论文标题
对半竞争风险的基于脆弱的疾病死亡模型的惩罚估计
Penalized Estimation of Frailty-Based Illness-Death Models for Semi-Competing Risks
论文作者
论文摘要
半竞争风险是指非末端事件的发生的生存分析设置受终端事件是否发生,但反之亦然。半竞争风险在广泛的临床环境中出现,一个新颖的例子是妊娠疾病前启示剂,只能在分娩的“末端”事件之前发生。确认半竞争风险的模型可以调查协变量与结果的联合时机之间的关系,但是缺乏高维度中半竞争风险的模型选择和预测方法。取而代之的是,研究人员通常仅分析单个或复合结果,丢失有价值的信息并限制临床实用性 - 在产科环境中,这意味着忽略先兆子痫开始后对交付时间的宝贵见解。为了解决这一差距,我们提出了一个新颖的刑罚估计框架,用于半竞争风险的基于脆弱的疾病多状态模型。我们的方法结合了非凸和结构化的融合惩罚,引起了全球稀疏性以及跨代码之间的简约。我们通过路径例程进行估计和模型选择,以进行非凸优化,并在此设置中证明了第一个统计误差绑定结果。我们提出了一项仿真研究,研究了估计误差和模型选择性能,以及该方法在利用电子健康记录中使用妊娠数据的前启示识别的联合风险建模和交付时间的全面应用。
Semi-competing risks refers to the survival analysis setting where the occurrence of a non-terminal event is subject to whether a terminal event has occurred, but not vice versa. Semi-competing risks arise in a broad range of clinical contexts, with a novel example being the pregnancy condition preeclampsia, which can only occur before the `terminal' event of giving birth. Models that acknowledge semi-competing risks enable investigation of relationships between covariates and the joint timing of the outcomes, but methods for model selection and prediction of semi-competing risks in high dimensions are lacking. Instead, researchers commonly analyze only a single or composite outcome, losing valuable information and limiting clinical utility -- in the obstetric setting, this means ignoring valuable insight into timing of delivery after preeclampsia has onset. To address this gap we propose a novel penalized estimation framework for frailty-based illness-death multi-state modeling of semi-competing risks. Our approach combines non-convex and structured fusion penalization, inducing global sparsity as well as parsimony across submodels. We perform estimation and model selection via a pathwise routine for non-convex optimization, and prove the first statistical error bound results in this setting. We present a simulation study investigating estimation error and model selection performance, and a comprehensive application of the method to joint risk modeling of preeclampsia and timing of delivery using pregnancy data from an electronic health record.