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带有脆弱项的非比例风险模型用于对存在长期幸存者证据的亚组进行建模:应用于肺癌数据集。

Nonproportional hazards model with a frailty term for modeling subgroups with evidence of long-term survivors: Application to a lung cancer dataset.

作者信息

Gazon Amanda B, Milani Eder A, Mota Alex L, Louzada Francisco, Tomazella Vera L D, Calsavara Vinicius F

机构信息

Department of Statistics, Federal University of São Carlos, São Carlos, São Paulo, Brazil.

Institute of Mathematical and Statistics, Federal University of Goiás, Goiânia, Goiás, Brazil.

出版信息

Biom J. 2022 Jan;64(1):105-130. doi: 10.1002/bimj.202000292. Epub 2021 Sep 27.

DOI:10.1002/bimj.202000292
PMID:34569095
Abstract

With advancements in medical treatments for cancer, an increase in the life expectancy of patients undergoing new treatments is expected. Consequently, the field of statistics has evolved to present increasingly flexible models to explain such results better. In this paper, we present a lung cancer dataset with some covariates that exhibit nonproportional hazards (NPHs). Besides, the presence of long-term survivors is observed in subgroups. The proposed modeling is based on the generalized time-dependent logistic model with each subgroup's effect time and a random term effect (frailty). In practice, essential covariates are not observed for several reasons. In this context, frailty models are useful in modeling to quantify the amount of unobservable heterogeneity. The frailty distribution adopted was the weighted Lindley distribution, which has several interesting properties, such as the Laplace transform function on closed form, flexibility in the probability density function, among others. The proposed model allows for NPHs and long-term survivors in subgroups. Parameter estimation was performed using the maximum likelihood method, and Monte Carlo simulation studies were conducted to evaluate the estimators' performance. We exemplify this model's use by applying data of patients diagnosed with lung cancer in the state of São Paulo, Brazil.

摘要

随着癌症医学治疗方法的进步,接受新治疗的患者预期寿命有望增加。因此,统计学领域不断发展,提出了越来越灵活的模型,以便更好地解释此类结果。在本文中,我们展示了一个包含一些呈现非比例风险(NPHs)协变量的肺癌数据集。此外,在亚组中观察到了长期存活者。所提出的建模基于广义时间依赖逻辑模型,包含每个亚组的效应时间和一个随机项效应(脆弱性)。在实际中,由于多种原因无法观测到关键协变量。在此背景下,脆弱性模型在建模中很有用,可用于量化不可观测的异质性程度。所采用的脆弱性分布是加权林德利分布,它具有一些有趣的特性,如封闭形式的拉普拉斯变换函数、概率密度函数的灵活性等。所提出的模型考虑了亚组中的NPHs和长期存活者。使用最大似然法进行参数估计,并进行蒙特卡罗模拟研究以评估估计量的性能。我们通过应用巴西圣保罗州被诊断为肺癌患者的数据来举例说明该模型的应用。

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