Characterizations of Competing Risks in Terms of Independent-Risks Proxy Models

In competing risks a failure time T and a cause C , one of p possible, are observed. A traditional representation is via a vector ( T ₁, ..., T_p ) of latent failure times such that T = min( T ₁, ..., T_p ); C is defined by T = T_C in the basic situation of failure from a single cause. There are several results in the literature to the effect that a joint distribution for ( T ₁, ..., T_p ), in which the T_j are independent, can always be constructed to yield any given bivariate distribution for ( C , T ). For this reason the prevailing wisdom is that independence cannot be assessed from competing risks data, not even with arbitrarily large sample sizes (e.g. Prentice et al. , 1978). A result was given by Crowder (1996) which shows that, under certain circumstances, independence can be assessed. The various results will be drawn together and a complete characterization can now be given in terms of independent-risks proxy models.     

A Test for Independence of Competing Risks with Discrete Failure Times

The identifiability problem in Competing Risks is well known. In particular, it implies that independent action or otherwise of the risks cannot be inferred from data alone. However, Crowder (1996) showed that, in the case of purely discrete failure times, an inference can be made. An algebraic criterion was derived which bears essentially on the independence in question. The condition was presented in a theoretical setting but it was pointed out that the quantities involved can be estimated from data and that, therefore, there is the potential to develop practical tests for the hypothesis of independence. It is the purpose of this paper to construct such a test. This revised version was published online in July 2006 with corrections to the Cover Date.     

The Identifiability of Dependent Competing Risks Models Induced by Bivariate Frailty Models

In this paper, we propose to use a special class of bivariate frailty models to study dependent censored data. The proposed models are closely linked to Archimedean copula models. We give sufficient conditions for the identifiability of this type of competing risks models. The proposed conditions are derived based on a property shared by Archimedean copula models and satisfied by several well‐known bivariate frailty models. Compared with the models studied by Heckman and Honoré and Abbring and van den Berg, our models are more restrictive but can be identified with a discrete (even finite) covariate. Under our identifiability conditions, expectation–maximization (EM) algorithm provides us with consistent estimates of the unknown parameters. Simulation studies have shown that our estimation procedure works quite well. We fit a dependent censored leukaemia data set using the Clayton copula model and end our paper with some discussions. © 2014 Board of the Foundation of the Scandinavian Journal of Statistics     

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.     

Inference for the Dependent Competing Risks Model with Masked Causes of Failure

The competing risks model is useful in settings in which individuals/units may die/fail for different reasons. The cause specific hazard rates are taken to be piecewise constant functions. A complication arises when some of the failures are masked within a group of possible causes. Traditionally, statistical inference is performed under the assumption that the failure causes act independently on each item. In this paper we propose an EM-based approach which allows for dependent competing risks and produces estimators for the sub-distribution functions. We also discuss identifiability of parameters if none of the masked items have their cause of failure clarified in a second stage analysis (e.g. autopsy). The procedures proposed are illustrated with two datasets.     

Comparison of cumulative incidence functions of current status competing risks data with discrete observation times

Abstract

Competing risks data with current status censoring arise frequently from transversal studies in demography, epidemiology and reliability theory; where the only information about lifetime is whether the event of interest has occurred or not before a monitoring time. In practice, the monitoring times are discrete, but most of the studies consider them as continuous in nature. In the present paper, we propose a non parametric test for comparing cumulative incidence functions of current status competing risks data while the observation (monitoring) times are discrete. Asymptotic distribution of the test statistic is also derived. A simulation study is conducted to assess the finite sample behavior of the test statistic. The practical utility of the procedure is well demonstrated using a real-life data set on menopausal history of 2423 women given in Jewell, van der Laan, and Henneman (2003 Jewell, N. P., M. van der Laan, and T. Henneman. 2003. Nonparametric estimation from current status data with competing risks. Biometrika 90 (1):183–197. doi: 10.1093/biomet/90.1.183.[Crossref], [Web of Science ®] , [Google Scholar]).     

Weibull accelerated life tests when there are competing causes of failure

Accelerated life testing of a product under more severe than normal conditions is commonly used to reduce test time and costs. Data collected at such accelerated conditions are used to obtain estimates of the parameters of a stress translation function. This function is then used to make inference about the product's life under normal operating conditions. We consider the problem of accelerated life tests when the product of interest is a p component series system. Each of the components is assumed to have an independent Weibull time to failure distribution with different shape parameters and different scale parameters which are increasing functions stress. A general model i s used for the scale parameter includes the standard engineering models as special This model also has an appealing biological interpretation     

Estimation of the marginal survival time in the presence of dependent competing risks using inverse probability of censoring weighted (IPCW) methods

In medical studies, there is interest in inferring the marginal distribution of a survival time subject to competing risks. The Kyushu Lipid Intervention Study (KLIS) was a clinical study for hypercholesterolemia, where pravastatin treatment was compared with conventional treatment. The primary endpoint was time to events of coronary heart disease (CHD). In this study, however, some subjects died from causes other than CHD or were censored due to loss to follow-up. Because the treatments were targeted to reduce CHD events, the investigators were interested in the effect of the treatment on CHD events in the absence of causes of death or events other than CHD. In this paper, we present a method for estimating treatment group-specific marginal survival curves of time-to-event data in the presence of dependent competing risks. The proposed method is a straightforward extension of the Inverse Probability of Censoring Weighted (IPCW) method to settings with more than one reason for censoring. The results of our analysis showed that the IPCW marginal incidence for CHD was almost the same as the lower bound for which subjects with competing events were assumed to be censored at the end of all follow-up. This result provided reassurance that the results in KLIS were robust to competing risks.     

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.     

Risk patterns in drug safety study using relative times by accelerated failure time models when proportional hazards assumption is questionable: an illustrative case study of cancer risk of patients on glucose‐lowering therapies

Observational drug safety studies may be susceptible to confounding or protopathic bias. This bias may cause a spurious relationship between drug exposure and adverse side effect when none exists and may lead to unwarranted safety alerts. The spurious relationship may manifest itself through substantially different risk levels between exposure groups at the start of follow‐up when exposure is deemed too short to have any plausible biological effect of the drug. The restrictive proportional hazards assumption with its arbitrary choice of baseline hazard function renders the commonly used Cox proportional hazards model of limited use for revealing such potential bias. We demonstrate a fully parametric approach using accelerated failure time models with an illustrative safety study of glucose‐lowering therapies and show that its results are comparable against other methods that allow time‐varying exposure effects. Our approach includes a wide variety of models that are based on the flexible generalized gamma distribution and allows direct comparisons of estimated hazard functions following different exposure‐specific distributions of survival times. This approach lends itself to two alternative metrics, namely relative times and difference in times to event, allowing physicians more ways to communicate patient's prognosis without invoking the concept of risks, which some may find hard to grasp. In our illustrative case study, substantial differences in cancer risks at drug initiation followed by a gradual reduction towards null were found. This evidence is compatible with the presence of protopathic bias, in which undiagnosed symptoms of cancer lead to switches in diabetes medication. Copyright © 2015 John Wiley & Sons, Ltd.