ObjectiveTo investigate the domestic and abroad hypertension-related clinical trial registration and to analyze the registration of hypertension-related clinical researches in China.MethodsUsing hypertension as the keyword, we searched ClinicalTrials.gov and Chinese Clinical Trial Registry (ChiCTR) from January 2008 to December 2018. We analyzed the collected data on the distribution of registered clinical researches, annual trends, sample sizes, trial progress, research types, study designs, blind methods, clinical stages, the number of participating institutions, the leading institutions, etc.ResultsThe total number of registered hypertension-related clinical trails was 4 991 all over the world, and 551 items were conducted in China. Most of the sample sizes of Chinese hypertension-related clinical trials were 100 to 999. The main types of trials were interventional studies (393 items, 71.32%), followed by observational studies (126 items, 22.87%). Randomized parallel control studies (300 items, 76.34%) were the key component of interventional studies, while cohort studies (61 items, 48.41%) were the chief component of observational studies. The main stages of clinical trials were stage Ⅲ (80 items) and stage Ⅳ (122 items). There were 369 domestic single-center clinical trials (66.97%), 89 domestic multi-center clinical trials (16.15%), and 93 international multi-center clinical trials (16.88%). Among the 93 international multi-center trials of hypertension, only 25 were led by China.ConclusionsThe number of Chinese hypertension-related clinical trial registrations increased year by year and then decreased slightly, but the amount of registrations is limited. The quantity and scale of multicenter clinical studies were not as good as America. China should strengthen the awareness of clinical research registration, strengthen the publicity and supervision of the registration of clinical researches by the department of science and management, improve the number of clinical trial registrations, make Chinese clinical researches more transparent, and strive to lead more international multi-center clinical trials.
ObjectivesTo analyze the metrological characteristics of hypertension-related clinical trials registered on Chinese Clinical Trial Registry (ChiCTR), and discuss the characteristics and developmental trends of hypertension clinical trials registration in China.MethodsChiCTR were searched to collect hypertension-related clinical trials from inception to March 25th, 2018. The characteristics of registered trials were analyzed.ResultsA total of 135 registered trials were included, in which the trials from Beijing, Guangdong, Jiangsu, Chongqing and Shanghai accounted for 55.5%. 115 trials were pre-registered. The top three funding sources were from finance (32, 23.7%), self-financing (25, 18.5%) and hospital (20, 14.8%), respectively. Of all 79 randomized controlled trials, 55 were blank/missing in the entry of blinding method.ConclusionsThe number of hypertension-related clinical trials in ChiCTR tends to increase, however there are large regional disparities and incomplete, non-standardiazed information in the registration of clinical trials. The relevant departments should increase the publicity on the registration of clinical trials, raise the awareness of registration, and promote the development and registration of high quality clinical trials.
Based on evidence-based medicine (EBM) and from the viewpoint of providing scientific evidence for clinical application, we found that Traditional Chinese Medicine (TCM) was short of adequate evidence to support its therapeutic effects due to lack of high quality clinical research. Data management plays a very important role in clinical research. Lack of adequate data management may lead to low quality clinical research. Thus, it is of great importance to establish a set of standards for data management so as to improve the quality of clinical research. Based on the real practice in Myocardial Infarction Secondary Prevention Study in TCM (MISPS-TCM), this article introduces methods on data audit in clinical trials of TCM.
Objective To detect the false-positive results of cumulative meta-analyses of Cochrane Urology Group with the trial sequential analysis (TSA). Methods The systematic reviews of Urology Group of The Cochrane Library were searched to collect meta-analyses with positive results. Two researchers independently screened literature and extracted data of included meta-analyses. Then, TSA was performed using TSA software version 0.9 beta. Results A total of 11 meta-analyses were included. The results of TSA showed that, 8 of 11 (72.7%) meta-analyses were potentially false-positive results for failing to surpass the trial sequential monitoring boundary and to reach the required information size. Conclusion TSA can help researchers to identify the false-positive results of meta-analyses.
ObjectivesTo analyze the research status and hot spots of hypertension-related clinical trials in special Chinese population registered on the Chinese Clinical Trial Registry (ChiCTR), so as to provide a basis for the development of hypertension-related research in special population in China.MethodsThe ChiCTR was searched online (up to August 31st, 2019, no limitation in the status of trial registration), all clinical trials on hypertension in special population were collected, and the general characteristics, researched diseases, research types, intervention measures and main outcomes of the trials were analyzed.ResultsA total of 64 hypertension-related clinical trials in special population registered in the ChiCTR were included, including 41 (64.1%) trials registered in last 3 years. The registration status of 46 (71.9%) trials was pre-registration. The registered authors were mainly from colleges and universities or medical institutions (n = 61, 95.3%), of which 60.9% were registered in Beijing, Shanghai, Guangdong, Zhejiang, Jiangsu and Hebei. The researched diseases mainly included elderly hypertension and hypertensive stroke, accounting for 50% of the total. Additionally, 37 (57.8%) clinical trials were intervention studies, of which 21 (56.7%) were drug-based intervention studies. Blood pressure, blood glucose, cardiovascular and cerebrovascular events, blood lipid, cranial MRI and Glasgow Coma Scale were the commonly used outcomes, accounting for 58.5% of the total outcomes. Most blood pressure measurements did not indicate the measurement method (n = 22, 64.7%).ConclusionsThe quantity of hypertension-related clinical trials in special population registered on the ChiCTR is increasing, however, there exists regional imbalance. The drug intervention-related clinical trials of elderly hypertension have become a research hot spot. However, blood pressure measurement method is not indicated in most trials, and some researchers do not register in time. Therefore, it is suggested that researchers should further strengthen the awareness of carrying out high-quality clinical trials.
Trial Sequential Analysis (TSA), one kind of cumulative meta-analysis, is a method which introduces sequential analysis into traditional meta-analysis to avoid random errors (false positive or false negative outcomes) that occurred during repeated updates when traditional meta-analysis is performing. It is also applied to calculate required information size (RIS) of a firm conclusion. This study aims to summarize the proposal, fundamental theory, application software, and current limitation of TSA, and to clarify the advantages of TSA on the basis of detailed examples, in order to attract more attention of researchers and promote the methodological development of meta-analysis in China.
In 2007, the findings from clinical trials on stroke treatment have been both encouraging and disappointing. In order to interpret the challenges and opportunity in evidence-based stroke practice, we reviewed several major clinical trials in stroke that were published last year. It revealed that we should strengthen the evidence base for acute stroke care by conducting more high-quality randomized controlled trials and by increasing the energy, resources and manpower available for these trials.
ObjectiveTo compare drug clinical trials between China, the United States, Europe and Japan in terms of study type, design, completion and results publication.MethodsWe randomly selected 190 clinical trials that were registered in ClinicalTrials.gov from 2009 to 2014, and followed up to December 31st, 2019. Comparisons were made for the type of sponsor, phase, design, and completion status by the sponsor’s country.ResultsAmong all included clinical trials, trials from the United States, Europe, Japan and China accounted for 50.5%, 34.2%, 9.0% and 6.3%, respectively. Among these trials, 71.1% had been completed and 69.5% disclosed results had been published publicly prior to the end of follow-up, and differences between countries were statistically significant (P<0.05). Two-thirds of the trials in China were phase Ⅲ/Ⅳ trials; in contrast, most of the clinical trials in the United States and Europe were phase Ⅰ/Ⅱ trials. The proportion of using double-blind, randomized controlled trial design was the highest in the United States (46.9%) and the lowest in China (8.3%). Chinese sponsors were mostly hospitals/universities (58.3%), while in other countries drug trials were mostly sponsored by the industry and in Japan the proportion was as high as 94.0%.ConclusionsThe number of drug trials registered in ClinicalTrials.gov from China is small and these trials are less likely to be completed and have results published/disclosed. Pharmaceutical companies in China should pay more attention to the public registration of their clinical trials, particularly those in early phases, and improve trial design and management.
The sample size of a meta-analysis should not be less than a single randomized controlled trial. Trial sequential analysis (TSA) can provide required information size and monitoring boundary to justify the conclusion of meta-analysis. However, the TSA software is only suitable for binary and continuous data, and it cannot analyze the time-to-event data. This paper aimed to introduce how to analyze the time-to-event data using TSA approach.
ObjectiveTo systematically evaluate the outcomes of drug-eluting balloon (DEB) in treating coronary artery in-stent restenosis (ISR) by using meta-analysis and trial sequential analysis (TSA). MethodsWe searched PubMed, EMbase, The Cochrane Library（Issue 4, 2016）, CNKI, CBM, VIP and WanFang Data to collect randomized controlled trials (RCTs) regarding the treatment of ISR by DEB from inception to April 2016. After two reviewers independently screened citations, extracted data and assessed the bias risk of included studies, we carried out meta-analysis and TSA analysis by using RevMan 5.3 version and TSA v0.9 respectively. ResultsA total of 10 RCTs involving 1909 patients were included. Seven-hundred and forty-seven patients were included with regard to the comparison between DEB and POBA, 1162 patients were recruited to compare DEB and drug-eluting stents (DES). The results of meta-analysis revealed that DEB was associated with decreased mortality (OR=0.36, 95%CI 0.14 to 0.93, P=0.04), compared with that of plain old balloon angioplasty (POBA). And TSA showed that cumulative Z-curve strode the conventional threshold value but not the TSA threshold value which suggested a false positive result of meta-analysis. In comparison with that of POBA, DEB had a lower incidence of target lesion revascularization (TLR) (OR=0.16, 95%CI 0.07 to 0.38, P＜0.01). And the result of TSA displayed that the cumulative Z-curve strode both the conventional and TSA threshold value which validated the result of meta-analysis. Besides, the results of meta-analysis showed that there were no significant differences in mortality (OR=0.84, 95%CI 0.41 to 1.72, P=0.63) and TLR (OR=1.55, 95%CI 0.76 to 3.16, P=0.22) between DEB and DES. However, the result of TSA revealed that the cumulative Z-curve did not strode both the conventional and TSA threshold value, and the included sample size less was than required information size which suggested that the reliability of the meta-analysis needed more studies to confirm. While the subgroup analysis of EES revealed that DEB had a higher incidence of TLR than that of DEB (OR=3.37, 95%CI 1.59 to 7.15, P＜0.01). And the result of TSA displayed that the cumulative Z-curve strode both the conventional and TSA threshold value which validated the result of meta-analysis. ConclusionCurrent evidence shows, EES is superior to DEB in decreasing the incidence of TLR in patients with ISR, while DEB is superior to POBA. However, the comparison of DEB and other strategies on reducing of mortality in patients with ISR still needed more studies to prove.