Lee Y J, Ellenberg J H, Hirtz D G, Nelson K B
National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892.
Stat Med. 1991 Oct;10(10):1595-605. doi: 10.1002/sim.4780101011.
The primary analysis of a randomized clinical trial should compare patients in their randomly assigned treatment groups (intention to treat analysis). When a substantial number of subjects fail to take a prescribed medication or are switched to a different study medication, it is tempting to consider treatment comparisons using only those subjects with treatment as actually received rather than as prescribed. There are several arguments against this approach: the prognostic balance brought about by randomization is likely to be disturbed; sample size will be reduced; and the validity of the statistical test procedures will be undermined. Further, results of analysis by treatment actually received may suffer from a bias introduced by using compliance, a factor often related to outcome independently of the treatment received, to determine the groups for comparison. The extent and nature of this bias will be related to the definition of compliance in an as treated analysis, a definition which could be unintentionally self-serving. We have investigated the problem of the definition of actual treatment in the context of a recent clinical trial. We used several definitions to classify patients as having received or not received treatment as prescribed. These definitions, when used in as treated analyses, provided results that were at times inconsistent or counter-intuitive, and which neither helped to confirm nor further explain the intention to treat analysis.
随机临床试验的主要分析应比较随机分配治疗组中的患者（意向性分析）。当大量受试者未服用规定药物或转用其他研究药物时，人们可能会倾向于仅使用实际接受治疗而非按规定治疗的受试者进行治疗比较。有几个反对这种方法的理由：随机化带来的预后平衡可能会受到干扰；样本量会减少；统计检验程序的有效性会被破坏。此外，按实际接受的治疗进行分析的结果可能会因使用依从性引入偏差，依从性是一个通常与结局独立于所接受治疗相关的因素，用于确定比较组。这种偏差的程度和性质将与在实际治疗分析中依从性的定义相关，该定义可能无意中对自身有利。我们在最近的一项临床试验背景下研究了实际治疗定义的问题。我们使用了几种定义将患者分类为是否按规定接受了治疗。这些定义在实际治疗分析中使用时，有时会提供不一致或违反直觉的结果，既无助于证实意向性分析，也无法进一步解释意向性分析。
