Department of Biostatistics, Mailman School of Public Health, Columbia University, New York, New York.
Department of Psychiatry, Columbia University Medical Center, New York, New York.
Stat Med. 2019 Jun 30;38(14):2632-2651. doi: 10.1002/sim.8105. Epub 2019 Mar 19.
Treatment response heterogeneity has long been observed in patients affected by chronic diseases. Administering an individualized treatment rule (ITR) offers an opportunity to tailor treatment strategies according to patient-specific characteristics. Overly complex machine learning methods for estimating ITRs may produce treatment rules that have higher benefit but lack transparency and interpretability. In clinical practices, it is desirable to derive a simple and interpretable ITR while maintaining certain optimality that leads to improved benefit in subgroups of patients, if not on the overall sample. In this work, we propose a tree-based robust learning method to estimate optimal piecewise linear ITRs and identify subgroups of patients with a large benefit. We achieve these goals by simultaneously identifying qualitative and quantitative interactions through a tree model, referred to as the composite interaction tree (CITree). We show that it has improved performance compared to existing methods on both overall sample and subgroups via extensive simulation studies. Lastly, we fit CITree to Research Evaluating the Value of Augmenting Medication with Psychotherapy trial for treating patients with major depressive disorders, where we identified both qualitative and quantitative interactions and subgroups of patients with a large benefit.
治疗反应的异质性在慢性疾病患者中早已得到观察。采用个体化治疗规则(ITR)可以根据患者的具体特征定制治疗策略。对于估计 ITR 的过于复杂的机器学习方法可能会产生具有更高收益但缺乏透明度和可解释性的治疗规则。在临床实践中,期望获得简单且可解释的 ITR,同时保持一定的最优性,从而为患者亚组带来改善的收益,如果不是对整个样本的话。在这项工作中,我们提出了一种基于树的稳健学习方法来估计最优分段线性 ITR,并识别具有较大收益的患者亚组。我们通过树模型(称为复合交互树(CITree))同时识别定性和定量交互,从而实现了这些目标。我们通过广泛的模拟研究表明,它在整体样本和亚组方面的性能均优于现有方法。最后,我们将 CITree 拟合到 Research Evaluating the Value of Augmenting Medication with Psychotherapy 试验中,用于治疗患有重度抑郁症的患者,我们在其中识别了定性和定量交互以及具有较大收益的患者亚组。