, we propose nonparametric estimators for the estimation of the joint survival function of three successive duration times. The asymptotic properties of the proposed estimators are established. The simple bootstrap methods are used to estimate standard deviations and construct interval estimators. A simulation study is conducted to investigate the finite sample properties of the proposed estimators.     

The weighted least square based estimators with censoring indicators missing at random

In this paper, we study linear regression analysis when some of the censoring indicators are missing at random. We define regression calibration estimate, imputation estimate and inverse probability weighted estimate for the regression coefficient vector based on the weighted least squared approach due to Stute (1993), and prove all the estimators are asymptotically normal. A simulation study was conducted to evaluate the finite properties of the proposed estimators, and a real data example is provided to illustrate our methods.     

Doubly robust empirical likelihood inference in covariate-missing data problems

Missing covariate data occurs often in regression analysis. We study methods for estimating the regression coefficients in an assumed conditional mean function when some covariates are completely observed but other covariates are missing for some subjects. We adopt the semiparametric perspective of Robins et al. [Estimation of regression coefficients when some regressors are not always observed. J Amer Statist Assoc. 1994;89:846–866] on regression analyses with missing covariates, in which they pioneered the use of two working models, the working propensity score model and the working conditional score model. A recent approach to missing covariate data analysis is the empirical likelihood method of Qin et al. [Empirical likelihood in missing data problems. J Amer Statist Assoc. 2009;104:1492–1503], which effectively combines unbiased estimating equations. In this paper, we consider an alternative likelihood approach based on the full likelihood of the observed data. This full likelihood-based method enables us to generate estimators for the vector of the regression coefficients that are (a) asymptotically equivalent to those of Qin et al. [Empirical likelihood in missing data problems. J Amer Statist Assoc. 2009;104:1492–1503] when the working propensity score model is correctly specified, and (b) doubly robust, like the augmented inverse probability weighting (AIPW) estimators of Robins et al. [Estimation of regression coefficients when some regressors are not always observed. J Am Statist Assoc. 1994;89:846–866]. Thus, the proposed full likelihood-based estimators improve on the efficiency of the AIPW estimators when the working propensity score model is correct but the working conditional score model is possibly incorrect, and also improve on the empirical likelihood estimators of Qin, Zhang and Leung [Empirical likelihood in missing data problems. J Amer Statist Assoc. 2009;104:1492–1503] when the reverse is true, that is, the working conditional score model is correct but the working propensity score model is possibly incorrect. In addition, we consider a regression method for estimation of the regression coefficients when the working conditional score model is correctly specified; the asymptotic variance of the resulting estimator is no greater than the semiparametric variance bound characterized by the theory of Robins et al. [Estimation of regression coefficients when some regressors are not always observed. J Amer Statist Assoc. 1994;89:846–866]. Finally, we compare the finite-sample performance of various estimators in a simulation study.     

缺失数据下的逆概率多重加权分位回归估计及其应用

数据缺失问题普遍存在于应用研究中。在随机缺失机制假定下,本文从模型推断角度出发,针对线性缺失分位回归模型,提出一种新的有效估计方法——逆概率多重加权（IPMW）估计。该方法是在逆概率加权（IPW）估计的基础上,结合倾向得分匹配及模型平均思想,经过多次估计,加权确定最终参数估计结果。该方法适用于响应变量是独立同分布或独立非同分布的情形,并适用于绝大多数缺失场景。经过理论推导及模拟研究发现,IPMW估计量在继承IPW估计量的优势上具有更稳健的性质。最后,将该方法应用于含有缺失数据的微观调查数据中,研究了经济较发达的准一线城市中等收入群体消费水平的影响因素,对比两种估计方法的估计结果及置信带,发现逆概率多重加权估计量的标准偏差更小,估计结果更稳健。     

Model selection and model averaging for semiparametric partially linear models with missing data

We study model selection and model averaging in semiparametric partially linear models with missing responses. An imputation method is used to estimate the linear regression coefficients and the nonparametric function. We show that the corresponding estimators of the linear regression coefficients are asymptotically normal. Then a focused information criterion and frequentist model average estimators are proposed and their theoretical properties are established. Simulation studies are performed to demonstrate the superiority of the proposed methods over the existing strategies in terms of mean squared error and coverage probability. Finally, the approach is applied to a real data case.     

Handling missing data by deleting completely observed records

When data are missing, analyzing records that are completely observed may cause bias or inefficiency. Existing approaches in handling missing data include likelihood, imputation and inverse probability weighting. In this paper, we propose three estimators inspired by deleting some completely observed data in the regression setting. First, we generate artificial observation indicators that are independent of outcome given the observed data and draw inferences conditioning on the artificial observation indicators. Second, we propose a closely related weighting method. The proposed weighting method has more stable weights than those of the inverse probability weighting method (Zhao, L., Lipsitz, S., 1992. Designs and analysis of two-stage studies. Statistics in Medicine 11, 769–782). Third, we improve the efficiency of the proposed weighting estimator by subtracting the projection of the estimating function onto the nuisance tangent space. When data are missing completely at random, we show that the proposed estimators have asymptotic variances smaller than or equal to the variance of the estimator obtained from using completely observed records only. Asymptotic relative efficiency computation and simulation studies indicate that the proposed weighting estimators are more efficient than the inverse probability weighting estimators under wide range of practical situations especially when the missingness proportion is large.     

A robust pairwise likelihood method for incomplete longitudinal binary data arising in clusters

Clustered longitudinal data feature cross‐sectional associations within clusters, serial dependence within subjects, and associations between responses at different time points from different subjects within the same cluster. Generalized estimating equations are often used for inference with data of this sort since they do not require full specification of the response model. When data are incomplete, however, they require data to be missing completely at random unless inverse probability weights are introduced based on a model for the missing data process. The authors propose a robust approach for incomplete clustered longitudinal data using composite likelihood. Specifically, pairwise likelihood methods are described for conducting robust estimation with minimal model assumptions made. The authors also show that the resulting estimates remain valid for a wide variety of missing data problems including missing at random mechanisms and so in such cases there is no need to model the missing data process. In addition to describing the asymptotic properties of the resulting estimators, it is shown that the method performs well empirically through simulation studies for complete and incomplete data. Pairwise likelihood estimators are also compared with estimators obtained from inverse probability weighted alternating logistic regression. An application to data from the Waterloo Smoking Prevention Project is provided for illustration. The Canadian Journal of Statistics 39: 34–51; 2011 © 2010 Statistical Society of Canada     

Empirical likelihood for generalized linear models with missing responses

The paper uses the empirical likelihood method to study the construction of confidence intervals and regions for regression coefficients and response mean in generalized linear models with missing response. By using the inverse selection probability weighted imputation technique, the proposed empirical likelihood ratios are asymptotically chi-squared. Our approach is to directly calibrate the empirical likelihood ratio, which is called as a bias-correction method. Also, a class of estimators for the parameters of interest is constructed, and the asymptotic distributions of the proposed estimators are obtained. A simulation study indicates that the proposed methods are comparable in terms of coverage probabilities and average lengths/areas of confidence intervals/regions. An example of a real data set is used for illustrating our methods.     

Hybrid pairwise‐likelihood estimation methods for incomplete longitudinal binary data

In longitudinal data, missing observations occur commonly with incomplete responses and covariates. Missing data can have a ‘missing not at random’ mechanism, a non‐monotone missing pattern, and moreover response and covariates can be missing not simultaneously. To avoid complexities in both modelling and computation, a two‐stage estimation method and a pairwise‐likelihood method are proposed. The two‐stage estimation method enjoys simplicities in computation, but incurs more severe efficiency loss. On the other hand, the pairwise approach leads to estimators with better efficiency, but can be cumbersome in computation. In this paper, we develop a compromise method using a hybrid pairwise‐likelihood framework. Our proposed approach has better efficiency than the two‐stage method, but its computational cost is still reasonable compared to the pairwise approach. The performance of the methods is evaluated empirically by means of simulation studies. Our methods are used to analyse longitudinal data obtained from the National Population Health Study.     

Efficient Robust Estimation for Linear Models with Missing Response at Random

Coefficient estimation in linear regression models with missing data is routinely carried out in the mean regression framework. However, the mean regression theory breaks down if the error variance is infinite. In addition, correct specification of the likelihood function for existing imputation approach is often challenging in practice, especially for skewed data. In this paper, we develop a novel composite quantile regression and a weighted quantile average estimation procedure for parameter estimation in linear regression models when some responses are missing at random. Instead of imputing the missing response by randomly drawing from its conditional distribution, we propose to impute both missing and observed responses by their estimated conditional quantiles given the observed data and to use the parametrically estimated propensity scores to weigh check functions that define a regression parameter. Both estimation procedures are resistant to heavy‐tailed errors or outliers in the response and can achieve nice robustness and efficiency. Moreover, we propose adaptive penalization methods to simultaneously select significant variables and estimate unknown parameters. Asymptotic properties of the proposed estimators are carefully investigated. An efficient algorithm is developed for fast implementation of the proposed methodologies. We also discuss a model selection criterion, which is based on an IC_Q ‐type statistic, to select the penalty parameters. The performance of the proposed methods is illustrated via simulated and real data sets.     

Semiparametric Analysis of Isotonic Errors-in-Variables Regression Models with Missing Response

This article is concerned with the estimation problem in the semiparametric isotonic regression model when the covariates are measured with additive errors and the response is missing at random. An inverse marginal probability weighted imputation approach is developed to estimate the regression parameters and a least-square approach under monotone constraint is employed to estimate the functional component. We show that the proposed estimator of the regression parameter is root-n consistent and asymptotically normal and the isotonic estimator of the functional component, at a fixed point, is cubic root-n consistent. A simulation study is conducted to examine the finite-sample properties of the proposed estimators. A data set is used to demonstrate the proposed approach.     

Marginal regression models with a time to event outcome and discrete multiple source predictors

Information from multiple informants is frequently used to assess psychopathology. We consider marginal regression models with multiple informants as discrete predictors and a time to event outcome. We fit these models to data from the Stirling County Study; specifically, the models predict mortality from self report of psychiatric disorders and also predict mortality from physician report of psychiatric disorders. Previously, Horton et al. found little relationship between self and physician reports of psychopathology, but that the relationship of self report of psychopathology with mortality was similar to that of physician report of psychopathology with mortality. Generalized estimating equations (GEE) have been used to fit marginal models with multiple informant covariates; here we develop a maximum likelihood (ML) approach and show how it relates to the GEE approach. In a simple setting using a saturated model, the ML approach can be constructed to provide estimates that match those found using GEE. We extend the ML technique to consider multiple informant predictors with missingness and compare the method to using inverse probability weighted (IPW) GEE. Our simulation study illustrates that IPW GEE loses little efficiency compared with ML in the presence of monotone missingness. Our example data has non-monotone missingness; in this case, ML offers a modest decrease in variance compared with IPW GEE, particularly for estimating covariates in the marginal models. In more general settings, e.g., categorical predictors and piecewise exponential models, the likelihood parameters from the ML technique do not have the same interpretation as the GEE. Thus, the GEE is recommended to fit marginal models for its flexibility, ease of interpretation and comparable efficiency to ML in the presence of missing data.     

Weighted Likelihood for Semiparametric Models and Two-phase Stratified Samples, with Application to Cox Regression

Abstract.  We consider semiparametric models for which solution of Horvitz–Thompson or inverse probability weighted (IPW) likelihood equations with two-phase stratified samples leads to consistent and asymptotically Gaussian estimators of both Euclidean and non-parametric parameters. For Bernoulli (independent and identically distributed) sampling, standard theory shows that the Euclidean parameter estimator is asymptotically linear in the IPW influence function. By proving weak convergence of the IPW empirical process, and borrowing results on weighted bootstrap empirical processes, we derive a parallel asymptotic expansion for finite population stratified sampling. Several of our key results have been derived already for Cox regression with stratified case–cohort and more general survey designs. This paper is intended to help interpret this previous work and to pave the way towards a general Horvitz–Thompson approach to semiparametric inference with data from complex probability samples.     

Estimation of treatment effects for heterogeneous matched‐pairs data with probit models

Estimating the effect of medical treatments on subject responses is one of the crucial problems in medical research. Matched‐pairs designs are commonly implemented in the field of medical research to eliminate confounding and improve efficiency. In this article, new estimators of treatment effects for heterogeneous matched‐pairs data are proposed. Asymptotic properties of the proposed estimators are derived. Simulation studies show that the proposed estimators have some advantages over the famous Heckman's estimator, the conditional maximum likelihood estimator, and the inverse probability weighted estimator. We apply the proposed methodology to a data set from a study of low‐birth‐weight infants.     

Additive hazards regression with censoring indicators missing at random

In this article, the authors consider a semiparametric additive hazards regression model for right‐censored data that allows some censoring indicators to be missing at random. They develop a class of estimating equations and use an inverse probability weighted approach to estimate the regression parameters. Nonparametric smoothing techniques are employed to estimate the probability of non‐missingness and the conditional probability of an uncensored observation. The asymptotic properties of the resulting estimators are derived. Simulation studies show that the proposed estimators perform well. They motivate and illustrate their methods with data from a brain cancer clinical trial. The Canadian Journal of Statistics 38: 333–351; 2010 © 2010 Statistical Society of Canada     

Dimension reduction in estimating equations with covariates missing at random

To estimate parameters defined by estimating equations with covariates missing at random, we consider three bias-corrected nonparametric approaches based on inverse probability weighting, regression and augmented inverse probability weighting. However, when the dimension of covariates is not low, the estimation efficiency will be affected due to the curse of dimensionality. To address this issue, we propose a two-stage estimation procedure by using the dimension-reduced kernel estimation in conjunction with bias-corrected estimating equations. We show that the resulting three estimators are asymptotically equivalent and achieve the desirable properties. The impact of dimension reduction in nonparametric estimation of parameters is also investigated. The finite-sample performance of the proposed estimators is studied through simulation, and an application to an automobile data set is also presented.