Objective To compare the balance of simple randomization, stratified blocked randomization and minimization. Methods Monte Carlo technique was employed to simulate the treatment allocation of simple randomization, stratified blocked randomization and minimization respectively, then the balance of treatment allocation in each group and the balance for every prognostic factor were compared. Results The simulation demonstrated that minimization provides the best performance to ensure balance in the number of patients between groups and prognostic factors. Balance in prognostic factors achieved with stratified blocked randomization was similar to that achieved with simple randomization. Conclusion Minimization offers the best balance in the number of patients and prognostic factors between groups.
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.
ObjectivesTo explore the characteristics of Chinese methodological studies on patient compliance in clinical trials so as to provide reference for clinical trial of patient compliance in future.MethodsCNKI, VIP, CBM and WanFang Data databases were electronically searched to collect methodological studies on patient compliance in clinical trials published in Chinese language from January 2000 to December 2018. Two reviewers independently screened literature, extracted data and then, qualitative analysis of document characteristics was then performed.ResultsA total of 84 articles were included, in which 68 were studies on Western medicine and 16 were studies on traditional Chinese medicine (TCM). The results showed that: the quantity of studies on patient compliance increased along with time. However, those in TCM field did not increase. All included studies summarized their strategies to improve patient compliance, however key information for quality evaluation were missing.ConclusionsThere is still a lack of research on how to improve patients’ compliance in clinical trials to ensure the reliability of the results. Existing studies have not systematically and comprehensively explored the influencing factors of patients’ compliance. Clinical trials researchers in China have not focused sufficiently to patients’ compliance and lack the proper methodology to frame studies.
Statistical analysis of clinical trials has traditionally relied on frequentist methods, but Bayesian statistics has attracted considerable attention from regulators and researchers in recent years due to its unique advantages, and its use in clinical trials is increasing. Despite the obvious advantages of Bayesian statistics, the complexity of its design, implementation and analysis poses a number of challenges to its practical application, which may lead to an increased risk of unregulated use. This study aims to comprehensively sort out the application scenarios, common methods, special considerations and key elements of reporting of Bayesian statistical methods in clinical trials, with the aim of providing researchers with references for conducting Bayesian clinical trials, and promoting the scientific and rational application of Bayesian statistical methods in clinical trials.
ObjectiveSham acupuncture control is a commonly employed method to assess the specific effects of acupuncture in clinical trials. However, due to the absence of specific reporting standards, the reporting quality of sham acupuncture in these trials is low. In order to standardize the reporting of sham acupuncture and improve the reporting quality of sham acupuncture, our project team has developed SHam Acupuncture REporting guidelines and a checklist in clinical trials (SHARE). MethodsThe development process included four parts: we conducted literature research to form initial items of sham acupuncture reporting; two rounds of Delphi surveys were carried out to evaluate the reporting necessity of these initial items; two expert consensus meetings were held to further discuss and agree upon the Delphi results and approve the SHARE checklist; a pilot testing was conducted to assess the feasibility and practicality of the list and make necessary revisions to generate the final SHARE checklist. ResultsThe SHARE checklist consisted of 10 categories with 19 items. The requirements for reporting sham acupuncture primarily focused on sham acupuncture detailed information as well as relevant background factors. ConclusionThe SHARE serves as specialized reporting guidelines for sham acupuncture that offers clear guidance on comprehensive and concise reporting of sham acupuncture.
To solve the problems such as the incomplete and non-standard reporting outcomes in clinical trials, international methodologists have simultaneously launched guidelines for reporting outcomes in trial protocols and reports in 2022 on the basis of the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) 2013 and the Consolidated Standards of Reporting Trials (CONSORT) statement 2010. The SPIRIT-Outcomes 2022 extension and CONSORT-Outcomes 2022 extension recommend outcome-specific reporting items should be included prospectively in trial protocols and reports, regardless of trial design or population. This paper introduces and interprets the two guidelines for reporting outcomes, and discusses their significance and enlightenment to the research in the field of traditional Chinese medicine. For example, using the outcome reporting guidelines will help clinical researchers comprehensively consider issues related to outcomes when reporting protocols or results, which may improve the quality of research design and reporting. For core outcome set, the five core elements of outcomes may help researchers extracting and analyzing outcomes, which will standardize research; the explanation of medical terminology in the outcome reporting guidelines will contribute to the improvement of methodology in the field of traditional Chinese medicine.
This article briefly introduces the management of clinical trials of investigational new drugs, hospital-made preparations, post-marketing drugs and other types of clinical trials. The WHO International Clinical Trial Register Platform (WHO ICTRP), Chinese Clinical Trial Register (ChiCTR) and Chinese Clinical Trial Registration and Publishing Collaboration (ChiCTRPC) are also described. People conducting trials are advised to apply the basic philosophy of evidence-based medicine in their implementation, which is considered to be one of the guarantees of the validity of clinical trials.
ObjectiveTo systematically reviewed the progress of Zelen’s design and its modifications in clinical research and clarified its methodological elements, advantages, and limitations. MethodsA systematic literature search was conducted for Zelen’s design from databases. The data were extracted. ResultsOne hundred and twenty-four trials were included. The dominant disease in this design was mental disorders, followed by osteoarthrosis diseases, cancer, cardiovascular diseases, and others. Regarding types of consent, more than half of the trials used a double-consent (71, 57.26%), and 42 used a single-consent. Eleven trials used a modified Zelen’s design nested within an observational study. This design used a two-stage informed consent. Stage 1, patients were invited to participate in a cohort study; Stage 2, patients randomized in the experimental group were informed of the allocation result and asked whether they would like to follow the treatment. Five trials used the McNulty-Zelen design, which could be applied in cluster randomized controlled trials and overcome the potential bias of the Hawthorne effect. Intention-to-treat analysis was the main population used in Zelen’s design. ConclusionZelen’s design has a broad application in the foreground in clinical trials. It could also be used to adapt to research needs by combining with various observational studies. Zelen’s design offers unique advantages in reducing recruitment difficulty, improving patient compliance, and minimizing bias. Although the randomization of patients without their prior consent raises potential ethical concerns, these can be addressed through methods such as nested observational studies or supplementary informed consent. In real-world applications of Zelen’s design, it is necessary to design a reasonable informed consent strategy and data statistical analysis method according to the research context. Attention must be paid to the impact of sample size, group shifting and selection of dataset on the results, to improve the interpretability and accuracy of the results.
In order to standardize the reporting of sham acupuncture and improve the quality of reporting of sham acupuncture, Beijing University of Chinese Medicine has developed a specific reporting guideline for sham acupuncture: SHam Acupuncture REporting (SHARE) which contains ten categories with nineteen items. This paper introduces the development methods and main contents of the guidelines to provide a reference for researchers to correctly understand and reasonably apply the guidelines.