Existing methods in estimating the mean outcome under a given dynamic treatment regime rely on intention-to-treat analyses which estimate the effect of following a certain dynamic treatment regime regardless of compliance behavior of patients. There are two major concerns with intention-to-treat analyses: (1) the estimated effects are often biased toward the null effect; (2) the results are not generalizable and reproducible due to the potential differential compliance behavior. These are particularly problematic in settings with high level of non-compliance such as substance use disorder treatments. Our work is motivated by the Adaptive Treatment for Alcohol and Cocaine Dependence study (ENGAGE), which is a multi-stage trial that aimed to construct optimal treatment strategies to engage patients in therapy. Due to the relatively low level of compliance in this trial, intention-to-treat analyses essentially estimate the effect of being randomized to a certain treatment sequence which is not of interest. We fill this important gap by defining the target parameter as the mean outcome under a dynamic treatment regime given potential compliance strata. We propose a flexible non-parametric Bayesian approach, which consists of a Gaussian copula model for the potential compliances, and a Dirichlet process mixture model for the potential outcomes. Our simulations highlight the need for and usefulness of this approach in practice and illustrate the robustness of our estimator in non-linear and non-Gaussian settings.
翻译:评估特定动态治疗制度下的平均结果的现有方法依赖于意图到治疗的分析,这种分析估计了无论病人的合规行为如何遵循某种动态治疗制度的效果。在意图到治疗的分析中,存在两个主要关切:(1) 估计效果往往偏向于无效效果;(2) 估计效果往往偏向于无效效果;(2) 由于潜在的不同合规行为,结果不普遍和可复制。在药物使用紊乱治疗等高度不合规的环境下,这些结果特别成问题。我们的工作受到“酒精和可卡因依赖性适应性治疗”研究(ENGAG)的推动。这是一项多阶段试验,旨在建立最佳治疗战略,使病人参与治疗。由于这一试验的合规程度相对较低,意图到研究基本上估计了随机到某种不感兴趣的治疗顺序的效果。我们通过界定目标参数作为动态治疗制度下的潜在结果来填补了这一重要差距。我们建议采用灵活的非理性巴耶斯治疗方法,其中包括一个高斯-查拉模型,旨在建立最佳治疗环境,使病人参与治疗。由于这一试验的合规性程度较低,因此,GA型研究基本上可以说明我们模拟这种不起作用。