Semiparametric Proportional Mean Residual Life Model With Censoring Indicators Missing at Random

For right-censored survival data, the information that whether the observed time is survival or censoring time is frequently lost. This is the case for the competing risk data. In this article, we consider statistical inference for the right-censored survival data with censoring indicators missing at random under the proportional mean residual life model. Simple and augmented inverse probability weighted estimating equation approaches are developed, in which the nonmissingness probability and some unknown conditional expectations are estimated by the kernel smoothing technique. The asymptotic properties of all the proposed estimators are established, while extensive simulation studies demonstrate that our proposed methods perform well under the moderate sample size. At last, the proposed method is applied to a data set from a stage II breast cancer trial.     

Linear regression analysis of survival data with missing censoring indicators

Linear regression analysis has been studied extensively in a random censorship setting, but typically all of the censoring indicators are assumed to be observed. In this paper, we develop synthetic data methods for estimating regression parameters in a linear model when some censoring indicators are missing. We define estimators based on regression calibration, imputation, and inverse probability weighting techniques, and we prove all three estimators are asymptotically normal. The finite-sample performance of each estimator is evaluated via simulation. We illustrate our methods by assessing the effects of sex and age on the time to non-ambulatory progression for patients in a brain cancer clinical trial.     

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.     

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     

Proportional hazards model for competing risks data with missing cause of failure

We consider the semiparametric proportional hazards model for the cause-specific hazard function in analysis of competing risks data with missing cause of failure. The inverse probability weighted equation and augmented inverse probability weighted equation are proposed for estimating the regression parameters in the model, and their theoretical properties are established for inference. Simulation studies demonstrate that the augmented inverse probability weighted estimator is doubly robust and the proposed method is appropriate for practical use. The simulations also compare the proposed estimators with the multiple imputation estimator of Lu and Tsiatis (2001). The application of the proposed method is illustrated using data from a bone marrow transplant study.     

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.     

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.     

Nonparametric estimation for survival data with censoring indicators missing at random

In this paper, we consider the problem of hazard rate estimation in the presence of covariates, for survival data with censoring indicators missing at random. We propose in the context usually denoted by MAR (missing at random, in opposition to MCAR, missing completely at random, which requires an additional independence assumption), nonparametric adaptive strategies based on model selection methods for estimators admitting finite dimensional developments in functional orthonormal bases. Theoretical risk bounds are provided, they prove that the estimators behave well in term of mean square integrated error (MISE). Simulation experiments illustrate the statistical procedure.     

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.     

CBPS-based estimation for linear models with responses missing at random

In this article, based on the covariate balancing propensity score (CBPS), estimators for the regression coefficients and the population mean are obtained, when the responses of linear models are missing at random. It is proved that the proposed estimators are asymptotically normal. In simulation studies and real example, the proposed estimators show improved performance relative to usual augmented inverse probability weighted estimators.     

Model averaging procedure for varying-coefficient partially linear models with missing responses

This paper is concerned with model averaging procedure for varying-coefficient partially linear models with missing responses. The profile least-squares estimation process and inverse probability weighted method are employed to estimate regression coefficients of the partially restricted models, in which the propensity score is estimated by the covariate balancing propensity score method. The estimators of the linear parameters are shown to be asymptotically normal. Then we develop the focused information criterion, formulate the frequentist model averaging estimators and construct the corresponding confidence intervals. Some simulation studies are conducted to examine the finite sample performance of the proposed methods. We find that the covariate balancing propensity score improves the performance of the inverse probability weighted estimator. We also demonstrate the superiority of the proposed model averaging estimators over those of existing strategies in terms of mean squared error and coverage probability. Finally, our approach is further applied to a real data example.     

Analysis of two-phase sampling data with semiparametric additive hazards models

Under the case-cohort design introduced by Prentice (Biometrica 73:1–11, 1986), the covariate histories are ascertained only for the subjects who experience the event of interest (i.e., the cases) during the follow-up period and for a relatively small random sample from the original cohort (i.e., the subcohort). The case-cohort design has been widely used in clinical and epidemiological studies to assess the effects of covariates on failure times. Most statistical methods developed for the case-cohort design use the proportional hazards model, and few methods allow for time-varying regression coefficients. In addition, most methods disregard data from subjects outside of the subcohort, which can result in inefficient inference. Addressing these issues, this paper proposes an estimation procedure for the semiparametric additive hazards model with case-cohort/two-phase sampling data, allowing the covariates of interest to be missing for cases as well as for non-cases. A more flexible form of the additive model is considered that allows the effects of some covariates to be time varying while specifying the effects of others to be constant. An augmented inverse probability weighted estimation procedure is proposed. The proposed method allows utilizing the auxiliary information that correlates with the phase-two covariates to improve efficiency. The asymptotic properties of the proposed estimators are established. An extensive simulation study shows that the augmented inverse probability weighted estimation is more efficient than the widely adopted inverse probability weighted complete-case estimation method. The method is applied to analyze data from a preventive HIV vaccine efficacy trial.     

Hazard function estimation from homogeneous right censored data with missing censoring indicators

The kernel smoothed Nelson–Aalen estimator has been well investigated, but is unsuitable when some of the censoring indicators are missing. A representation introduced by Dikta, however, facilitates hazard estimation when there are missing censoring indicators. In this article, we investigate (i) a kernel smoothed semiparametric hazard estimator and (ii) a kernel smoothed “pre-smoothed” Nelson–Aalen estimator. We derive the asymptotic normality of the proposed estimators and compare their asymptotic variances.     

Efficient inverse probability weighting method for quantile regression with nonignorable missing data

Quantitle regression (QR) is a popular approach to estimate functional relations between variables for all portions of a probability distribution. Parameter estimation in QR with missing data is one of the most challenging issues in statistics. Regression quantiles can be substantially biased when observations are subject to missingness. We study several inverse probability weighting (IPW) estimators for parameters in QR when covariates or responses are subject to missing not at random. Maximum likelihood and semiparametric likelihood methods are employed to estimate the respondent probability function. To achieve nice efficiency properties, we develop an empirical likelihood (EL) approach to QR with the auxiliary information from the calibration constraints. The proposed methods are less sensitive to misspecified missing mechanisms. Asymptotic properties of the proposed IPW estimators are shown under general settings. The efficiency gain of EL-based IPW estimator is quantified theoretically. Simulation studies and a data set on the work limitation of injured workers from Canada are used to illustrated our proposed methodologies.     

Ensemble Approaches to Estimating the Population Mean with Missing Response

We propose new ensemble approaches to estimate the population mean for missing response data with fully observed auxiliary variables. We first compress the working models according to their categories through a weighted average, where the weights are proportional to the square of the least‐squares coefficients of model refitting. Based on the compressed values, we develop two ensemble frameworks, under which one is to adjust weights in the inverse probability weighting procedure and the other is built upon an additive structure by reformulating the augmented inverse probability weighting function. The asymptotic normality property is established for the proposed estimators through the theory of estimating functions with plugged‐in nuisance parameter estimates. Simulation studies show that the new proposals have substantial advantages over existing ones for small sample sizes, and an acquired immune deficiency syndrome data example is used for illustration.     

Nonparametric Estimation of Sojourn Time Distributions for Truncated Serial Event Data—a Weight-adjusted Approach

In follow-up studies, survival data often include subjects who have had a certain event at recruitment and may potentially experience a series of subsequent events during the follow-up period. This kind of survival data collected under a cross-sectional sampling criterion is called truncated serial event data. The outcome variables of interest in this paper are serial sojourn times between successive events. To analyze the sojourn times in truncated serial event data, we need to confront two potential sampling biases arising simultaneously from a sampling criterion and induced informative censoring. In this study, nonparametric estimation of the joint probability function of serial sojourn times is developed by using inverse probabilities of the truncation and censoring times as weight functions to accommodate these two sampling biases under various situations of truncation and censoring. Relevant statistical properties of the proposed estimators are also discussed. Simulation studies and two real data are presented to illustrate the proposed methods.     

Nonparametric estimation in the illness-death model using prevalent data

We study nonparametric estimation of the illness-death model using left-truncated and right-censored data. The general aim is to estimate the multivariate distribution of a progressive multi-state process. Maximum likelihood estimation under censoring suffers from problems of uniqueness and consistency, so instead we review and extend methods that are based on inverse probability weighting. For univariate left-truncated and right-censored data, nonparametric maximum likelihood estimation can be considerably improved when exploiting knowledge on the truncation distribution. We aim to examine the gain in using such knowledge for inverse probability weighting estimators in the illness-death framework. Additionally, we compare the weights that use truncation variables with the weights that integrate them out, showing, by simulation, that the latter performs more stably and efficiently. We apply the methods to intensive care units data collected in a cross-sectional design, and discuss how the estimators can be easily modified to more general multi-state models.     

Product-limit Estimators and Cox Regression with Missing Censoring Information

The Kaplan–Meier estimator of a survival function requires that the censoring indicator is always observed. A method of survival function estimation is developed when the censoring indicators are missing completely at random (MCAR). The resulting estimator is a smooth functional of the Nelson–Aalen estimators of certain cumulative transition intensities. The asymptotic properties of this estimator are derived. A simulation study shows that the proposed estimator has greater efficiency than competing MCAR-based estimators. The approach is extended to the Cox model setting for the estimation of a conditional survival function given a covariate.     

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     

Quantile Regression For Longitudinal Biomarker Data Subject to Left Censoring and Dropouts

Quantile regression is increasingly used in biomarker analysis to handle nonnormal or heteroscedastic data. However, in some biomedical studies, the biomarker data can be censored by detection limits of the bioassay or missing when the subjects drop out from the study. Inappropriate handling of these two issues leads to biased estimation results. We consider the censored quantile regression approach to account for the censoring data and apply the inverse weighting technique to adjust for dropouts. In particular, we develop a weighted estimating equation for censored quantile regression, where an individual’s contribution is weighted by the inverse probability of dropout at the given occasion. We conduct simulation studies to evaluate the properties of the proposed estimators and demonstrate our method with a real data set from Genetic and Inflammatory Marker of Sepsis (GenIMS) study.