International Traditional Medicine Clinical Trial Registry: A meaningful initiative and its future development

Abstract

Traditional medicine (TM) has become an indispensable resource worldwide and it makes great contributions to global health. Searching for “traditional medicine” and related items by setting filters for clinical trials and randomized controlled trials, returns almost 17,000 items in the PubMed database till 2024 April. Moreover, more than 22,000 TM clinical studies have been found in the WHO International Clinical Trial Registry Platform (ICTRP) when conducting a systematic search. Despite the growing interest and number of clinical studies in TM, issues concerning the quality of the evidence have emerged.^{1, 2} Empirical studies have found that studies with positive results are more likely to be published, and outcomes with significant effect estimates are very likely to be fully reported.³ Similar to conventional medicine, selective outcome reporting is widespread in TM, accounting for almost one-third of relative clinical studies when comparing between the registered outcomes and the reported ones in the publications.² Conclusions based on biased evidence due to selective reporting can be misleading. An alternative approach to solve this issue is the registration of the protocol before the conduct of the clinical study.

To register the key administrative and scientific information of clinical studies on an open-access platform before enrolling participants has been imperative from ethical, scientific, and even legal perspectives.^{4, 5} Since 2005, the initiative by the WHO to develop ICTRP marks an important milestone in which region- or country-based registration platforms have been developed following unified standards, and ensuring that all registered trials receive a unique identification number for global searching.⁶ Many efforts have been made to promote the transparency of the design and reporting the results of clinical studies; however, it seems that there is still a long way to go.⁷ In a recent analysis of the registration of TM clinical studies, Zhang et al. have analyzed a total of 3339 Traditional Chinese Medicine studies registered in WHO ICTRP and found that 39% of the studies were retrospectively registered, and only 12.8% of studies shared resultant publications.⁸ Compared to the 20 items required by WHO, none of the registered studies had a 100% reporting rate, and 11 items had a reporting rate lower than 65%. The fact that the registration quality of clinical studies in TM is not satisfactory is thought-provoking.

First, a unified portal for registering clinical studies in TM is necessary. Before 2023, people conducting TM clinical studies mainly registered the protocols by selecting one of the registries of WHO ICTRP or other publicly accessible registries such as ClinicalTrials.gov available in their regions or countries. Therefore, registered TM clinical studies are scattered in different registries. Moreover, in addition to the registration standards set by WHO ICTRP, each registry can make its requirements. The inconsistency between some registries limits the possibility of integration and comparison of clinical studies in the same field such as TM, and it takes longer for researchers to search for certain kinds of clinical studies across different registries. Second, based on the minimum data set required by the WHO, extended registration items may be needed to promote the reporting transparency of TM clinical studies, as TM takes a different approach to health and healing compared to modern medicine, and the clinical data have unique informational content in terms of diagnosis patterns, disease signs, and symptoms.^{9, 10} Moreover, the assessment of TM interventions raises specific methodological issues regarding the complexity of the intervention, for example the interactivity between doctors and patients for TM techniques such as acupuncture and tuina.¹¹

In such circumstances, the project of developing a unified registry focusing on TM clinical studies was initiated in 2019 by the China Center for Evidence-based Traditional Chinese Medicine (CCEBTCM). After more than 3-year preparation, the International Traditional Medicine Clinical Trial Registry (ITMCTR, http://itmctr.ccebtcm.org.cn/; Email: [email protected]) was officially recognized as a primary registry of WHO ICTRP in February 2023. The building ITMCTR is a great initiative to promote the transparency of research in TM and to help avoid selective reporting of the results by registering the protocols on a publicly accessible portal before the recruitment of the first participant. In addition to the existing national and global registries under WHO, ITMCTR is a unique platform focusing on a single theme (i.e., TM) across countries and regions, aimed to develop a complete database of TM clinical studies using uniform registration standards, and to display the trend of the design and the results of all ongoing and finished TM clinical studies. Clinical studies accepted for registration within ITMCTR are those conducted in the field ofTM including but not limited to Chinese medicine, acupuncture, herbal medicine, ayurveda, homeopathy, Unani, complementary and supplementary medicines. In terms of the types of study design, both interventional and observational studies are accepted according to different objectives, including randomized controlled trials, cohort studies, case-control studies, case reports, cross-sectional studies, etc. To respect for the patient's values, patient-centered studies are encouraged, such as using patient-centered outcomes.

Besides the registration function, ITMCTR is also a database of registered clinical studies that stores rich evidence resources related to TM for its potential users. For governments and policy makers, it can help to allocate funding toward research efficiently without duplicating efforts after knowing what is already funded.¹² For researchers or clinical doctors, the research gap could be identified by learning what has been obtained from past studies as well as the successes and challenges that can be adopted or avoided for their studies. Moreover, collaboration opportunities with other researchers are possible. For the public or the patients who have been or will be involved in the clinical studies, access to the results will facilitate their medical knowledge as well as the beliefs to the researchers.¹²

Challenges to the implementation of ITMCTR exist as well, including inadequate dissemination, language barrier, and misunderstanding of registration practices by users. Till December 2023, there are over 4200 TM clinical studies registered in the ITMCTR database. Except for the very few studies from countries such as South Korea, Canada, Pakistan, Malaysia, Austria, the majority of the current registered clinical studies in ITMCTR were from China, not conforming to the global aim of the platform and reminding us that more efforts are still needed to promote this new registry to everyone who is conducting TM clinical studies. Language barrier is another challenge as supportive files including ethical review approval and informed consent documents of certain registered clinical studies have been provided to the registry in languages other than English or Chinese. The current approach of asking applicants for additional English versions may have increased the communication cost and led to a prolonged time of audit approvals. Moreover, applicants being not familiar with or having misunderstandings of some registration items also limit the registration efficiency.

A strategic plan to establish a clinical trial registration collaboration in TM (abbreviated as Collaboration) has been proposed to improve the publicity and increase the efficiency of the platform, which will unite all interested stakeholders, especially other primary registries of WHO (Figure 1). Also based in China, ChiCTR has helped quite a lot since the initial setup of ITMCTR. To avoid confusion in choosing registries, these two platforms have reached a consensus that TM clinical studies will not be accepted by ChiCTR, and if there are applications, they will be transferred into ITMCTR.¹³ Other primary registries have also collections of TM clinical studies, and their experience during their implementation is believed to provide constructive suggestions for ITMCTR in its growth period.^{14, 15} If possible, a cooperation project with other registries could be developed to perform a joint audit of the registered clinical studies in TM, which can be an effective solution for the challenge of language barriers mentioned above. Besides, journals, publishers, health management agencies, academic and medical institutions/organizations, and other stakeholders can also collaborate to contribute to the promotion of ITMCTR. The call of this Collaboration will help ITMCTR with the registration process, audit, and dissemination activities.

Considering the importance of TM to worldwide health, it deserves a unified platform for the registration of clinical studies to facilitate the transparency of TM studies by performing uniform standards and highlighting specified features of clinical practice and research design in TM. After over three years of preparation and almost one year of implementation, ITMCTR is making every effort to get better despite the multiple challenges, and it could be improved by implementing efficient strategies for future developments.

The authors declare no conflicts of interest.