适应性平台试验比多个独立试验高效多少? 一项全面的模拟研究,以在流行病期间简化药物开发
Masanao Sasaki1, Hiroyuki Sato1, Yukari Uemura2
1Department of Clinical Biostatistics, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo, Japan.
适应性平台临床试验 (APT) 可能比药物开发的多个独立试验更有效,可能减少总开发时间和样本大小. 然而,他们的效率取决于各种因素,包括招生速度和试验设计的复杂性.
科学领域:
- 临床试验方法论 临床试验方法论
- 药物开发 药物开发
- 流行病学 流行病学
背景情况:
- 随着COVID-19的流行,人们对适应性平台临床试验 (APT) 的兴趣增加了.
- APT将多种药物与常见的对照组进行比较,允许在试验期间添加/排除药物.
- 与多个独立试验相比,APT的比较效率仍未得到充分探索.
研究的目的:
- 模拟和比较APT和COVID-19药物开发的多个独立试验的效率.
- 评估总开发期,样本大小和统计操作特征.
- 确定影响APT效率的因素.
主要方法:
- 对住院COVID-19患者进行药物开发的模拟研究.
- 场景评估了带有和没有分阶段添加药物的APT.
- 关键指标包括总开发期,总样本大小和统计运营特征.
主要成果:
- 没有分阶段添加药物的APT显示了比独立试验更短的开发周期,但随着加快招生,这种优势下降了.
- 在某些情况下,分阶段添加药物的APT可能会缩短开发时间.
- 根据招生速度,样本大小,错误率调整,分配比率和药物添加间隔,效率的提高有所不同.
结论:
- 与独立试验相比,APT可以提高效率 (总开发期,样本大小),而不会影响统计有效性.
- 改善的程度取决于几个动态试验参数.
- 仔细规划和考虑APT的复杂性至关重要,特别是在流行病期间.
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