新型冠状病毒肺炎临床试验评价指标及相关问题

Outcomes and related issues of clinical trials for COVID-19

关键词:  新型冠状病毒肺炎  临床试验  评价指标  核心指标集

Key words:  coronavirus disease 2019  clinical trial  outcome  core outcome set

摘要:

[目的] 对已注册的新型冠状病毒肺炎（COVID-19）临床研究方案的评价指标进行分析，为提高相关临床研究疗效评价指标的合理性及核心指标集研制提供参考。[方法] 以新型冠状病毒肺炎、Novel coronavirus pneumonia、2019-nCoV等为关键词，分别检索中国临床试验注册中心（www.chictr.org.cn）与美国临床试验注册平台（clinicaltrials.gov），获取各种干预措施防治COVID-19的临床研究方案，提取研究基本信息与所有疗效评价指标数据，对评价指标情况进行描述性分析。[结果] 共纳入研究方案78个，使用259个评价指标，共计596次，其中主要评价指标104个，使用184次，次要评价指标205个，使用412次。单个研究使用评价指标数量为1~15个，平均为8个。通过规范化处理，最终将259个指标统一为132个，涵盖临床症状、理化检查、病原学检测、重大事件、生活质量、疾病转归、中医指标、安全性指标8个指标域。[结论] 目前COVID-19临床试验方案采用的评价指标存在表述不规范、测量时点不清、相似研究评价指标差异大、指标与研究目的不匹配等问题，需要建立COVID-19临床试验核心指标集（COS-COVID），为相关方案优化和新研究开展提供依据。

Abstract:

[Objective] To analyze the outcomes in registered clinical trial protocols for coronavirus disease 2019 (COVID-19),in order to provide information for improving the rationality of outcomes of relative research as well as for developing core outcome set.[Methods] The website of the Clinical Trial Registry www.chictr.org.cn and clinicaltrials.gov were searched with the key words of novel coronavirus pneumonia,2019-nCOV,COVID-19. Research protocols of all kinds of interventions for COVID-19 were screened,and data were extracted in regard to basic information as well as outcomes. Descriptive analysis was conducted.[Results] A total of 78 research protocols on COVID-19 were included. 259 outcomes were reported with a frequency of 596,including 104 primary outcomes with 184 times and 205 secondary outcomes with 412 times. The number of outcomes adopted by a single research ranged from 1 to 15,with an average of 8. After standardization,132 outcomes were finally concluded from the 259,covering 8 domains of clinical symptoms,laboratory examination,etiology test,important clinical events,quality of life,prognosis,traditional Chinese medicine indicators and safety index.[Conclusion] There were several problems in the outcomes adopted in clinical study protocols of COVID-19,such as irregular expression,unclear timing of measurement,significant outcomes difference among similar researches and mismatch of target and research purpose as well. It is necessary to establish a core outcome set for clinical trials of COVID-19 (COS-COVID),so as to provide references for the optimization of relevant protocols and the development of new researches.