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.     

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.     

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.     

Interval censoring: Model characterizations for the validity of the simplified likelihood

In survival data analysis, the interval censoring problem has generally been treated via likelihood methods. Because this likelihood is complex, it is often assumed that the censoring mechanisms do not affect the mortality process. The authors specify conditions that ensure the validity of such a simplified likelihood. They prove the equivalence between different characterizations of noninformative censoring and define a constant‐sum condition analogous to the one derived in the context of right censoring. They also prove that when the noninformative or constant‐sum condition holds, the simplified likelihood can be used to obtain the nonparametric maximum likelihood estimator of the death time distribution function.     

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.     

Most Likely Transformations

We propose and study properties of maximum likelihood estimators in the class of conditional transformation models. Based on a suitable explicit parameterization of the unconditional or conditional transformation function, we establish a cascade of increasingly complex transformation models that can be estimated, compared and analysed in the maximum likelihood framework. Models for the unconditional or conditional distribution function of any univariate response variable can be set up and estimated in the same theoretical and computational framework simply by choosing an appropriate transformation function and parameterization thereof. The ability to evaluate the distribution function directly allows us to estimate models based on the exact likelihood, especially in the presence of random censoring or truncation. For discrete and continuous responses, we establish the asymptotic normality of the proposed estimators. A reference software implementation of maximum likelihood‐based estimation for conditional transformation models that allows the same flexibility as the theory developed here was employed to illustrate the wide range of possible applications.     

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.     

Likelihood Estimation for Censored Random Vectors

This article shows how to construct a likelihood for a general class of censoring problems. This likelihood is proven to be valid, i.e. its maximizer is consistent and the respective root-n estimator is asymptotically efficient and normally distributed under regularity conditions. The method generalizes ordinary maximum likelihood estimation as well as several standard estimators for censoring problems (e.g. tobit type I-tobit type V).     

A new two sample type-II progressive censoring scheme

In this paper we introduce a new type-II progressive censoring scheme for two samples. It is observed that the proposed censoring scheme is analytically more tractable than the existing joint progressive type-II censoring scheme proposed by Rasouli and Balakrishnan. The maximum likelihood estimators of the unknown parameters are obtained and their exact distributions are derived. Based on the exact distributions of the maximum likelihood estimators exact confidence intervals are also constructed. For comparison purposes we have used bootstrap confidence intervals also. One data analysis has been performed for illustrative purposes. Finally we propose some open problems.     

Inference and optimal censoring schemes for progressively censored Birnbaum–Saunders distribution

The aim of this paper is twofold. First we discuss the maximum likelihood estimators of the unknown parameters of a two-parameter Birnbaum–Saunders distribution when the data are progressively Type-II censored. The maximum likelihood estimators are obtained using the EM algorithm by exploiting the property that the Birnbaum–Saunders distribution can be expressed as an equal mixture of an inverse Gaussian distribution and its reciprocal. From the proposed EM algorithm, the observed information matrix can be obtained quite easily, which can be used to construct the asymptotic confidence intervals. We perform the analysis of two real and one simulated data sets for illustrative purposes, and the performances are quite satisfactory. We further propose the use of different criteria to compare two different sampling schemes, and then find the optimal sampling scheme for a given criterion. It is observed that finding the optimal censoring scheme is a discrete optimization problem, and it is quite a computer intensive process. We examine one sub-optimal censoring scheme by restricting the choice of censoring schemes to one-step censoring schemes as suggested by Balakrishnan (2007), which can be obtained quite easily. We compare the performances of the sub-optimal censoring schemes with the optimal ones, and observe that the loss of information is quite insignificant.     

A semiparametric regression cure model for interval-censored and left-truncated data

Medical advancements have made it possible for patients to be cured of certain types of diseases. In follow-up studies, the disease event time can be subject to left truncation and interval censoring. In this article, we propose a semiparametric nonmixture cure model for the regression analysis of left-truncated and interval-censored (LTIC) data. We develop semiparametric maximum likelihood estimation for the nonmixture cure model with LTIC data. A simulation study is conducted to investigate the performance of the proposed estimators.     

Parameter Estimation of Type-II Hybrid Censored Weighted Exponential Distribution

A hybrid censoring scheme is a mixture of Type-I and Type-II censoring schemes. We study the estimation of parameters of weighted exponential distribution based on Type-II hybrid censored data. By applying the EM algorithm, maximum likelihood estimators are evaluated. Using Fisher information matrix, asymptotic confidence intervals are provided. By applying Markov chain Monte Carlo techniques, Bayes estimators, and corresponding highest posterior density confidence intervals of parameters are obtained. Monte Carlo simulations are performed to compare the performances of the different methods, and one dataset is analyzed for illustrative purposes.     

Regression analysis of interval-censored failure time data with cured subgroup and mismeasured covariates

Abstract

Failure time data occur in many areas and also in various forms and in particular, many authors have discussed regression analysis of failure time data in the presence of interval censoring, a cured subgroup or mismeasured covariates. However, it does not seem to exist an established procedure that can deal with all three issues together. Corresponding to this, we propose a sieve maximum likelihood estimation procedure that takes into account all three issues with the use of the SIMEX algorithm. The asymptotic properties of the proposed estimators are established, and an extensive simulation study is also conducted and suggests that the proposed method works well for practical situations.     

Generalized inverted exponential distribution under hybrid censoring

The hybrid censoring scheme is a mixture of Type-I and Type-II censoring schemes. Based on hybrid censored samples, we first derive the maximum likelihood estimators of the unknown parameters and the expected Fisher’s information matrix of the generalized inverted exponential distribution (GIED). Monte Carlo simulations are performed to study the performance of the maximum likelihood estimators. Next we consider Bayes estimation under the squared error loss function. These Bayes estimates are evaluated by applying Lindley’s approximation method, the importance sampling procedure and Metropolis–Hastings algorithm. The importance sampling technique is used to compute the highest posterior density credible intervals. Two data sets are analyzed for illustrative purposes. Finally, we discuss a method of obtaining the optimum hybrid censoring scheme.     

An analytic method for randomized trials with informative censoring: Part II

Consider a randomized trial in which time to the occurrence of a particular disease, say pneumocystic pneumonia in an AIDS trial or breast cancer in a mammographic screening trial, is the failure time of primary interest. Suppose that time to disease is subject to informative censoring by the minimum of time to death, loss to and end of follow-up. In such a trial, the potential censoring time is observed for all study subjects, including failures. In the presence of informative censoring, it is not possible to consistently estimate the effect of treatment on time to disease without imposing additional non-identifiable assumptions. Robins (1995) specified two non-identifiable assumptions that allow one to test for and estimate an effect of treatment on time to disease in the presence of informative censoring. The goal of this paper is to provide a class of consistent and reasonably efficient semiparametric tests and estimators for the treatment effect under these assumptions. The tests in our class, like standard weighted-log-rank tests, are asymptotically distribution-free -level tests under the null hypothesis of no causal effect of treatment on time to disease whenever the censoring and failure distributions are conditionally independent given treatment arm. However, our tests remain asymptotically distribution-free -level tests in the presence of informative censoring provided either of our assumptions are true. In contrast, a weighted log-rank test will be an -level test in the presence of informative censoring only if (1) one of our two non-identifiable assumptions hold, and (2) the distribution of time to censoring is the same in the two treatment arms. We also study the estimation, in the presence of informative censoring, of the effect of treatment on the evolution over time of the mean of repeated measures outcome such as CD4 count.     

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.     

Analysis of quality-of-life adjusted failure time data in the presence of competing, possibly informative, censoring mechanisms

We derive estimators of the mean of a function of a quality-of-life adjusted failure time, in the presence of competing right censoring mechanisms. Our approach allows for the possibility that some or all of the competing censoring mechanisms are associated with the endpoint, even after adjustment for recorded prognostic factors, with the degree of residual association possibly different for distinct censoring processes. Our methods generalize from a single to many censoring processes and from ignorable to non-ignorable censoring processes.     

Regression analysis of longitudinal data with outcome‐dependent sampling and informative censoring

We consider a regression analysis of longitudinal data in the presence of outcome‐dependent observation times and informative censoring. Existing approaches commonly require a correct specification of the joint distribution of longitudinal measurements, the observation time process, and informative censoring time under the joint modeling framework and can be computationally cumbersome due to the complex form of the likelihood function. In view of these issues, we propose a semiparametric joint regression model and construct a composite likelihood function based on a conditional order statistics argument. As a major feature of our proposed methods, the aforementioned joint distribution is not required to be specified, and the random effect in the proposed joint model is treated as a nuisance parameter. Consequently, the derived composite likelihood bypasses the need to integrate over the random effect and offers the advantage of easy computation. We show that the resulting estimators are consistent and asymptotically normal. We use simulation studies to evaluate the finite‐sample performance of the proposed method and apply it to a study of weight loss data that motivated our investigation.     

On the estimation of the extreme value and normal distribution parameters based on progressive type-II hybrid-censored data

A progressive hybrid censoring scheme is a mixture of type-I and type-II progressive censoring schemes. In this paper, we mainly consider the analysis of progressive type-II hybrid-censored data when the lifetime distribution of the individual item is the normal and extreme value distributions. Since the maximum likelihood estimators (MLEs) of these parameters cannot be obtained in the closed form, we propose to use the expectation and maximization (EM) algorithm to compute the MLEs. Also, the Newton–Raphson method is used to estimate the model parameters. The asymptotic variance–covariance matrix of the MLEs under EM framework is obtained by Fisher information matrix using the missing information and asymptotic confidence intervals for the parameters are then constructed. This study will end up with comparing the two methods of estimation and the asymptotic confidence intervals of coverage probabilities corresponding to the missing information principle and the observed information matrix through a simulation study, illustrated examples and real data analysis.     

Regression analysis of case-cohort studies in the presence of dependent interval censoring

The case-cohort design is widely used as a means of reducing the cost in large cohort studies, especially when the disease rate is low and covariate measurements may be expensive, and has been discussed by many authors. In this paper, we discuss regression analysis of case-cohort studies that produce interval-censored failure time with dependent censoring, a situation for which there does not seem to exist an established approach. For inference, a sieve inverse probability weighting estimation procedure is developed with the use of Bernstein polynomials to approximate the unknown baseline cumulative hazard functions. The proposed estimators are shown to be consistent and the asymptotic normality of the resulting regression parameter estimators is established. A simulation study is conducted to assess the finite sample properties of the proposed approach and indicates that it works well in practical situations. The proposed method is applied to an HIV/AIDS case-cohort study that motivated this investigation.