具有统计意义的III期瘤学试验的可复制性:一个In Silico元流行病学分析
Alexander D Sherry1, Pavlos Msaouel2, Avital M Miller3
1Department of Radiation Oncology, Division of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Department of Radiation Oncology, Mayo Clinic, Rochester, MN, USA.
概括
在III期瘤学试验中的统计学显著性 (P ≤ 0.05) 并不能保证可重现的效果. 先进的建模显示P=0.05的复制概率很低,强调仅仅是显著性并不保证可靠的发现.
科学领域:
- 在瘤学瘤学.
- 生物统计学 生物统计学
- 临床试验设计 临床试验设计
背景情况:
- 统计学意义的P值≤0.05的传统值越来越多地被审查,因为它对可重复的研究结果的影响.
- 这一问题在瘤学中尤为关键,因为III期试验经常指导临床实践,并且很少被重复.
研究的目的:
- 在III期瘤学试验中研究P值与治疗效果的可重现性之间的关系.
- 根据其统计学意义,评估瘤学试验中观察到的影响成功复制的概率.
主要方法:
- 利用了来自632项III期瘤学试验 (496,219名患者) 的信号噪声比分布.
- 使用高级建模估计成功复制概率,正确标志概率,覆盖概率和夸大因子.
- 开发了一个用于估计个体试验复制概率的网络界面.
主要成果:
- 中位数的夸张系数为1.09.
- 对于P ≤0.05的试验,平均正确标志概率≥97%,覆盖概率在93%至96%之间.
- 对于0.05,0.01和0.001的P值,平均复制概率分别为43%,60%和77%. 对于导致监管批准的总生存终点试验,复制概率的中位数为66%.
结论:
- 虽然P ≤ 0.05表明效应的方向可能是正确的,但在III期瘤学试验中,效应的大小可能无法可靠地复制.
- 仅仅是统计学显著性不应等同于成功复制的高概率;需要进一步评估.
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