论文标题
贝叶斯半参数模型,用于序列治疗决策,内容丰富的时机
Bayesian Semiparametric Model for Sequential Treatment Decisions with Informative Timing
论文作者
论文摘要
我们开发了一个贝叶斯半参数模型,用于估计动态治疗规则对诊断为儿童急性髓样白血病(AML)的患者的生存影响。数据由参与III阶段AAML1031临床试验的患者的一部分组成,其中患者通过四个治疗课程的序列移动。在每门课程中,他们都会接受可能包括或不包括蒽环类药物(法案)的治疗。虽然已知ACT可有效治疗AML,但它也具有心脏毒性,可能会导致某些患者早期死亡。我们的任务是在假设的动态ACT治疗策略下估计潜在的生存概率,但有几种障碍。首先,由于ACT在试验中没有随机分配,因此随着时间的推移,其对生存的影响会混淆。其次,受试者根据他们从上一门课程中恢复的何时启动下一课程,从而使时间安排有可能随后的治疗和生存提供信息。第三,在完成完整治疗序列之前,患者可能会死亡或辍学。我们开发了一种基于伽玛工艺先验的生成性贝叶斯半参数模型,以解决这些复杂性。在每个治疗课程中,该模型都会根据给定规则捕获受试者在连续时间内的后续治疗或死亡的过渡。使用G委托程序来计算后验优于潜在的生存概率,该概率是针对时变的混杂而调整的。使用这种方法,我们对基于不断发展的心脏功能动态修改ACT的假设治疗规则的功效进行后推断。
We develop a Bayesian semi-parametric model for the estimating the impact of dynamic treatment rules on survival among patients diagnosed with pediatric acute myeloid leukemia (AML). The data consist of a subset of patients enrolled in the phase III AAML1031 clinical trial in which patients move through a sequence of four treatment courses. At each course, they undergo treatment that may or may not include anthracyclines (ACT). While ACT is known to be effective at treating AML, it is also cardiotoxic and can lead to early death for some patients. Our task is to estimate the potential survival probability under hypothetical dynamic ACT treatment strategies, but there are several impediments. First, since ACT was not randomized in the trial, its effect on survival is confounded over time. Second, subjects initiate the next course depending on when they recover from the previous course, making timing potentially informative of subsequent treatment and survival. Third, patients may die or drop out before ever completing the full treatment sequence. We develop a generative Bayesian semi-parametric model based on Gamma Process priors to address these complexities. At each treatment course, the model captures subjects' transition to subsequent treatment or death in continuous time under a given rule. A g-computation procedure is used to compute a posterior over potential survival probability that is adjusted for time-varying confounding. Using this approach, we conduct posterior inference for the efficacy of hypothetical treatment rules that dynamically modify ACT based on evolving cardiac function.