A Proportional Hazards Regression Model for the Subdistribution with Covariates‐adjusted Censoring Weight for Competing Risks Data

With competing risks data, one often needs to assess the treatment and covariate effects on the cumulative incidence function. Fine and Gray proposed a proportional hazards regression model for the subdistribution of a competing risk with the assumption that the censoring distribution and the covariates are independent. Covariate‐dependent censoring sometimes occurs in medical studies. In this paper, we study the proportional hazards regression model for the subdistribution of a competing risk with proper adjustments for covariate‐dependent censoring. We consider a covariate‐adjusted weight function by fitting the Cox model for the censoring distribution and using the predictive probability for each individual. Our simulation study shows that the covariate‐adjusted weight estimator is basically unbiased when the censoring time depends on the covariates, and the covariate‐adjusted weight approach works well for the variance estimator as well. We illustrate our methods with bone marrow transplant data from the Center for International Blood and Marrow Transplant Research. Here, cancer relapse and death in complete remission are two competing risks.     

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.     

Estimation of the cumulative incidence function under multiple dependent and independent censoring mechanisms

Competing risks occur in a time-to-event analysis in which a patient can experience one of several types of events. Traditional methods for handling competing risks data presuppose one censoring process, which is assumed to be independent. In a controlled clinical trial, censoring can occur for several reasons: some independent, others dependent. We propose an estimator of the cumulative incidence function in the presence of both independent and dependent censoring mechanisms. We rely on semi-parametric theory to derive an augmented inverse probability of censoring weighted (AIPCW) estimator. We demonstrate the efficiency gained when using the AIPCW estimator compared to a non-augmented estimator via simulations. We then apply our method to evaluate the safety and efficacy of three anti-HIV regimens in a randomized trial conducted by the AIDS Clinical Trial Group, ACTG A5095.     

An additive subdistribution hazard model for competing risks data

The cumulative incidence function plays an important role in assessing its treatment and covariate effects with competing risks data. In this article, we consider an additive hazard model allowing the time-varying covariate effects for the subdistribution and propose the weighted estimating equation under the covariate-dependent censoring by fitting the Cox-type hazard model for the censoring distribution. When there exists some association between the censoring time and the covariates, the proposed coefficients’ estimations are unbiased and the large-sample properties are established. The finite-sample properties of the proposed estimators are examined in the simulation study. The proposed Cox-weighted method is applied to a competing risks dataset from a Hodgkin's disease study.     

Predictive analysis for joint progressive censoring plans: a Bayesian approach

Comparative lifetime experiments are of particular importance in production processes when one wishes to determine the relative merits of several competing products with regard to their reliability. This paper confines itself to the data obtained by running a joint progressive Type-II censoring plan on samples in a combined manner. The problem of Bayesian predicting failure times of surviving units is discussed in details when parent populations are exponential. Two real data sets are analyzed in order to illustrate all the inferential procedures developed here. When destructive experiments under a censoring scheme finished, the researchers are usually interested to estimate remaining lifetimes of surviving units for sequel experiments. Findings of this paper are useful for these purposes specially when samples are non-homogeneous such as those taken from industrial storages.     

Statistical analysis of competing risks model from Marshall–Olkin extended Chen distribution under adaptive progressively interval censoring with random removals

In this paper, a new censoring scheme named by adaptive progressively interval censoring scheme is introduced. The competing risks data come from Marshall–Olkin extended Chen distribution under the new censoring scheme with random removals. We obtain the maximum likelihood estimators of the unknown parameters and the reliability function by using the EM algorithm based on the failure data. In addition, the bootstrap percentile confidence intervals and bootstrap-t confidence intervals of the unknown parameters are obtained. To test the equality of the competing risks model, the likelihood ratio tests are performed. Then, Monte Carlo simulation is conducted to evaluate the performance of the estimators under different sample sizes and removal schemes. Finally, a real data set is analyzed for illustration purpose.     

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.     

Semiparametric analysis of mixture regression models with competing risks data

In the analysis of competing risks data, cumulative incidence function is a useful summary of the overall crude risk for a failure type of interest. Mixture regression modeling has served as a natural approach to performing covariate analysis based on this quantity. However, existing mixture regression methods with competing risks data either impose parametric assumptions on the conditional risks or require stringent censoring assumptions. In this article, we propose a new semiparametric regression approach for competing risks data under the usual conditional independent censoring mechanism. We establish the consistency and asymptotic normality of the resulting estimators. A simple resampling method is proposed to approximate the distribution of the estimated parameters and that of the predicted cumulative incidence functions. Simulation studies and an analysis of a breast cancer dataset demonstrate that our method performs well with realistic sample sizes and is appropriate for practical use.     

Calibrated predictions for multivariate competing risks models

Prediction models for time-to-event data play a prominent role in assessing the individual risk of a disease, such as cancer. Accurate disease prediction models provide an efficient tool for identifying individuals at high risk, and provide the groundwork for estimating the population burden and cost of disease and for developing patient care guidelines. We focus on risk prediction of a disease in which family history is an important risk factor that reflects inherited genetic susceptibility, shared environment, and common behavior patterns. In this work family history is accommodated using frailty models, with the main novel feature being allowing for competing risks, such as other diseases or mortality. We show through a simulation study that naively treating competing risks as independent right censoring events results in non-calibrated predictions, with the expected number of events overestimated. Discrimination performance is not affected by ignoring competing risks. Our proposed prediction methodologies correctly account for competing events, are very well calibrated, and easy to implement.     

Asymptotic efficiency of a competing risks model: A two-sample case

A generalized Cox regression model is studied for the covariance analysis of competing risks data subject to independent random censoring. The information of the maximum partial likelihood estimates is compared with that of maximum likelihood estimates assuming a log linear hazard function.The method of generalized variance is used to define the efficiency of estimation between the two models. This is then applied to two-sample problems with two exponentially censoring rates. Numerical results are summarized ane presented graphically.The detailed results indicate that the semi-parametric model wrks well for a higher rate of censoring. A method of generalizing the result to type 1 censoring and the efficiency of estimating the coefficient of the covariate are discussecd. A brief account of using the results to help design experiments is also given.     

Statistical methods for dependent competing risks

Many biological and medical studies have as a response of interest the time to occurrence of some event,X, such as the occurrence of cessation of smoking, conception, a particular symptom or disease, remission, relapse, death due to some specific disease, or simply death. Often it is impossible to measureX due to the occurrence of some other competing event, usually termed a competing risk. This competing event may be the withdrawal of the subject from the study (for whatever reason), death from some cause other than the one of interest, or any eventuality that precludes the main event of interest from occurring. Usually the assumption is made that all such censoring times and lifetimes are independent. In this case one uses either the Kaplan-Meier estimator or the Nelson-Aalen estimator to estimate the survival function. However, if the competing risk or censoring times are not independent ofX, then there is no generally acceptable way to estimate the survival function. There has been considerable work devoted to this problem of dependent competing risks scattered throughout the statistical literature in the past several years and this paper presents a survey of such work.     

Competing risk and the Cox proportional hazard model

We propose a heuristic for evaluating model adequacy for the Cox proportional hazard model by comparing the population cumulative hazard with the baseline cumulative hazard. We illustrate how recent results from the theory of competing risk can contribute to analysis of data with the Cox proportional hazard model. A classical theorem on independent competing risks allows us to assess model adequacy under the hypothesis of random right censoring, and a recent result on mixtures of exponentials predicts the patterns of the conditional subsurvival functions of random right censored data if the proportional hazard model holds.     

Exact inference for competing risks model with generalized type-I hybrid censored exponential data

Recently, exact inference under hybrid censoring scheme has attracted extensive attention in the field of reliability analysis. However, most of the authors neglect the possibility of competing risks model. This paper mainly discusses the exact likelihood inference for the analysis of generalized type-I hybrid censoring data with exponential competing failure model. Based on the maximum likelihood estimates for unknown parameters, we establish the exact conditional distribution of parameters by conditional moment generating function, and then obtain moment properties as well as exact confidence intervals (CIs) for parameters. Furthermore, approximate CIs are constructed by asymptotic distribution and bootstrap method as well. We also compare their performances with exact method through the use of Monte Carlo simulations. And finally, a real data set is analysed to illustrate the validity of all the methods developed here.     

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.     

Modelling of dependence between critical failure and preventive maintenance: The repair alert model

We consider the competing risks problem for a repairable unit which at each sojourn may be subject to either a critical failure, or a preventive maintenance (PM) action, where the latter will prevent the failure. It is reasonable to expect a dependence between the failure mechanism and the PM regime. The paper presents a new model, called the repair alert model, for handling such cases. This model is a special case of random signs censoring, which was introduced by Roger Cooke [1993. The total time on test statistic and age-dependent censoring. Statist. Probab. Lett., 18, 307–312]. The pleasant feature of random signs censoring is that the marginal distribution of the failure time is identifiable. The repair alert model introduces the so-called repair alert function, which characterizes the “alertness” of the maintenance crew, and which is shown to be uniquely identifiable from field data. Statistical estimation is considered both nonparametrically and parametrically.     

Inference for a simple step-stress model with progressively censored competing risks data from Weibull distribution

In reliability analysis, it is common to consider several causes, either mechanical or electrical, those are competing to fail a unit. These causes are called “competing risks.” In this paper, we consider the simple step-stress model with competing risks for failure from Weibull distribution under progressive Type-II censoring. Based on the proportional hazard model, we obtain the maximum likelihood estimates (MLEs) of the unknown parameters. The confidence intervals are derived by using the asymptotic distributions of the MLEs and bootstrap method. For comparison, we obtain the Bayesian estimates and the highest posterior density (HPD) credible intervals based on different prior distributions. Finally, their performance is discussed through simulations.     

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.     

Power-transformed linear regression on quantile residual life for censored competing risks data

ABSTRACT

This paper proposes a power-transformed linear quantile regression model for the residual lifetime of competing risks data. The proposed model can describe the association between any quantile of a time-to-event distribution among survivors beyond a specific time point and the covariates. Under covariate-dependent censoring, we develop an estimation procedure with two steps, including an unbiased monotone estimating equation for regression parameters and cumulative sum processes for the Box–Cox transformation parameter. The asymptotic properties of the estimators are also derived. We employ an efficient bootstrap method for the estimation of the variance–covariance matrix. The finite-sample performance of the proposed approaches are evaluated through simulation studies and a real example.     

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.     

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.