在三阶段临床试验中重新计算样本大小及其评估
Björn Bokelmann1, Geraldine Rauch2,3, Jan Meis4
1Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Biometry and Clinical Epidemiology, Charitéplatz 1, Berlin, 10117, Germany. bjoern.bokelmann@gmx.de.
BMC medical research methodology
|September 25, 2024
概括
样本大小重新计算,一种在研究中期调整试验大小的方法,扩展到三阶段临床试验. 虽然三级设计可以提高功率并减少样本大小,但重新计算的好处根据所需的试验结果而有所不同.
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
- 统计研究设计 统计研究设计
背景情况:
- 在临床试验中确定适当的样本大小是复杂的,因为对效果大小和干扰参数的不确定性.
- 样本大小的重新计算,包括临时分析以适应未来的样本大小,是管理这种不确定性的关键策略.
- 现有的研究主要侧重于在两阶段试验框架内重新计算样本大小.
研究的目的:
- 将样本大小再计算方法扩展到三阶段临床试验.
- 适应现有的两阶段再计算规则,用于三阶段设计.
- 在三阶段试验中评估样本大小重新计算的性能,使用条件性能得分.
主要方法:
- 修改了现有的样本大小重新计算规则,从两阶段试验到三阶段试验的应用.
- 在三阶段试验中应用了条件性能得分来评估重新计算规则.
- 进行了模拟研究,比较了两个阶段和三个阶段的组序列设计,有和没有重新计算.
主要成果:
- 与两阶段设计相比,三阶段设计显示出更好的统计能力和更小的预期样本大小.
- 在三阶段试验中,应用样本大小重新计算规则的优势取决于所使用的特定绩效指标.
- 当使用三阶段设计而不是两阶段设计时,观察到在功率和预期样本大小上显著的有利影响.
结论:
- 样本大小重新计算是三阶段临床试验设计中可行的和适用的方法.
- 在三阶段试验中,样本大小重新计算的实际好处取决于研究申请人对特定试验特征的优先考虑.
- 重计算的实用性取决于优化功率,样本大小或其他性能指标是否是主要目标.
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