Using modified intention-to-treat as a principal stratum estimator for failure to initiate treatment.
Using modified intention-to-treat as a principal stratum estimator for failure to initiate treatment.
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DOI：
10.1177/17407745231160074
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发表时间：
2023-06
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影响因子：
--
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中科院分区：
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影响许多试验的常见并发事件是一些受试者没有开始其分配的治疗。例如，在双盲药物试验中，一些受试者可能未接受任何剂量的研究药物。许多试验使用“改良的意向治疗”方法，即不开始治疗的参与者被排除在分析之外。然而，尚不清楚（a）这种方法所针对的被估量和（B）这种方法无偏所需的假设。使用潜在结局符号，我们证明了排除未开始治疗的受试者的改良意向治疗分析正在估计主要分层被估量（即，将开始开始治疗的受试者亚群中的治疗效果，无论他们被分配到哪个组）。假设并发事件不受分配的治疗组影响，即在一个治疗组中开始治疗的受试者也会在另一个治疗组中开始治疗（即，如果有人开始干预，他们也会开始对照，反之亦然），则改良的意向治疗估计量对于主要分层估计量是无偏的。我们确定了两个关键标准，以确定修改后的意向治疗估计量是否可能是无偏的：首先，我们必须能够测量每个治疗组中经历并发事件的参与者，其次，治疗分配不会影响参与者是否开始治疗的假设必须是合理的。大多数双盲试验将满足这些标准，因为开始治疗的决定不受分配的影响，我们提供了一个开放标签试验的例子，其中这些标准也可能得到满足，这意味着排除未开始治疗的受试者的改良意向治疗分析是这些环境中主分层效应的无偏估计量。我们还给出了两个不满足这些标准的例子（一项比较了主动干预与常规治疗，我们无法确定哪些常规治疗受试者会开始主动干预，另一项以非盲方式比较了两种主动干预，对分配的治疗组的了解可能会影响受试者选择是否开始开始），这意味着修改的意向治疗估计量在这些设置中会有偏差。排除未开始治疗的受试者的改良意向治疗分析可以作为主要分层被估量的无偏估计量。我们的框架可以帮助确定无偏性假设何时可能成立，从而确定修改后的意向治疗是否合适。
A common intercurrent event affecting many trials is when some participants do not begin their assigned treatment. For example, in a double-blind drug trial, some participants may not receive any dose of study medication. Many trials use a ‘modified intention-to-treat’ approach, whereby participants who do not initiate treatment are excluded from the analysis. However, it is not clear (a) the estimand being targeted by such an approach and (b) the assumptions necessary for such an approach to be unbiased. Using potential outcome notation, we demonstrate that a modified intention-to-treat 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 modified intention-to-treat 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 (i.e. if someone began the intervention, they would also have begun the control, and vice versa). We identify two key criteria in determining whether the modified intention-to-treat 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, as the decision to start treatment cannot be influenced by the allocation, and we provide an example of an open-label trial where these criteria are likely to be satisfied as well, implying that a modified intention-to-treat analysis which excludes participants who do not begin treatment is an unbiased estimator for the principal stratum effect in these settings. We also give two examples where these criteria will not be satisfied (one comparing an active intervention vs usual care, where we cannot identify which usual care participants would have initiated the active intervention, and another comparing two active interventions in an unblinded manner, where knowledge of the assigned treatment arm may affect the participant’s choice to begin or not), implying that a modified intention-to-treat estimator will be biased in these settings. 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.
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影响因子：
158.5
作者：
Rahman, Najib M.;Maskell, Nicholas A.;Davies, Robert J. O.
通讯作者：
Davies, Robert J. O.
影响因子：
1.9
作者：
Frangakis, CE;Rubin, DB
通讯作者：
Rubin, DB
DOI：
10.1136/bmj.c332
发表时间：
2010-03-23
期刊：
BMJ (Clinical research ed.)
影响因子：
--
作者：
Schulz KF;Altman DG;Moher D;CONSORT Group
通讯作者：
CONSORT Group
DOI：
10.1136/bmj.c2697
发表时间：
2010-06-14
期刊：
BMJ (Clinical research ed.)
影响因子：
--
作者：
Abraha I;Montedori A
通讯作者：
Montedori A
影响因子：
4.5
作者：
McRobbie, Hayden;Hajek, Peter;Smith, Katie Myers
通讯作者：
Smith, Katie Myers