Aalen's linear model for doubly censored data

Double censoring often occurs in registry studies when left censoring is present in addition to right censoring. In this work, we examine estimation of Aalen's nonparametric regression coefficients based on doubly censored data. We propose two estimation techniques. The first type of estimators, including ordinary least squared (OLS) estimator and weighted least squared (WLS) estimators, are obtained using martingale arguments. The second type of estimator, the maximum likelihood estimator (MLE), is obtained via expectation-maximization (EM) algorithms that treat the survival times of left censored observations as missing. Asymptotic properties, including the uniform consistency and weak convergence, are established for the MLE. Simulation results demonstrate that the MLE is more efficient than the OLS and WLS estimators.     

Estimation of bivariate and marginal distributions with censored data

Summary. Consider a pair of random variables, both subject to random right censoring. New estimators for the bivariate and marginal distributions of these variables are proposed. The estimators of the marginal distributions are not the marginals of the corresponding estimator of the bivariate distribution. Both estimators require estimation of the conditional distribution when the conditioning variable is subject to censoring. Such a method of estimation is proposed. The weak convergence of the estimators proposed is obtained. A small simulation study suggests that the estimators of the marginal and bivariate distributions perform well relatively to respectively the Kaplan–Meier estimator for the marginal distribution and the estimators of Pruitt and van der Laan for the bivariate distribution. The use of the estimators in practice is illustrated by the analysis of a data set.     

Estimation of a Change Point in a Hazard Function Based on Censored Data

The hazard function plays an important role in reliability or survival studies since it describes the instantaneous risk of failure of items at a time point, given that they have not failed before. In some real life applications, abrupt changes in the hazard function are observed due to overhauls, major operations or specific maintenance activities. In such situations it is of interest to detect the location where such a change occurs and estimate the size of the change. In this paper we consider the problem of estimating a single change point in a piecewise constant hazard function when the observed variables are subject to random censoring. We suggest an estimation procedure that is based on certain structural properties and on least squares ideas. A simulation study is carried out to compare the performance of this estimator with two estimators available in the literature: an estimator based on a functional of the Nelson-Aalen estimator and a maximum likelihood estimator. The proposed least squares estimator tums out to be less biased than the other two estimators, but has a larger variance. We illustrate the estimation method on some real data sets.     

Improved precision in the analysis of randomized trials with survival outcomes,without assuming proportional hazards

We present a new estimator of the restricted mean survival time in randomized trials where there is right censoring that may depend on treatment and baseline variables. The proposed estimator leverages prognostic baseline variables to obtain equal or better asymptotic precision compared to traditional estimators. Under regularity conditions and random censoring within strata of treatment and baseline variables, the proposed estimator has the following features: (i) it is interpretable under violations of the proportional hazards assumption; (ii) it is consistent and at least as precise as the Kaplan–Meier and inverse probability weighted estimators, under identifiability conditions; (iii) it remains consistent under violations of independent censoring (unlike the Kaplan–Meier estimator) when either the censoring or survival distributions, conditional on covariates, are estimated consistently; and (iv) it achieves the nonparametric efficiency bound when both of these distributions are consistently estimated. We illustrate the performance of our method using simulations based on resampling data from a completed, phase 3 randomized clinical trial of a new surgical treatment for stroke; the proposed estimator achieves a 12% gain in relative efficiency compared to the Kaplan–Meier estimator. The proposed estimator has potential advantages over existing approaches for randomized trials with time-to-event outcomes, since existing methods either rely on model assumptions that are untenable in many applications, or lack some of the efficiency and consistency properties (i)–(iv). We focus on estimation of the restricted mean survival time, but our methods may be adapted to estimate any treatment effect measure defined as a smooth contrast between the survival curves for each study arm. We provide R code to implement the estimator.

     

An inverse-probability-weighted approach to estimation of the bivariate survival function under left-truncation and right-censoring

In this note, we consider estimating the bivariate survival function when both survival times are subject to random left truncation and one of the survival times is subject to random right censoring. Motivated by Satten and Datta [2001. The Kaplan–Meier estimator as an inverse-probability-of-censoring weighted average. Amer. Statist. 55, 207–210], we propose an inverse-probability-weighted (IPW) estimator. It involves simultaneous estimation of the bivariate survival function of the truncation variables and that of the censoring variable and the truncation variable of the uncensored components. We prove that (i) when there is no censoring, the IPW estimator reduces to NPMLE of van der Laan [1996a. Nonparametric estimation of the bivariate survival function with truncated data. J. Multivariate Anal. 58, 107–131] and (ii) when there is random left truncation and right censoring on only one of the components and the other component is always observed, the IPW estimator reduces to the estimator of Gijbels and Gürler [1998. Covariance function of a bivariate distribution function estimator for left truncated and right censored data. Statist. Sin. 1219–1232]. Based on Theorem 3.1 of van der Laan [1996a. Nonparametric estimation of the bivariate survival function with truncated data. J. Multivariate Anal. 58, 107–131, 1996b. Efficient estimation of the bivariate censoring model and repairing NPMLE. Ann. Statist. 24, 596–627], we prove that the IPW estimator is consistent under certain conditions. Finally, we examine the finite sample performance of the IPW estimator in some simulation studies. For the special case that censoring time is independent of truncation time, a simulation study is conducted to compare the performances of the IPW estimator against that of the estimator proposed by van der Laan [1996a. Nonparametric estimation of the bivariate survival function with truncated data. J. Multivariate Anal. 58, 107–131, 1996b. Efficient estimation of the bivariate censoring model and repairing NPMLE. Ann. Statist. 24, 596–627]. For the special case (i), a simulation study is conducted to compare the performances of the IPW estimator against that of the estimator proposed by Huang et al. (2001. Nonnparametric estimation of marginal distributions under bivariate truncation with application to testing for age-of-onset application. Statist. Sin. 11, 1047–1068).     

Using categorical markers as auxiliary variables in log‐rank tests and hazard ratio estimation

Markers, which are prognostic longitudinal variables, can be used to replace some of the information lost due to right censoring. They may also be used to remove or reduce bias due to informative censoring. In this paper, the authors propose novel methods for using markers to increase the efficiency of log‐rank tests and hazard ratio estimation, as well as parametric estimation. They propose a «plug‐in» methodology that consists of writing the test statistic or estimate of interest as a functional of Kaplan–Meier estimators. The latter are then replaced by an efficient estimator of the survival curve that incorporates information from markers. Using simulations, the authors show that the resulting estimators and tests can be up to 30% more efficient than the usual procedures, provided that the marker is highly prognostic and that the frequency of censoring is high.     

Cure-rate estimation under Case-1 interval censoring

We consider nonparametric estimation of cure-rate based on mixture model under Case-1 interval censoring. We show that the nonparametric maximum-likelihood estimator (NPMLE) of cure-rate is non-unique as well as inconsistent, and propose two estimators based on the NPMLE of the distribution function under this censoring model. We present a cross-validation method for choosing a ‘cut-off’ point needed for the estimators. The limiting distributions of the latter are obtained using extreme-value theory. Graphical illustration of the procedures based on simulated data is provided.     

Wavelet estimation of density for censored data with censoring indicator missing at random

In this paper, we define the nonlinear wavelet estimator of density for the right censoring model with the censoring indicator missing at random (MAR), and develop its asymptotic expression for mean integrated squared error (MISE). Unlike for kernel estimator, the MISE expression of the estimator is not affected by the presence of discontinuities in the curve. Meanwhile, asymptotic normality of the estimator is established. The proposed estimator can reduce to the estimator defined by Li [Non-linear wavelet-based density estimators under random censorship. J Statist Plann Inference. 2003;117(1):35–58] when the censoring indicator MAR does not occur and a bandwidth in non-parametric estimation is close to zero. Also, we define another two nonlinear wavelet estimators of the density. A simulation is done to show the performance of the three proposed estimators.     

Interval estimation of the joint survival function for successive duration times under left truncation and right censoring

In incident cohort studies, survival data often include subjects who have had an initiate event at recruitment and may potentially experience two successive events (first and second) during the follow-up period. Since the second duration process becomes observable only if the first event has occurred, left truncation and dependent censoring arise if the two duration times are correlated. To confront the two potential sampling biases, we propose two inverse-probability-weighted (IPW) estimators for the estimation of the joint survival function of two successive duration times. One of them is similar to the estimator proposed by Chang and Tzeng [Nonparametric estimation of sojourn time distributions for truncated serial event data – a weight adjusted approach, Lifetime Data Anal. 12 (2006), pp. 53–67]. The other is the extension of the nonparametric estimator proposed by Wang and Wells [Nonparametric estimation of successive duration times under dependent censoring, Biometrika 85 (1998), pp. 561–572]. The weak convergence of both estimators are established. Furthermore, the delete-one jackknife and simple bootstrap methods are used to estimate standard deviations and construct interval estimators. A simulation study is conducted to compare the two IPW approaches.     

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.     

Estimating stage occupation probabilities in non-Markov models

We study non-Markov multistage models under dependent censoring regarding estimation of stage occupation probabilities. The individual transition and censoring mechanisms are linked together through covariate processes that affect both the transition intensities and the censoring hazard for the corresponding subjects. In order to adjust for the dependent censoring, an additive hazard regression model is applied to the censoring times, and all observed counting and “at risk” processes are subsequently given an inverse probability of censoring weighted form. We examine the bias of the Datta–Satten and Aalen–Johansen estimators of stage occupation probability, and also consider the variability of these estimators by studying their estimated standard errors and mean squared errors. Results from different simulation studies of frailty models indicate that the Datta–Satten estimator is approximately unbiased, whereas the Aalen–Johansen estimator either under- or overestimates the stage occupation probability due to the dependent nature of the censoring process. However, in our simulations, the mean squared error of the latter estimator tends to be slightly smaller than that of the former estimator. Studies on development of nephropathy among diabetics and on blood platelet recovery among bone marrow transplant patients are used as demonstrations on how the two estimation methods work in practice. Our analyses show that the Datta–Satten estimator performs well in estimating stage occupation probability, but that the censoring mechanism has to be quite selective before a deviation from the Aalen-Johansen estimator is of practical importance. N. Gunnes—Supported by a grant from the Norwegian Cancer Society.     

Adjusted Hazard Rate Estimator Based on a Known Censoring Probability

In most reliability studies involving censoring, one assumes that censoring probabilities are unknown. We derive a nonparametric estimator for the survival function when information regarding censoring frequency is available. The estimator is constructed by adjusting the Nelson–Aalen estimator to incorporate censoring information. Our results indicate significant improvements can be achieved if available information regarding censoring is used. We compare this model to the Koziol–Green model, which is also based on a form of proportional hazards for the lifetime and censoring distributions. Two examples of survival data help to illustrate the differences in the estimation techniques.     

Nonparametric estimation of a survival function under progressive Type-I multistage censoring

Failure time data subject to three progressive Type-I multistage censoring schemes are studied. Product limit estimators are proposed for the estimation of the survival function. It is shown that the resulting estimators are asymptotically equivalent to the corresponding estimators where the data are subject to a random iid right censoring scheme. Many well-known results on confidence bands and tests for randomly right censored data hold for these progressive censoring schemes.     

A self-consistent estimator of marginal survival functions based on dependent competing risk data and an assumed copula

When the time to death, X, and the time to censoring, Y, are associated some additional information is need to identify the marginal survival functions. A natural function which provides this additional information is the copula of X and Y. Assuming that the copula is known, we use the notion of self consistency to construct an estimator of the marginal survival functions based on dependent competing risk data. Results of a small simulation study are shown to compare this estimator to other estimators of the marginal survival function based on an assumed copula.     

Stratified proportional subdistribution hazards model with covariate-adjusted censoring weight for case-cohort studies

The case-cohort study design is widely used to reduce cost when collecting expensive covariates in large cohort studies with survival or competing risks outcomes. A case-cohort study dataset consists of two parts: (a) a random sample and (b) all cases or failures from a specific cause of interest. Clinicians often assess covariate effects on competing risks outcomes. The proportional subdistribution hazards model directly evaluates the effect of a covariate on the cumulative incidence function under the non-covariate-dependent censoring assumption for the full cohort study. However, the non-covariate-dependent censoring assumption is often violated in many biomedical studies. In this article, we propose a proportional subdistribution hazards model for case-cohort studies with stratified data with covariate-adjusted censoring weight. We further propose an efficient estimator when extra information from the other causes is available under case-cohort studies. The proposed estimators are shown to be consistent and asymptotically normal. Simulation studies show (a) the proposed estimator is unbiased when the censoring distribution depends on covariates and (b) the proposed efficient estimator gains estimation efficiency when using extra information from the other causes. We analyze a bone marrow transplant dataset and a coronary heart disease dataset using the proposed method.     

Bayesian inference using product of spacings function for Progressive hybrid Type-I censoring scheme

This article is devoted to the development of product of spacings estimator for a Progressive hybrid Type-I censoring scheme with binomial removals. The experimental units are assumed to follow inverse Lindley distribution. We propose a Bayes estimator of associated scale parameter based on the product of spacings function and simultaneously compare it with that obtained under a usual Bayesian estimation procedure. The estimators are obtained under the squared error loss function along with corresponding HP intervals evaluated by using the Markov chain Monte-Carlo technique. The classical product of spacings estimator has also been derived and compared with the maximum likelihood estimator in addition to 95% average asymptotic confidence intervals. The applicability of the proposed methods is demonstrated by analysing a real data of guinea pigs affected with tuberculosis for the considered censoring scheme.     

A Comparison of Survival Function Estimators in the Koziol–Green Model

In this paper, three competing survival function estimators are compared under the assumptions of the so-called Koziol– Green model, which is a simple model of informative random censoring. It is shown that the model specific estimators of Ebrahimi and Abdushukurov, Cheng, and Lin are asymptotically equivalent. Further, exact expressions for the (noncentral) moments of these estimators are given, and their biases are analytically compared with the bias of the familiar Kaplan–Meier estimator. Finally, MSE comparisons of the three estimators are given for some selected rates of censoring.     

Nonparametric estimation of the bivariate survival function with left-truncated and right-censored data

In this note, we consider estimating the bivariate survival function when both components are subject to left truncation and right censoring. We propose two types of estimators as generalizations of the Dabrowska and Campbell and Földes estimators. The consistency of the proposed estimators is established. A simple bootstrap method is used for obtaining precision estimation of the proposed estimators. A simulation study is conducted to investigate the performance of the proposed estimators.     

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.     

Nonparametric estimation of the mean function of a stochastic process with missing observations

In an attempt to identify similarities between methods for estimating a mean function with different types of response or observation processes, we explore a general theoretical framework for nonparametric estimation of the mean function of a response process subject to incomplete observations. Special cases of the response process include quantitative responses and discrete state processes such as survival processes, counting processes and alternating binary processes. The incomplete data are assumed to arise from a general response-independent observation process, which includes right- censoring, interval censoring, periodic observation, and mixtures of these as special cases. We explore two criteria for defining nonparametric estimators, one based on the sample mean of available data and the other inspired by the construction of Kaplan-Meier (or product-limit) estimator [J. Am. Statist. Assoc. 53 (1958) 457] for right-censored survival data. We show that under regularity conditions the estimated mean functions resulting from both criteria are consistent and converge weakly to Gaussian processes, and provide consistent estimators of their covariance functions. We then evaluate these general criteria for specific responses and observation processes, and show how they lead to familiar estimators for some response and observation processes and new estimators for others. We illustrate the latter with data from an recently completed AIDS clinical trial.