Rosa Karen C, Calsavara Vinicius F, Louzada Francisco
Institute of Mathematical and Computer Sciences, University of São Paulo, São Carlos, São Paulo, Brazil.
Department of Computational Biomedicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
J Appl Stat. 2024 May 14;52(1):1-27. doi: 10.1080/02664763.2024.2354443. eCollection 2025.
Survival data analysis often uses the Cox proportional hazards (PH) model. This model is widely applied due to its straightforward interpretation of the hazard ratio under the assumption that the hazard rates for two subjects remain constant over time. However, in several randomized clinical trials with long-term survival data comparing two new treatments, it is frequently observed that Kaplan-Meier plots exhibit crossing survival curves. This violation of the PH assumption of the Cox PH model can not be applied to evaluate the treatment's effect on survival. This paper introduces a novel long-term survival model with non-PH that incorporates a frailty term into the hazard function. This model allows us to examine the effect of prognostic factors on survival and quantify the degree of unobservable heterogeneity. The model parameters are estimated using the maximum likelihood estimation procedure, and we evaluate the performance of the proposed models through simulation studies. Additionally, we demonstrate the applicability of our approach by fitting the models to a real skin cancer dataset.
生存数据分析通常使用Cox比例风险(PH)模型。由于在两个受试者的风险率随时间保持恒定的假设下,该模型对风险比的解释简单明了,因此被广泛应用。然而,在一些比较两种新治疗方法的长期生存数据的随机临床试验中,经常观察到Kaplan-Meier图呈现交叉的生存曲线。Cox PH模型的这种PH假设的违背使得其无法用于评估治疗对生存的影响。本文介绍了一种新的非PH长期生存模型,该模型在风险函数中纳入了一个脆弱项。该模型使我们能够研究预后因素对生存的影响,并量化不可观察的异质性程度。使用最大似然估计程序估计模型参数,并通过模拟研究评估所提出模型的性能。此外,我们通过将模型拟合到一个真实的皮肤癌数据集来证明我们方法的适用性。