论文标题
由Covid-19-19大流行的影响：营救的自适应设计？
Clinical trials impacted by the COVID-19 pandemic: Adaptive designs to the rescue?
论文作者
论文摘要
最近，发现了新的病原体严重急性呼吸道综合症冠状病毒2（SARS-COV-2），2019年冠状病毒病（Covid-19）宣布世界卫生组织的大流行。大流行对在非旋转19条件下正在进行的临床试验的后果有许多后果。由目前正在进行的各种疾病领域正在进行的临床试验的动机，我们说明了大流行面临的挑战，并草拟了包括自适应设计在内的可能的解决方案。在（i）盲目适应可以帮助的情况下提供了指导； （ii）如果需要，如何实现I型错误率控制； （iii）如何处理潜在的治疗效果异质性； （iv）如何利用早期读数； （v）如何利用贝叶斯技术。在更详细的方法中，开发了调整受大流行的试验的大小方法，包括考虑早期停止试验的考虑，使用组序列设计或样本量调整。所考虑的所有方法均在免费可用的R Shiny应用程序中实现。此外，讨论了监管和操作问题，包括数据监视委员会的作用。
Very recently the new pathogen severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified and the coronavirus disease 2019 (COVID-19) declared a pandemic by the World Health Organization. The pandemic has a number of consequences for the ongoing clinical trials in non-COVID-19 conditions. Motivated by four currently ongoing clinical trials in a variety of disease areas we illustrate the challenges faced by the pandemic and sketch out possible solutions including adaptive designs. Guidance is provided on (i) where blinded adaptations can help; (ii) how to achieve type I error rate control, if required; (iii) how to deal with potential treatment effect heterogeneity; (iv) how to utilize early readouts; and (v) how to utilize Bayesian techniques. In more detail approaches to resizing a trial affected by the pandemic are developed including considerations to stop a trial early, the use of group-sequential designs or sample size adjustment. All methods considered are implemented in a freely available R shiny app. Furthermore, regulatory and operational issues including the role of data monitoring committees are discussed.
