随机对照试验的危险 假设治疗效果减弱的生存推断:为什么边际和有条件估计之间的区别很重要
Angus C Jennings1, Mark J Rutherford1, Nicholas R Latimer2
1Biostatistics Research Group, Department of Population Health Sciences, University of Leicester, Leicester, England, UK.
概括
推断生存益处需要仔细考虑治疗效果的减弱. 将边际危险比率 (HR) 强制定为1可能会高估长期生存收益并低估成本,特别是在经济评估中.
科学领域:
- 卫生经济学 卫生经济学
- 生物统计学 生物统计学
- 对生存分析的分析.
背景情况:
- 从临床试验中推断经济评估的长期生存益处依赖于关于治疗效果减弱的假设.
- 假设治疗效果恒定或强制将边际危险比率 (HR) 设为1可能不会准确地反映个人层面的减弱效应,因为HR选择偏差.
研究的目的:
- 探索边缘HRs在逐渐减弱的条件 (个人层面) 治疗效应下的行为.
- 通过强迫边际HR为1来证明引入的偏差,当真正的估计是个体水平下降的生存差异时.
主要方法:
- 在不同异质性和治疗效果的四个参数组合下模拟数据.
- 估计的时间变异边际HRs在真实条件HR减弱为1的场景中.
- 通过将受限制的平均生存时间差异 (有限制的边际HR=1) 与真值进行比较来评估偏差.
主要成果:
- 在条件治疗效应减弱的情况下,由于共变量失衡,边际HRs超过1.
- 将边际HR限制为1导致受限平均生存时间差异偏差,高达0.8年 (57%的增长).
- 偏差随着初始保护性治疗效应的程度增加而增加.
结论:
- 基于边际与条件治疗效果减弱的生存推断之间存在显著差异.
- 限制边际HR为1对于个人层面的减弱效应,高估了生存效益.
- 这种高估导致低估了增量成本效益比率.
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