Ezintsha, Faculty of Health Sciences, University of the Witwatersrand, Building C, 32 Princess of Wales Terrace, Johannesburg, 2001, South Africa.
Magenta Communications Ltd, Abingdon, Oxfordshire, UK.
Trials. 2023 Oct 4;24(1):635. doi: 10.1186/s13063-023-07577-6.
Repeated COVID-19 waves and corresponding mitigation measures have impacted health systems globally with exceptional challenges. In response to the pandemic, researchers, regulators, and funders rapidly pivoted to COVID-19 research activities. However, many clinical drug studies were not completed, due to often complex and rapidly evolving research conditions.
We outline our experience of planning and managing a randomised, adaptive, open-label, phase 2 clinical trial to evaluate the safety and efficacy of four repurposed drug regimens versus standard-of-care (SOC) in outpatients with 'mild to moderate' COVID-19 in Johannesburg, South Africa, in the context of a partnership with multiple stakeholders. The study was conducted between 3 September 2020 and 23 August 2021 during changing COVID-19 restrictions, significant morbidity and mortality waves, and allied supply line, economic, and political instability.
Our clinical study design was pragmatic, including low-risk patients who were treated open label. There was built-in flexibility, including provision for some sample size adjustment and a range of secondary efficacy outcomes. Barriers to recruitment included the timing of waves, staff shortages due to illness, late presentation of patients, COVID-19 misinformation, and political unrest. Mitigations were the use of community health workers, deployment of mobile clinical units, and simplification of screening. Trial management required a radical reorganisation of logistics and processes to accommodate COVID-19 restrictions. These included the delivery of staff training and monitoring remotely, electronic consent, patient training and support to collect samples and report data at home, and the introduction of tele-medicine. These measures were successful for data collection, safe, and well received by patients.
Completing a COVID-19 trial in outpatients during the height of the pandemic required multiple innovations in nearly every aspect of clinical trial management, a high commitment level from study staff and patients, and support from study sponsors. Our experience has generated a more robust clinical research infrastructure, building in efficiencies to clinical trial management beyond the pandemic.
反复出现的 COVID-19 浪潮和相应的缓解措施给全球卫生系统带来了特殊的挑战。为应对大流行，研究人员、监管机构和资助者迅速转向 COVID-19 研究活动。然而，由于研究条件通常复杂且迅速演变，许多临床药物研究并未完成。
我们概述了在与多个利益相关者合作的背景下，在南非约翰内斯堡，我们规划和管理一项随机、适应性、开放标签、2 期临床试验的经验，该试验旨在评估四种重新定位药物方案与标准治疗（SOC）在患有“轻度至中度”COVID-19 的门诊患者中的安全性和有效性。该研究于 2020 年 9 月 3 日至 2021 年 8 月 23 日进行，期间 COVID-19 限制措施不断变化，出现了严重的发病率和死亡率浪潮，以及相关的供应线、经济和政治不稳定。
我们的临床研究设计是务实的，包括接受开放标签治疗的低风险患者。设计具有内置的灵活性，包括提供一些样本量调整和一系列次要疗效终点。招募的障碍包括浪潮的时间、因疾病导致的员工短缺、患者就诊较晚、COVID-19 错误信息和政治动荡。缓解措施包括使用社区卫生工作者、部署移动临床单位以及简化筛选。试验管理需要对后勤和流程进行彻底重组，以适应 COVID-19 限制。这包括远程提供员工培训和监测、电子同意、患者培训以及在家收集样本和报告数据的支持，以及引入远程医疗。这些措施在数据收集方面取得了成功，是安全的，并且深受患者欢迎。
在大流行高峰期在门诊患者中完成 COVID-19 试验需要在临床试验管理的几乎每个方面都进行多项创新，研究人员和患者的高度承诺，以及研究赞助商的支持。我们的经验产生了一个更强大的临床研究基础设施，为超越大流行的临床试验管理建立了效率。
