External data borrowing in clinical trial designs has increased in recent years. This is accomplished in the Bayesian framework by specifying informative prior distributions. To mitigate the impact of potential inconsistency (bias) between external and current data, robust approaches have been proposed. One such approach is the robust mixture prior arising as a mixture of an informative prior and a more dispersed prior inducing dynamic borrowing. This prior requires the choice of four quantities: the mixture weight, mean, dispersion and parametric form of the robust component. To address the challenge associated with choosing these quantities, we perform a case-by-case study of their impact on specific operating characteristics in one-arm and hybrid-control trials with a normal endpoint. All four quantities were found to strongly impact the operating characteristics. As already known, variance of the robust component is linked to robustness. Less known, however, is that its location can have severe impact on test and estimation error. Further, the impact of the weight choice is strongly linked with the robust component's location and variance. We provide recommendations for the choice of the robust component parameters, prior weight, alternative functional form for this component and considerations for evaluating operating characteristics.
翻译:近年来,临床试验设计中对外部数据的借用日益增多。在贝叶斯框架下,这通过设定信息性先验分布来实现。为减轻外部数据与当前数据间潜在不一致性(偏倚)的影响,研究者提出了稳健方法。其中一种方法是稳健混合先验,它由信息性先验与一个更分散的先验混合构成,以实现动态借用。该先验需要确定四个量:混合权重、均值、离散度以及稳健成分的参数形式。为应对选择这些量所面临的挑战,我们针对正态终点单臂试验和混合对照试验,逐例研究了它们对特定操作特征的影响。研究发现所有四个量均对操作特征有显著影响。已知稳健成分的方差与稳健性相关,但较少被认识到的是其位置参数可能对检验和估计误差产生严重影响。此外,权重选择的影响与稳健成分的位置和方差密切相关。本文就稳健成分参数、先验权重的选择、该成分的替代函数形式以及操作特征评估的考量提供了建议。