论文标题
匹配设计,用于增强具有外部控制的随机临床试验
A matching design for augmenting a randomized clinical trial with external control
论文作者
论文摘要
使用来自现实世界的信息来评估医疗产品的有效性正在变得越来越流行,并且被监管机构越来越可接受。根据美国食品和药物管理局发表的战略现实证据框架,这是一项混合随机对照试验,该试验通过现实世界中的数据增强内部控制部门是一种务实的方法,值得更多关注。在本文中,我们旨在改善这种混合随机对照试验的现有匹配设计。特别是,我们建议与整个并发的随机临床试验(RCT)匹配,以便(1)用于增强内部控制臂的匹配的外部控制受试者与RCT人群尽可能可比,(2)与同一对照组进行多个治疗的RCT中的每个主动治疗组,并且可以进行(3)匹配的锁定率,以便在匹配的设置中保持匹配的锁定效果,以更好地保持数据组合。除了加权估计器外,我们还引入了一种引导方法来获得其方差估计。根据实际临床试验的数据,通过模拟评估所提出方法的有限样本性能。
The use of information from real world to assess the effectiveness of medical products is becoming increasingly popular and more acceptable by regulatory agencies. According to a strategic real-world evidence framework published by U.S. Food and Drug Administration, a hybrid randomized controlled trial that augments internal control arm with real-world data is a pragmatic approach worth more attention. In this paper, we aim to improve on existing matching designs for such a hybrid randomized controlled trial. In particular, we propose to match the entire concurrent randomized clinical trial (RCT) such that (1) the matched external control subjects used to augment the internal control arm are as comparable as possible to the RCT population, (2) every active treatment arm in an RCT with multiple treatments is compared with the same control group, and (3) matching can be conducted and the matched set locked before treatment unblinding to better maintain the data integrity. Besides a weighted estimator, we also introduce a bootstrap method to obtain its variance estimation. The finite sample performance of the proposed method is evaluated by simulations based on data from a real clinical trial.