Regression analysis of restricted mean survival time based on pseudo-observations for competing risks data

Competing risks data often occur in many medical follow-up studies. When the survival time is the outcome variable, the restricted mean survival time has heuristic and clinically meaningful interpretation. In this article, we propose a class of regression models for the restricted mean survival time in the competing risks setting. We adopt a technique of pseudo-observations to develop estimating equation approaches for the model parameters and establish asymptotic properties of the resulting estimators. The finite-sample behavior of the proposed method is evaluated through simulation studies, and an application to the Women’s Interagency HIV Study is provided.     

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.     

Quantile regression for competing risks analysis under case-cohort design

The case-cohort design brings cost reduction in large cohort studies. In this paper, we consider a nonlinear quantile regression model for censored competing risks under the case-cohort design. Two different estimation equations are constructed with or without the covariates information of other risks included, respectively. The large sample properties of the estimators are obtained. The asymptotic covariances are estimated by using a fast resampling method, which is useful to consider further inferences. The finite sample performance of the proposed estimators is assessed by simulation studies. Also a real example is used to demonstrate the application of the proposed methods.     

Flexible competing risks regression modeling and goodness-of-fit

In this paper we consider different approaches for estimation and assessment of covariate effects for the cumulative incidence curve in the competing risks model. The classic approach is to model all cause-specific hazards and then estimate the cumulative incidence curve based on these cause-specific hazards. Another recent approach is to directly model the cumulative incidence by a proportional model (Fine and Gray, J Am Stat Assoc 94:496–509, 1999), and then obtain direct estimates of how covariates influences the cumulative incidence curve. We consider a simple and flexible class of regression models that is easy to fit and contains the Fine–Gray model as a special case. One advantage of this approach is that our regression modeling allows for non-proportional hazards. This leads to a new simple goodness-of-fit procedure for the proportional subdistribution hazards assumption that is very easy to use. The test is constructive in the sense that it shows exactly where non-proportionality is present. We illustrate our methods to a bone marrow transplant data from the Center for International Blood and Marrow Transplant Research (CIBMTR). Through this data example we demonstrate the use of the flexible regression models to analyze competing risks data when non-proportionality is present in the data.     

On a deconvolution problem under competing risks

Bagai and Prakasa Rao [Analysis of survival data with two dependent competing risks. Biometr J. 1992;7:801–814] considered a competing risks model with two dependent risks. The two risks are initially independent but dependence arises because of the additive effect of an independent risk on the two initially independent risks. They showed that the ratio of failure rates are identifiable in the nonparametric set-up. In this paper, we consider it as a measurement error/deconvolution problem and suggest a nonparametric kernel-type estimator for the ratio of two failure rates. The local error properties of the proposed estimator are studied. Simulation studies show the efficacy of the proposed estimator.     

The alert-delay competing risks model for maintenance analysis

The paper considers the modelling of the dependency between corrective maintenance and condition-based preventive maintenance of complex repairable systems. A new model of dependent competing risks is proposed, called the alert-delay (AD) model. This model has different properties from that of the delay-time, repair-alert and proportional warning constant inspection models and happens to fit some data sets which could not be fitted by the previous models. The main features of the AD model are derived: probabilistic properties and statistical analysis. Simulation results and an application to real data are presented.     

Modelling and analysis of recall-based competing risks data

In this paper we consider the analysis of recall-based competing risks data. The chance of an individual recalling the exact time to event depends on the time of occurrence of the event and time of observation of the individual. In particular, it is assumed that the probability of recall depends on the time elapsed since the occurrence of an event. In this study we consider the likelihood-based inference for the analysis of recall-based competing risks data. The likelihood function is constructed by incorporating the information about the probability of recall. We consider the maximum likelihood estimation of parameters. Simulation studies are carried out to examine the performance of the estimators. The proposed estimation procedure is applied to a real life data set.     

Multiple imputation for competing risks regression with interval-censored data

ABSTRACT

We present here an extension of Pan's multiple imputation approach to Cox regression in the setting of interval-censored competing risks data. The idea is to convert interval-censored data into multiple sets of complete or right-censored data and to use partial likelihood methods to analyse them. The process is iterated, and at each step, the coefficient of interest, its variance–covariance matrix, and the baseline cumulative incidence function are updated from multiple posterior estimates derived from the Fine and Gray sub-distribution hazards regression given augmented data. Through simulation of patients at risks of failure from two causes, and following a prescheduled programme allowing for informative interval-censoring mechanisms, we show that the proposed method results in more accurate coefficient estimates as compared to the simple imputation approach. We have implemented the method in the MIICD R package, available on the CRAN website.     

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.     

A martingale-based test for independence of time to failure and cause of failure for competing risks models

In this article, we introduce a class of tests, using a martingale approach, for testing independence of failure time and cause of failure for competing risks data. Asymptotic distribution of the proposed test statistic is derived. The procedure is illustrated with a real-life data. A simulation study is carried out to assess the level and power of the test.     

An improper form of Weibull distribution for competing risks analysis with Bayesian approach

ABSTRACT

In survival analysis, individuals may fail due to multiple causes of failure called competing risks setting. Parametric models such as Weibull model are not improper that ignore the assumption of multiple failure times. In this study, a novel extension of Weibull distribution is proposed which is improper and then can incorporate to the competing risks framework. This model includes the original Weibull model before a pre-specified time point and an exponential form for the tail of the time axis. A Bayesian approach is used for parameter estimation. A simulation study is performed to evaluate the proposed model. The conducted simulation study showed identifiability and appropriate convergence of the proposed model. The proposed model and the 3-parameter Gompertz model, another improper parametric distribution, are fitted to the acute lymphoblastic leukemia dataset.     

Hazards regression for freemium products and services: a competing risks approach

We propose a competing risks approach to analyse customer behaviours in freemium products and services. The event of interest is when a customer starts to pay for additional features or functionalities. The observation of such an event may be preempted by an event where the customer quits using the product before paying and consuming the additional features or functionalities. One such freemium service is the online game category. The Fine-Gray regression model was implemented for an online game player activity data to study how covariates affect the paying hazard. Some covariates are hypothesized to have different discrete effects at multiple change points. We extend the model to allow for possible change points in the analysis.     

A proportional hazards model for the analysis of doubly censored competing risks data

ABSTRACT

Competing risks data are common in medical research in which lifetime of individuals can be classified in terms of causes of failure. In survival or reliability studies, it is common that the patients (objects) are subjected to both left censoring and right censoring, which is refereed as double censoring. The analysis of doubly censored competing risks data in presence of covariates is the objective of this study. We propose a proportional hazards model for the analysis of doubly censored competing risks data, using the hazard rate functions of Gray (1988 Gray, R.J. (1988). A class of k-sample tests for comparing the cumulative incidence of a competing risk. Ann. Statist. 16:1141–1154.[Crossref], [Web of Science ®] , [Google Scholar]), while focusing upon one major cause of failure. We derive estimators for regression parameter vector and cumulative baseline cause specific hazard rate function. Asymptotic properties of the estimators are discussed. A simulation study is conducted to assess the finite sample behavior of the proposed estimators. We illustrate the method using a real life doubly censored competing risks data.     

On adaptive progressively Type-II censored competing risks data

In this article, a competing risks model based on exponential distributions is considered under the adaptive Type-II progressively censoring scheme introduced by Ng et al. [2009, Naval Research Logistics 56:687-698], for life testing or reliability experiment. Moreover, we assumed that some causes of failures are unknown. The maximum likelihood estimators (MLEs) of unknown parameters are established. The exact conditional and the asymptotic distributions of the obtained estimators are derived to construct the confidence intervals as well as the two different bootstraps of different unknown parameters. Under suitable priors on the unknown parameters, Bayes estimates and the corresponding two sides of Bayesian probability intervals are obtained. Also, for the purpose of evaluating the average bias and mean square error of the MLEs, and comparing the confidence intervals based on all mentioned methods, a simulation study was carried out. Finally, we present one real dataset to conduct the proposed methods.     

Case-cohort analysis with semiparametric transformation models

Semiparametric transformation models provide flexible regression models for survival analysis, including the Cox proportional hazards and the proportional odds models as special cases. We consider the application of semiparametric transformation models in case-cohort studies, where the covariate data are observed only on cases and on a subcohort randomly sampled from the full cohort. We first propose an approximate profile likelihood approach with full-cohort data, which amounts to the pseudo-partial likelihood approach of Zucker [2005. A pseudo-partial likelihood method for semiparametric survival regression with covariate errors. J. Amer. Statist. Assoc. 100, 1264–1277]. Simulation results show that our proposal is almost as efficient as the nonparametric maximum likelihood estimator. We then extend this approach to the case-cohort design, applying the Horvitz–Thompson weighting method to the estimating equations from the approximated profile likelihood. Two levels of weights can be utilized to achieve unbiasedness and to gain efficiency. The resulting estimator has a closed-form asymptotic covariance matrix, and is found in simulations to be substantially more efficient than the estimator based on martingale estimating equations. The extension to left-truncated data will be discussed. We illustrate the proposed method on data from a cardiovascular risk factor study conducted in Taiwan.     

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.     

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.     

Conditional tests in a competing risks model

Testing for equality of competing risks based on their cumulative incidence functions (CIFs) or their cause specific hazard rates (CSHRs) has been considered by many authors. The finite sample distributions of the existing test statistics are in general complicated and the use of their asymptotic distributions can lead to conservative tests. In this paper we show how to perform some of these tests using the conditional distributions of their corresponding test statistics instead (conditional on the observed data). The resulting conditional tests are initially developed for the case of k = 2 and are then extended to k > 2 by performing a sequence of two sample tests and by combining several risks into one. A simulation study to compare the powers of several tests based on their conditional and asymptotic distributions shows that using conditional tests leads to a gain in power. A real life example is also discussed to show how to implement such conditional tests.     

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.     

Tests for comparison of competing risks under the additive risk model

It is of interest that researchers study competing risks in which subjects may fail from any one of k causes. Comparing any two competing risks with covariate effects is very important in medical studies. In this paper, we develop tests for comparing cause-specific hazard rates and cumulative incidence functions at specified covariate levels under the additive risk model by a weighted difference of estimates of cumulative cause-specific hazard rates. Motivated by McKeague et al. (2001), we construct simultaneous confidence bands for the difference of two conditional cumulative incidence functions as a useful graphical tool. In addition, we conduct a simulation study, and the simulation result shows that the proposed procedure has a good finite sample performance. A melanoma data set in clinical trial is used for the purpose of illustration.