在对随机对照试验的样本大小计算中,线性假设有多重要?在随机对照试验中,预计治疗会影响变化速率
Katy E Morgan1, Ian R White2, Chris Frost3
1Department of Medical Statistics, London School of Hygiene and Tropical Medicine, London, UK. katy.morgan@lshtm.ac.uk.
BMC medical research methodology
|November 22, 2023
概括
临床试验的样本大小计算需要仔细考虑轨迹假设. 不匹配的访问时间表或不成比例的治疗效应可以显著影响试验功率,需要替代的建模方法.
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
- 纵向数据分析 纵向数据分析
背景情况:
- 治疗通常旨在减缓疾病的进展,以持续的结果来衡量.
- 随机斜率模型分析连续测量的变化,假设线性轨迹和随时间的比例处理效应.
- 样本大小计算通常涉及对现有数据的差异估计和应用标准公式.
研究的目的:
- 评估非线性轨迹和非比例治疗效应对临床试验功率的影响.
- 在不同的假设下评估样本大小计算的准确性.
主要方法:
- 模拟被用来建模四种类型的轨迹 (线性和非线性).
- 模拟了观察性研究以获得样本大小.
- 试验模拟包括比例和非比例的治疗效应.
主要成果:
- 试验功率与比例效应的标称水平紧密相匹配,并与访问时间表相匹配,即使与非线性轨迹.
- 观察数据和试验之间的不匹配的访问时间表导致了功率偏差.
- 使用随机斜率模型时,不成比例的处理效应导致了显著的功率差异.
结论:
- 对于非线性轨迹,观察数据应与试验的访问时间表相匹配,以准确计算样本大小.
- 随机斜率模型对于不成比例的治疗效应是不合适的.
- 建议采用容纳自由轨迹变化的替代模型进行动力试验,当效应不成比例或轨迹复杂时.
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