终点延迟对多臂多阶段试验效率的影响
Aritra Mukherjee1, James M S Wason1
1Population Health Sciences Institute, Newcastle University, Newcastle Upon Tyne, UK.
Statistics in medicine
|September 15, 2025
概括
多臂多阶段 (MAMS) 试验设计有效评估治疗方法,但由于结果延迟而失去显著的样本大小好处. 为了最大限度地提高效率,确保结果延迟不超过总招聘时间的三分之一.
科学领域:
- 临床试验方法论 临床试验方法论
- 生物统计学 生物统计学
- 适应性试验设计的设计
背景情况:
- 多臂多阶段 (MAMS) 设计通过自适应地评估多种治疗方法,在临床试验中提供效率.
- 这些设计可以减少与传统单阶段试验相比的样本大小要求.
- 然而,延迟的初级结局可能会导致"管道"患者不必要地被招募,从而减少效率的提高.
研究的目的:
- 为了量化MAMS设计中由于结果延迟而导致的效率损失.
- 分析"管道"患者对预期样本大小 (ESS) 的影响.
- 评估结果延迟,中间分析时间和整体试验效率之间的关系.
主要方法:
- 根据各种招募模型,对"管道"患者的分析估计.
- 考虑到结果延迟的ESS计算.
- 基于ESS和延迟持续时间的效率损失 (EL) 的评估.
- 评估阶段数量和中间分析时间的影响.
主要成果:
- 当结果延迟超过总招聘时间的三分之一时,效率损失超过50%.
- 试验阶段的数量对效率损失的影响最小.
- 与相等间隔的分析相比,早期的中间分析可能会对MAMS设计效率产生负面影响,结果延迟.
结论:
- 结果延迟显著降低了MAMS设计的样本大小优势.
- 将结果延迟最小化到不到招聘时间的三分之一,对于最大限度地提高MAMS效率至关重要.
- 临时分析的战略时机对于优化延迟结果的MAMS设计很重要.
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