1 Division of Biostatistics, Medical College of Wisconsin, Milwaukee, WI, USA.
2 School of Mathematical and Statistical Sciences, Arizona State University, Tempe, AZ, USA.
Stat Methods Med Res. 2019 Apr;28(4):1079-1093. doi: 10.1177/0962280217746191. Epub 2017 Dec 18.
Individualized treatment rules can improve health outcomes by recognizing that patients may respond differently to treatment and assigning therapy with the most desirable predicted outcome for each individual. Flexible and efficient prediction models are desired as a basis for such individualized treatment rules to handle potentially complex interactions between patient factors and treatment. Modern Bayesian semiparametric and nonparametric regression models provide an attractive avenue in this regard as these allow natural posterior uncertainty quantification of patient specific treatment decisions as well as the population wide value of the prediction-based individualized treatment rule. In addition, via the use of such models, inference is also available for the value of the optimal individualized treatment rules. We propose such an approach and implement it using Bayesian Additive Regression Trees as this model has been shown to perform well in fitting nonparametric regression functions to continuous and binary responses, even with many covariates. It is also computationally efficient for use in practice. With Bayesian Additive Regression Trees, we investigate a treatment strategy which utilizes individualized predictions of patient outcomes from Bayesian Additive Regression Trees models. Posterior distributions of patient outcomes under each treatment are used to assign the treatment that maximizes the expected posterior utility. We also describe how to approximate such a treatment policy with a clinically interpretable individualized treatment rule, and quantify its expected outcome. The proposed method performs very well in extensive simulation studies in comparison with several existing methods. We illustrate the usage of the proposed method to identify an individualized choice of conditioning regimen for patients undergoing hematopoietic cell transplantation and quantify the value of this method of choice in relation to the optimal individualized treatment rule as well as non-individualized treatment strategies.
个体化治疗规则可以通过认识到患者对治疗的反应可能不同,并为每个个体分配最理想的预测结果的治疗来改善健康结果。需要灵活高效的预测模型作为个体化治疗规则的基础,以处理患者因素和治疗之间潜在的复杂相互作用。现代贝叶斯半参数和非参数回归模型在这方面提供了一个有吸引力的途径,因为这些模型允许对患者特定治疗决策的自然后验不确定性进行量化,以及基于预测的个体化治疗规则在人群中的价值。此外,通过使用这些模型,还可以对最优个体化治疗规则的价值进行推断。我们提出了这样一种方法,并使用贝叶斯加性回归树来实现,因为该模型在拟合连续和二分类响应的非参数回归函数方面表现良好,即使有许多协变量。它在实践中也具有计算效率。我们使用贝叶斯加性回归树来研究一种利用贝叶斯加性回归树模型对患者结局进行个体化预测的治疗策略。使用每个治疗下的患者结局的后验分布来分配最大化期望后验效用的治疗。我们还描述了如何用一个临床可解释的个体化治疗规则来近似这样的治疗策略,并量化其预期结果。与几种现有的方法相比,该方法在广泛的模拟研究中表现非常出色。我们说明了如何使用所提出的方法为接受造血细胞移植的患者确定个体化的预处理方案,并量化这种选择方法相对于最优个体化治疗规则以及非个体化治疗策略的价值。