Regression analysis for cumulative incidence probability under competing risks and left-truncated sampling

The cumulative incidence function provides intuitive summary information about competing risks data. Via a mixture decomposition of this function, Chang and Wang (Statist. Sinca 19:391–408, 2009) study how covariates affect the cumulative incidence probability of a particular failure type at a chosen time point. Without specifying the corresponding failure time distribution, they proposed two estimators and derived their large sample properties. The first estimator utilized the technique of weighting to adjust for the censoring bias, and can be considered as an extension of Fine’s method (J R Stat Soc Ser B 61: 817–830, 1999). The second used imputation and extends the idea of Wang (J R Stat Soc Ser B 65: 921–935, 2003) from a nonparametric setting to the current regression framework. In this article, when covariates take only discrete values, we extend both approaches of Chang and Wang (Statist Sinca 19:391–408, 2009) by allowing left truncation. Large sample properties of the proposed estimators are derived, and their finite sample performance is investigated through a simulation study. We also apply our methods to heart transplant survival data.     

Semiparametric estimation of the cumulative incidence function under competing risks and left-truncated sampling

In this article, we propose semiparametric methods to estimate the cumulative incidence function of two dependent competing risks for left-truncated and right-censored data. The proposed method is based on work by Huang and Wang (1995). We extend previous model by allowing for a general parametric truncation distribution and a third competing risk before recruitment. Based on work by Vardi (1989), several iterative algorithms are proposed to obtain the semiparametric estimates of cumulative incidence functions. The asymptotic properties of the semiparametric estimators are derived. Simulation results show that a semiparametric approach assuming the parametric truncation distribution is correctly specified produces estimates with smaller mean squared error than those obtained in a fully nonparametric model.     

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]).     

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.     

Nonparametric estimation of the cumulative intensities in an interval censored competing risks model

The nonparametric maximum likelihood estimation (NPMLE) of the distribution function from the interval censored (IC) data has been extensively studied in the extant literature. The NPMLE was also developed for the subdistribution functions in an IC competing risks model and in an illness-death model under various interval-censoring scenarios. But the important problem of estimation of the cumulative intensities (CIs) in the interval-censored models has not been considered previously. We develop the NPMLE of the CI in a simple alive/dead model and of the CIs in a competing risks model. Assuming that data are generated by a discrete and finite mixed case interval censoring mechanism we provide a discussion and the simulation study of the asymptotic properties of the NPMLEs of the CIs. In particular we show that they are asymptotically unbiased; in contrast the ad hoc estimators presented in extant literature are substantially biased. We illustrate our methods with the data from a prospective cohort study on the longevity of dental veneers.     

Approximate tests for the equality of two cumulative incidence functions of a competing risk

In the context of a competing risks set-up, we discuss different inference procedures for testing equality of two cumulative incidence functions, where the data may be subject to independent right-censoring or left-truncation. To this end, we compare two-sample Kolmogorov–Smirnov- and Cramér–von Mises-type test statistics. Since, in general, their corresponding asymptotic limit distributions depend on unknown quantities, we utilize wild bootstrap resampling as well as approximation techniques to construct adequate test decisions. Here, the latter procedures are motivated from tests for heteroscedastic factorial designs but have not yet been proposed in the survival context. A simulation study shows the performance of all considered tests under various settings and finally a real data example about bloodstream infection during neutropenia is used to illustrate their application.     

The response functions for competing risks

The competing risks data consist of a pair (T,δ) where T≧0 can be interpreted as the failure time and δ as the identifier of the risk causing the failure. In many practical situations, the main interest lies in studying the inter-relationships between the probability structures of the failure time under various risks. Here, we consider two risks and propose the Junctional relationships between the probability structure of (T,δ=1) and (T,δ=2) by time-dependent scale and shape shifts. Also, a model which raptures the relative aging of a unit under the two risks is proposed. The necessary theory for confidence estimation of these shift functions is developed. These techniques are illustrated through several data sets available in the literature.     

Estimation of cumulative incidence functions when the lifetime distributions are uniformly stochastically ordered

In the competing risks problem an important role is played by the cumulative incidence function (CIF), whose value at time t is the probability of failure by time t from a particular type of risk in the presence of other risks. Assume that the lifetime distributions of two populations are uniformly stochastically ordered. Since this ordering may not hold for the empiricals due to sampling variability, it is natural to estimate these distributions under this constraint. This will in turn affect the estimation of the CIFs. This article considers this estimation problem. We do not assume that the risk sets in the two populations are related, give consistent estimators of all the CIFs and study the weak convergence of the resulting processes. We also report the results of a simulation study that show that our restricted estimators outperform the unrestricted ones in terms of mean square error. A real life example is used to illustrate our theoretical results.     

Estimation in a competing risks proportional hazards model under length-biased sampling with censoring

What population does the sample represent? The answer to this question is of crucial importance when estimating a survivor function in duration studies. As is well-known, in a stationary population, survival data obtained from a cross-sectional sample taken from the population at time $t_0$ represents not the target density $f(t)$ but its length-biased version proportional to $tf(t)$ , for $t>0$ . The problem of estimating survivor function from such length-biased samples becomes more complex, and interesting, in presence of competing risks and censoring. This paper lays out a sampling scheme related to a mixed Poisson process and develops nonparametric estimators of the survivor function of the target population assuming that the two independent competing risks have proportional hazards. Two cases are considered: with and without independent censoring before length biased sampling. In each case, the weak convergence of the process generated by the proposed estimator is proved. A well-known study of the duration in power for political leaders is used to illustrate our results. Finally, a simulation study is carried out in order to assess the finite sample behaviour of our estimators.     

Identifiability of distributions under competing risks and complementary risks model

Let X₁,X₂,…,X_p be p random variables with cdf's F₁(x),F₂(x),…,F_p(x)respectively. Let U = min(X₁,X₂,…,X_p) and V = max(X₁,X₂,…,X_p).In this paper we study the problem of uniquely determining and estimating the marginal distributions F₁,F₂,…,F_p given the distribution of U or of V.

First the problem of competing and complementary risks are introduced with examples and the corresponding identification problems are considered when the X₁'s are independently distributed and U(V) is identified, as well as the case when U(V) is not identified. The case when the X₁'s are dependent is considered next. Finally the problem of estimation is considered.     

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.     

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.     

Estimation of weibull parameters for grouped data with competing risks

We consider the problem of estimating Weibull parameters for grouped data when competing risks are present. We propose two simple methods of estimation and derive their asymptotic properties. A Monte Carlo study was carried out to evaluate the performance of these two methods.     

Estimation of conditional cumulative incidence functions under generalized semiparametric regression models with missing covariates,with application to analysis of biomarker correlates in vaccine trials

This article presents generalized semiparametric regression models for conditional cumulative incidence functions with competing risks data when covariates are missing by sampling design or happenstance. A doubly robust augmented inverse probability weighted (AIPW) complete-case approach to estimation and inference is investigated. This approach modifies IPW complete-case estimating equations by exploiting the key features in the relationship between the missing covariates and the phase-one data to improve efficiency. An iterative numerical procedure is derived to solve the nonlinear estimating equations. The asymptotic properties of the proposed estimators are established. A simulation study examining the finite-sample performances of the proposed estimators shows that the AIPW estimators are more efficient than the IPW estimators. The developed method is applied to the RV144 HIV-1 vaccine efficacy trial to investigate vaccine-induced IgG binding antibodies to HIV-1 as correlates of acquisition of HIV-1 infection while taking account of whether the HIV-1 sequences are near or far from the HIV-1 sequences represented in the vaccine construct.     

Estimation and test of several multivariate normal means under an order restriction when the dimension is larger than two

Suppose that an order restriction is imposed among several p-variate normal mean vectors. We are interested in the problems of estimating these mean vectors and testing their homogeneity under this restriction. These problems are multivariate extensions of Bartholomew's (1959) ones. For the bivariate case, these problems have been studied by Sasabuchi et al. (1983) and (1998) and some others. In the present paper we examine the convergence of an iterative algorithm for computing the maximum likelihood estimator when p is larger than two. We also study some test procedures for testing homogeneity when p is larger than two.     

Applying competing risks regression models: an overview

In many clinical research applications the time to occurrence of one event of interest, that may be obscured by another??so called competing??event, is investigated. Specific interventions can only have an effect on the endpoint they address or research questions might focus on risk factors for a certain outcome. Different approaches for the analysis of time-to-event data in the presence of competing risks were introduced in the last decades including some new methodologies, which are not yet frequently used in the analysis of competing risks data. Cause-specific hazard regression, subdistribution hazard regression, mixture models, vertical modelling and the analysis of time-to-event data based on pseudo-observations are described in this article and are applied to a dataset of a cohort study intended to establish risk stratification for cardiac death after myocardial infarction. Data analysts are encouraged to use the appropriate methods for their specific research questions by comparing different regression approaches in the competing risks setting regarding assumptions, methodology and interpretation of the results. Notes on application of the mentioned methods using the statistical software R are presented and extensions to the presented standard methods proposed in statistical literature are mentioned.     

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.