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针对住院患者的 COVID-19 急性呼吸窘迫综合征的临床试验失败:常见的疏忽和简化临床有效疗法的开发。

Failed clinical trials on COVID-19 acute respiratory distress syndrome in hospitalized patients: common oversights and streamlining the development of clinically effective therapeutics.

机构信息

Dipartimento di Anestesia e Rianimazione, Policlinico San Martino, IRCCS per l'Oncologia e le Neuroscienze, Genoa, Italy.

Laboratory of Pulmonary Investigation, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.

出版信息

Expert Opin Investig Drugs. 2022 Oct;31(10):995-1015. doi: 10.1080/13543784.2022.2120801. Epub 2022 Sep 13.

Abstract

INTRODUCTION

The coronavirus disease 2019 (COVID-19) pandemic has put a strain on global healthcare systems. Despite admirable efforts to develop rapidly new pharmacotherapies, supportive treatments remain the standard of care. Multiple clinical trials have failed due to design issues, biased patient enrollment, small sample sizes, inadequate control groups, and lack of long-term outcomes monitoring.

AREAS COVERED

This narrative review depicts the current situation around failed and success COVID-19 clinical trials and recommendations in hospitalized patients with COVID-19, oversights and streamlining of clinically effective therapeutics. PubMed, EBSCO, Cochrane Library, and WHO and NIH guidelines were searched for relevant literature up to 5 August 2022.

EXPERT OPINION

The WHO, NIH, and IDSA have issued recommendations to better clarify which drugs should be used during the different phases of the disease. Given the biases and high heterogeneity of published studies, interpretation of the current literature is difficult. Future clinical trials should be designed to standardize clinical approaches, with appropriate organization, patient selection, addition of control groups, and careful identification of disease phase to reduce heterogeneity and bias and should rely on the integration of scientific societies to promote a consensus on interpretation of the data and recommendations for optimal COVID-19 therapies.

摘要

简介

2019 年冠状病毒病(COVID-19)大流行给全球医疗保健系统带来了压力。尽管在迅速开发新的药物治疗方法方面做出了令人钦佩的努力,但支持性治疗仍是护理标准。由于设计问题、患者入组存在偏差、样本量小、对照组不足以及缺乏长期结果监测,多项临床试验均以失败告终。

涵盖领域

本叙述性综述描绘了目前 COVID-19 临床试验失败和成功的情况,并对 COVID-19 住院患者的推荐治疗方案、临床有效治疗方法的疏忽和简化进行了介绍。检索了截至 2022 年 8 月 5 日PubMed、EBSCO、Cochrane 图书馆以及世界卫生组织(WHO)和美国国立卫生研究院(NIH)指南中的相关文献。

专家意见

WHO、NIH 和 IDSA 已发布建议,以更好地阐明在疾病的不同阶段应使用哪些药物。鉴于已发表研究存在偏倚和高度异质性,目前文献的解读存在困难。未来的临床试验应设计为规范临床方法,适当组织、患者选择、增加对照组,并仔细确定疾病阶段,以减少异质性和偏倚,并应依靠科学协会的整合,促进对数据的共识解读以及对 COVID-19 最佳治疗方法的建议。

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