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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
1

MULTI-STATE MODELS FOR INTERVAL CENSORED DATA WITH COMPETING RISK

Wei, Shaoceng 01 January 2015 (has links)
Multi-state models are often used to evaluate the effect of death as a competing event to the development of dementia in a longitudinal study of the cognitive status of elderly subjects. In this dissertation, both multi-state Markov model and semi-Markov model are used to characterize the flow of subjects from intact cognition to dementia with mild cognitive impairment and global impairment as intervening transient, cognitive states and death as a competing risk. Firstly, a multi-state Markov model with three transient states: intact cognition, mild cognitive impairment (M.C.I.) and global impairment (G.I.) and one absorbing state: dementia is used to model the cognitive panel data. A Weibull model and a Cox proportional hazards (Cox PH) model are used to fit the time to death based on age at entry and the APOE4 status. A shared random effect correlates this survival time with the transition model. Secondly, we further apply a Semi-Markov process in which we assume that the wait- ing times are Weibull distributed except for transitions from the baseline state, which are exponentially distributed and we assume no additional changes in cognition occur between two assessments. We implement a quasi-Monte Carlo (QMC) method to calculate the higher order integration needed for the likelihood based estimation. At the end of this dissertation we extend a non-parametric “local EM algorithm” to obtain a smooth estimator of the cause-specific hazard function (CSH) in the presence of competing risk. All the proposed methods are justified by simulation studies and applications to the Nun Study data, a longitudinal study of late life cognition in a cohort of 461 subjects.

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