在早期剂量检测临床试验中处理不完全或晚发性毒性:当前实践和未来前景
Zhulin Yin1, Adrian P Mander2, Johann S de Bono3
1Clinical Trials and Statistics Unit, Institute of Cancer Research, London, United Kingdom.
JCO precision oncology
|January 5, 2024
概括
早期临床试验使用时间到事件连续重新评估方法 (TITE-CRM) 往往缺乏足够的可重现性报告. 提高先进试验设计的透明度对于准确解释结果至关重要.
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
- 药物开发 药物开发
背景情况:
- 管理晚发性毒性对临床试验结果和患者安全至关重要.
- 早期剂量检测试验往往面临挑战,在新招聘之前,参与者进行毒性评估的随访.
- 先进的试验设计旨在在招募参与者期间有效管理毒性信息.
研究的目的:
- 审查已公布的早期剂量检测试验,使用考虑部分和完整毒性信息的设计.
- 评估这些先进的试验设计的实施和报告.
- 确定是否提供足够的信息,以确保试验结果的可复制性.
主要方法:
- 在2023年3月26日之前确定的141项已公布的早期剂量检测临床试验的方法审查.
- 包括的试验使用了诸如滚动6的设计,时间到事件的持续重新评估方法 (TITE-CRM) 等.
- 提取的数据包括临床环境,设计参数,实际考虑和剂量限制毒性 (DLT) 信息.
主要成果:
- 最常见的是滚动6设计 (53.9%) 和TITE-CRM (43.3%).
- 使用TITE-CRM的试验与滚动6相比,DLT评估窗口要长得多.
- 高比例的TITE-CRM试验 (91.8%) 无法描述可重现性的基本参数,只有8.2%提供了足够的信息.
结论:
- 使用TITE-CRM的试验显示,与滚动6设计相比,在报告可重复性至关重要的细节方面存在重大缺陷.
- 对基于先进模型的试验设计报告不足,损害了其可信度.
- 提供了建议,以提高透明度,可复制性和准确解释这些设计的结果.
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