Bias corrected estimation for generalized probit regression with covariate measurement error and censored responses

In this paper, we propose a bias corrected estimate of the regression coefficient for the generalized probit regression model when the covariates are subject to measurement error and the responses are subject to interval censoring. The main improvement of our method is that it reduces most of the bias that the naive estimates have. The great advantage of our method is that it is baseline and censoring distribution free, in a sense that the investigator does not need to calculate the baseline or the censoring distribution to obtain the estimator of the regression coefficient, an important property of Cox regression model. A sandwich estimator for the variance is also proposed. Our procedure can be generalized to general measurement error distribution as long as the first four moments of the measurement error are known. The results of extensive simulations show that our approach is very effective in eliminating the bias when the measurement error is not too large relative to the error term of the regression model.     

Quantile regression for interval censored data

As direct generalization of the quantile regression for complete observed data, an estimation method for quantile regression models with interval censored data is proposed, and the property of consistency is obtained. The property of asymptotic normality is also established with a bias converging to zero, and to reduce the bias, two bias correction methods are proposed. Methods proposed in this paper do not require the censoring vectors to be identically distributed, and can be applied to models with various covariates. Simulation results show that the proposed methods work well.     

Likelihood-based confidence sets for partially identified parameters

There has been growing interest in partial identification of probability distributions and parameters. This paper considers statistical inference on parameters that are partially identified because data are incompletely observed, due to nonresponse or censoring, for instance. A method based on likelihood ratios is proposed for constructing confidence sets for partially identified parameters. The method can be used to estimate a proportion or a mean in the presence of missing data, without assuming missing-at-random or modeling the missing-data mechanism. It can also be used to estimate a survival probability with censored data without assuming independent censoring or modeling the censoring mechanism. A version of the verification bias problem is studied as well.     

Slope estimation of covariates that influence renal outcome following renal transplant adjusting for informative right censoring

A new statistical model is proposed to estimate population and individual slopes that are adjusted for covariates and informative right censoring. Individual slopes are assumed to have a mean that depends on the population slope for the covariates. The number of observations for each individual is modeled as a truncated discrete distribution with mean dependent on the individual subjects’ slopes. Our simulation study results indicated that the associated bias and mean squared errors for the proposed model were comparable to those associated with the model that only adjusts for informative right censoring. The proposed model was illustrated using renal transplant dataset to estimate population slopes for covariates that could impact the outcome of renal function following renal transplantation.     

Estimation for two-parameter weibull distribution and extreme-value distribution under multiply type-II censoring

Compared to Type-II censoring, multiply Type-II censoring is a more general, yet mathematically and numerically much more complicated censoring scheme. For multiply Type II censored data from a two-parameter Weibull distribution, we propose several estimators, including MLE, approximate MLE, and estimators corresponding to the BLUE and BLIE from estimating parameters in extreme-value distribution. An approximately unbiased estimator for the shape parameter is also proposed which has the smallest MSE. Numerical examples show that this estimator is the best in terms of bias and MSE. Numerical examples also show that the approximate MLE which admits a closed form is better for estimating the scale parameter.     

Interval-censored data with misclassification: a Bayesian approach

Survival data involving silent events are often subject to interval censoring (the event is known to occur within a time interval) and classification errors if a test with no perfect sensitivity and specificity is applied. Considering the nature of this data plays an important role in estimating the time distribution until the occurrence of the event. In this context, we incorporate validation subsets into the parametric proportional hazard model, and show that this additional data, combined with Bayesian inference, compensate the lack of knowledge about test sensitivity and specificity improving the parameter estimates. The proposed model is evaluated through simulation studies, and Bayesian analysis is conducted within a Gibbs sampling procedure. The posterior estimates obtained under validation subset models present lower bias and standard deviation compared to the scenario with no validation subset or the model that assumes perfect sensitivity and specificity. Finally, we illustrate the usefulness of the new methodology with an analysis of real data about HIV acquisition in female sex workers that have been discussed in the literature.     

Left truncation in linked data: A practical guide to understanding left truncation and applying it using SAS and R

Time-to-event data such as time to death are broadly used in medical research and drug development to understand the efficacy of a therapeutic. For time-to-event data, right censoring (data only observed up to a certain point of time) is common and easy to recognize. Methods that use right censored data, such as the Kaplan–Meier estimator and the Cox proportional hazard model, are well established. Time-to-event data can also be left truncated, which arises when patients are excluded from the sample because their events occur before a specific milestone, potentially resulting in an immortal time bias. For example, in a study evaluating the association between biomarker status and overall survival, patients who did not live long enough to receive a genomic test were not observed in the study. Left truncation causes selection bias and often leads to an overestimate of survival time. In this tutorial, we used a nationwide electronic health record-derived de-identified database to demonstrate how to analyze left truncated and right censored data without bias using example code from SAS and R.     

Bias-correction for Weibull common shape estimation

A general method for correcting the bias of the maximum likelihood estimator (MLE) of the common shape parameter of Weibull populations, allowing a general right censorship, is proposed in this paper. Extensive simulation results show that the new method is very effective in correcting the bias of the MLE, regardless of censoring mechanism, sample size, censoring proportion and number of populations involved. The method can be extended to more complicated Weibull models.     

Continuous covariate frailty models for censored and truncated clustered data

Using some logarithmic and integral transformation we transform a continuous covariate frailty model into a polynomial regression model with a random effect. The responses of this mixed model can be ‘estimated’ via conditional hazard function estimation. The random error in this model does not have zero mean and its variance is not constant along the covariate and, consequently, these two quantities have to be estimated. Since the asymptotic expression for the bias is complicated, the two-large-bandwidth trick is proposed to estimate the bias. The proposed transformation is very useful for clustered incomplete data subject to left truncation and right censoring (and for complex clustered data in general). Indeed, in this case no standard software is available to fit the frailty model, whereas for the transformed model standard software for mixed models can be used for estimating the unknown parameters in the original frailty model. A small simulation study illustrates the good behavior of the proposed method. This method is applied to a bladder cancer data set.     

Approximate MLE for the scale parameter of the generalized exponential distribution under random censoring

In this paper, we consider the maximum likelihood estimator (MLE) of the scale parameter of the generalized exponential (GE) distribution based on a random censoring model. We assume the censoring distribution also follows a GE distribution. Since the estimator does not provide an explicit solution, we propose a simple method of deriving an explicit estimator by approximating the likelihood function. In order to compare the performance of the estimators, Monte Carlo simulation is conducted. The results show that the MLE and the approximate MLE are almost identical in terms of bias and variance.     

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.     

Bias reduction for nonparametric correlation coefficients under the bivariate normal copula assumption with known detection limits

The authors derive the asymptotic mean and bias of Kendall's tau and Spearman's rho in the presence of left censoring in the bivariate Gaussian copula model. They show that tie corrections for left‐censoring brings the value of these coefficients closer to zero. They also present a bias reduction method and illustrate it through two applications.     

Variable selection for semiparametric proportional hazards model under progressive Type-II censoring

Variable selection is an effective methodology for dealing with models with numerous covariates. We consider the methods of variable selection for semiparametric Cox proportional hazards model under the progressive Type-II censoring scheme. The Cox proportional hazards model is used to model the influence coefficients of the environmental covariates. By applying Breslow’s “least information” idea, we obtain a profile likelihood function to estimate the coefficients. Lasso-type penalized profile likelihood estimation as well as stepwise variable selection method are explored as means to find the important covariates. Numerical simulations are conducted and Veteran’s Administration Lung Cancer data are exploited to evaluate the performance of the proposed method.     

Model averaging for treatment effect estimation in subgroups

In many clinical trials, biological, pharmacological, or clinical information is used to define candidate subgroups of patients that might have a differential treatment effect. Once the trial results are available, interest will focus on subgroups with an increased treatment effect. Estimating a treatment effect for these groups, together with an adequate uncertainty statement is challenging, owing to the resulting “random high” / selection bias. In this paper, we will investigate Bayesian model averaging to address this problem. The general motivation for the use of model averaging is to realize that subgroup selection can be viewed as model selection, so that methods to deal with model selection uncertainty, such as model averaging, can be used also in this setting. Simulations are used to evaluate the performance of the proposed approach. We illustrate it on an example early‐phase clinical trial.     

A Profile Conditional Likelihood Approach for the Semiparametric Transformation Regression Model with Missing Covariates

We propose a profile conditional likelihood approach to handle missing covariates in the general semiparametric transformation regression model. The method estimates the marginal survival function by the Kaplan-Meier estimator, and then estimates the parameters of the survival model and the covariate distribution from a conditional likelihood, substituting the Kaplan-Meier estimator for the marginal survival function in the conditional likelihood. This method is simpler than full maximum likelihood approaches, and yields consistent and asymptotically normally distributed estimator of the regression parameter when censoring is independent of the covariates. The estimator demonstrates very high relative efficiency in simulations. When compared with complete-case analysis, the proposed estimator can be more efficient when the missing data are missing completely at random and can correct bias when the missing data are missing at random. The potential application of the proposed method to the generalized probit model with missing continuous covariates is also outlined.     

Recurrent events analysis in the presence of time-dependent covariates and dependent censoring

Summary.  Recurrent events models have had considerable attention recently. The majority of approaches show the consistency of parameter estimates under the assumption that censoring is independent of the recurrent events process of interest conditional on the covariates that are included in the model. We provide an overview of available recurrent events analysis methods and present an inverse probability of censoring weighted estimator for the regression parameters in the Andersen–Gill model that is commonly used for recurrent event analysis. This estimator remains consistent under informative censoring if the censoring mechanism is estimated consistently, and it generally improves on the naïve estimator for the Andersen–Gill model in the case of independent censoring. We illustrate the bias of ad hoc estimators in the presence of informative censoring with a simulation study and provide a data analysis of recurrent lung exacerbations in cystic fibrosis patients when some patients are lost to follow-up.     

Bias From Censored Regressors

We study the bias that arises from using censored regressors in estimation of linear models. We present results on bias in ordinary least aquares (OLS) regression estimators with exogenous censoring and in instrumental variable (IV) estimators when the censored regressor is endogenous. Bound censoring such as top-coding results in expansion bias, or effects that are too large. Independent censoring results in bias that varies with the estimation method—attenuation bias in OLS estimators and expansion bias in IV estimators. Severe biases can result when there are several regressors and when a 0–1 variable is used in place of a continuous regressor.     

Adjusting win statistics for dependent censoring

For composite outcomes whose components can be prioritized on clinical importance, the win ratio, the net benefit and the win odds apply that order in comparing patients pairwise to produce wins and subsequently win proportions. Because these three statistics are derived using the same win proportions and they test the same hypothesis of equal win probabilities in the two treatment groups, we refer to them as win statistics. These methods, particularly the win ratio and the net benefit, have received increasing attention in methodological research and in design and analysis of clinical trials. For time-to-event outcomes, however, censoring may introduce bias. Previous work has shown that inverse-probability-of-censoring weighting (IPCW) can correct the win ratio for bias from independent censoring. The present article uses the IPCW approach to adjust win statistics for dependent censoring that can be predicted by baseline covariates and/or time-dependent covariates (producing the CovIPCW-adjusted win statistics). Theoretically and with examples and simulations, we show that the CovIPCW-adjusted win statistics are unbiased estimators of treatment effect in the presence of dependent censoring.     

Survival analysis for the missing censoring indicator model using kernel density estimation techniques

This article concerns asymptotic theory for a new estimator of a survival function in the missing censoring indicator model of random censorship. Specifically, the large sample results for an inverse probability-of-non-missingness weighted estimator of the cumulative hazard function, so far not available, are derived, including an almost sure representation with rate for a remainder term, and uniform strong consistency with rate of convergence. The estimator is based on a kernel estimate for the conditional probability of non-missingness of the censoring indicator. Expressions for its bias and variance, in turn leading to an expression for the mean squared error as a function of the bandwidth, are also obtained. The corresponding estimator of the survival function, whose weak convergence is derived, is asymptotically efficient. A numerical study, comparing the performances of the proposed and two other currently existing efficient estimators, is presented.