Estimating progression-free survival in paediatric brain tumour patients when some progression statuses are unknown

In oncology, progression-free survival time, which is defined as the minimum of the times to disease progression or death, often is used to characterize treatment and covariate effects. We are motivated by the desire to estimate the progression time distribution on the basis of data from 780 paediatric patients with choroid plexus tumours, which are a rare brain cancer where disease progression always precedes death. In retrospective data on 674 patients, the times to death or censoring were recorded but progression times were missing. In a prospective study of 106 patients, both times were recorded but there were only 20 non-censored progression times and 10 non-censored survival times. Consequently, estimating the progression time distribution is complicated by the problems that, for most of the patients, either the survival time is known but the progression time is not known, or the survival time is right censored and it is not known whether the patient's disease progressed before censoring. For data with these missingness structures, we formulate a family of Bayesian parametric likelihoods and present methods for estimating the progression time distribution. The underlying idea is that estimating the association between the time to progression and subsequent survival time from patients having complete data provides a basis for utilizing covariates and partial event time data of other patients to infer their missing progression times. We illustrate the methodology by analysing the brain tumour data, and we also present a simulation study.     

Bayesian Analysis of Different Hybrid and Progressive Life Tests

Type-I and Type-II censoring schemes are the widely used censoring schemes available for life testing experiments. A mixture of Type-I and Type-II censoring schemes is known as a hybrid censoring scheme. Different hybrid censoring schemes have been introduced in recent years. In the last few years, a progressive censoring scheme has also received considerable attention. In this article, we mainly consider the Bayesian inference of the unknown parameters of two-parameter exponential distribution under different hybrid and progressive censoring schemes. It is observed that in general the Bayes estimate and the associated credible interval of any function of the unknown parameters, cannot be obtained in explicit form. We propose to use the Monte Carlo sampling procedure to compute the Bayes estimate and also to construct the associated credible interval. Monte Carlo Simulation experiments have been performed to see the effectiveness of the proposed method in case of Type-I hybrid censored samples. The performances are quite satisfactory. One data analysis has been performed for illustrative purposes.     

Residual plots for linear regression models with censored outcome data: A refined method for visualizing residual uncertainty

Residual plots are a standard tool for assessing model fit. When some outcome data are censored, standard residual plots become less appropriate. Here, we develop a new procedure for producing residual plots for linear regression models where some or all of the outcome data are censored. We implement two approaches for incorporating parameter uncertainty. We illustrate our methodology by examining the model fit for an analysis of bacterial load data from a trial for chronic obstructive pulmonary disease. Simulated datasets show that the method can be used when the outcome data consist of a variety of types of censoring.     

PROGRESSIVE INTERVAL CENSORING: SOME MATHEMATICAL RESULTS WITH APPLICATIONS TO INFERENCE

In this paper, we will introduce a union of two methods of collecting Type-I censored data, namely interval censoring and progressive censoring. We will call the resulting sample a progressively Type-I interval censored sample.We will discuss likelihood point and interval estimation, and simulation of such a censored sample from a random sample of units put on test whose lifetime distribution is continuous. An illustrative example will also be presented.

     

Estimation with Interval Censored Data and Covariates

In biostatistical applications interest often focuses on the estimation of the distribution of time T between two consecutive events. If the initial event time is observed and the subsequent event time is only known to be larger or smaller than an observed monitoring time C, then the data conforms to the well understood singly-censored current status model, also known as interval censored data, case I. Additional covariates can be used to allow for dependent censoring and to improve estimation of the marginal distribution of T. Assuming a wrong model for the conditional distribution of T, given the covariates, will lead to an inconsistent estimator of the marginal distribution. On the other hand, the nonparametric maximum likelihood estimator of FT requires splitting up the sample in several subsamples corresponding with a particular value of the covariates, computing the NPMLE for every subsample and then taking an average. With a few continuous covariates the performance of the resulting estimator is typically miserable. In van der Laan, Robins (1996) a locally efficient one-step estimator is proposed for smooth functionals of the distribution of T, assuming nothing about the conditional distribution of T, given the covariates, but assuming a model for censoring, given the covariates. The estimators are asymptotically linear if the censoring mechanism is estimated correctly. The estimator also uses an estimator of the conditional distribution of T, given the covariates. If this estimate is consistent, then the estimator is efficient and if it is inconsistent, then the estimator is still consistent and asymptotically normal. In this paper we show that the estimators can also be used to estimate the distribution function in a locally optimal way. Moreover, we show that the proposed estimator can be used to estimate the distribution based on interval censored data (T is now known to lie between two observed points) in the presence of covariates. The resulting estimator also has a known influence curve so that asymptotic confidence intervals are directly available. In particular, one can apply our proposal to the interval censored data without covariates. In Geskus (1992) the information bound for interval censored data with two uniformly distributed monitoring times at the uniform distribution (for T has been computed. We show that the relative efficiency of our proposal w.r.t. this optimal bound equals 0.994, which is also reflected in finite sample simulations. Finally, the good practical performance of the estimator is shown in a simulation study. This revised version was published online in July 2006 with corrections to the Cover Date.     

Interval censored and truncated data: Rate of convergence of NPMLE of the density

We consider survival data that are both interval censored and truncated. Under appropriate assumptions on the involved distributions, the censoring, truncation and survival, we prove the consistency of the NPMLE of the density of the survival, and give the rate of convergence. Finally, we give an example where the joint law of the censoring and truncation can be explicitly computed.     

Bayesian analysis of competing risks with partially masked cause of failure

Summary. Bayesian analysis of system failure data from engineering applications under a competing risks framework is considered when the cause of failure may not have been exactly identified but has only been narrowed down to a subset of all potential risks. In statistical literature, such data are termed masked failure data. In addition to masking, failure times could be right censored owing to the removal of prototypes at a prespecified time or could be interval censored in the case of periodically acquired readings. In this setting, a general Bayesian formulation is investigated that includes most commonly used parametric lifetime distributions and that is sufficiently flexible to handle complex forms of censoring. The methodology is illustrated in two engineering applications with a special focus on model comparison issues.     

Inference for mixed generalized exponential distribution under progressively type-II censored samples

In industrial life tests, reliability analysis and clinical trials, the type-II progressive censoring methodology, which allows for random removals of the remaining survival units at each failure time, has become quite popular for analyzing lifetime data. Parameter estimation under progressively type-II censored samples for many common lifetime distributions has been investigated extensively. However, how to estimate unknown parameters of the mixed distribution models under progressive type-II censoring schemes is still a challenging and interesting problem. Based on progressively type-II censored samples, this paper addresses the estimation problem of mixed generalized exponential distributions. In addition, it is observed that the maximum-likelihood estimates (MLEs) cannot be easily obtained in closed form due to the complexity of the likelihood function. Thus, we make good use of the expectation-maximization algorithm to obtain the MLEs. Finally, some simulations are implemented in order to show the performance of the proposed method under finite samples and a case analysis is illustrated.     

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.     

Exact inference for the two-parameter exponential distribution under Type-II hybrid censoring

Epstein (1954) introduced the Type-I hybrid censoring scheme as a mixture of Type-I and Type-II censoring schemes. Childs et al. (2003) introduced the Type-II hybrid censoring scheme as an alternative to Type-I hybrid censoring scheme, and provided the exact distribution of the maximum likelihood estimator of the mean of a one-parameter exponential distribution based on Type-II hybrid censored samples. The associated confidence interval also has been provided. The main aim of this paper is to consider a two-parameter exponential distribution, and to derive the exact distribution of the maximum likelihood estimators of the unknown parameters based on Type-II hybrid censored samples. The marginal distributions and the exact confidence intervals are also provided. The results can be used to derive the exact distribution of the maximum likelihood estimator of the percentile point, and to construct the associated confidence interval. Different methods are compared using extensive simulations and one data analysis has been performed for illustrative purposes.     

Inverse regression estimation for censored data

An inverse regression methodology for assessing predictor performance in the censored data setup is developed along with inference procedures and a computational algorithm. The technique developed here allows for conditioning on the unobserved failure time along with a weighting mechanism that accounts for the censoring. The implementation is nonparametric and computationally fast. This provides an efficient methodological tool that can be used especially in cases where the usual modeling assumptions are not applicable to the data under consideration. It can also be a good diagnostic tool that can be used in the model selection process. We have provided theoretical justification of consistency and asymptotic normality of the methodology. Simulation studies and two data analyses are provided to illustrate the practical utility of the procedure.     

The analysis of mixed interval-censored and complete data

The article focuses mainly on a conditional imputation algorithm of quantile-filling to analyze a new kind of censored data, mixed interval-censored and complete data related to interval-censored sample. With the algorithm, the imputed failure times, which are the conditional quantiles, are obtained within the censoring intervals in which some exact failure times are. The algorithm is viable and feasible for the parameter estimation with general distributions, for instance, a case of Weibull distribution that has a moment estimation of closed form by log-transformation. Furthermore, interval-censored sample is a special case of the new censored sample, and the conditional imputation algorithm can also be used to deal with the failure data of interval censored. By comparing the interval-censored data and the new censored data, using the imputation algorithm, in the view of the bias of estimation, we find that the performance of new censored data is better than that of interval censored.     

THE ASYMPTOTIC EQUIVALENCE OF THE FISHER INFORMATION MATRICES FOR TYPE I AND TYPE II CENSORED DATA FROM LOCATION-SCALE FAMILIES

Type I and Type II censored data arise frequently in controlled laboratory studies concerning time to a particular event (e.g., death of an animal or failure of a physical device). Log-location-scale distributions (e.g., Weibull, lognormal, and loglogistic) are commonly used to model the resulting data. Maximum likelihood (ML) is generally used to obtain parameter estimates when the data are censored. The Fisher information matrix can be used to obtain large-sample approximate variances and covariances of the ML estimates or to estimate these variances and covariances from data. The derivations of the Fisher information matrix proceed differently for Type I (time censoring) and Type II (failure censoring) because the number of failures is random in Type I censoring, but length of the data collection period is random in Type II censoring. Under regularity conditions (met with the above-mentioned log-location-scale distributions), we outline the different derivations and show that the Fisher information matrices for Type I and Type II censoring are asymptotically equivalent.     

A relation between product-limit estimate and joint-risk estimate

The joint-risk estimate of the survival function, used for censored survival data grouped into fixed intervals, is shown to be the geometric mean of all the product-limit estimates that correspond to all the possible orderings of all the failure times and censoring times in the group. The joint-risk estimate is proposed as a more appropriate and better means of dealing with ties for data containing tied failure times and censoring times. It is also applicable to competing risk problems with tied failure times involving different causes. It could be used as a substitute for the product-limit estimate in discrete failure time analysis.     

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.     

On the Kullback–Leibler information of hybrid censored data

ABSTRACT

A hybrid censoring is a mixture of Type I and Type II censoring where the experiment terminates when either rth failure or predetermined censoring time comes first or later. In this article, we consider order statistics of the Type I censored data and provide a simple expression for their Kullback–Leibler (KL) information. Then, we provide the expressions for the KL information of the Type I and Type II hybrid censored data.     

Bias in linear model power and sample size due to estimating variance

Planning a study using the General Linear Univariate Model often involves sample size calculation based on a variance estimated in an earlier study. Noncentrality, power, and sample size inherit the randomness. Additional complexity arises if the estimate has been censored. Left censoring occurs when only significant tests lead to a power calculation, while right censoring occurs when only non-significant tests lead to a power calculation. We provide simple expressions for straightforward computation of the distribution function, moments, and quantiles of the censored variance estimate, estimated noncentrality, power, and sample size. We also provide convenient approximations and evaluate their accuracy. The results allow demonstrating that ignoring right censoring falsely widens confidence intervals for noncentrality and power, while ignoring left censoring falsely narrows the confidence intervals. The new results allow assessing and avoiding the potentially substantial bias that censoring may create.     

Estimation for Location-Scale Models with Censored Data

This article considers a class of estimators for the location and scale parameters in the location-scale model based on ‘synthetic data’ when the observations are randomly censored on the right. The asymptotic normality of the estimators is established using counting process and martingale techniques when the censoring distribution is known and unknown, respectively. In the case when the censoring distribution is known, we show that the asymptotic variances of this class of estimators depend on the data transformation and have a lower bound which is not achievable by this class of estimators. However, in the case that the censoring distribution is unknown and estimated by the Kaplan–Meier estimator, this class of estimators has the same asymptotic variance and attains the lower bound for variance for the case of known censoring distribution. This is different from censored regression analysis, where asymptotic variances depend on the data transformation. Our method has three valuable advantages over the method of maximum likelihood estimation. First, our estimators are available in a closed form and do not require an iterative algorithm. Second, simulation studies show that our estimators being moment-based are comparable to maximum likelihood estimators and outperform them when sample size is small and censoring rate is high. Third, our estimators are more robust to model misspecification than maximum likelihood estimators. Therefore, our method can serve as a competitive alternative to the method of maximum likelihood in estimation for location-scale models with censored data. A numerical example is presented to illustrate the proposed method.     

Testing the validity of the exponential model for hybrid Type-I censored data

The exponential distribution has been used in life-testing and reliability studies. In this article, we first express the entropy of Type-I hybrid censoring scheme in terms of hazard function and provide an estimate of the entropy of Type-I hybrid censored data. Then, we construct a goodness-of-fit test statistic based on Kullback–Leibler information for Type-I hybrid censored data. The test statistic is used to test for exponentiality. A Monte Carlo simulation is conducted to obtain the power of the proposed test against various alternatives. Finally, a data example is presented for illustrative purpose.     

Variable screening for survival data in the presence of heterogeneous censoring

Variable screening for censored survival data is most challenging when both survival and censoring times are correlated with an ultrahigh-dimensional vector of covariates. Existing approaches to handling censoring often make use of inverse probability weighting by assuming independent censoring with both survival time and covariates. This is a convenient but rather restrictive assumption which may be unmet in real applications, especially when the censoring mechanism is complex and the number of covariates is large. To accommodate heterogeneous (covariate-dependent) censoring that is often present in high-dimensional survival data, we propose a Gehan-type rank screening method to select features that are relevant to the survival time. The method is invariant to monotone transformations of the response and of the predictors, and works robustly for a general class of survival models. We establish the sure screening property of the proposed methodology. Simulation studies and a lymphoma data analysis demonstrate its favorable performance and practical utility.