Faculty for Informatics and Data Science, University Regensburg, Germany.
MRC Biostatistics Unit, University of Cambridge, UK.
Stat Methods Med Res. 2024 Nov;33(11-12):2115-2130. doi: 10.1177/09622802241288348. Epub 2024 Oct 14.
In the search for effective treatments for COVID-19, the initial emphasis has been on re-purposed treatments. To maximize the chances of finding successful treatments, novel treatments that have been developed for this disease in particular, are needed. In this article, we describe and evaluate the statistical design of the AGILE platform, an adaptive randomized seamless Phase I/II trial platform that seeks to quickly establish a safe range of doses and investigates treatments for potential efficacy. The bespoke Bayesian design (i) utilizes randomization during dose-finding, (ii) shares control arm information across the platform, and (iii) uses a time-to-event endpoint with a formal testing structure and error control for evaluation of potential efficacy. Both single-agent and combination treatments are considered. We find that the design can identify potential treatments that are safe and efficacious reliably with small to moderate sample sizes.
在寻找有效的 COVID-19 治疗方法时,最初的重点是重新利用已有的治疗方法。为了最大程度地提高找到成功治疗方法的机会,需要开发专门针对这种疾病的新治疗方法。在本文中,我们描述并评估了 AGILE 平台的统计设计,AGILE 平台是一个适应性随机无缝的 I/II 期试验平台,旨在快速确定安全剂量范围,并研究潜在有效的治疗方法。该定制的贝叶斯设计 (i) 在剂量发现过程中利用随机化,(ii) 在平台内共享对照臂信息,以及 (iii) 使用具有正式测试结构和错误控制的时事件终点来评估潜在的疗效。既考虑单药治疗,也考虑联合治疗。我们发现,该设计可以在小到中等样本量下可靠地识别出安全有效的潜在治疗方法。
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