Noor Nurulamin M, Pett Sarah L, Esmail Hanif, Crook Angela M, Vale Claire L, Sydes Matthew R, Parmar Mahesh K B
Medical Research Council Clinical Trials Unit, University College London, London, WC1V6LJ, UK.
F1000Res. 2020 Sep 9;9:1109. doi: 10.12688/f1000research.26253.2. eCollection 2020.
Global health pandemics, such as coronavirus disease 2019 (COVID-19), require efficient and well-conducted trials to determine effective interventions, such as treatments and vaccinations. Early work focused on rapid sequencing of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), subsequent and work, along with greater understanding of the different clinical phases of the infection, have helped identify a catalogue of potential therapeutic agents requiring assessment. In a pandemic, there is a need to quickly identify efficacious treatments, and reject those that are non-beneficial or even harmful, using randomised clinical trials. Whilst each potential treatment could be investigated across multiple, separate, competing two-arm trials, this is a very inefficient process. Despite the very large numbers of interventional trials for COVID-19, the vast majority have not used efficient trial designs. Well conducted, adaptive platform trials utilising a multi-arm multi-stage (MAMS) approach provide a solution to overcome limitations of traditional designs. The multi-arm element allows multiple different treatments to be investigated simultaneously against a shared, standard-of-care control arm. The multi-stage element uses interim analyses to assess accumulating data from the trial and ensure that only treatments showing promise continue to recruitment during the next stage of the trial. The ability to test many treatments at once and drop insufficiently active interventions significantly speeds up the rate at which answers can be achieved. This article provides an overview of the benefits of MAMS designs and successes of trials, which have used this approach to COVID-19. We also discuss international collaboration between trial teams, including prospective agreement to synthesise trial results, and identify the most effective interventions. We believe that international collaboration will help provide faster answers for patients, clinicians, and health care systems around the world, including for each further wave of COVID-19, and enable preparedness for future global health pandemics.
全球卫生大流行，如2019冠状病毒病（COVID-19），需要高效且开展良好的试验来确定有效的干预措施，如治疗方法和疫苗接种。早期工作聚焦于严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的快速测序，随后的工作以及对感染不同临床阶段的深入了解，有助于确定一系列需要评估的潜在治疗药物。在大流行期间，需要通过随机临床试验快速确定有效的治疗方法，并排除那些无益甚至有害的方法。虽然每种潜在治疗方法都可以在多个单独的、相互竞争的双臂试验中进行研究，但这是一个非常低效的过程。尽管针对COVID-19进行了大量的干预试验，但绝大多数试验都没有采用高效的试验设计。采用多臂多阶段（MAMS）方法进行的精心设计的适应性平台试验为克服传统设计的局限性提供了解决方案。多臂元素允许同时针对一个共同的标准治疗对照臂研究多种不同的治疗方法。多阶段元素使用中期分析来评估试验中积累的数据，并确保只有显示出前景的治疗方法在下一阶段的试验中继续招募患者。一次测试多种治疗方法并放弃活性不足的干预措施的能力显著加快了获得答案的速度。本文概述了MAMS设计的益处以及采用这种方法进行COVID-19试验的成功案例。我们还讨论了试验团队之间的国际合作，包括合成试验结果的前瞻性协议，并确定最有效的干预措施。我们相信，国际合作将有助于为世界各地的患者、临床医生和医疗保健系统更快地提供答案，包括应对COVID-19的每一波疫情，并为未来的全球卫生大流行做好准备。
