Correcting for non-compliance in randomized non-inferiority trials with active and placebo control using structural models
Correcting for non-compliance in randomized non-inferiority trials with active and placebo control using structural models
复制标题
使用结构模型纠正主动对照和安慰剂对照随机非劣效性试验中的不依从性
DOI：
10.1002/sim.6392
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发表时间：
2015-03-15
影响因子：
2
通讯作者：
Zhou, Xiaohua
中科院分区：
文献类型：
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作者：
Wu, Ying;Zhao, Liang;Zhou, Xiaohua
三组临床试验设计（包括试验治疗、活性参比药物和安慰剂对照）是评估非劣效性的金标准。在存在不依从性的情况下，一个常见的问题是意向治疗（ITT）分析（这是非劣效性试验的标准方法）往往会增加错误得出非劣效性结论的可能性，这表明符合方案（PP）分析可能更适用于非劣效性试验，尽管其存在固有偏倚。本文的目的是开发统计方法，用于处理三组非劣效性试验中删失的至事件时间数据的不依从性。在这里，治疗的改变被认为是唯一的不依从形式。本文提出了一种利用三臂保秩结构失效时间模型和G估计分析的方法。使用模拟，使用ITT、PP分析和当前提出的方法详细研究了非依从性对非劣效性试验的影响。结果表明，所提出的方法具有良好的特性，ITT或PP分析都不能保证非劣效性结论的有效性。可根据要求向作者提供用于实施拟定试验程序的统计分析系统程序。版权所有（C）2014约翰威利父子有限公司
The three-arm clinical trial design, which includes a test treatment, an active reference, and placebo control, is the gold standard for the assessment of non-inferiority. In the presence of non-compliance, one common concern is that an intent-to-treat (ITT) analysis (which is the standard approach to non-inferiority trials), tends to increase the chances of erroneously concluding non-inferiority, suggesting that the per-protocol (PP) analysis may be preferable for non-inferiority trials despite its inherent bias. The objective of this paper was to develop statistical methodology for dealing with non-compliance in three-arm non-inferiority trials for censored, time-to-event data. Changes in treatment were here considered the only form of non-compliance. An approach using a three-arm rank preserving structural failure time model and G-estimation analysis is here presented. Using simulations, the impact of non-compliance on non-inferiority trials was investigated in detail using ITT, PP analyses, and the present proposed method. Results indicate that the proposed method shows good characteristics, and that neither ITT nor PP analyses can always guarantee the validity of the non-inferiority conclusion. A Statistical Analysis System program for the implementation of the proposed test procedure is available from the authors upon request. Copyright (C) 2014 John Wiley & Sons, Ltd.