论文标题

关于在平台试验中使用非电流控件:范围审查

On the use of non-concurrent controls in platform trials: A scoping review

论文作者

Roig, Marta Bofill, Burgwinkel, Cora, Garczarek, Ursula, Koenig, Franz, Posch, Martin, Nguyen, Quynh, Hees, Katharina

论文摘要

在过去的几年中,通过允许在试验开始时进入新的实验武器,平台试验与多臂试验相比提高了灵活性。与单独的试验相比,在平台试验中使用共享对照组提高了试验效率。由于某些实验治疗臂的后期进入,共享对照组包括并发和非连通控制数据。对于给定的实验臂,非连通对照是指在ARM进入试验之前分配给对照组的患者,而并发对照则指的是对照患者,这些患者同时同时将其与实验组合进行。如果未使用适当的方法并且未达到假设,则使用非电流控件在时间趋势的情况下会导致估计值偏差。在本文中,我们面临两个主要目标。首先,我们旨在确定当前可用于合并非连续控件的方法,澄清关键概念和假设,并命名每种方法的主要特征。为此,我们系统地搜索了有关方法的研究文章,以包括非连续控制。第二个目标是总结当前对非连流控制的监管观点,以阐明关键概念和当前的指导。因此,我们在监管指南中进行了系统的搜索,以使用非连续控件,并总结了最相关的论点和推荐方法。最后,我们讨论了使用非连续控制的优势和潜在警告。

Platform trials gained popularity during the last few years as they increase flexibility compared to multi-arm trials by allowing new experimental arms entering when the trial already started. Using a shared control group in platform trials increases the trial efficiency compared to separate trials. Because of the later entry of some of the experimental treatment arms, the shared control group includes concurrent and non-concurrent control data. For a given experimental arm, non-concurrent controls refer to patients allocated to the control arm before the arm enters the trial, while concurrent controls refer to control patients that are randomised concurrently to the experimental arm. Using non-concurrent controls can result in bias in the estimate in case of time trends if the appropriate methodology is not used and the assumptions are not met. In this paper, we faced two main objectives. In the first, we aimed to identify the methods currently available for incorporating non-concurrent controls, clarify the key concepts and assumptions, and name the main characteristics of each method. For this purpose, we systematically searched research articles on methods to include non-concurrent controls. The second objective is to summarise the current regulatory view on non-concurrent controls to clarify the key concepts and current guidance. Therefore, we conducted a systematic search in regulatory guidelines regarding using non-concurrent controls and summarised the most relevant arguments and recommended methods. Finally, we discuss the advantages and potential caveats of using non-concurrent controls.

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