集团顺序设计,主要终点的外部驱动的变化
Amin Yarahmadi1, Lori E Dodd2, Peter Horby3
1Clinical Trials Unit, Warwick Medical School, University of Warwick, Coventry, UK.
适应性临床试验可以在研究中期调整主要终点. 这种方法控制了在改变终点时的统计错误率,即使是相关的,确保可靠的试验结果.
科学领域:
- 生物统计学 生物统计学
- 临床试验设计 临床试验设计
- 流行病学 流行病学
背景情况:
- 适应性临床试验设计在高不确定性新兴疾病环境中是有价值的.
- 疾病自然史,效应大小和人口的不确定性可能需要在试验期间改变主要终点.
研究的目的:
- 开发用于控制I型错误率的统计方法,当初级终点在适应性试验中期改变时.
- 在采用新的初级终点时,应对基于初级初级终点的中间分析的挑战.
主要方法:
- 修改组序列方法以调整初始主终点的中间分析.
- 模拟研究评估I型错误率控制在初始和新初级终点之间的不同相关性场景下.
- 使用模拟的remdesivir临床试验用于COVID-19的插图.
主要成果:
- 拟议的分组顺序方法有效地控制了新初级终点的I型错误率,无论对初始终点的治疗效应如何.
- 即使从试验数据估计初始和新初级终点之间的相关性,I型错误率也得到了充分控制.
结论:
- 修改后的组序列方法为具有主要终点变化的适应性试验提供了强大的框架.
- 这种方法确保了临床试验的统计有效性,因为临床试验面临着不断变化的不确定性,正如COVID-19流行病背景中所示的那样.
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