PDF(Pubmed)
Abstract：
BACKGROUND: In early 2020, the coronavirus disease 2019 (COVID-19) pandemic spread worldwide, overwhelming hospitals with severely ill patients and posing the urgent need for clinical evidence to guide patient care. First treatment options available were repurposed drugs to fight inflammation, coagulopathy, and viral replication. A vast number of clinical studies were launched globally to test their efficacy and safety. Our analysis describes the development of global evidence on repurposed drugs, in particular corticosteroids, anticoagulants, and (hydroxy)chloroquine in hospitalized COVID-19 patients based on different study types. We track the incorporation of clinical data in international and national treatment guidelines and identify factors that characterize studies and analyses with the greatest impact on treatment recommendations.
METHODS: A literature search in MEDLINE was conducted to assess the clinical evidence on treatment with corticosteroids, anticoagulants, and (hydroxy)chloroquine in hospitalized COVID-19 patients during the first year of the pandemic. Adoption of the evidence from this clinical data in treatment guidelines of the World Health Organization (WHO), Germany, and United States (US) was evaluated over time.
RESULTS: We identified 106 studies on corticosteroids, 141 studies on anticoagulants, and 115 studies on (hydroxy)chloroquine. Most studies were retrospective cohort studies; some were randomized clinical trials (RCTs), and a few were platform trials. These studies were compared to studies directly and indirectly referred to in WHO (7 versions), German (5 versions), and US (21 versions) guidelines. We found that initially large, well-adjusted, mainly retrospective cohort studies and ultimately large platform trials or coordinated meta-analyses of RCTs provided best available clinical evidence supporting treatment recommendations.
CONCLUSIONS: Particularly early in the pandemic, evidence for the efficacy and safety of repurposed drugs was of low quality, since time and scientific rigor seemed to be competing factors. Pandemic preparedness, coordinated efforts, and combined analyses were crucial to generating timely and robust clinical evidence that informed national and international treatment guidelines on corticosteroids, anticoagulants, and (hydroxy)chloroquine. Multi-arm platform trials with master protocols and coordinated meta-analyses proved particularly successful, with researchers joining forces to answer the most pressing questions as quickly as possible.
METHODS: A literature search in MEDLINE was conducted to assess the clinical evidence on treatment with corticosteroids, anticoagulants, and (hydroxy)chloroquine in hospitalized COVID-19 patients during the first year of the pandemic. Adoption of the evidence from this clinical data in treatment guidelines of the World Health Organization (WHO), Germany, and United States (US) was evaluated over time.
RESULTS: We identified 106 studies on corticosteroids, 141 studies on anticoagulants, and 115 studies on (hydroxy)chloroquine. Most studies were retrospective cohort studies; some were randomized clinical trials (RCTs), and a few were platform trials. These studies were compared to studies directly and indirectly referred to in WHO (7 versions), German (5 versions), and US (21 versions) guidelines. We found that initially large, well-adjusted, mainly retrospective cohort studies and ultimately large platform trials or coordinated meta-analyses of RCTs provided best available clinical evidence supporting treatment recommendations.
CONCLUSIONS: Particularly early in the pandemic, evidence for the efficacy and safety of repurposed drugs was of low quality, since time and scientific rigor seemed to be competing factors. Pandemic preparedness, coordinated efforts, and combined analyses were crucial to generating timely and robust clinical evidence that informed national and international treatment guidelines on corticosteroids, anticoagulants, and (hydroxy)chloroquine. Multi-arm platform trials with master protocols and coordinated meta-analyses proved particularly successful, with researchers joining forces to answer the most pressing questions as quickly as possible.
摘要：
背景：2020年初，2019年冠状病毒病（COVID-19）大流行在全球范围内蔓延，医院的重症患者不堪重负，迫切需要临床证据来指导患者护理。第一个可用的治疗选择是重新利用药物来对抗炎症，凝血病,和病毒复制。在全球范围内开展了大量临床研究，以测试其有效性和安全性。我们的分析描述了关于再利用药物的全球证据的发展，特别是皮质类固醇，抗凝剂,根据不同的研究类型，住院COVID-19患者的（羟基）氯喹。我们跟踪国际和国家治疗指南中临床数据的纳入情况，并确定对治疗建议影响最大的研究和分析的特征因素。
方法：在MEDLINE中进行了文献检索，以评估皮质类固醇治疗的临床证据，抗凝剂,大流行第一年住院COVID-19患者的（羟基）氯喹。在世界卫生组织（WHO）的治疗指南中采用这些临床数据中的证据，德国,随着时间的推移，对美国（US）进行了评估。
结果：我们确定了106项关于皮质类固醇的研究，141项抗凝剂研究，和115项关于（羟基）氯喹的研究。大多数研究是回顾性队列研究；一些是随机临床试验(RCTs)，还有一些是平台试验。这些研究与世卫组织直接和间接提及的研究(7个版本)进行了比较，德语（5个版本）和美国（21个版本）指南。我们发现最初很大，调整得很好，主要是回顾性队列研究和最终的大型平台试验或随机对照试验的协调荟萃分析提供了支持治疗建议的最佳可用临床证据.
结论：特别是在大流行的早期，再利用药物的有效性和安全性的证据质量低，因为时间和科学的严谨性似乎是竞争因素。大流行的准备，协调努力,和组合分析对于产生及时而有力的临床证据以了解国家和国际皮质类固醇治疗指南至关重要，抗凝剂,和（羟基）氯喹。具有主协议和协调荟萃分析的多臂平台试验被证明特别成功，研究人员联手尽快回答最紧迫的问题。
方法：在MEDLINE中进行了文献检索，以评估皮质类固醇治疗的临床证据，抗凝剂,大流行第一年住院COVID-19患者的（羟基）氯喹。在世界卫生组织（WHO）的治疗指南中采用这些临床数据中的证据，德国,随着时间的推移，对美国（US）进行了评估。
结果：我们确定了106项关于皮质类固醇的研究，141项抗凝剂研究，和115项关于（羟基）氯喹的研究。大多数研究是回顾性队列研究；一些是随机临床试验(RCTs)，还有一些是平台试验。这些研究与世卫组织直接和间接提及的研究(7个版本)进行了比较，德语（5个版本）和美国（21个版本）指南。我们发现最初很大，调整得很好，主要是回顾性队列研究和最终的大型平台试验或随机对照试验的协调荟萃分析提供了支持治疗建议的最佳可用临床证据.
结论：特别是在大流行的早期，再利用药物的有效性和安全性的证据质量低，因为时间和科学的严谨性似乎是竞争因素。大流行的准备，协调努力,和组合分析对于产生及时而有力的临床证据以了解国家和国际皮质类固醇治疗指南至关重要，抗凝剂,和（羟基）氯喹。具有主协议和协调荟萃分析的多臂平台试验被证明特别成功，研究人员联手尽快回答最紧迫的问题。
