响应适应性随机化与不完美的中间终点
Yousra Kherabi1,2,3, Michael A Proschan4, Lori E Dodd3,4
1Infectious and Tropical Diseases Department, Bichat-Claude Bernard Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.
Clinical trials (London, England)
|February 25, 2026
概括
使用不完美的中间终点的响应适应性随机化,如结核病试验中的培养转换,可能无法可靠地将患者分配给最佳治疗. 终点的准确性对于有效的患者分配至关重要.
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
- 传染病研究 传染病研究
背景情况:
- 响应适应性随机化是有争议的,特别是在长期初级结果方面.
- 中间终点用于更新需要延长后续的试验中的随机化.
- 结核病试验是评估具有不完美的数据的适应性设计的背景.
研究的目的:
- 为了评估响应适应性随机化的影响,利用一个不完美的中间终点.
- 评估适应性设计在将参与者分配到高级治疗臂中的有效性.
- 检查中间终点准确度和时间趋势对试验结果的影响.
主要方法:
- 模拟了一个响应适应性随机化设计,用于三臂优势试验.
- 用8周的培养转换作为73周主要结果 (治疗成功) 的中间终点.
- 多种敏感度,特异性和真正的治疗疗效,以分析自适应随机化性能和I型错误.
主要成果:
- 即使具有完美的中间终点准确度,适应性随机化也没有始终有利于更好的手臂.
- 中间终点的精度较低显著降低了将更多患者分配到上臂的目标.
- 时间趋势增加了I型错误;分层纠正了这一点,但降低了统计能力.
结论:
- 响应适应性随机化对于高效评估多种疗法具有吸引力.
- 然而,它需要高度准确的中间终点,这不能保证可靠的患者分配.
- 响应适应性随机化的可靠性在不完美的中间终点下是可疑的.
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