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BITEs:生存数据的平衡个体治疗效果。

BITES: balanced individual treatment effect for survival data.

机构信息

Department of Medical Bioinformatics, University Medical Center Göttingen, Göttingen 37077, Germany.

Department of Physics, Institute of Theoretical Physics, University of Regensburg, Regensburg 93051, Germany.

出版信息

Bioinformatics. 2022 Jun 24;38(Suppl 1):i60-i67. doi: 10.1093/bioinformatics/btac221.

Abstract

MOTIVATION

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 are 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).

RESULTS

We show in simulation studies that this approach outperforms the state of the art. Furthermore, 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.

AVAILABILITY AND IMPLEMENTATION

We provide BITES as an easy-to-use python implementation including scheduled hyper-parameter optimization (https://github.com/sschrod/BITES). The data underlying this article are available in the CRAN repository at https://rdrr.io/cran/survival/man/gbsg.html and https://rdrr.io/cran/survival/man/rotterdam.html.

SUPPLEMENTARY INFORMATION

Supplementary data are available at Bioinformatics online.

摘要

动机

估计干预措施对患者结局的影响是个性化医学的关键方面之一。其推断常常受到以下事实的挑战:训练数据仅包含给予治疗的结果,而不包含替代治疗(所谓的反事实结果)。已经提出了几种基于观察数据的方法来解决此问题,即干预措施不是随机应用的数据,适用于连续和二分类结局变量。然而,患者结局通常以生存数据的时间到事件数据的形式记录,如果事件在观察期内未发生,则包含右删失事件时间。尽管它们非常重要,但时间到事件数据很少用于治疗优化。我们提出了一种名为 BITES(生存数据的平衡个体治疗效果)的方法,该方法将特定于治疗的半参数 Cox 损失与治疗平衡的深度神经网络相结合;即,我们使用积分概率度量(IPM)来规范治疗患者和未治疗患者之间的差异。

结果

我们在模拟研究中表明,这种方法优于现有技术。此外,我们在对乳腺癌患者队列的应用中表明,可以基于六个常规参数来优化激素治疗。我们在独立队列中成功验证了这一发现。

可用性和实施

我们提供了易于使用的 Python 实现 BITES,包括预定的超参数优化(https://github.com/sschrod/BITES)。本文所依据的数据可在 CRAN 存储库中获得,网址为 https://rdrr.io/cran/survival/man/gbsg.htmlhttps://rdrr.io/cran/survival/man/rotterdam.html。

补充信息

补充数据可在生物信息学在线获得。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7209/9235492/3b840df47b37/btac221f1.jpg

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