随机临床试验的设计与二进制的终点:有条件对无条件分析的二对二表
Edward L Korn1, Boris Freidlin1
1Biometric Research Program, National Cancer Institute, Bethesda, Maryland, USA.
Statistics in medicine
|May 23, 2024
概括
像Boschloo这样的无条件精确测试,对于具有二进制结果的随机临床试验,比Fisher的精确测试更强大. 这导致更小的样本大小,使他们更适合临床试验设计.
科学领域:
- 生物统计学 生物统计学
- 临床试验设计 临床试验设计
- 统计推理 统计推理
背景情况:
- 用二进制终点进行随机临床试验 (RCT) 的样本大小确定严重依赖于所选择的假设测试程序.
- 费舍尔的精确测试,这是2x2表的常用方法,在条件分析时,提供1型错误率小于或等于名义水平.
- 无条件精确测试也保留了1型错误,但通常不那么保守,比费舍尔精确测试更强大.
研究的目的:
- 在RCT中批判性地评估支持条件分析的统计论据,使用费舍尔精确测试.
- 突出在临床试验设计中使用无条件精确测试的样本大小优势,例如Boschloo的测试.
- 探索在使用预先规定的响应率的无条件测试中进一步提高功率的潜力.
主要方法:
- 在RCT的背景下,对2x2表的条件分析进行统计论证的审查.
- 费舍尔精确测试与无条件精确测试 (例如Boschloo测试) 的功率和1型错误特征的比较.
- 探索使用目标零和替代响应率来提高无条件测试功率的影响.
主要成果:
- 在RCT中对2x2表进行条件分析的论点在这个特定的背景下被发现在很大程度上是无关紧要的或没有说服力的.
- 无条件精确测试,特别是Boschloo的测试,与费舍尔的精确测试相比,显示出更高的功率,使得临床试验样本大小更小.
- 有潜力通过结合零和替代反应率的先前知识来增强无条件测试的力量.
结论:
- 无条件精确试验的样本大小优势使其在设计具有二进制终点的随机临床试验时得到推.
- 仅在RCT中使用有条件的费舍尔精确测试的统计理由是微弱的,特别是当样本大小的减少是首要任务时.
- 未来的研究应该专注于利用目标响应率来优化无条件精确测试的力量,以实现更高效的临床试验设计.
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