Systematic review of the registered clinical trials for coronavirus disease 2019 (COVID-19)
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Abstract
Background
Since the outbreak of coronavirus disease 2019 (COVID-19), many researchers in China have performed related clinical research. However, systematic reviews of the registered clinical trials are still lacking. Therefore, we conducted a systematic review of clinical trials for COVID-19 to summarize their characteristics.
Methods
This study is based on the PRISMA recommendations in the Cochrane handbook. The Chinese Clinical Registration Center and the ClinicalTrials.gov databases were searched to identify registered clinical trials related to COVID-19. The retrieval inception date was February 9, 2020. Two researchers independently selected the literature based on the inclusion and exclusion criteria, extracted data, and evaluated the risk of bias.
Results
A total of 75 registered clinical trials (63 interventional studies and 12 observational studies) for COVID-19 were identified. The majority of clinical trials were sponsored by Chinese hospitals. Only 11 trials have begun to recruit patients, and none of the registered clinical trials have been completed; 34 trials were early clinical exploratory trials or in the pre-experiment stage, 13 trials were phase III, and four trials were phase IV. The intervention methods included traditional Chinese medicine in 26 trials, Western medicine in 30 trials, and integrated traditional Chinese medicine and Western medicine in 19 trials. The subjects were primarily non-critical adult patients (≥ 18 years old). The median sample size of the trials was 100 (IQR: 60–200), and the median length of the trial periods was 179 d (IQR: 94–366 d). The main outcomes were clinical observation and examinations. Overall, the methodological quality of both the interventional trials and observational studies was low.
Conclusions
Intensive clinical trials on the treatment of COVID-19 using traditional Chinese medicine and Western medicine are ongoing or will be performed in China. However, based on the uncertain methodological quality, small sample size, and long trial duration, we will not be able to obtain reliable, high-quality clinical evidence regarding the treatment of COVID-19 in the near future. Improving the quality of study design, prioritizing promising drugs, and using different designs and statistical methods are worth advocating and recommending for clinical trials of COVID-19 in the future.
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SciScore for 10.1101/2020.03.01.20029611: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization The randomized controlled trial was based on Cochrane risk of bias items, which includes: randomization sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data, selective reporting, and other bias [19]. Blinding Data extraction: The contents that were extracted mainly included registration number, project name, research leader, research type, study design, sponsor, implementation unit, start time, completion period, research site, research institute, stage, research object, inclusion standard, exclusion standard, sample size, setting, location, … SciScore for 10.1101/2020.03.01.20029611: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization The randomized controlled trial was based on Cochrane risk of bias items, which includes: randomization sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data, selective reporting, and other bias [19]. Blinding Data extraction: The contents that were extracted mainly included registration number, project name, research leader, research type, study design, sponsor, implementation unit, start time, completion period, research site, research institute, stage, research object, inclusion standard, exclusion standard, sample size, setting, location, recruitment period, intervention group measures, control group measures, random methods, blind methods, distribution concealment and measurement indicators. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
Software and Algorithms Sentences Resources Inclusion criteria: This review was performed according to the Cochrane Handbook for Systematic Reviews of Interventions [17] and presented based on Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines [18]. Cochrane Handbooksuggested: NoneNon-parametric data are represented by median and 95% CI and the statistical analysis used MedCalc statistical software (version 15.2.2, MedCalc Software bvba, Ostend, Belgium; http://www.medcalc.org; 2015). MedCalcsuggested: (MedCalc, RRID:SCR_015044)The bias plot was performed by Review Manager (RevMan) [Computer program] (version 5.2, Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2012). RevMansuggested: (RevMan, RRID:SCR_003581)Cochrane Collaborationsuggested: NoneResults from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:From these registered clinical studies, we found a serious limitation: most of the registered clinical research did not consider the “timeliness”, and still followed the conservative traditional study design paradigm. The median execute time (days) of the studies was 179 d (IQR: 94 – 366 d), which is highly unfavorable in the current critical situation. We believe that, in the current situation, the “timeliness” factor should be given importance in the design of clinical trials, so that the research does not lose its social significance. Therefore, in this critical situation, it is better to refer to the “sequential design” for clinical trials; “sequential design” not only requires small sample size, but also significantly shortens the research during, therefore, it is very conducive to the screening and discovery of drugs with significant efficacy [36, 37]. In addition, a very difficult problem is the treatment of severe and critical patients with COVID-19. For these patients, we suggested that: based on the “compassionate use drug” principle, with safe and obvious antiviral potential drugs, to conduct a staged small batch and single-arm clinical trials is feasible. We believed that “compassionate use drug” can not only meet the special needs of patients but also perform clinical effectiveness observation, research and analysis, so as to enhance the efficiency of research and benefit the patients [38-42]. Also, given a large number of clinical cases have accumulated informat...
Results from TrialIdentifier: We found the following clinical trial numbers in your paper:
Identifier Status Title NCT04262921 Recruiting French COVID Cohort NCT04259892 Recruiting Viral Excretion in Contact Subjects at High/Moderate Risk of… NCT04252664 Suspended A Trial of Remdesivir in Adults With Mild and Moderate COVID… NCT04257656 Terminated A Trial of Remdesivir in Adults With Severe COVID-19 NCT04252274 Recruiting Efficacy and Safety of Darunavir and Cobicistat for Treatmen… NCT04261517 Completed Efficacy and Safety of Hydroxychloroquine for Treatment of C… Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
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