Analysis of Interval-Censored Failure Time Data with Long-Term Survivors

This dissertation, "Analysis of Interval-censored Failure Time Data With Long-term Survivors" by Kin-yau, Wong, 黃堅祐, was obtained from The University of Hong Kong (Pokfulam, Hong Kong) and is being sold pursuant to Creative Commons: Attribution 3.0 Hong Kong License. The content of this dissertation has not been altered in any way. We have altered the formatting in order to facilitate the ease of printing and reading of the dissertation. All rights not granted by the above license are retained by the author. Abstract: Failure time data analysis, or survival analysis, is involved in various research fields, such as medicine and public health. One basic assumption in standard survival analysis is that every individual in the study population will eventually experience the event of interest. However, this assumption is usually violated in practice, for example when the variable of interest is the time to relapse of a curable disease resulting in the existence of long-term survivors. Also, presence of unobservable risk factors in the group of susceptible individuals may introduce heterogeneity to the population, which is not properly addressed in standard survival models. Moreover, the individuals in the population may be grouped in clusters, where there are associations among observations from a cluster. There are methodologies in the literature to address each of these problems, but there is yet no natural and satisfactory way to accommodate the coexistence of a non-susceptible group and the heterogeneity in the susceptible group under a univariate setting. Also, various kinds of associations among survival data with a cure are not properly accommodated. To address the above-mentioned problems, a class of models is introduced to model univariate and multivariate data with long-term survivors. A semiparametric cure model for univariate failure time data with long-term survivors is introduced. It accommodates a proportion of non-susceptible individuals and the heterogeneity in the susceptible group using a compound- Poisson distributed random effect term, which is commonly called a frailty. It is a frailty-Cox model which does not place any parametric assumption on the baseline hazard function. An estimation method using multiple imputation is proposed for right-censored data, and the method is naturally extended to accommodate interval-censored data. The univariate cure model is extended to a multivariate setting by introducing correlations among the compound- Poisson frailties for individuals from the same cluster. This multivariate cure model is similar to a shared frailty model where the degree of association among each pair of observations in a cluster is the same. The model is further extended to accommodate repeated measurements from a single individual leading to serially correlated observations. Similar estimation methods using multiple imputation are developed for the multivariate models. The univariate model is applied to a breast cancer data and the multivariate models are applied to the hypobaric decompression sickness data from National Aeronautics and Space Administration, although the methodologies are applicable to a wide range of data sets. DOI: 10.5353/th_b4819947 Subjects: Failure time data analysis Survival analysis (Biometry)