School of Medicine, Imperial College London, London, UK.
Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
Trials. 2021 Jan 15;22(1):59. doi: 10.1186/s13063-021-05024-y.
Several drugs are being repurposed for the treatment of the coronavirus disease 2019 (COVID-19) pandemic based on in vitro or early clinical findings. As these drugs are being used in varied regimens and dosages, it is important to enable synthesis of existing safety data from clinical trials. However, availability of safety information is limited by a lack of timely reporting of overall clinical trial results on public registries or through academic publication. We aimed to analyse the evidence gap in this data by conducting a rapid review of results posting on ClinicalTrials.gov and in academic publications to quantify the number of trials missing results for drugs potentially being repurposed for COVID-19.
ClinicalTrials.gov was searched for 19 drugs that have been identified as potential treatments for COVID-19. Relevant clinical trials for any prior indication were listed by identifier (NCT number) and checked for results and for timely result reporting (within 395 days of the primary completion date). Additionally, PubMed and Google Scholar were searched to identify publications of results not listed on the registry. A second, blinded search of 10% of trials was conducted to assess reviewer concordance.
Of 3754 completed trials, 1516 (40.4%) did not post results on ClinicalTrials.gov or in the academic literature. Tabular results were available on ClinicalTrials.gov for 1172 (31.2%) completed trials. A further 1066 (28.4%) had published results in the academic literature, but did not report results on ClinicalTrials.gov . Key drugs missing clinical trial results include hydroxychloroquine (37.0% completed trials unreported), favipiravir (77.8%) and lopinavir (40.5%).
There is an important evidence gap for the safety of drugs being repurposed for COVID-19. This uncertainty could cause unnecessary additional morbidity and mortality during the pandemic. We recommend caution in experimental drug use for non-severe disease and urge clinical trial sponsors to report missing results retrospectively.
基于体外或早期临床发现，有几种药物正在被重新用于治疗 2019 年冠状病毒病（COVID-19）大流行。由于这些药物正在以不同的方案和剂量使用，因此有必要综合临床试验中的现有安全性数据。然而，由于缺乏及时在公共注册处或通过学术出版物报告总体临床试验结果，因此安全性信息的可用性受到限制。我们旨在通过对 ClinicalTrials.gov 上和学术出版物中发布的结果进行快速审查，分析该数据中的证据差距，以量化正在重新用于 COVID-19 的潜在药物的临床试验中缺少结果的数量。
在 ClinicalTrials.gov 上搜索了 19 种被认为是 COVID-19 潜在治疗方法的药物。列出了任何先前适应症的相关临床试验，并按标识符（NCT 编号）进行了检查，以检查结果和及时报告结果（在主要完成日期后的 395 天内）。此外，还在 PubMed 和 Google Scholar 上搜索了未在注册处列出的结果出版物。对 10%的试验进行了第二次、盲法搜索，以评估审核员的一致性。
在 3754 项已完成的试验中，有 1516 项（40.4%）未在 ClinicalTrials.gov 或学术文献中公布结果。ClinicalTrials.gov 上提供了 1172 项（31.2%）已完成试验的表格结果。另外，1066 项（28.4%）在学术文献中发表了结果，但未在 ClinicalTrials.gov 上报告结果。关键药物缺少临床试验结果，包括羟氯喹（未报告完成试验的 37.0%）、法匹拉韦（77.8%）和洛匹那韦（40.5%）。
正在重新用于治疗 COVID-19 的药物的安全性存在重要的证据差距。这种不确定性可能会在大流行期间导致不必要的额外发病率和死亡率。我们建议在非严重疾病中谨慎使用实验性药物，并敦促临床试验赞助商追溯报告缺失的结果。
