更高效,更包容的时间到事件试验与共变量调整:一个模拟研究研究
Raphaëlle Momal1, Honghao Li1, Paul Trichelair1
1Owkin Inc, New York, USA.
Trials
|June 6, 2023
概括
在临床试验中的预后因素的调整大大减少了样本大小的需求,特别是高事件率. 这种共变量调整提高了试验的效率和包容性,特别是对于晚期癌症.
科学领域:
- 临床试验设计 临床试验设计
- 生物统计学 生物统计学
- 生存分析的分析.
背景情况:
- 众所周知,共变量调整在随机试验中增加了统计能力,结果是连续的.
- 在时间与事件的试验中,影响来自共变量调整的功率增益的因素不太清楚.
- 扩大资格标准往往会降低临床试验中的统计能力.
研究的目的:
- 调查在临床试验中影响统计能力和样本大小要求的因素.
- 量化通过共变量调整可实现的样本大小减少.
- 在扩大资格标准时,评估共变量调整对维持功率的影响.
主要方法:
- 用参数模拟来建模时间到事件结果.
- 模拟使用了来自癌症基因组图谱 (TCGA) 肝细胞癌 (HCC) 队列的数据.
- 共变量 (C指数) 的预后性能和累积发病率是关键的模拟参数.
主要成果:
- 随着共变量的预后表现 (C指数) 和事件的累积发病率,由共变量调整减少的样本大小增加.
- 对于C指数=0.65的共变量,样本大小的减少范围从3.1% (10%的累积发病率) 到29.1% (90%的累积发病率).
- 在扩大资格标准时,共变量调整保持了统计力,在HCC辅助试验模拟中,查患者减少了2.4倍.
结论:
- 对预后共变量进行系统调整可以提高临床试验的效率和包容性,特别是那些累积发病率高的临床试验.
- 同变量调整对于在具有广泛资格标准的试验中保持统计能力至关重要,这在晚期癌症研究中很常见.
- 考克斯 - 斯内尔R平方提供了一个保守的估计,样本大小减少的好处从共变量调整.
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