Dillman Alison, Zoratti Michael J, Park Jay J H, Hsu Grace, Dron Louis, Smith Gerald, Harari Ofir, Rayner Craig R, Zannat Noor-E, Gupta Alind, Mackay Eric, Arora Paul, Lee Zelyn, Mills Edward J
School of Public Health, Faculty of Medicine, Imperial College London, London, England.
Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Canada.
Infect Drug Resist. 2020 Dec 22;13:4577-4587. doi: 10.2147/IDR.S288399. eCollection 2020.
A multitude of randomized controlled trials (RCTs) have emerged in response to the novel coronavirus disease (COVID-19) pandemic. Understanding the distribution of trials among various settings is important to guide future research priorities and efforts. The purpose of this review was to describe the emerging evidence base of COVID-19 RCTs by stages of disease progression, from pre-exposure to hospitalization.
We collated trial data across international registries: ClinicalTrials.gov; International Standard Randomised Controlled Trial Number Registry; Chinese Clinical Trial Registry; Clinical Research Information Service; EU Clinical Trials Register; Iranian Registry of Clinical Trials; Japan Primary Registries Network; German Clinical Trials Register (up to 7 October 2020). Active COVID-19 RCTs in international registries were eligible for inclusion. We extracted trial status, intervention(s), control, sample size, and clinical context to generate descriptive frequencies, network diagram illustrations, and statistical analyses including odds ratios and the Mann-Whitney -test.
Our search identified 11503 clinical trials registered for COVID-19 and identified 2388 RCTs. After excluding 45 suspended RCTs and 480 trials with unclear or unreported disease stages, 1863 active RCTs were included and categorized into four broad disease stages: pre-exposure (n=107); post-exposure (n=208); outpatient treatment (n=266); hospitalization, including the intensive care unit (n=1376). Across all disease stages, most trials had two arms (n=1500/1863, 80.52%), most often included (hydroxy)chloroquine (n=271/1863, 14.55%) and were US-based (n=408/1863, 21.90%). US-based trials had lower odds of including (hydroxy)chloroquine than trials in other countries (OR: 0.63, 95% CI: 0.45-0.90) and similar odds of having two arms compared to other geographic regions (OR: 1.05, 95% CI: 0.80-1.38).
There is a marked difference in the number of trials across settings, with limited studies on non-hospitalized persons. Focus on pre- and post-exposure, and outpatients, is worthwhile as a means of reducing infections and lessening the health, social, and economic burden of COVID-19.
针对新型冠状病毒肺炎（COVID-19）大流行，出现了大量随机对照试验（RCT）。了解不同环境下试验的分布情况对于指导未来的研究重点和工作非常重要。本综述的目的是按疾病进展阶段（从暴露前到住院）描述COVID-19随机对照试验新出现的证据基础。
我们整理了国际注册库中的试验数据：美国国立医学图书馆临床试验数据库（ClinicalTrials.gov）；国际标准随机对照试验编号注册库；中国临床试验注册中心；韩国临床研究信息服务系统；欧盟临床试验注册库；伊朗临床试验注册库；日本初级注册网络；德国临床试验注册库（截至2020年10月7日）。国际注册库中正在进行的COVID-19随机对照试验符合纳入标准。我们提取了试验状态、干预措施、对照、样本量和临床背景，以生成描述性频率、网络图说明以及包括优势比和曼-惠特尼检验在内的统计分析。
我们的检索确定了11503项注册的COVID-19临床试验，并识别出2388项随机对照试验。在排除45项暂停的随机对照试验和480项疾病阶段不明确或未报告的试验后，纳入了1863项正在进行的随机对照试验，并将其分为四个广泛的疾病阶段：暴露前（n = 107）；暴露后（n = 208）；门诊治疗（n = 266）；住院，包括重症监护病房（n = 1376）。在所有疾病阶段，大多数试验有两个组（n = 1500/1863，80.52%），最常包括（羟）氯喹（n = 271/1863，14.55%），且以美国为基地（n = 408/1863，21.90%）。与其他国家的试验相比，以美国为基地的试验纳入（羟）氯喹的可能性较低（优势比：0.63，95%置信区间：0.45 - 0.90），与其他地理区域相比，有两个组的可能性相似（优势比：1.05，95%置信区间：0.80 - 1.38）。
不同环境下试验数量存在显著差异，针对未住院人群的研究有限。关注暴露前、暴露后和门诊患者是有价值的，可作为减少感染以及减轻COVID-19的健康、社会和经济负担的一种方式。
