ABSTRACT

The COVID-19 pandemic has led to an unprecedented response in terms of clinical research activity. An important part of this research has been focused on randomized controlled clinical trials to evaluate potential therapies for COVID-19. The results from this research need to be obtained as rapidly as possible. This presents a number of challenges associated with considerable uncertainty over the natural history of the disease and the number and characteristics of patients affected, and the emergence of new potential therapies. These challenges make adaptive designs for clinical trials a particularly attractive option. Such designs allow a trial to be modified on the basis of interim analysis data or stopped as soon as sufficiently strong evidence has been observed to answer the research question, without compromising the trial’s scientific validity or integrity. In this article, we describe some of the adaptive design approaches that are available and discuss particular issues and challenges associated with their use in the pandemic setting. Our discussion is illustrated by details of four ongoing COVID-19 trials that have used adaptive designs.

摘要

COVID-19 大流行引发了临床研究活动前所未有的反应。这项研究的一个重要部分集中在随机对照临床试验上，以评估 COVID-19 的潜在疗法。这项研究的结果需要尽快获得。这带来了许多挑战，这些挑战与疾病的自然史、受影响患者的数量和特征以及新的潜在疗法的出现存在相当大的不确定性相关。这些挑战使得临床试验的适应性设计成为特别有吸引力的选择。这种设计允许根据中期分析数据修改试验，或者在观察到足够有力的证据来回答研究问题后立即停止试验，而不会损害试验的科学有效性或完整性。在本文中，我们描述了一些可用的自适应设计方法，并讨论了与其在大流行环境中使用相关的特定问题和挑战。我们的讨论通过四项正在进行的使用适应性设计的 COVID-19 试验的细节进行了说明。