分析方法用于具有共同变量约束的集群随机试验,具有时间到事件结果
Amy M Crisp1, M Elizabeth Halloran2,3, Matt D T Hitchings4
1Department of Biostatistics, University of Florida, Gainesville, Florida, USA. amy.crisp@jax.ufl.edu.
BMC medical research methodology
|January 23, 2025
概括
集群随机试验中的受约束随机化改善了时间到事件结果的统计能力. 一个新的排列测试提供了对I型错误率的可靠控制,在模拟中优于基于模型的测试.
科学领域:
- 生物统计学 生物统计学
- 临床试验方法论 临床试验方法论
- 流行病学 流行病学
背景情况:
- 集群随机试验 (CRT) 通常涉及很少的集群,需要有效的随机化技术.
- 约束随机化平衡CRT中的共变量,先前的工作重点是连续或二进制结果.
- 将协变量调整分析扩展到CRT中的时间到事件结果对于稳健的试验设计至关重要.
研究的目的:
- 用受约束随机化评估集群随机试验中的时间到事件结果的统计方法.
- 为了比较一种新的换测试与现有的基于模型的方法 (Cox模型) 来分析CRT中的时间到事件数据.
- 评估共变量平衡对不同集群号的统计能力和I型错误率的影响.
主要方法:
- 一项模拟研究比较了简单的随机化与受约束的随机化,具有预后和非预后共变量.
- 评估了三种分析方法:具有强大的方差的半参数考克斯模型,混合效应的考克斯模型,以及使用偏差残余的顺序测试.
- 评估I型错误率和统计能力,对每个试验组的不同数量的集群进行评估.
主要成果:
- 排列试验保持了I型名义错误率,显示了稳定性,与只有少数集群的基于模型的试验不同.
- 这三种方法都表现得足够好,每只手臂有25个集群,就像动机示例中的那样.
- 与简单的随机化相比,受约束的随机化改善了时间到事件结果的功率,而收益取决于集群数量.
结论:
- 同变量受约束的随机化增强了对集群随机试验中时间到事件结果的统计能力.
- 开发的顺序测试对I型错误膨胀比基于模型的考克斯回归方法更强大.
- 在分析阶段对共变量进行调整会对功率产生重大影响,尤其受到每个试验臂集群数量的影响.
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