在早期瘤学试验中评估混合控制方法:基于MORPHEUS-UC试验的模拟研究
Guanbo Wang1,2,3, Melanie Poulin-Costello3, Herbert Pang4
1CAUSALab, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, USA.
Pharmaceutical statistics
|September 25, 2023
概括
结合历史试验数据的混合对照在早期瘤药物开发中提高了统计准确性. 有非信息先验的频率主义方法和贝叶斯方法是首选的,特别是在异质治疗效应的情况下.
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:
- 第Ib/II期瘤学试验对于新药开发决策至关重要.
- 小样本大小可能会限制统计准确度.
- 混合控制,整合历史试验数据 (HTD),可以增加当前的试验臂.
研究的目的:
- 为了评估组合两个罗氏HTD源用于构建混合控制器的有效性.
- 评估使用混合对照的向治疗决策方法.
- 调查潜在并发症的影响,如异质性和模型错误规范.
主要方法:
- 广泛的模拟研究,使用来自MORPHEUS-UC试验的真实数据和两个Roche HTD用于阿特佐利祖马布单一治疗.
- 评估频率主义方法 (Cox和Weibull加速失效时间模型).
- 评估贝叶斯动态借贷与相应的先验 (韦布尔AFT模型) 和共变量调整.
主要成果:
- 建议采用联合频率主义方法和贝叶斯动态借用与非信息先验 (无共变量调整) 的方法.
- 这些方法表现良好,特别是当试验中的治疗效果异质时.
- 该研究确定了评估治疗对生存结果影响的首选方法.
结论:
- 混合控制方法,特别是联合频率主义方法和贝叶斯动态借贷与非信息先验,可以提高早期瘤学试验的决策.
- 这些方法即使在异质治疗效果下也是可靠的.
- 建议进行进一步的模拟研究,以更广泛地概括混合控制方法.
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