In addition to the average treatment effect (ATE) for all randomized patients, sometimes it is important to understand the ATE for a principal stratum, a subset of patients defined by one or more post-baseline variables. For example, what is the ATE for those patients who could be compliant with the experimental treatment? Commonly used assumptions include monotonicity, principal ignorability, and cross-world assumptions of principal ignorability and principal strata independence. Most of these assumptions cannot be evaluated in clinical trials with parallel treatment arms. In this article, we evaluate these assumptions through a 2x2 cross-over study in which the potential outcomes under both treatments can be observed, provided there are no carry-over and study period effects. From this example, it seemed the monotonicity assumption and the within-treatment principal ignorability assumptions did not hold well. On the other hand, the assumptions of cross-world principal ignorability and cross-world principal stratum independence conditional on baseline covaraites seemed to hold well. With the latter assumptions, we estimated the ATE for principal strata, defined by whether the blood glucose standard deviation increased in each treatment period, without relying on the cross-over feature. These estimates were very close to the ATE estimate when exploiting the cross-over feature of the trial. To the best of our knowledge, this article is the first attempt to evaluate the plausibility of commonly used assumptions for estimating ATE for principal strata using the setting of a cross-over trial.
翻译:除了所有随机患者的平均治疗效果(ATE)之外,有时还必须理解主要直流患者(一个或一个以上基底变量界定的一组患者)的平均治疗效果(ATE)之外,有时还必须理解主要直流患者(一个或一个以上基底变量界定的一组患者)的ATE。例如,那些能够符合实验治疗的患者的ATE是什么?通常使用的假设包括单调、主要可忽略性、以及主要可忽略性和主要阶层独立性的跨世界假设。这些假设大多无法在临床试验中以平行治疗为武器来评估。在本条款中,我们通过一项交叉研究来评估这些假设。在这项研究中可以观察到两种治疗的潜在结果,条件是没有结转和研究时期的影响。从这个例子看,单一假设和治疗中的主要可忽略性假设似乎没有很好。另一方面,跨世界主要可忽略性和跨世界主要阶层主要直系独立的假设似乎维持良好。在后一种假设中,我们估算主要阶层的ATE是主要阶层的,其定义是,在每一治疗期间的血压标准偏差是否增加,而无需依靠这一跨阶段的估算。