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用于高斯端点动态和特定参数信息借用的修正条件逐部分幂先验法。

Modified Conditional Borrowing-By-Part Power Prior for Dynamic and Parameter-Specific Information Borrowing of the Gaussian Endpoint.

作者信息

Wang Kai, Cao Han, Yao Chen

机构信息

Peking University Clinical Research Institute, Peking University First Hospital, Beijing, China.

Department of Biostatistics, Peking University First Hospital, Beijing, China.

出版信息

Biom J. 2025 Apr;67(2):e70029. doi: 10.1002/bimj.70029.

Abstract

Borrowing external controls to augment the concurrent control arm is a popular topic in clinical trials. Bayesian dynamic borrowing methods adaptively discount external controls according to prior-data conflict. For the Gaussian endpoint, parameter-specific information borrowing enables differential discounting between the population mean and variance. The borrowing-by-part power prior employs two power parameters to separately downweight external likelihoods concerning the sample mean and variance. However, within the fully Bayesian framework, the posterior inference of the average treatment effect (ATE) defined as the population mean difference is significantly affected by the variance-specific prior-data conflict that reflects the heterogeneity of population variance. Here, we propose the modified conditional borrowing-by-part power prior (MCBPP) that separately discounts the external sample mean and variance according to parameter-specific prior-data conflicts, resulting in a more stable posterior estimation of ATE than its competitors under the same degree of mean-specific prior-data conflict. By fully discounting the external sample variance, the robust MCBPP (rMCBPP) can yield robust posterior inference of ATE against the variance-specific prior-data conflict. Although the population variance is considered a nuisance parameter, its homogeneity is equally important to justify information borrowing. We recommend the rMCBPP for borrowing external controls with a similar sample variance to concurrent controls because it exhibits better control of bias and Type I error rate than the modified power prior (MPP) assuming unknown variance in the absence of population variance heterogeneity. However, when faced with a significant sample variance discrepancy, the MPP assuming unknown variance is preferred given its better performance under severe population variance heterogeneity.

摘要

借用外部对照来扩充同期对照臂是临床试验中的一个热门话题。贝叶斯动态借用方法会根据先验数据冲突对外部对照进行自适应折扣。对于高斯终点,特定参数的信息借用能够在总体均值和方差之间进行差异折扣。逐部分幂先验借用方法采用两个幂参数分别对关于样本均值和方差的外部似然进行降权。然而,在全贝叶斯框架内,定义为总体均值差异的平均治疗效应(ATE)的后验推断会受到反映总体方差异质性的方差特定先验数据冲突的显著影响。在此,我们提出了修正的逐部分条件幂先验(MCBPP),它根据特定参数的先验数据冲突分别对外部样本均值和方差进行折扣,在相同程度的均值特定先验数据冲突下,与其他方法相比,能得到更稳定的ATE后验估计。通过完全折扣外部样本方差,稳健的MCBPP(rMCBPP)能够针对方差特定的先验数据冲突得出稳健的ATE后验推断。尽管总体方差被视为一个干扰参数,但其同质性对于证明信息借用的合理性同样重要。我们推荐rMCBPP用于借用与同期对照样本方差相似的外部对照,因为在不存在总体方差异质性且假设方差未知的情况下,它比修正幂先验(MPP)能更好地控制偏差和I型错误率。然而,当面临显著的样本方差差异时,假设方差未知的MPP因其在严重总体方差异质性下表现更好而更受青睐。

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