Disentangling estimands and the intention-to-treat principle
Disentangling estimands and the intention-to-treat principle
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DOI：
10.1002/pst.1791
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发表时间：
2017-01-01
影响因子：
1.5
通讯作者：
Benda, Norbert
中科院分区：
文献类型：
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作者：
Leuchs, Ann-Kristin;Brandt, Andreas;Benda, Norbert
随机对照试验（RCT）旨在提供治疗获益的可靠估计。缺失数据和不依从治疗是明显的问题，可以大大阻碍这项任务。在实践中，由于不依从而导致的缺失数据的处理会影响所解决的问题，这一事实往往被忽视。估计值允许精确地预先定义利息问题。估计值是关于人群、终点和随机化后事件（例如，不依从）处理的估计值的定义。根据情况，不同的被估量是相关的。因此，重要的是，意向治疗（ITT）原则，这被认为是分析RCT的金标准，不限制RCT的主要目标，只有几个相关的被估量之一。尽管关于ITT原则的构成存在很多模糊性，但许多人将ITT与完全随访所有患者并将所有随机化患者的所有数据纳入分析相关联。这将把主要目标局限于估计治疗政策的效果，当然不是在所有情况下都有必要。为了保持明确建议遵循ITT原则的优势，同时允许将各种相关被估量作为主要目标，我们认为适当的前进方向是将ITT定义为将所有随机化患者纳入分析集，并将每例患者分配至其随机化治疗。这一定义包含ITT的实际意图，也可以在无法进行完整随访的情况下充分实施。
Randomized controlled trials (RCTs) aim at providing reliable estimates of treatment benefit. Missing data and nonadherence to treatment are distinct problems that can substantially impede this task. In practice, the fact that the handling of missing data due to nonadherence affects the question that is addressed is often ignored. Estimands allow precisely predefining the question of interest. Estimands are definitions of that which is being estimated with regard to population, endpoint, and handling of postrandomization events (eg, nonadherence). Depending on the situation, different estimands are of relevance. Therefore, it is important that the intention-to-treat (ITT) principle, which is considered the gold standard for analyzing RCTs, does not restrict an RCT's primary objective to only one of several relevant estimands. Although much ambiguity is involved around what is considered to constitute the ITT principle, many associate ITT with completely following up all patients and including all data of all randomized patients as allocated into the analysis. This would restrict primary objectives to estimating the effect of treatment policy and is certainly not warranted in all situations. To maintain the advantage of having the clear recommendation to follow the ITT principle while allowing for various relevant estimands as primary objective, we argue that the appropriate way forward is to define ITT as including all randomized patients into the analysis set and each patient is to be allocated to his or her randomized treatment. This definition comprises the actual intent of ITT and can be fully implemented also in settings where complete follow-up is impossible.