Identification of longitudinal biomarkers for survival by a score test derived from a joint model of longitudinal and competing risks data

In this paper, we consider joint modelling of repeated measurements and competing risks failure time data. For competing risks time data, a semiparametric mixture model in which proportional hazards model are specified for failure time models conditional on cause and a multinomial model for the marginal distribution of cause conditional on covariates. We also derive a score test based on joint modelling of repeated measurements and competing risks failure time data to identify longitudinal biomarkers or surrogates for a time to event outcome in competing risks data.     

Statistical analysis of dependent competing risks model in accelerated life testing under progressively hybrid censoring using copula function

This article considers statistical analysis of dependent competing risks model from Weibull distribution in accelerated life testing, in which copula function is used to examine the dependence structure between competing failure modes. We derive the maximum likelihood estimates, the approximate, and Bootstrap confidence intervals of the parameters. The effects of different dependence structures on the estimates of parameters are investigated. The simulation is given to compare the performance of the estimates when the competing failure modes are dependent with those when the failure modes are independent. Finally, one dataset was used for illustrative purpose in conclusion.     

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.     

Testing equality of cause-specific hazard rates corresponding to m competing risks among K groups

In this paper, a class of tests is developed for comparing the cause-specific hazard rates of m competing risks simultaneously in K ( 2) groups. The data available for a unit are the failure time of the unit along with the identifier of the risk claiming the failure. In practice, the failure time data are generally right censored. The tests are based on the difference between the weighted averages of the cause-specific hazard rates corresponding to each risk. No assumption regarding the dependence of the competing risks is made. It is shown that the proposed test statistic has asymptotically chi-squared distribution. The proposed test is shown to be optimal for a specific type of local alternatives. The choice of weight function is also discussed. A simulation study is carried out using multivariate Gumbel distribution to compare the optimal weight function with a proposed weight function which is to be used in practice. Also, the proposed test is applied to real data on the termination of an intrauterine device.An erratum to this article can be found at     

Inference for cumulative incidence on discrete failure times with competing risks

In the competing risks analysis, most inferences have been developed based on continuous failure time data. However, failure times are sometimes observed as being discrete. We propose nonparametric inferences for the cumulative incidence function for pure discrete data with competing risks. When covariate information is available, we propose semiparametric inferences for direct regression modelling of the cumulative incidence function for grouped discrete failure time data with competing risks. Simulation studies show that the procedures perform well. The proposed methods are illustrated with a study of contraceptive use in Indonesia.     

Accelerated failure time models for the analysis of competing risks

Competing risks are common in clinical cancer research, as patients are subject to multiple potential failure outcomes, such as death from the cancer itself or from complications arising from the disease. In the analysis of competing risks, several regression methods are available for the evaluation of the relationship between covariates and cause-specific failures, many of which are based on Cox’s proportional hazards model. Although a great deal of research has been conducted on estimating competing risks, less attention has been devoted to linear regression modeling, which is often referred to as the accelerated failure time (AFT) model in survival literature. In this article, we address the use and interpretation of linear regression analysis with regard to the competing risks problem. We introduce two types of AFT modeling framework, where the influence of a covariate can be evaluated in relation to either a cause-specific hazard function, referred to as cause-specific AFT (CS-AFT) modeling in this study, or the cumulative incidence function of a particular failure type, referred to as crude-risk AFT (CR-AFT) modeling. Simulation studies illustrate that, as in hazard-based competing risks analysis, these two models can produce substantially different effects, depending on the relationship between the covariates and both the failure type of principal interest and competing failure types. We apply the AFT methods to data from non-Hodgkin lymphoma patients, where the dataset is characterized by two competing events, disease relapse and death without relapse, and non-proportionality. We demonstrate how the data can be analyzed and interpreted, using linear competing risks regression models.     

Score tests for independence in semiparametric competing risks models

A popular model for competing risks postulates the existence of a latent unobserved failure time for each risk. Assuming that these underlying failure times are independent is attractive since it allows standard statistical tools for right-censored lifetime data to be used in the analysis. This paper proposes simple independence score tests for the validity of this assumption when the individual risks are modeled using semiparametric proportional hazards regressions. It assumes that covariates are available, making the model identifiable. The score tests are derived for alternatives that specify that copulas are responsible for a possible dependency between the competing risks. The test statistics are constructed by adding to the partial likelihoods for the individual risks an explanatory variable for the dependency between the risks. A variance estimator is derived by writing the score function and the Fisher information matrix for the marginal models as stochastic integrals. Pitman efficiencies are used to compare test statistics. A simulation study and a numerical example illustrate the methodology proposed in this paper.     

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.     

Analysis of interval censored failure time data with competing risk

In this article, we analyze interval censored failure time data with competing risks. A new estimator for the cumulative incidence function is derived using an approximate likelihood and a test statistic to compare two samples is then obtained by extending Sun's test statistic. Small sample properties of the proposed methods are examined by conducting simulations and a cohort dataset from AIDS patients is analyzed as a real example.     

Competing failure modes in accelerated life testing

There is a vast amount of literature on accelerated life testing, however, most of this literature ignores the possibility of competing modes of failure. The literature that attempts to address this problem often uses a maximum likelihood estimation method which may require large samples. Even in the case of a single failure mode, a small sample data is expected to be generated by an ALT procedure applied to expensive components. In this article we present a Bayesian framework for the analysis of ALT data with possible multiple failure modes. We illustrate the applicability of our model on some competing risk data sets available in the literature.     

Analysis of Competing Risks by Using Bayesian Smoothing

We consider the competing risks set-up. In many practical situations, the conditional probability of the cause of failure given the failure time is of direct interest. We propose to model the competing risks by the overall hazard rate and the conditional probabilities rather than the cause-specific hazards. We adopt a Bayesian smoothing approach for both quantities of interest. Illustrations are given at the end.     

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.     

Test for independence between time to failure and cause of failure in competing risks with k causes

In this paper, we develop a simple nonparametric test for testing the independence of time to failure and cause of failure in competing risks set up. We generalise the test to the situation where failure data is right censored. We obtain the asymptotic distribution of the test statistics for complete and censored data. The efficiency loss due to censoring is studied using Pitman efficiency. The performance of the proposed test is evaluated through simulations. Finally we illustrate our test procedure using three real data sets.     

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.     

Analysis of interval censored competing risk data with missing causes of failure using pseudo values approach

Competing risks often occur when subjects may fail from one of several mutually exclusive causes. For example, when a patient suffering a cancer may die from other cause, we are interested in the effect of a certain covariate on the probability of dying of cancer at a certain time. Several approaches have been suggested to analyse competing risk data in the presence of complete information of failure cause. In this paper, our interest is to consider the occurrence of missing causes as well as interval censored failure time. There exist no method to discuss this problem. We applied a Klein–Andersen's pseudo-value approach [Klein, JP Andersen PK. Regression modeling of competing risks data based on pseudovalues of the cumulative incidence function. Biometrics. 2005;61:223–229] based on the estimated cumulative incidence function and a regression coefficient is estimated through a multiple imputation. We evaluate the suggested method by comparing with a complete case analysis in several simulation settings.     

Tests of independence for censored bivariate failure time data

Bivariate failure time data is widely used in survival analysis, for example, in twins study. This article presents a class of chi2-type tests for independence between pairs of failure times after adjusting for covariates. A bivariate accelerated failure time model is proposed for the joint distribution of bivariate failure times while leaving the dependence structures for related failure times completely unspecified. Theoretical properties of the proposed tests are derived and variance estimates of the test statistics are obtained using a resampling technique. Simulation studies show that the proposed tests are appropriate for practical use. Two examples including the study of infection in catheters for patients on dialysis and the diabetic retinopathy study are also given to illustrate the methodology.     

Progressively Type-II censored competing risks data for exponential distributions based on sequential order statistics

We consider the progressively Type-II censored competing risks model based on sequential order statistics. It is assumed that the latent failure times are independent and the failure of each unit influences the lifetime distributions of the latent failure times of surviving units. We provide explicit expressions for the likelihood function of the available data under the conditional proportional hazard rate (CPHR) and the power trend conditional proportional hazard rate (PTCPHR) models. Under CPHR and PTCPHR models and assumption that the baseline distributions of the latent failure times are exponential, classical and Bayesian estimates of the unknown parameters are provided. Monte Carlo simulations are then performed for illustrative purposes. Finally, two datasets are analyzed.     

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.     

Identification of Longitudinal Biomarkers in Survival Analysis for Competing Risks Data

In recent years, joint analysis of longitudinal measurements and survival data has received much attention. However, previous work has primarily focused on a single failure type for the event time. In this article, we consider joint modeling of repeated measurements and competing risks failure time data to allow for more than one distinct failure type in the survival endpoint so we fit a cause-specific hazards sub-model to allow for competing risks, with a separate latent association between longitudinal measurements and each cause of failure. Besides, previous work does not focus on the hypothesis to test a separate latent association between longitudinal measurements and each cause of failure. In this article, we derive a score test to identify longitudinal biomarkers or surrogates for a time to event outcome in competing risks data. With a carefully chosen definition of complete data, the maximum likelihood estimation of the cause-specific hazard functions is performed via an EM algorithm. We extend this work and allow random effects to be present in both the longitudinal biomarker and underlying survival function. The random effects in the biomarker are introduced via an explicit term while the random effect in the underlying survival function is introduced by the inclusion of frailty into the model.

We use simulations to explore how the number of individuals, the number of time points per individual and the functional form of the random effects from the longitudinal biomarkers considering heterogeneous baseline hazards in individuals influence the power to detect the association of a longitudinal biomarker and the survival time.     

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.