论文标题
连续时间的个性化动态治疗方案:一种用于使用时间安排优化临床决策的贝叶斯方法
Personalized Dynamic Treatment Regimes in Continuous Time: A Bayesian Approach for Optimizing Clinical Decisions with Timing
论文作者
论文摘要
准确的临床作用模型及其对疾病进展的影响对于在医疗/健康研究中估算个性化最佳动态治疗方案(DTR)至关重要,尤其是在管理慢性病中。 DTR的传统统计方法通常着重于估计每种给定的医疗干预措施的最佳治疗或剂量,但忽略了“何时应发生这种干预”的重要问题。我们通过开发两步的贝叶斯方法来填补这一空白,以通过时间安排优化临床决策。在第一步中,我们为一系列医疗干预措施构建了生成模型,这是连续时间中的离散事件,并带有标记的时间点过程(MTPP),其中商标是分配的治疗或剂量。然后,该临床动作模型嵌入了贝叶斯关节框架中,其中其他组件模拟了临床观察结果,包括纵向医学测量和事件时间的数据条件。在第二步中,我们提出了一种政策梯度方法,以学习个性化的最佳临床决策,该方法通过与临床观察的模型相互作用,从而最大程度地提高了患者的生存,同时在第一步中从贝叶斯联合模型的后推理中学到了临床观察中的不确定性。拟议方法的签名应用是安排随访探访,并在肾脏移植后为患者分配剂量。我们评估了我们的方法与模拟和实际数据集的替代方法进行比较。在我们的实验中,提出的方法在临床上做出的个性化决定是有用的:它们是可解释的,可以成功地改善患者的生存。
Accurate models of clinical actions and their impacts on disease progression are critical for estimating personalized optimal dynamic treatment regimes (DTRs) in medical/health research, especially in managing chronic conditions. Traditional statistical methods for DTRs usually focus on estimating the optimal treatment or dosage at each given medical intervention, but overlook the important question of "when this intervention should happen." We fill this gap by developing a two-step Bayesian approach to optimize clinical decisions with timing. In the first step, we build a generative model for a sequence of medical interventions-which are discrete events in continuous time-with a marked temporal point process (MTPP) where the mark is the assigned treatment or dosage. Then this clinical action model is embedded into a Bayesian joint framework where the other components model clinical observations including longitudinal medical measurements and time-to-event data conditional on treatment histories. In the second step, we propose a policy gradient method to learn the personalized optimal clinical decision that maximizes the patient survival by interacting the MTPP with the model on clinical observations while accounting for uncertainties in clinical observations learned from the posterior inference of the Bayesian joint model in the first step. A signature application of the proposed approach is to schedule follow-up visitations and assign a dosage at each visitation for patients after kidney transplantation. We evaluate our approach with comparison to alternative methods on both simulated and real-world datasets. In our experiments, the personalized decisions made by the proposed method are clinically useful: they are interpretable and successfully help improve patient survival.