Background: A common intercurrent event affecting many trials is when some participants do not begin their assigned treatment. Many trials use a modified intention-to-treat (mITT) approach, whereby participants who do not initiate treatment are excluded from the analysis. However, it is not clear the estimand being targeted by such an approach or the assumptions necessary for it to be unbiased. Methods: We demonstrate that a mITT analysis which excludes participants who do not begin treatment is estimating a principal stratum estimand (i.e. the treatment effect in the subpopulation of participants who would begin treatment, regardless of which arm they were assigned to). The mITT estimator is unbiased for the principal stratum estimand under the assumption that the intercurrent event is not affected by the assigned treatment arm, that is, participants who initiate treatment in one arm would also do so in the other arm. Results: We identify two key criteria in determining whether the mITT estimator is likely to be unbiased: first, we must be able to measure the participants in each treatment arm who experience the intercurrent event, and second, the assumption that treatment allocation will not affect whether the participant begins treatment must be reasonable. Most double-blind trials will satisfy these criteria, and we provide an example of an open-label trial where these criteria are likely to be satisfied as well. Conclusions: A modified intention-to-treat analysis which excludes participants who do not begin treatment can be an unbiased estimator for the principal stratum estimand. Our framework can help identify when the assumptions for unbiasedness are likely to hold, and thus whether modified intention-to-treat is appropriate or not.
翻译:背景:影响许多审判的一个常见的间流事件是,一些参与者没有开始指定治疗方法。许多审判都采用修改的意向至治疗方法(MITT),不启动治疗的参与者被排除于分析之外。然而,尚不清楚这种方法或必要的假设是否具有针对性,从而无法使这种方法或假设具有公正性。方法:我们证明,将不开始治疗的参与者排除在外的MITT分析正在估计主要的直流估计值(即,对将开始治疗的参与者的亚群的治疗效果,不管他们被指派给哪个臂章。MITT估计值对主要直流估计值和未启动治疗的参与者来说是公正的。因此,MITT估计值对主平流估计值和假设对主估值没有影响。 也就是说,启动一臂治疗的参与者也会在另一臂中这样做。 结果:我们确定两个关键标准是确定 mITT 修改的估测值是否可能是公正的:首先,我们必须测量每个治疗臂的参与者的参与者,而不是他们被指派的公正,因此, 多数假设是能够确定一个合理的分析标准。