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.
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。