Brain and Mind Centre, The University of Sydney, Sydney, Australia.
School of Mathematical and Physical Sciences, Macquarie University, Sydney, Australia.
Biom J. 2024 Dec;66(8):e202300203. doi: 10.1002/bimj.202300203.
In practical survival analysis, the situation of no event for a patient can arise even after a long period of waiting time, which means a portion of the population may never experience the event of interest. Under this circumstance, one remedy is to adopt a mixture cure Cox model to analyze the survival data. However, if there clearly exhibits an acceleration (or deceleration) factor among their survival times, then an accelerated failure time (AFT) model will be preferred, leading to a mixture cure AFT model. In this paper, we consider a penalized likelihood method to estimate the mixture cure semiparametric AFT models, where the unknown baseline hazard is approximated using Gaussian basis functions. We allow partly interval-censored survival data which can include event times and left-, right-, and interval-censoring times. The penalty function helps to achieve a smooth estimate of the baseline hazard function. We will also provide asymptotic properties to the estimates so that inferences can be made on regression parameters and hazard-related quantities. Simulation studies are conducted to evaluate the model performance, which includes a comparative study with an existing method from the smcure R package. The results show that our proposed penalized likelihood method has acceptable performance in general and produces less bias when faced with the identifiability issue compared to smcure. To illustrate the application of our method, a real case study involving melanoma recurrence is conducted and reported. Our model is implemented in our R package aftQnp which is available from https://github.com/Isabellee4555/aftQnP.
在实际生存分析中,即使等待时间很长,患者也可能不会发生事件,这意味着一部分人群可能永远不会经历感兴趣的事件。在这种情况下,可以采用混合治愈 Cox 模型来分析生存数据。但是,如果他们的生存时间明显存在加速(或减速)因素,则倾向于采用加速失效时间(AFT)模型,从而得到混合治愈 AFT 模型。在本文中,我们考虑采用惩罚似然法来估计混合治愈半参数 AFT 模型,其中未知的基线风险函数使用高斯基函数进行近似。我们允许部分区间删失的生存数据,其中包括事件时间和左、右删失时间和区间删失时间。惩罚函数有助于实现基线风险函数的平滑估计。我们还将提供估计量的渐近性质,以便对回归参数和与风险相关的数量进行推断。进行了模拟研究以评估模型性能,包括与 smcure R 包中的现有方法进行的比较研究。结果表明,我们提出的惩罚似然法总体上具有可接受的性能,并且与 smcure 相比,在面对可识别性问题时产生的偏差较小。为了说明我们方法的应用,我们进行了涉及黑色素瘤复发的实际案例研究,并进行了报告。我们的模型在我们的 aftQnp R 包中实现,可从 https://github.com/Isabellee4555/aftQnP 获得。