Estimating the effects of interventions on patient outcome is one of the key aspects of personalized medicine. Their inference is often challenged by the fact that the training data comprises only the outcome for the administered treatment, and not for alternative treatments (the so-called counterfactual outcomes). Several methods were suggested for this scenario based on observational data, i.e.~data where the intervention was not applied randomly, for both continuous and binary outcome variables. However, patient outcome is often recorded in terms of time-to-event data, comprising right-censored event times if an event does not occur within the observation period. Albeit their enormous importance, time-to-event data is rarely used for treatment optimization. We suggest an approach named BITES (Balanced Individual Treatment Effect for Survival data), which combines a treatment-specific semi-parametric Cox loss with a treatment-balanced deep neural network; i.e.~we regularize differences between treated and non-treated patients using Integral Probability Metrics (IPM). We show in simulation studies that this approach outperforms the state of the art. Further, we demonstrate in an application to a cohort of breast cancer patients that hormone treatment can be optimized based on six routine parameters. We successfully validated this finding in an independent cohort. BITES is provided as an easy-to-use python implementation.
翻译:估计干预对患者结果的影响是个人化医学的关键方面之一。他们的推断常常受到以下事实的挑战:培训数据只包括治疗结果,而不是替代治疗结果(所谓的反事实结果)。根据观察数据,即对连续和二进制结果变量不随机适用干预对患者结果的影响的数据,提出了几种方法。然而,患者结果往往记录在时间到活动的数据方面,包括:在观察期间没有发生事件的情况下,由正确检查的事件次数构成。尽管培训数据的重要性巨大,但很少使用时间到活动的数据来优化治疗。我们建议采用称为BITES(个人治疗对生存数据的影响)的方法,这种方法将特定治疗的半参数损失与治疗平衡的深度神经网络结合起来;但是,病人结果往往记录在时间到活动的时间到活动的时间方面,包括:如果在观察期间没有发生事件,则由正确检查的事件发生次数。我们在模拟研究中显示,这种方法超越了病人的简单标准。我们建议采用的一种方法,就是在常规化的癌症中,我们可以成功地验证这种方法。