在临床试验中安全监测的统计规则
Michael J Martens1,2, Brent R Logan1,2
1Division of Biostatistics, Medical College of Wisconsin, Milwaukee, WI, USA.
Clinical trials (London, England)
|October 25, 2023
概括
本研究比较了临床试验安全停止规则的统计方法. 建议使用具有较弱先验的Pocock或Beta-Binomial方法,以最大限度地减少患者接触有毒疗法.
科学领域:
- 临床试验 临床试验
- 生物统计学 生物统计学
- 患者安全 患者安全
背景情况:
- 在临床试验中,患者安全至关重要,需要严格监测.
- 协议规定的停止规则对于停止过度毒性研究至关重要.
- 统计方法有助于制定有效的停车规则,以保护患者,同时最大限度地减少虚假警报.
研究的目的:
- 建立在临床试验中重复监测安全事件的框架.
- 调查和比较统计技术,以制定安全停车标准.
- 引入一个软件工具来构建和评估这些停止规则.
主要方法:
- 波考克,奥布莱恩-弗莱明测试,贝叶斯贝塔双项模型和顺序概率比率测试 (SPRT) 的比较.
- 开发R包"停止规则"用于规则构建和评估.
- 使用 BMT CTN 0601 对儿科状细胞病患者的案例研究进行演示.
主要成果:
- 积极的早期停止方法 (Pocock,弱前Beta-Binomial) 有允许的后期阶段标准.
- 有一个权衡:积极的早期监测减少了预期的毒性,但可能会降低统计能力.
- 修改后的SPRT对毒性率的选择敏感;最大化的SPRT可能会产生更多的毒性和更低的功率.
结论:
- 建议Pocock或Beta-Binomial (弱先) 方法用于安全停止规则,以最大限度地减少患者暴露于不安全的疗法.
- 在试验设计过程中强调在各种毒性率下评估操作特征.
- 突出了"停止规则"R包对于知情的规则选择的实用性.
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