异质性对具有正常分布结果的平台试验分析的影响
Kim May Lee1,2, Richard Emsley3,4
1Department of Biostatistics and Health Informatics, Institute of Psychiatry, Psychology and Neuroscience, King's College London, 16 De Crespigny Park, SE5 8AF, London, UK. kim.lee@kcl.ac.uk.
BMC medical research methodology
|July 30, 2024
概括
平台试验通过允许新的治疗方法来加速药物发现. 这项研究表明异质性影响分析,但一些方法控制错误,建议适应性设计,以获得稳健的结果.
科学领域:
- 临床试验 临床试验
- 生物统计学 生物统计学
- 药学研究 药学研究
背景情况:
- 平台试验通过为正在进行的研究增加武器,使有效的干预发现成为可能.
- 虽然讨论了非并发的控制,但由于标准的变化而导致的平台试验中的异质性较少被探索.
- 在平台试验中,招生标准和招聘策略的修改可能导致异质性.
研究的目的:
- 调查异质性对两阶段平台试验设计分析的影响.
- 评估假设测试程序和模拟策略在异质性和异种性.
- 评估标准回归和一种新的对对试验分析方法的性能.
主要方法:
- 进行了一个模拟研究来分析一个两阶段的平台试验设计.
- 治疗效果的异质性和结果数据的异质性被认为是正常的终点.
- 标准回归和对对试验分析进行了比较,后者对治疗比较进行了调整.
主要成果:
- 几种测试策略保持了I型错误率,具有异性或随机队列效应.
- 在一些模型中,治疗效果的估计代表了整体或特定阶段的效果.
- 估计的特征在很大程度上不受随机队列效应或异种复杂性的影响.
结论:
- 在平台试验中,零假设的规范可能需要由于治疗效果异质性而进行细化.
- 建议采用适应性设计测试程序,而不是标准回归模型.
- 将双对试验分析和回归模型与相互作用术语进行比较,可以揭示异质性水平.
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