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.
Response-adaptive randomization (RAR) dynamically adjusts the probability of assigning patients to different groups, optimizing treatment efficacy and participant welfare. It is particularly suitable for clinical studies involving multiple interventions or dose-finding and seamless phase II/III trials. This paper systematically introduces the concept, principles, and types of RAR, as well as its application in clinical trials (including traditional Chinese medicine research). It also provides R implementation code, offering researchers practical tools aimed at promoting the adoption of RAR in clinical practice.
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.
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.
The calculation of sample size is a critical component in the design phase of clinical trials incorporating health economic evaluations. A reasonable sample size is essential to ensure the scientific validity and accuracy of trial results. This paper summarizes the sample size calculation methods in the frequentist framework based on two health economic evaluation indicators: incremental cost-effectiveness ratio (ICER) and net benefit and examines these methods in terms of their applicable conditions, advantages, and limitations. The ICER method derives the sample size calculation formula by computing the ratio of incremental cost to incremental effect, while the net benefit method determines the economic viability of interventions by calculating incremental net benefit, subsequently leading to the formulation of the sample size calculation. Furthermore, this paper briefly discusses other sample size calculation methods, such as the classical Bayesian approach and the value of information analysis, providing a reference for calculating sample size in clinical trials with integrated health economic evaluations.
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.
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.
Objective To introduce the use of Central Randomization System in clinical trials. Methods We discussed the application of Central Randomization System in clinical trials from object management, drug management and user management, and made a brief description of minimization method. Results Central Randomization Systems can guarantee the nnplementation of the scheme of randomization, and can be used in clinical trials with minimization. Conclusion Central Randomization Systems are feasible in clinical trials especially in traditional Chinese medicine and open clinical trials.
Objective To analyze the current research status, characteristics and development trends of traditional medicine-related clinical trials registration, and to provide ideas and directions for further development of traditional medicine clinical trials. Methods The International Traditional Medicine Clinical Trial Registry (ITMCTR) database was searched by computer from inception to June 30, 2024, with unlimited trial registration status, to collect all the clinical trials on traditional medicine, and analyze the basic information of the trials, the diseases studied and the interventions. Results A total of 4 349 clinical trials related to traditional medicine were included, with the number of registrations peaking in the second half of 2020, and showing a steady upward trend after 2023. The trial sponsors of the study covered 9 countries and a total of 34 provinces/autonomous regions/municipalities in China, led by Beijing, Shanghai, Guangdong, Sichuan, and Zhejiang provinces, accounting for 69.72% of the total. The financial support for the studies was dominated by local government funds in various provinces and cities, accounting for 29.66%. Disease types studied were mainly circulatory system diseases, musculoskeletal system or connective tissue diseases, and tumor diseases, accounting for 29.91% of the total. A total of 3 751 (86.3%) clinical trials were interventional studies, of which randomized parallel control was predominant, and 213 large-sample studies with a sample size of more than 1 000 cases were included. A total of 20 types of interventions were involved, of which 1 114 (29.86%) clinical trials utilized oral prescription of herbal medicine interventions. Conclusion Clinical trial enrollment in traditional medicine has increased overall, but with significant geographic unevenness. Oral herbal soup/granule intervention studies are the mainstream hotspots. It is recommended to strengthen international cooperation, enrich the types of interventions, refine the trial design, and raise the awareness of researchers about the registration of high-quality traditional medicine clinical trials.
Controversy exists regarding the ethics of using placebo control groups in clinical trials when effective treatments exist. The debate was fueled by the announcement of the 5th revision of the Declaration of Helsinki (2000). This study reviews the history and scientific background surrounding the controversy and investigates the prevailing attitudes of Hong Kong researchers regarding this issue. The controversy has centered on a few issues. The first involves the methodological superiority of placebo-controlled trials in discerning treatment effects. Secondly, it is unclear if the treatment effects encompass absolute treatment effects (including placebo effects) or are confined to treatment-specific effects (excluding placebo effects). Thirdly, there are worries that subjects in the placebo group could be exposed to higher risk for developing serious adverse events. Fourthly, it is debated whether the standard of best available treatment should be a local one, or an international one. Preliminary research findings suggest that the opinions of the Hong Kong researchers seemed to be divided on the use of placebo control groups in clinical trials when effective treatment exists. Further researcher on the topic is therefore warranted, training and consensus meeting may be necessary to minimize the confusion related to this issue.