Competing risks regression for clustered data.
Ontology highlight
ABSTRACT:
SUBMITTER: Zhou B
PROVIDER: S-EPMC3372942 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Clustered competing risks data are commonly encountered in multicenter studies. The analysis of such data is often complicated due to informative cluster size (ICS), a situation where the outcomes under study are associated with the size of the cluster. In addition, the cause of failure is frequently incompletely observed in real-world settings. To the best of our knowledge, there is no methodology for population-averaged analysis with clustered competing risks data with an ICS and missing causes of failure. To address this problem, we consider the semiparametric marginal proportional cause-specific hazards model and propose a maximum partial pseudolikelihood estimator under a missing at random assumption. To make the latter assumption more plausible in practice, we allow for auxiliary variables that may be related to the probability of missingness. The proposed method does not impose assumptions regarding the within-cluster dependence and allows for ICS. The asymptotic properties of the proposed estimators for both regression coefficients and infinite-dimensional parameters, such as the marginal cumulative incidence functions, are rigorously established. Simulation studies show that the proposed method performs well and that methods that ignore the within-cluster dependence and the ICS lead to invalid inferences. The proposed method is applied to competing risks data from a large multicenter HIV study in sub-Saharan Africa where a significant portion of causes of failure is missing.
| S-EPMC10345995 | biostudies-literature
Project description:For competing risks data, the Fine-Gray proportional hazards model for subdistribution has gained popularity for its convenience in directly assessing the effect of covariates on the cumulative incidence function. However, in many important applications, proportional hazards may not be satisfied, including multicenter clinical trials, where the baseline subdistribution hazards may not be common due to varying patient populations. In this article, we consider a stratified competing risks regression, to allow the baseline hazard to vary across levels of the stratification covariate. According to the relative size of the number of strata and strata sizes, two stratification regimes are considered. Using partial likelihood and weighting techniques, we obtain consistent estimators of regression parameters. The corresponding asymptotic properties and resulting inferences are provided for the two regimes separately. Data from a breast cancer clinical trial and from a bone marrow transplantation registry illustrate the potential utility of the stratified Fine-Gray model.
| S-EPMC3431205 | biostudies-literature
Project description:BackgroundIn many clinical trials the study interest lies in the comparison of a treatment to a control group regarding a time to event endpoint like time to myocardial infarction, time to relapse, or time to a specific cause of death. Thereby, an event can occur before the primary event of interest that alters the risk for or prohibits observing the latter, i.e. a competing event. Furthermore, multi-center studies are often conducted. Hence, a cluster structure might be observed. However, commonly only the aspect of competing events or the aspect of the cluster structure is modelled within primary analysis, although both are given within the study design. Methods to adequately analyze data in such a design were recently described but were not systematically compared yet.MethodsWithin this work we provide a systematic comparison of four approaches for the analysis of competing events where a cluster structure is present based on a real life data set and a simulation study. The considered methods are the commonly applied cause-specific Cox proportional hazards model with a frailty, the Fine and Gray model for considering competing risks, and extensions of the latter model by Katsahian et al. and Zhou et al. RESULTS: Based on our simulation results, the model by Katsahian et al. showed the best performance in bias, square root of mean squared error, and power in nearly all scenarios. In contrast to the other three models this approach allows both unbiased effect estimation and prognosis.ConclusionThe provided comparison and simulations help to guide applied researchers to choose an adequate method for the analysis of competing events where a cluster structure is present. Based on our simulation results the approach by Katsahian et al. can be recommended.
| S-EPMC10084627 | biostudies-literature
Project description:Bandeen-Roche and Liang (2002, Modelling multivariate failure time associations in the presence of a competing risk. Biometrika 89, 299-314.) tailored Oakes (1989, Bivariate survival models induced by frailties. Journal of the American Statistical Association 84, 487-493.)'s conditional hazard ratio to evaluate cause-specific associations in bivariate competing risks data. In many population-based family studies, one observes complex multivariate competing risks data, where the family sizes may be > 2, certain marginals may be exchangeable, and there may be multiple correlated relative pairs having a given pairwise association. Methods for bivariate competing risks data are inadequate in these settings. We show that the rank correlation estimator of Bandeen-Roche and Liang (2002) extends naturally to general clustered family structures. Consistency, asymptotic normality, and variance estimation are easily obtained with U-statistic theories. A natural by-product is an easily implemented test for constancy of the association over different time regions. In the Cache County Study on Memory in Aging, familial associations in dementia onset are of interest, accounting for death prior to dementia. The proposed methods using all available data suggest attenuation in dementia associations at later ages, which had been somewhat obscured in earlier analyses.
| S-EPMC2800162 | biostudies-literature
Project description:Interval-censored competing risks data arise when each study subject may experience an event or failure from one of several causes and the failure time is not observed directly but rather is known to lie in an interval between two examinations. We formulate the effects of possibly time-varying (external) covariates on the cumulative incidence or sub-distribution function of competing risks (i.e., the marginal probability of failure from a specific cause) through a broad class of semiparametric regression models that captures both proportional and non-proportional hazards structures for the sub-distribution. We allow each subject to have an arbitrary number of examinations and accommodate missing information on the cause of failure. We consider nonparametric maximum likelihood estimation and devise a fast and stable EM-type algorithm for its computation. We then establish the consistency, asymptotic normality, and semiparametric efficiency of the resulting estimators for the regression parameters by appealing to modern empirical process theory. In addition, we show through extensive simulation studies that the proposed methods perform well in realistic situations. Finally, we provide an application to a study on HIV-1 infection with different viral subtypes.
| S-EPMC5561531 | biostudies-literature
Project description:Competing risks data often exist within a center in multi-center randomized clinical trials where the treatment effects or baseline risks may vary among centers. In this paper, we propose a subdistribution hazard regression model with multivariate frailty to investigate heterogeneity in treatment effects among centers from multi-center clinical trials. For inference, we develop a hierarchical likelihood (or h-likelihood) method, which obviates the need for an intractable integration over the frailty terms. We show that the profile likelihood function derived from the h-likelihood is identical to the partial likelihood, and hence it can be extended to the weighted partial likelihood for the subdistribution hazard frailty models. The proposed method is illustrated with a dataset from a multi-center clinical trial on breast cancer as well as with a simulation study. We also demonstrate how to present heterogeneity in treatment effects among centers by using a confidence interval for the frailty for each individual center and how to perform a statistical test for such heterogeneity using a restricted h-likelihood.
| S-EPMC5771528 | biostudies-literature
Project description:This paper considers generalized linear quantile regression for competing risks data when the failure type may be missing. Two estimation procedures for the regression co-efficients, including an inverse probability weighted complete-case estimator and an augmented inverse probability weighted estimator, are discussed under the assumption that the failure type is missing at random. The proposed estimation procedures utilize supplemental auxiliary variables for predicting the missing failure type and for informing its distribution. The asymptotic properties of the two estimators are derived and their asymptotic efficiencies are compared. We show that the augmented estimator is more efficient and possesses a double robustness property against misspecification of either the model for missingness or for the failure type. The asymptotic covariances are estimated using the local functional linearity of the estimating functions. The finite sample performance of the proposed estimation procedures are evaluated through a simulation study. The methods are applied to analyze the 'Mashi' trial data for investigating the effect of formula-versus breast-feeding plus extended infant zidovudine prophylaxis on HIV-related death of infants born to HIV-infected mothers in Botswana.
| S-EPMC3742132 | biostudies-literature
Project description:In some applications, the clustered survival data are arranged spatially such as clinical centers or geographical regions. Incorporating spatial variation in these data not only can improve the accuracy and efficiency of the parameter estimation, but it also investigates the spatial patterns of survivorship for identifying high-risk areas. Competing risks in survival data concern a situation where there is more than one cause of failure, but only the occurrence of the first one is observable. In this paper, we considered Bayesian subdistribution hazard regression models with spatial random effects for the clustered HIV/AIDS data. An intrinsic conditional autoregressive (ICAR) distribution was employed to model the areal spatial random effects. Comparison among competing models was performed by the deviance information criterion. We illustrated the gains of our model through application to the HIV/AIDS data and the simulation studies.
| S-EPMC9041729 | biostudies-literature
Project description:Censored quantile regression models, which offer great flexibility in assessing covariate effects on event times, have attracted considerable research interest. In this study, we consider flexible estimation and inference procedures for competing risks quantile regression, which not only provides meaningful interpretations by using cumulative incidence quantiles but also extends the conventional accelerated failure time model by relaxing some of the stringent model assumptions, such as global linearity and unconditional independence. Current method for censored quantile regressions often involves the minimization of the L1 -type convex function or solving the nonsmoothed estimating equations. This approach could lead to multiple roots in practical settings, particularly with multiple covariates. Moreover, variance estimation involves an unknown error distribution and most methods rely on computationally intensive resampling techniques such as bootstrapping. We consider the induced smoothing procedure for censored quantile regressions to the competing risks setting. The proposed procedure permits the fast and accurate computation of quantile regression parameter estimates and standard variances by using conventional numerical methods such as the Newton-Raphson algorithm. Numerical studies show that the proposed estimators perform well and the resulting inference is reliable in practical settings. The method is finally applied to data from a soft tissue sarcoma study.
| S-EPMC6156950 | biostudies-literature
Project description:The cause of failure in cohort studies that involve competing risks is frequently incompletely observed. To address this, several methods have been proposed for the semiparametric proportional cause-specific hazards model under a missing at random assumption. However, these proposals provide inference for the regression coefficients only, and do not consider the infinite dimensional parameters, such as the covariate-specific cumulative incidence function. Nevertheless, the latter quantity is essential for risk prediction in modern medicine. In this paper we propose a unified framework for inference about both the regression coefficients of the proportional cause-specific hazards model and the covariate-specific cumulative incidence functions under missing at random cause of failure. Our approach is based on a novel computationally efficient maximum pseudo-partial-likelihood estimation method for the semiparametric proportional cause-specific hazards model. Using modern empirical process theory we derive the asymptotic properties of the proposed estimators for the regression coefficients and the covariate-specific cumulative incidence functions, and provide methodology for constructing simultaneous confidence bands for the latter. Simulation studies show that our estimators perform well even in the presence of a large fraction of missing cause of failures, and that the regression coefficient estimator can be substantially more efficient compared to the previously proposed augmented inverse probability weighting estimator. The method is applied using data from an HIV cohort study and a bladder cancer clinical trial.
| S-EPMC7381366 | biostudies-literature