Adaptive platform trials using multi-arm, multi-stage protocols: getting fast answers in pandemic settings.
Adaptive platform trials using multi-arm, multi-stage protocols: getting fast answers in pandemic settings.
复制标题
DOI：
10.12688/f1000research.26253.2
复制
发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Parmar MKB
中科院分区：
文献类型：
--
作者：
Noor NM;Pett SL;Esmail H;Crook AM;Vale CL;Sydes MR;Parmar MKB
全球健康流行病，例如 2019 年冠状病毒病 (COVID-19)，需要进行有效且良好的试验来确定有效的干预措施，例如治疗和疫苗接种。早期工作重点是严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 的快速测序，随后的体外和计算机模拟工作，以及对感染不同临床阶段的更深入了解，有助于确定需要评估的潜在治疗药物目录。 在大流行期间，需要利用随机临床试验快速确定有效的治疗方法，并拒绝那些无益甚至有害的治疗方法。虽然每种潜在的治疗方法都可以通过多个、独立的、竞争性的双臂试验进行研究，但这是一个非常低效的过程。尽管针对 COVID-19 的干预试验数量非常多，但绝大多数都没有使用有效的试验设计。 利用多臂多级 (MAMS) 方法进行的良好的自适应平台试验提供了克服传统设计局限性的解决方案。多臂元件允许针对共享的标准护理控制臂同时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，并确保只有显示出希望的治疗方法才能在试验的下一阶段继续招募。 同时测试多种治疗方法并放弃不够积极的干预措施的能力显着加快了获得答案的速度。本文概述了 MAMS 设计的优势以及使用这种方法治疗 COVID-19 的试验的成功。我们还讨论试验团队之间的国际合作，包括综合试验结果的预期协议，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提供更快的答案，包括应对每一波新冠肺炎 (COVID-19) 疫情，并为未来的全球健康流行病做好准备。
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 in-vitro and in-silico 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.