Chen Yuan, Zeng Donglin, Wang Yuanjia
Department of Epidemiology and Biostatistics, 5803 Memorial Sloan Kettering Cancer Center , 633 3rd Avenue, New York, NY 10016, USA.
Department of Biostatistics, University of Michigan, Ann Arbor, MI 48109, USA.
Int J Biostat. 2024 Sep 26;20(2):437-453. doi: 10.1515/ijb-2024-0068. eCollection 2024 Nov 1.
Learning individualized treatment rules (ITRs) for a target patient population with mental disorders is confronted with many challenges. First, the target population may be different from the training population that provided data for learning ITRs. Ignoring differences between the training patient data and the target population can result in sub-optimal treatment strategies for the target population. Second, for mental disorders, a patient's underlying mental state is not observed but can be inferred from measures of high-dimensional combinations of symptomatology. Treatment mechanisms are unknown and can be complex, and thus treatment effect moderation can take complicated forms. To address these challenges, we propose a novel method that connects measurement models, efficient weighting schemes, and flexible neural network architecture through latent variables to tailor treatments for a target population. Patients' underlying mental states are represented by a compact set of latent state variables while preserving interpretability. Weighting schemes are designed based on lower-dimensional latent variables to efficiently balance population differences so that biases in learning the latent structure and treatment effects are mitigated. Extensive simulation studies demonstrated consistent superiority of the proposed method and the weighting approach. Applications to two real-world studies of patients with major depressive disorder have shown a broad utility of the proposed method in improving treatment outcomes in the target population.
为患有精神障碍的目标患者群体学习个性化治疗规则(ITRs)面临诸多挑战。首先,目标人群可能与为学习ITRs提供数据的训练人群不同。忽视训练患者数据与目标人群之间的差异可能导致针对目标人群的次优治疗策略。其次,对于精神障碍,患者的潜在心理状态无法直接观察到,但可以从症状学的高维组合测量中推断出来。治疗机制未知且可能很复杂,因此治疗效果调节可能呈现复杂的形式。为应对这些挑战,我们提出了一种新颖的方法,该方法通过潜在变量将测量模型、高效加权方案和灵活的神经网络架构连接起来,为目标人群量身定制治疗方案。患者的潜在心理状态由一组紧凑的潜在状态变量表示,同时保持可解释性。基于低维潜在变量设计加权方案,以有效平衡人群差异,从而减轻学习潜在结构和治疗效果时的偏差。广泛的模拟研究证明了所提出方法和加权方法始终具有优越性。将其应用于两项针对重度抑郁症患者的真实世界研究表明,该方法在改善目标人群的治疗结果方面具有广泛的实用性。