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Frailty in Competing Risks Models

Random effects or frailty in competing risk models consist of two underlying distributions:

the conditional distribution of the response variables (failure times), given the random effect

depending on the explanatory variables each with a failure type specific random effect; and

the distribution of the random effect in the population (frailty distribution). In this situation,

the distribution of interest is the unconditional distribution of the response variables which

may or may not have a tractable form. Bandeen-Roche and Liang (2002) described the

association of time to multivariate failure in the presence of a competing risk. As mentioned

above frailty models in the presence of competing risks involve the conditional distribution

failure time given the frailty and the distribution of the frailty. Fahrmeir and Tutz (1994) and

Oskrochi and Davies (1997) implemented the Cholesky decomposition for multivariate frailty

models. The Cholesky decomposition decomposes the frailty variance-covariance matrix into

triangular matrices to convert the integration over a multivariate distribution to multiple

Univariate data ID Yi δi xi1 · · · xip 1 Y1 δ1 x11 · · · x1p 2 Y2 δ2 x21 · · · x2p . . . . . . . . . . . . n Yn δn xn1 · · · xnp Multivariate data

ID Yij cluster δij xij1 · · · xijp

1 Y11 1 δ11 x111 x11p 2 Y21 1 δ21 x211 x21p . . . . . . . . . . . . n1 Yn11 1 δn11 xn111 · · · xn11p . . . . . . . . . . . . 1 Y1J J δ1J x1J 1 x1J p 2 Y2J J δ2J x2J 1 x2J p . . . . . . . . . . . . nJ YnJJ J δnJJ xnJJ 1 · · · xnJJ p

Competing risk data

ID Yi δi1 · · · δiK xi1 · · · xip 1 Y1 δ11 · · · δ1K x11 · · · x1p 2 Y2 δ21 · · · δ2K x21 · · · x2p . . . . . . . . . . . . n Yn δn1 · · · δnK xn1 · · · xnp

Fine and Gray (1999) proposed a novel semi-parametric proportional hazards model for

the sub-distribution. Using the partial likelihood principle and weighting techniques, they

derived estimation and inference procedures for the finite-dimensional regression parameters

under a variety of censoring scenarios. They gave a uniformly consistent estimator for

the predicted cumulative incidence for an individual with certain covariates, confidence

intervals and bands can be obtained analytically or with an easy-to-implement simulation

technique. Fine et al. (2001) considered semi-competing risk models, in which a terminal

event censors a non-terminal event but not vice versa. The joint distribution of the events is

formulated via Gamma frailty model with marginal distributions unspecified. They showed

that the dependence between morbidity and mortality can be estimated separately from their

marginals under a Gamma frailty copula in the region of observable data. Jiang et al. (2004)

considered semi-competing risk models where mortality and morbidity may be correlated

and mortality may censor morbidity. They proposed a semi-parametric estimator for the

survival function based on a joint model for the two time-to-event variables, which utilises

the Gamma frailty specification in the region of the observable data. They extended the

methods of Fine et al. (2001) for the left truncated semi-competing risk problem, developed

an estimator for the Gamma frailty parameter under left truncation and derived a closed

form estimator for the marginal distribution of the non-terminal event. Naskar et al. (2005)

proposed a dependent competing risks model where dependency is induced through the

mixture of various failure types and a frailty component. The frailty term is modelled non-

parametrically using a Dirichlet Process (DP). They considered a semi-parametric mixture

model for analysing clustered competing risks data. Conditional on cluster-specific quantities,

the joint distribution of the failure time and event indicator can be expressed as a mixture

of the distribution of time to failure due to a certain type (or specific cause), and the failure

(competing risks) are logistic functions of some covariates. The cluster-specific quantities are

subject to some unknown distribution that causes frailty. Lu and Tsiatis (2005) compared

two approaches for the competing risks model with missing cause of failure. Under the

assumption that the cause of death is missing at random, they compared the Goetghebeur

and Ryan (1995) partial likelihood approach with the one by Dewanji (1992). They showed

that the Dewanji partial likelihood estimator for the regression coefficients is consistent and

asymptotically Normal. While the Goetghebeur and Ryan estimator is more robust estimator

against mis-specification of proportional baseline hazards. Finkelstein and Esaulovac (2006,

2008) discussed the asymptotic behaviour of competing risks models with correlated frailty

in univariate and bivariate cases. They consider a set of absolutely continuous distributions

of a lifetime random variable.

In the next section, a review the correlated Gamma frailty and its application to competing

risks framework is given. In section 4.7, a new proposed correlated Inverse Gaussian frailty

model and its application to competing risks are presented. A general multivariate Inverse

Gaussian frailty model without any restriction on the correlation structure between the

frailties is given in section 4.8. In addition, a flexible multivariate frailty model that can

be applied whatever the original distribution of the frailty in section 4.10 is proposed. In this

model, a non-parametric multivariate frailty presented.

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