• The Korean Journal of Applied Statistics
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• v.29 no.7
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• pp.1311-1327
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• 2016

We propose a multi-state model for analyzing semi-competing risks data with interval-censored or missing intermediate events. This model is an extension of the 'illness-death model', which composes three states, such as 'healthy', 'diseased', and 'dead'. The state of 'diseased' can be considered as an intermediate event. Two more states are added into the illness-death model to describe missing events caused by a loss of follow-up before the end of the study. One of them is a state of 'LTF', representing a lost-to-follow-up, and the other is an unobservable state that represents the intermediate event experienced after LTF occurred. Given covariates, we employ the Cox proportional hazards model with a normal frailty and construct a full likelihood to estimate transition intensities between states in the multi-state model. Marginalization of the full likelihood is completed using the adaptive Gaussian quadrature, and the optimal solution of the regression parameters is achieved through the iterative Newton-Raphson algorithm. Simulation studies are carried out to investigate the finite-sample performance of the proposed estimation procedure in terms of the empirical coverage probability of the true regression parameter. Our proposed method is also illustrated with the dataset adapted from Helmer et al. (2001).

• The Korean Journal of Applied Statistics
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• v.30 no.4
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• pp.539-553
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• 2017

We propose a multi-state model to analyze semi-competing risks data with interval-censored or missing intermediate events. This model is an extension of the three states of the illness-death model: healthy, disease, and dead. The 'diseased' state can be considered as the intermediate event. Two more states are added into the illness-death model to incorporate the missing events, which are caused by a loss of follow-up before the end of a study. One of them is a state of the lost-to-follow-up (LTF), and the other is an unobservable state that represents an intermediate event experienced after the occurrence of LTF. Given covariates, we employ the Lin and Ying additive hazards model with log-normal frailty and construct a conditional likelihood to estimate transition intensities between states in the multi-state model. A marginalization of the full likelihood is completed using adaptive importance sampling, and the optimal solution of the regression parameters is achieved through an iterative quasi-Newton algorithm. Simulation studies are performed to investigate the finite-sample performance of the proposed estimation method in terms of empirical coverage probability of true regression parameters. Our proposed method is also illustrated with a dataset adapted from Helmer et al. (2001).

• The Korean Journal of Applied Statistics
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• v.33 no.4
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• pp.379-393
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• 2020

A terminal event such as death may censor an intermediate event such as relapse, but not vice versa in semi-competing risks data, which is often seen in medicine, public health, and epidemiology. We propose a Weibull regression model with a normal frailty to analyze semi-competing risks data when all three transition times of the illness-death model are possibly interval-censored. We construct the conditional likelihood separately depending on the types of subjects: still alive with or without the intermediate event, dead with or without the intermediate event, and dead with the intermediate event missing. Optimal parameter estimates are obtained from the iterative quasi-Newton algorithm after the marginalization of the full likelihood using the adaptive importance sampling. We illustrate the proposed method with extensive simulation studies and PAQUID (Personnes Agées Quid) data.