论文标题
精密医学的潜在模型
Latent-state models for precision medicine
论文作者
论文摘要
观察性纵向研究是研究慢性精神疾病治疗效率和安全性的常见手段。在许多这样的研究中,患者或其临床医生可能会引发治疗变化,因此在其时间,数量和类型的患者中可能会差异很大。的确,在这项工作的动机之一的二极性抑郁症研究的观察性纵向途径中,即使在每周一次的时间尺度上进行诊所就诊之后,也没有两名患者具有相同的治疗病史。使用此类数据对最佳治疗方案进行估计是一项挑战,因为人们不能像基于反相反的概率加权的方法所要求的那样,将具有相同治疗史的患者汇集在一起,也无法像Q学习及其变异中那样对决策点进行倒退诱导。因此,需要额外的结构来有效地在患者和患者内部汇总信息。许多慢性精神疾病的当前科学理论认为,患者的疾病状况可以概念化为在少数离散状态之间过渡。我们使用该理论来告知患者健康轨迹的部分可观察到的马尔可夫决策过程模型,其中观察到的健康结果由患者的潜在健康状况决定。使用此模型,我们在两个常见的范式下得出并评估最佳治疗方案的估计量,以量化长期患者健康。通过一系列仿真实验和应用于Step-BD研究的观察途径,证明了所提出的估计量的有限样本性能。我们发现,所提出的方法在未经临时修改的情况下无法采用现有方法提供了最佳治疗策略的高质量估计。
Observational longitudinal studies are a common means to study treatment efficacy and safety in chronic mental illness. In many such studies, treatment changes may be initiated by either the patient or by their clinician and can thus vary widely across patients in their timing, number, and type. Indeed, in the observational longitudinal pathway of the STEP-BD study of bipolar depression, one of the motivations for this work, no two patients have the same treatment history even after coarsening clinic visits to a weekly time-scale. Estimation of an optimal treatment regime using such data is challenging as one cannot naively pool together patients with the same treatment history, as is required by methods based on inverse probability weighting, nor is it possible to apply backwards induction over the decision points, as is done in Q-learning and its variants. Thus, additional structure is needed to effectively pool information across patients and within a patient over time. Current scientific theory for many chronic mental illnesses maintains that a patient's disease status can be conceptualized as transitioning among a small number of discrete states. We use this theory to inform the construction of a partially observable Markov decision process model of patient health trajectories wherein observed health outcomes are dictated by a patient's latent health state. Using this model, we derive and evaluate estimators of an optimal treatment regime under two common paradigms for quantifying long-term patient health. The finite sample performance of the proposed estimator is demonstrated through a series of simulation experiments and application to the observational pathway of the STEP-BD study. We find that the proposed method provides high-quality estimates of an optimal treatment strategy in settings where existing approaches cannot be applied without ad hoc modifications.