Frailty-Based Competing Risks Model for Multivariate Survival Data (original) (raw)
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Correlated survival times can be modelled by introducing a random effect, or frailty component, into the hazard function. For multivariate survival data, we extend a non-proportional hazards (PH) model, the generalized time-dependent logistic survival model, to include random effects. The hierarchical likelihood procedure, which obviates the need for marginalization over the random effect distribution, is derived for this extended model and its properties are discussed. The extended model leads to a robust estimation result for the regression parameters against the misspecification of the form of the basic hazard function or frailty distribution compared to PH-based alternatives. The proposed method is illustrated by two practical examples and a simulation study which demonstrate the advantages of the new model.
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Journal of the Royal Statistical Society: Series B (Statistical Methodology), 2003
We propose a simple estimation procedure for a proportional hazards frailty regression model for clustered survival data in which the dependence is generated by a positive stable distribution. Inferences for the frailty parameter can be obtained by using output from Cox regression analyses. The computational burden is substantially less than that of the other approaches to estimation. The large sample
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Frailty models are becoming increasingly popular in multivariate survival analysis. Shared frailty models in particular are often used despite their limitations. To overcome their disadvantages numerous correlated frailty models were established during the last decade. In the present study, we examine bivariate correlated frailty models, and especially the behavior of the parameter estimates when using different estimation strategies. We consider three different bivariate frailty models: the gamma model and two versions of the log-normal model. The traditional maximum likelihood procedure of parameter estimation in the gamma case with an explicit available likelihood function is compared with maximum likelihood methods based on numerical integration and a Bayesian approach using MCMC methods with the help of a comprehensive simulation study. We detected a strong dependence between the two parameter estimates (variance and correlation of frailties) in the bivariate correlated frailty...
Biometrika, 2006
In this work we provide a simple estimation procedure for a general frailty model for analysis of prospective correlated failure times. Rigorous large-sample theory for the proposed estimators of both the regression coefficient vector and the dependence parameter is given, including consistent variance estimators. In a simulation study under the widely used gamma frailty model, our proposed approach was found to have essentially the same efficiency as the EM-based estimator considered by other authors, with negligible difference between the standard errors of the two estimators. The proposed approach, however, provides a framework capable of handling general frailty distributions with finite moments and yields an explicit consistent variance estimator.
Journal of Statistical Software, 2012
Frailty models are very useful for analysing correlated survival data, when observations are clustered into groups or for recurrent events. The aim of this article is to present the new version of an R package called frailtypack. This package allows to fit Cox models and four types of frailty models (shared, nested, joint, additive) that could be useful for several issues within biomedical research. It is well adapted to the analysis of recurrent events such as cancer relapses and/or terminal events (death or lost to follow-up). The approach uses maximum penalized likelihood estimation. Right-censored or left-truncated data are considered. It also allows stratification and time-dependent covariates during analysis.
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We develop a joint model for the analysis of longitudinal and survival data in the presence of data clustering. We use a mixed effects model for the repeated measures that incorporates both subject-and cluster-level random effects, with subjects nested within clusters. A Cox frailty model is used for the survival model in order to accommodate the clustering. We then link the two responses via the common cluster-level random effects, or frailties. This model allows us to simultaneously evaluate the effect of covariates on the two types of responses, while accounting for both the relationship between the responses and data clustering. The model was motivated by a study of end-stage renal disease patients undergoing hemodialysis, where we wished to evaluate the effect of iron treatment on both the patients' hemoglobin levels and survival times, with the patients clustered by enrollment site.
parfm : Parametric Frailty Models in R
Journal of Statistical Software, 2012
Frailty models are getting more and more popular to account for overdispersion and/or clustering in survival data. When the form of the baseline hazard is somehow known in advance, the parametric estimation approach can be used advantageously. Nonetheless, there is no unified widely available software that deals with the parametric frailty model. The new parfm package remedies that lack by providing a wide range of parametric frailty models in R. The available baseline hazard failies are: exponential, Weibull, inverse Weibull (Fréchet), Gompertz, lognormal, log-kewNormal, and loglogistic. The gamma, positive stable, inverse Gaussian, and lognormal frailty distributions can be specified, together with five different baseline hazards. Parameter estimation is done by maximising the marginal log-likelihood, with right-censored and possibly left-truncated data. In the multivariate setting, the inverse Gaussian may encounter numerical difficulties with a huge number of events in at least one cluster. The positive stable model shows analogous difficulties but an ad-hoc solution is implemented, whereas the gamma model is very resistant due to the simplicity of its Laplace transform.
An Accelerated Failure Time Regression Model for Illness-Death Data: A Frailty Approach
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This work presents a new model and estimation procedure for the illness-death survival data where the hazard functions follow accelerated failure time (AFT) models. A shared frailty variate induces positive dependence among failure times of a subject for handling the unobserved dependency between the non-terminal and the terminal failure times given the observed covariates. Semi-parametric maximum likelihood estimation procedure is developed via a kernel smoothed-aided EM algorithm, and variances are estimated by weighted bootstrap. The model is presented in the context of existing frailty-based illness-death models, emphasizing the contribution of the current work. The breast cancer data of the Rotterdam tumor bank are analyzed using the proposed and existing illness-death models. The results are contrasted and evaluated based on a new graphical goodness-of-fit procedure. Simulation results and data analysis nicely demonstrate the practical utility of the shared frailty variate with the AFT regression model under the illness-death framework.