关于在平台试验中使用非并发控制:一个范围审查
Marta Bofill Roig1, Cora Burgwinkel2,3, Ursula Garczarek4
1Center for Medical Data Science, Medical University of Vienna, Vienna, Austria. marta.bofillroig@meduniwien.ac.at.
Trials
|June 15, 2023
概括
平台试验可以使用非并发的控制,但偏差是一个风险. 现有统计方法可以纳入这些数据,尽管对平台试验的监管指导仍然有限.
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
- 监管科学 监管科学
背景情况:
- 平台试验通过允许新武器和使用共享控制组来提供灵活性和效率.
- 平台试验中的共享控制组可以包括并发和非并发数据.
- 非并发的对照组,在实验组进入之前随机选择的患者,如果不考虑时间趋势,风险偏差.
研究的目的:
- 审查在平台试验中使用非并发控制的统计方法.
- 审查关于在平台试验中使用非并发控制的监管指南.
- 评估外部和历史控制数据的整合.
主要方法:
- 对统计方法 (43篇文章) 和监管指导 (37条指导方针) 进行了系统的文献审查.
- 搜索包括PubMed的统计方法和EMA/FDA网站的监管文件.
- 扩大范围,包括外部和历史控制数据的使用.
主要成果:
- 很少有文章 (7/43) 和指导方针 (4/37) 专门针对平台试验.
- 贝叶斯式方法 (28/43) 是常见的,用于整合非并发的控制,低权衡非并发数据的方法普遍存在 (34/43).
- 监管指导方针承认了诸如非可比性 (30/37) 和偏差 (16/37) 等问题,接受罕见疾病或特定适应症的非并发控制.
结论:
- 在平台试验中整合非并发控制的统计方法是可用的,在数据组合和趋势处理方面有所不同.
- 现有的方法往往适应外部或历史控制的方法.
- 目前专门针对平台试验中的非并发控制的监管指导是有限的.
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