【作者】 于颖；

【导师】 宋立新；

【作者基本信息】 大连理工大学 ， 应用统计（专业学位）， 2016， 硕士

【摘要】 在生存分析中,我们通常认为,如果随访的时间足够长,所有的个体都将经历感兴趣的事件.但是,由于现代医学治疗水平的不断发展,癌症患者最终被治愈的情况越来越多.本文我们将考虑总体中包含可治愈个体的相依竞争风险事件率的估计,并且假设总体中有一部分个体会遭受一种可治愈的风险事件,而另一部分个体可能遭受其他的竞争风险.我们首先使用AFT混合治愈模型为主要感兴趣的事件率构造一个单变量风险指标得分预测,应用EM算法估计出其中的未知参数,然后利用非参数函数估计方法,使用局部多项式似然的非参数光滑技术为具有相同指标得分的个体的平均竞争风险作一个联合推断.通过这样一个两阶段程序,我们可以为未来的某一个体的所有感兴趣的竞争风险构造一个可靠的预测准则,从而帮助相关的风险决策人员作出一个风险有益的决定.我们将使用数值模拟实验来验证我们方法的估计性能,并对骨髓移植数据和黑色素瘤数据进行实例分析.本文组织安排如下：第一部分,将介绍生存分析、竞争风险和治愈模型相关方面的基础知识,以及现有的一些估计方法.第二部分,描述半参数AFT混合治愈模型和竞争风险框架,提出两阶段估计方法,给出关于风险得分事件率的逐点和联合置信区间估计.第三部分,通过模拟实验探究提出来的估计方法的性能.第四部分将提出来的方法应用到骨髓移植数据和黑色素瘤数据的研究中.最后,第五部分对本文进行总结和展望.更多还原

【Abstract】 In surival analysis, usually, we think that if the follow up period is long enough, all individ-uals will eventually experience the event of interest. However, with the advanced development of new cancer treatments in clinical trials, a substantial proportion of individuals may never ex-perience the event, that is, those individuals are cured. In this paper, we consider the predictive inference of dependent competing risks with a cure fraction, and argue that some patients are exposed only to the risk which can be cured, whereas the uncured patients are exposed to other hazards. Specifically, we employ AFT mixture cure model to create a univariate risk index s-core predictive to the event rate of the primary interest risk, using EM algorithm to estimate the parameters. We then use nonparameteric function estimation method, making joint inferences about the average competing risks for subjects who have the same index score through a local multinomial likelihood for nonparametric smoothing technique. Through the two-stage proce-dure, we could construct a reliable prediction rule for the future subject’s profile of all competing risks of interest for risk-benefit decision making. We show a simulation study to assess the per-formance of proposed estimation method, and the proposed inference procedure is applied to bone marrow transplant data and melanoma survival data.The organization of this paper is as follows. Section 1 is the introduction, will introduce some basis knowledge of survival analysis, competing risks and cure models, and the estimation method is also included. Section 2 describes the semiparametric AFT mixture cure model and competing risks frameworks, then the two-stage estimation method is proposed, showing the point-wise and simultaneous confidence intervals for event rates over the risk score. In section 3, we will show a simulation study to assess the performance of proposed estimation method. In section 4, the proposed inference procedure is applied to bone marrow transplant data and melanoma survival data. The paper is concluded with a discussion in section 5.更多还原