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带有混合效应的轨迹集群分类模型:考虑到分类不确定性的推理
Charlotte Dugourd1,2,3,4, Amna Abichou-Klich1,2,3,4, René Ecochard1,2,3,4
1Service de Biostatistique, Hospices Civils de Lyon, Lyon, France.
Statistics in medicine
|August 15, 2023
概括
本研究引入了一个随机EM算法 (SEM),通过考虑不确定性来改善患者生物标志物轨迹分类. 对于了解患者子组和治疗效应,SEM提供了更准确的置信区间.
科学领域:
- 生物统计学 生物统计学
- 临床研究方法论 临床研究方法论
- 制药指标 (Pharmacometrics) 是一个指标.
背景情况:
- 在临床研究中,将患者的生物标志物轨迹分为不同的组是至关重要的.
- 混合效应模型用于纵向数据异质性,CEM算法估计轨迹.
- 由于未解决的分类不确定性,目前的CEM方法低估了参数估计差异.
研究的目的:
- 引入随机EM算法 (SEM) 作为一种将分类不确定性纳入参数方差估计的方法.
- 评估SEM在为生物标志物轨迹模型提供准确的置信区间方面的表现.
- 将SEM方法应用于现实世界的临床数据,以识别患者子组.
主要方法:
- 随着CEM算法的趋同,实施了随机EM算法 (SEM).
- 模拟研究以评估SEM产生的95%置信区间的覆盖概率.
- 将SEM应用于低循环试验数据,比较低剂量与标准剂量的环素A.
主要成果:
- 在模拟中,SEM证明了对95%置信区间的正确覆盖概率,表明准确度有所提高.
- 覆盖概率接近95%,在典型轨迹中偏差较高的场景中略有偏差.
- 对低循环试验的分析确定了可能受益于低剂量循环氨酸A的患者组,尽管剂量影响估计存在显著的不确定性.
结论:
- 随机EM算法 (SEM) 有效地解释了生物标志物轨迹的混合效应模型中的分类不确定性.
- 与标准CEM相比,SEM提供了更可靠的置信区间,提高了参数估计的精度.
- 在低循环试验中的应用凸显了SEM在识别患者子组中的实用性,但也强调了由于固有的不确定性,需要仔细解释结果.
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