Mainoli Beatrice, Machado Tiago, Duarte Gonçalo S, Prada Luísa, Gonçalves Nilza, Ferreira Joaquim J, Costa João
Laboratory of Clinical Pharmacology and Therapeutics, Faculdade de Medicina, Universidade de Lisboa, Avenida Prof. Egas Moniz, 1649-028, Lisbon, Portugal.
Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.
BMC Med Res Methodol. 2021 Feb 26;21(1):42. doi: 10.1186/s12874-021-01233-w.
The COVID-19 pandemic continues to rage on, and clinical research has been promoted worldwide. We aimed to assess the clinical and methodological characteristics of treatment clinical trials that have been set forth as an early response to the COVID-19 pandemic.
First, we reviewed all registered clinical trials on COVID-19. The World Health Organization International Trials Registry Platform and national trial registries were searched for COVID-19 trials through April 19th, 2020. For each record, independent researchers extracted interventions, participants, and methodological characteristics. Second, on September 14th, 2020 we evaluated the recruitment status and availability of the results of COVID-19 treatment trials previously identified.
In April 2020, a total of 580 trials evaluating COVID-19 treatment were registered. Reporting quality was poor (core participant information was missing in 24.1 to 92.7%). Between 54.0 and 93.8% of the trials did not plan to include older people or those with a higher baseline risk. Most studies were randomised (67.9%), single-centre (58.3%), non-industry-funded (81.1%), to be conducted in China (47.6%), with a median duration of 184 days and a median sample size of 100 participants. Core endpoints (mortality, clinical status, and hospitalization length) were planned to be assessed in 5.2 to 13.1% of the trials. Five months later, 66 trials (11.4%) were reported as "Completed", and only 46 (7.9%) had public results available. One hundred forty-four of 580 trials (24.8%) either had the status "Not yet recruiting" or "Suspended", and 18 (3.1%) trials were prematurely stopped ("Terminated" or "Withdrawn") The number of completed trials and trials with results are much lower than anticipated, considering the planned follow-up.
Our results raise concerns about the success of the initial global research effort on COVID-19 treatment. The clinical and methodological characteristics of early COVID-19 treatment trials limit their capability to produce clear answers to critical questions in the shortest possible time.
新冠疫情仍在肆虐，全球范围内的临床研究得到了推动。我们旨在评估作为对新冠疫情的早期应对而开展的治疗性临床试验的临床和方法学特征。
首先，我们检索了所有注册的关于新冠的临床试验。通过检索世界卫生组织国际临床试验注册平台和各国的试验注册机构，查找截至2020年4月19日的新冠试验。对于每条记录，由独立研究人员提取干预措施、参与者和方法学特征。其次，在2020年9月14日，我们评估了之前确定的新冠治疗试验的招募状态和结果的可获取情况。
2020年4月，共有580项评估新冠治疗的试验注册。报告质量较差（24.1%至92.7%的试验缺少核心参与者信息）。54.0%至93.8%的试验未计划纳入老年人或基线风险较高的人群。大多数研究为随机试验（67.9%）、单中心试验（58.3%）、非行业资助试验（81.1%），在中国开展（47.6%），中位持续时间为184天，中位样本量为100名参与者。5.2%至13.1%的试验计划评估核心终点（死亡率、临床状况和住院时长）。五个月后，66项试验（11.4%）报告为 “已完成”，只有46项（7.9%）有公开结果。580项试验中有144项（24.8%）的状态为 “尚未招募” 或 “暂停”，18项（3.1%）试验提前终止（“终止” 或 “撤回”）。考虑到计划的随访情况，已完成试验和有结果的试验数量远低于预期。
我们的结果引发了对全球最初新冠治疗研究工作能否成功的担忧。早期新冠治疗试验的临床和方法学特征限制了它们在尽可能短的时间内对关键问题给出明确答案的能力。
