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W Li1,2, V Cornelius3, S Finfer4,5,6
1MRC Biostatistics Unit, East Forvie Building, University of Cambridge, Cambridge, CB2 0QY, UK. wenyue.li@mrc-bsu.cam.ac.uk.
BMC medical research methodology
|October 18, 2023
概括
适应性临床试验在重症监护研究中提供了灵活性和效率. 探索各种适应性设计可以优化样本大小和决策,改善试验结果.
科学领域:
- 关键护理医学 关键护理医学
- 临床试验方法论 临床试验方法论
- 生物统计学 生物统计学
背景情况:
- 适应性临床试验越来越受欢迎,因为它们的灵活性,效率和伦理优势超过传统的固定设计.
- 尽管它们的使用越来越多,特别是在COVID-19研究中,但适应性设计在重症监护试验中未得到充分利用.
- 对不同适应性设计的全面理解对于促进其在重症监护机构的采用和准确解释至关重要.
研究的目的:
- 评估频率主义和贝叶斯适应方法在重症监护试验中的表现.
- 为了比较各种适应性设计的效率和准确性,使用两项主要重症监护试验的回顾性分析.
- 提供可以指导未来重症监护研究最佳适应方法的选择的见解.
主要方法:
- 使用频率主义和贝叶斯适应方法对两个大型重症监护试验 (ADRENAL和NICE-SUGAR) 的回顾性分析.
- 模拟了1万项试验,其中有1,2,4和9个均等间隔的临时试验,以评估错误率,决策概率和样本大小.
- 用90天死亡率作为结果的逻辑回归建模,在0.05.05的双面显著性水平 (α) 上测试零假设.
主要成果:
- 在所有适应性方法中,增加临时的数量始终降低了预期的样本大小.
- 频率主义组序列方法有效控制了I型错误率,而贝叶斯式方法显示了I型错误率的通货膨胀.
- 贝叶斯预测概率和奥布莱恩-弗莱明方法表明,正确地提前停止试验的概率很高 (约95%).
- 贝叶斯方法在正确停止ADRENAL试验的有效性方面表现出色 (约91%),而Haybittle-Peto方法在NICE-SUGAR试验中表现出更大的力量.
- 治疗效果估计越来越低估,中间期的数量越来越多.
结论:
- 适应性设计可以达到与固定设计类似的结论,样本大小显著减少.
- 增加过渡期的效率提升对于大规模的,晚期重症监护试验具有很短的后续期特别有价值.
- 在试验设计阶段对适应性方法的系统评估对于选择最合适的方法至关重要,从而增强重症监护研究.
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