Ramalata Aluwani, Adekpedjou Akim, Lesaoana Maseka
Department of Statistics and Operations Research, University of Limpopo, Polokwane, Limpopo, South Africa.
Department of Mathematics and Statistics, Missouri University of Science and Technology, Rolla, Missouri, United States.
PLoS One. 2025 May 7;20(5):e0320521. doi: 10.1371/journal.pone.0320521. eCollection 2025.
In survival analysis, it is often assumed that all individuals will eventually experience the event of interest if followed long enough. However, in many real-world scenarios, a subset of individuals remains event-free indefinitely. For instance, in clinical studies, some patients never relapse and are considered cured rather than censored. Traditional survival models are inadequate for capturing this heterogeneity. Mixture cure models address this limitation by distinguishing between cured and susceptible individuals while modeling the survival of the latter. A key challenge in mixture cure modeling is selecting relevant covariates, particularly when dealing with time-varying effects. This study develops a penalized logistic/Cox proportional hazards mixture cure model incorporating time-varying covariates for both the incidence and latency components. The model is implemented using the smoothly clipped absolute deviation (SCAD) penalty to facilitate variable selection and improve model interpretability. To achieve this, we modified the penPHcure package to accommodate SCAD regularization and generate time-varying covariates. The proposed approach is applied to real-world data on the time to death for hospitalized COVID-19 patients in Limpopo Province, South Africa, demonstrating its practical applicability in survival analysis.
在生存分析中,通常假定如果随访时间足够长,所有个体最终都会经历感兴趣的事件。然而,在许多实际情况中,一部分个体将无限期地保持无事件状态。例如,在临床研究中,一些患者从未复发,被视为治愈而非删失。传统的生存模型不足以捕捉这种异质性。混合治愈模型通过区分治愈个体和易感个体,同时对后者的生存情况进行建模,解决了这一局限性。混合治愈建模中的一个关键挑战是选择相关协变量,尤其是在处理随时间变化的效应时。本研究开发了一种惩罚逻辑/考克斯比例风险混合治愈模型,该模型为发病率和潜伏期成分纳入了随时间变化的协变量。该模型使用平滑截断绝对偏差(SCAD)惩罚来实现,以促进变量选择并提高模型的可解释性。为实现这一点,我们修改了penPHcure软件包以适应SCAD正则化并生成随时间变化的协变量。所提出的方法应用于南非林波波省住院COVID-19患者的死亡时间的实际数据,证明了其在生存分析中的实际适用性。