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BackgroundDevelopment of a core outcome set (COS) for clinical trials for COVID-19 is urgent because of the pandemic wreaking havoc worldwide and the heterogeneity of outcomes in clinical trials. MethodsA preliminary list of outcomes were developed after a systematic review of protocols of clinical trials for COVID-19. Then, two rounds of the Delphi survey were conducted. Stakeholders were traditional Chinese medicine (TCM) experts, Western medicine (WM) experts, nurses and the public. Patients with confirmed COVID-19 were also invited to participate in a questionnaire written in understandable language. Frontline clinicians, as well as nurse, methodologist, evidence based-medicine researcher, and staff from the Chinese Clinical Trials Registry participated by video conference to vote. ResultsNinety-seven eligible study protocols were identified from 160 clinical trials. Seventy-six outcomes were identified from TCM clinical trials and 126 outcomes were identified from WM clinical trials. Finally, 145 outcomes were included in the first round of the Delphi survey. Then, a COS for clinical trials of TCM and WM was developed. The COS include clinical outcomes (recovery/improvement/progression/death), etiology (SARS-CoV-2 nucleic-acid tests, viral load), inflammatory factor (C-reactive protein), vital signs (temperature, respiration), blood and lymphatic-system parameters (lymphocytes, virus antibody), respiratory outcomes (Pulmonary imaging, blood oxygen saturation, PaO2/FiO2 ratio, arterial blood gas analysis, mechanical ventilation, oxygen intake, pneumonia severity index), clinical efficacy (prevalence of preventing patients with mild-to-moderate disease progressing to severe disease), symptoms (clinical symptom score). Outcomes were recommended according to different types of disease. Outcome measurement instrument/definition were also recommended. ConclusionA COS for COVID-19 may improve consistency of outcome reporting in clinical trials.
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ObjectivesTo examine heterogeneity of outcomes in protocols of clinical trials of Coronavirus Disease 2019 (COVID-19) and to identify outcomes for prioritization in developing a core outcome set (COS) in this field. DesignThis study is a review. Data sourcesDatabases of ICMJE-accepted clinical trial registry platform were searched on February 14, 2020. Eligibility CriteriaRandomized controlled trials (RCTs) and non-RCTs of COVID-19 were considered. Conditions of patients include common type, severe type or critical type. Interventions include traditional Chinese medicine (TCM) and Western medicine. We excluded trials that for discharged patients, psychological intervention and complications of COVID-19. Data extraction and synthesisThe general information and outcomes, outcome measurement instruments and measurement times were extracted. The results were analysed by descriptive analysis. Results19 registry platforms were searched. A total of 97 protocols were included from 160 protocols. For protocols of TCM clinical trials, 76 outcomes from 16 outcome domains were reported, and almost half (34/76, 44.74%) of outcomes were reported only once; the most frequently reported outcome was time of SARS-CoV-2 RNA turns to negative. 27 (27/76, 35.53%) outcomes were provided one or more outcome measurement instruments. 10 outcomes were provided one or more measurement time frame. For protocols of western medicine clinical trials, 126 outcomes from 17 outcome domains were reported; almost half (62/126, 49.21%) of outcomes were reported only once; the most frequently reported outcome was proportion of patients with negative SARS-CoV-2. 27 outcomes were provided one or more outcome measurement instruments. 40 (40/126, 31.75%) outcomes were provided one or more measurement time frame. ConclusionOutcome reporting in protocols of clinical trials of COVID-19 is inconsistent. Thus, developing a core outcome set is necessary. Strengths and limitations of this study1. This review is the first to describe variation in outcomes, outcome measurement instruments and outcome measurement time reporting in clinical trials for Coronavirus Disease 2019 (COVID-19). 2. All the database of ICMJE-accepted clinical trial registry platform were searched, and randomized controlled trials and observational studies were considered. 4. The aim of this review was to provide a list of outcomes for clinical trials of COVID-19, both interventions of Traditional Chinese Medicine and western medicine were considered. 5. When the searching was conducted, no clinical trials were registered by countries out of China, so all of included protocols were from China.
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Objective: To evaluate the effect of Danhong injection on endothelial function after percutaneous coronaryintervention (PCI) in coronary heart disease (CHD) . It provides the basis for further research and design. Methods: Sevendatabases of CNKI, VIP, Wanfang Data, CBM, PubMed, The Cochrane Library, Embase and others were searched bycomputer cents with coronary heart disease treated by Danhong injection combined with conventional drugs. Twoevaluators independently sifted the literature, extracted the data and evaluated the bias risk in the study. The data werestatistically analyzed by RevMan 5.3 software. Results: A total of 12 RCTs, involving 1325 patients were included. Metaanalysis showed that the treatment group (Danhong injection combined with routine therapy) was superior to the controlgroup in improving the endothelium index after operation. The index NO[MD=9.57, 95％CI (8.22, 10.93), P ＜ 0.00001], vWF [MD=-31.60, 95％CI (-41.47, -21.72), P ＜ 0.00001], ET-1 [MD=-2.19, 95％CI (-3.11, -1.27), P ＜ 0.00001], ET[SMD=-0.92, 95％CI (-1.49, -0.35), P ＜ 0.01], FMD[MD = 1.81, 95％CI (1.26, 2.37), P ＜ 0.00001]. There was statisticalsignificance between each index. Conclusion: Danhong injection combined with conventional therapy can improveendothelial function after PCI. However, due to the low quality of included studies and the problem of heterogeneity, these conclusions need to be further verified by high quality multicenter, large sample and double blind randomizedcontrolled trials.
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Objective: To conduct a comprehensive and systematic review of the efficacy and safety of Wenxin Keli (WXKL) in the treatment of atrial fibrillation (AF) . Methods: Seven databases (PubMed, The Cochrane Library, Web ofScience, CNKI, Wanfang Database, VIP and SinoMed) were searched to identify relevant randomized controlled trials (RCTs) from inceptions to 1 October, 2018. Two review authors independently assessed the methodological quality andanalyzed data by Cochrane handbook and the Rev Man 5.3 software. Begg.s test was conducted to assess publication biasvia Stata 14 software. Results: Twenty-four RCTs with 2246 patients were included in this review. Compared with blankcontrol, placebo or western medicine alone, WXKL alone or combined with western medicine could effectively reducerapid ventricular rate (MD=-7.14, 95％CI:-8.42——5.87), the frequency and duration of AF. It could also shorten thesinus rhythm conversion time (MD=-3.04, 95％CI:-3.47——2.61), increase the sinus rhythm conversion rate (RR=1.19, 95％ CI: 1.09～1.29) and decrease recurrence rate of AF (RR=0.28, 95％ CI: 0.13-0.59) . Besides, WXKL alone orcombined with western medicine was beneficial for improving the left ventricular ejection fraction (LVEF) (MD=3.44, 95％ CI: 0.87-6.01), left ventricular end diastolic diameter (LVEDD) (MD=-2.47, 95％ CI:-2.86——2.08), left atrialdiameter (LAd) (MD=-0.91, 95％CI:-1.58——0.25) and P wave dispersion (Pd) (MD=-4.04, 95％CI:-4.15——3.93) .WXKL combined with low-dose amiodarone was superior to conventional-dose amiodarone alone in improving themaximum P wave (Pmax) (MD=-8.25, 95％ CI:-10.33——6.17), and WXKL combined with conventional-doseamiodarone is more effective (MD=-13.10, 95％CI:-13.65——12.55) . Compared with the control group, the treatmentgroup had fewer adverse reactions, and the Begg.s test did not find any publication bias. Conclusion: WXKL alone orcombined with western medicine exhibited better therapeutic effects in the treatment of AF, but these results still needhigh-quality evidence to verify.
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Objective: To summarize the clinical effects of Shuxuening Injection on diseases and evaluate the quality of evidence to provide reference for the clinical application of Shuxuening Injection. Methods: Journal articles and conference papers were retrieved from the databases CNKI, Wanfang, VIP, CBM, EMbase, Pubmed and Cochrane with thematic word"Shuxuening"in Chinese and English, then all forms of clinical studies were screened and the disease types and frequency were analyzed, the dominant disease types of Shuxuening Injection were identified. Futhermore, RCT was extracted, and the literature quality was graded using the cochrane manual recommendation method, and its effectiveness and safety were evaluated. Results: All clinical research results show that Shuxuening Injection to treat disease with as many as 74 kinds of varieties, mainly circulation system disease and neural system disease, followed by endocrine disease, respiratory disease, scattered remaining research in ten other system diseases. These researches appeared with the highest frequency of the three diseases were cerebral infarction and its aftermath, angina pectoris and coronary heart disease, diabetes mellitus and its complication. A total of 337 RCT articles were included, all of which were of poor quality. In general, the efficiency of Shuxuening Injection treatment group was significantly higher than that of the control group, with a total efficiency of 84.48％. There were 21.96％ references to adverse reactions, but all of them were minor adverse reactions, such as pruritus, which generally got better by itself or after treatment. Conclusion:Shuxuening Injection has a wide range of clinical application and remarkable effect, especially for the ischemic diseases of cardiovascular and cerebrovascular diseases with good efficacy, less adverse reactions and safety. However, the quality of evidence is generally poor, which needs further study.
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Objective: To refine and evaluate the clinical evidence, and provide proof and reference for Xinxuening's clinical program establishment from the perspective of evidence-based medicine through screening the clinical studies of cardiovascular disease by Xinxuening.s treatment. Method: The included and excluded criteria was established before the setting of search terms, eligible databases (PubMed, Web of Science, Ovid, Embase, Cochrane, CNKI, CBM, Wanfang and Vip) were searched and the quality evaluation and evidence classification was conducted for eligible documents. The software RevMan was used to evaluate the clinical evidence of Xinxuening in the treatment of cardiovascular disease (primary hypertension, coronary heart disease, heart failure and hyperlipidemia) and to explore the specific mechanism.Results: A total of 16 suitable studies were included, of which 15 were RCTs and 1 was observation study. 9 of the 16 studies were the C level evidence and 7 were the D level. The included studies were all low quality. The outcome indicators of clinical treatment for cardiovascular disease were: the efficacy of hypertension therapy, the level of systolic and diastolic blood pressure after therapy, the efficacy of angina pectoris and hyperlipidemia treatment, and the total cholesterol and triglyceride levels after treatment. The results showed that Xinxuening could significantly reduce the level of blood pressure for patients with hypertension, improve the symptoms of angina pectoris in patients with coronary heart disease, and reduce the levels of blood lipids (triglycerides and total cholesterol) . The results have statistical differences (P ＜ 0.05) . However, it the specific mechanism of Xinxuening in the treatment of cardiovascular disease was not found.Conclusion: Xinxuening has higher clinical effect on the treatment of some cardiovascular diseases compared with some western drugs and other proprietary Chinese medicine. However, it still needs further exploration of the specific clinical mechanism and to conduct high-quality clinical research.
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The insufficient reporting of adverse reactions of Chinese proprietary medicines is common. In addition, there is a lack of safety information in the specifications of Chinese proprietary medicines, which led to less evidence for clinical safety of Chinese proprietary medicines in clinical practice. It is urgent to carry out post-marketing clinical safety re-evaluation of Chinese proprietary medicine. Developing a clinical safety evaluation data set for Chinese proprietary medicine may reduce the insufficient reporting of safety information and the inconsistency of data reporting in similar studies, as well as include more studies in systematic reviews, so that they can provide higher-level evidence for clinical safety of Chinese proprietary medicine. This paper proposes a method for developing core data set of clinical safety evaluation of Chinese proprietary medicine: firstly, the application scope of core data set for clinical safety evaluation was determined according to the characteristics of diseases, population, research objectives, administration methods, evaluation methods, etc. Systematic reviews and semi-structured interviews should be conducted to develop the list of original items for clinical safety evaluation. Based on the list, Delphi surveys can be developed in different stakeholders. Then the final core data set can be developed via consensus meetings.
