Highlights of WHO TRDS-TCM 2020
The WHO TRDS-TCM 2020 checklist finally includes a total of 11 extension item for TCM, which highlighted the fundamental concepts of TCM Pattern  and the features of three TCM interventions, namely CHM formula, acupuncture and moxibustion. Compared with the standard items of TRDS (V.1.3.1), this Extension elaborates on ten of the 24 TRDS items and one of the optional items. The total 11 items are: Source(s) of Monetary or Material Support (Item 4), Scientific Title (Item 10a and 10b), Countries of Recruitment (Item 11), Health Condition(s) or Problem(s) Studied (Item 12), Intervention(s) (Item 13a, 13b and 13c), Key Inclusion and Exclusion Criteria (Item 14), Primary and Key Secondary Outcomes (Item 19 to 20), and Lay Summary (B1). The checklist is presented in the Table 1; elaborations of TCM extensions are italicized. Explanations of corresponding items are given below, and available examples of good registration are provided in Additional file 3.
Explanations of WHO TRDS-TCM 2020
Item 4: Source(s) of Monetary or Material Support.
TCM Extension item: Statement of whether any conflicts of interest exist.
Authors should report the sources of funding for the trial, as this is essential information for readers assessing a trial. An increasing number of TCM clinical trials, especially CHM interventional trials, are funded by the pharmaceutical industry. Studies have shown that research sponsored by the pharmaceutical industry are more likely to produce results favoring the product made by the company sponsoring the research than studies funded by other sources . The level of involvement by a funder and their influence on the design, conduct, analysis, and reporting of a trial varies. It is therefore important that the authors describe in detail the role of the funders . For the records of trial registration, we suggest researchers to report whether any conflicts of interest will possibly exist between the funder and research. And we also want to point out that it is necessary to apply this requirement to all trial registration, not just for TCM.
Item 10: Scientific Title.
TCM extension items:
10a. Statement of whether the trial targets a TCM Pattern, or a Western medicine–defined disease, or a Western medicine–defined disease with a specific TCM Pattern.
10b. Illustration of the name of the TCM intervention, in terms of 1) Chinese herbal medicine (CHM) or CHM formula, 2) acupuncture, 3) moxibustion, or 4) other TCM therapies (i.e. cupping, Taichi, etc.).
Every trial should have a self-explanatory scientific title, which provides a first description of the trial design and research question. For trial registration, both public title (e.g., Item 9) and scientific title (e.g., Item 10) are needed. While the public title should be written to easily understood by the laymen, the scientific title is necessarily technical; it must include all elements of the PICOS (Participants, Intervention, Comparator, Outcomes and Study design). In general, the scientific title of a trial as it appears in the protocol submitted for funding and ethical review can be used . For TCM trial registrations, the specific name of target disease and/or TCM Pattern and the TCM intervention(s) should be at least reported.
If the TCM pattern(s) will be involved in participant recruitment of a trial, the registered scientific title should provide the standard name(s), such as “spleen-deficiency syndrome”, or a generalized term of “TCM syndrome differentiation” or “TCM pattern-based”, indicating that Pattern(s) will be studied. For TCM interventions, we also recommend researchers to report the specific name (e.g., style of intervention), if applicable. For example, Chinese herbal medicines are typically administered as either single herbs or formulas; names of them can be presented in English, in Chinese Pinyin, or as the acronym , such as “Cordyceps sinensis”, “Xijiao Dihuang Decoction” , “PSORI-CM01(YXBCM01) Granule” , etc. In comparison, the non-herbal therapies include acupuncture, moxibustion, massage, cupping, Taichi, etc., and their names can be specified in terms of materials used and the details of procedures. With moxibustion as an example, the style of moxibustion used could be direct moxibustion, indirect moxibustion, medicinal moxibustion, heat-sensitive moxibustion, warming needle moxibustion, and natural moxibustion . If a trial intends to include a broad category of TCM interventions (e.g., complex/comprehensive interventions), an overall, summary name, such as Chinese medicine antiviral therapy , could be used in the title; in such a case mentioning every intervention would result in an unreasonably long title.
Item 11: Countries of Recruitment.
TCM extension item: The research setting(s) or centre(s) from which participants will be, are being, or have been recruited at the time of registration.
Although reporting the recruitment countries of a study would be sufficient at the time of registration, some registries require reporting the research settings or centres, at least provide the name(s). For example, the Chinese Clinical Trial Registry (ChiCTR) item, “Countries of recruitment and research settings”, requests information regarding Province, City, Institution hospital and Level of the institution as well as country . The Clinical Research Information Service-Republic of Korea (CRiS) item, “Name of Study Site” ; International Standard Randomized Controlled Trial Number Register (ISRCTN) item, “Locations”, requests Countries of recruitment and Trial participating centre . The Clinical Trials Registry-India (CTRI) requests “Countries of Recruitment and Sites of Study” ; the Iranian Registry of Clinical Trials (IRCT) and Pan African Clinical Trial Registry (PACTR) request “Recruitment centres” [35-36]. The research setting is a factor in assessing the nature and credibility of the trial will be conducted; also more generally it is used as a part of descriptions for trial design (e.g., single centre or multi-centre). Thus, we recommend researchers to provide information (e.g., name or total number) about the research setting(s) or centre(s), if applicable.
Item 12: Health Condition(s) or Problem(s) Studied.
TCM extension item: If the study is conducted on participants with a TCM Pattern, or a Western medicine–defined disease with a specific TCM Pattern, enter the specific name(s) of TCM Pattern(s) studied (e.g., qi deficiency pattern, deficiency of stomach yin pattern, qi stagnation pattern).
In our previous study, among 2,955 TCM interventional trials that registered from 2003 to 2017, there are 376 (12.7%) trials that included the TCM pattern . In TCM clinical practice, accurate TCM pattern differentiation is vital for the determination of TCM treatment . If a trial will include TCM Pattern(s), or a Western medicine–defined disease with a specific TCM Pattern, researchers should report the name(s) of primary condition(s) and TCM Pattern(s) studied, such as “Leucopenia (deficiency of both qi and blood syndrome)” . Furthermore, we recommend researchers to use the Pattern name(s) according to the international standards of “WHO International Standard Terminologies on Traditional Medicine in the West Pacific Region”  or the “International Standard Chinese-English Basic Nomenclature of Chinese Medicine” , which were published by World Federation of Chinese Medicine Societies in 2007. Different from Western condition(s)/disease(s), a TCM pattern may have different translations [42-45]. Thus, the use of internationally recognized, standardized terminology is highly recommended.
Item 13: Intervention(s).
TCM extension items:
13a. Descriptions of TCM interventions.
Details for the three most common interventions (Chinese herbal medicine formulas, acupuncture and moxibustion) are given below:
- Chinese herbal medicine formulas
1) For fixed CHM formulas: name (e.g., Chinese Pinyin, Latin, or English), source (if any), dosage form, dosage and administration route of the CHM formula; name and dosage of each medical substance.
2) For individualized CHM formulas: add the rationale/criteria for modifying the formula.
3) For patent proprietary CHM formulas: add a statement of whether the formula used in the trial is for a condition the formula is originally targeted.
1) The names (or location, if without standard name) of points (uni/bilateral) used, in Chinese (Pinyin) and international code; depth estimation of insertion (if any); the criteria of response sought (e.g., De-qi or muscle twitch response); needle stimulation (e.g., methods of tonifying, or reduction, or even reinforcement and reduction); needle retention time; needle type, if applicable; number of treatment sessions, frequency and duration of treatment sessions.
2) For electroacupuncture, the planned implementation requirements or criteria (e.g., mode of stimulation (continuous, dense disperse), waveform and stimulus intensity). It is also recommended to provide, the brand and manufacturer of the utilized apparatus.
The materials used for moxibustion; names (or location if no standard name) of points (uni/bilateral) used for moxibustion, in Chinese (Pinyin) and international code; procedure and technique for moxibustion; criteria for response sought (e.g., warm feeling); number of treatment sessions, frequency and duration of treatment sessions.
A detailed description of TCM intervention(s) at the time of trial registration is beneficial to prevent publication bias and unnecessary duplication, as well as to keep data transparent for the public and healthcare professionals. Generally, the three most common interventions are CHM formulas, acupuncture and moxibustion. Therefore, item 13 (Interventions) is extended to include the registration recommendations for common types of CHM formulas (e.g., fixed, individualized, and patent proprietary), acupuncture (e.g., manual acupuncture and electroacupuncture), moxibustion and their controls (e.g., CHM placebo, active and sham acupuncture/moxibustion). During the development process, the checklist items of SPIRIT-TCM Extension 2018 , CONSORT-CHM Formulas 2017 , STRICTA (Revised STandards for Reporting Interventions in Clinical Trials of Acupuncture)  and STRICTOM (The STandards for Reporting Interventions in Clinical Trials Of Moxibustion) were referred, respectively . Researchers can follow the extension items for each type of intervention.
In all cases, we understand there must be a balance between what is practical and what is ideal; nevertheless, striving for the ideal will improve reporting. In particular, for CHM formulas, the checklist does not set the information about processing, production, quality control and safety assessment as required reporting items in the registration, but this does not mean that such information can be ignored. From the preparation of trial registration, efforts should be made to produce data transparent, comprehensive and accurate. Taking quality control of a CHM formula as an example, reporting any pre-designed quantitative and/or qualitative testing method(s), or providing the name(s) of potential CHM manufacturer would be valuable.
13b. Descriptions of control group(s).
For interventions with the control group(s), descriptions of the control groups should include the following:
1) Placebo control: name and amount of each ingredient (if applicable); description whether the placebo is the physical identical to the tested drug and pharmacological inert (if any); quality control and safety assessment (if any); administration route, regimen, and dosage; production information (e.g., planned manufacturer).
2) Active control: if a CHM formula was used, see recommendations for CHM formulas above; if a chemical drug was used, the name, administration route, dosage and regime should be reported.
- For acupuncture or moxibustion
1) Blank/waitlist control: special arrangement(s) during pre-treatment, treatment and post-treatment periods.
2) Sham acupuncture or Sham moxibustion: details in accordance with the recommendations for acupuncture and moxibustion above. For example, key information of sham acupuncture control should include needling (penetrating or non-penetrating the skin), acupoint (non-acupoint/ irrelevant acupoint), and manipulation (non- or low- grade manipulation).
A control group is essential in clinical trials attempting to evaluate the efficacy of an intervention. Among these, the placebo design of TCM interventions has been the topic for years, specifically including placebos for CHM formula, sham acupuncture and sham moxibustion . In our previous study, 889 CHM interventional trials were identified in WHO registries from 1999 to 2017, and 40.8% (363) of them included placebo control. Unfortunately, the quality of CHM placebo design and reporting is often poor . Due to the unique color, taste and smell of CHM formulas, creating a quality placebo, that is, physically identical and pharmacologically inert, is quite difficult . Thus, transparently reporting the details about the placebo, as suggested above, are essential for readers to assess the study design and results.
For sham acupuncture and sham moxibustion, a description of these control interventions, especially about the differences from interventions, should be provided. Specifically, information on penetrating or non-penetrating the skin, non-manipulation or low-grade manipulation, and any variation of the acupoint location should be described for the group of sham acupuncture . For sham moxibustion, how the “sham” situation is achieved, e.g, by burning away from the traditional location or by adding insulation below the moxa, should be stated . Particularly, we encourage researchers to describe what the sham acupuncture or moxibustion is intended to control for, such as for point specificity, or for the type and duration of stimulation. In addition, sources that led to the design of sham acupuncture or moxibustion, such as literature or expert opinion, should also be supplied.
13c. Statement of the qualifications or experiences criteria of possible treatment providers, if applicable.
The qualification and experience of treatment providers will influence the nature of the TCM intervention given and is therefore a variable that may significantly affect the trial outcome. Clinical doctors are not necessarily the clinical researchers, and not all researchers of TCM trials have the background of TCM knowledge. Therefore, it is necessary to provide the qualifications or experience of treatment providers, thus to make sure the readers understand who design and implement the trials. For trial registration, researchers could provide a list of who will implement the intervention as well as their qualifications. If not applicable, a pre-designed criteria of treatment providers should be provided, such as the requirements of qualification or professional title, years in TCM practice, or any other experience that may be relevant to the trial interventions. Besides, if the intervention requires patients to provide self-treatment, details of any training in advance or any other measures used for standardizing the intervention should be clearly reported.
Item 14: Key Inclusion and Exclusion Criteria
TCM extension item: Statement of whether participants with a specific TCM Pattern will be recruited, in terms of 1) diagnostic criteria and 2) inclusion and exclusion criteria, if applicable. All criteria used should be universally recognized, or reference given to where detailed explanation can be found.
If the Pattern concept is involved in the participant selection, information of how the Pattern is diagnosed and what criteria are used for including and excluding participants should be described. However, in our previous study, we found that among 376 TCM trial registrations that included Pattern(s) for participants, only 27 (7.2%) trials reported the diagnostic criteria for the Pattern studied. Furthermore, 61 (16.2%) trials did not provide the specific name of the Pattern studied . Such vagueness prevents readers from properly interpreting results and reproducing the study. As recommendations in the CONSORT-CHM formulas 2017 , citing nationally or internationally recognized Pattern diagnosis criteria are important to TCM clinical trials. We herewith emphasize that the diagnostic criteria of Pattern should be reported at the time of trial registration, which enables researchers to apply these criteria consistently throughout the trial. We suggest researchers to report the international Pattern standard for clustering of symptoms and signs; if necessary, with detailed explanation or reference(s) where explanations can be found.
Item 19: Primary Outcome(s) and Item 20: Key Secondary Outcomes.
TCM extension item: If TCM-related outcome (e.g., Pattern outcome) involved, illustration of method of measurement in detail, if applicable.
The validity and reliability of trial outcomes are fundamental to interpretation of results; only valid, reliable results can reflect the true efficacy and safety of a given intervention . The primary outcomes usually appear in the sample size calculation (Item 17), and the number of them should be as small as possible; while the remaining outcomes constitute the secondary outcomes. For TCM interventional trials, the commonly used outcomes can be categorized into Western medicine–specific outcomes and TCM-specific, or Pattern-based, outcomes . The Pattern outcomes are more likely to include symptoms and signs assessed by TCM diagnostic methods [52-53], which can be measured in terms of occurrence (e.g., presence or absence of symptoms or signs), by a rating scale (e.g., score assessment), or an assessment questionnaire (e.g., validated Pattern survey). If a TCM interventional trial included Pattern outcome(s), the information about the name(s), measurement(s), time point(s) should be reported. The methods for measurements are particularly important. In different trials, even the same Pattern outcome could be assessed with various measures according to different rationale; some researchers may develop their own methods for outcome measurements. Thus, we recommend researchers to report the methods of measurement(s) in detail, such as the assessment procedures and supporting references. To improve the quality of assessment, it is better to provide a statement of who will evaluate Pattern outcome(s) (e.g., certified Chinese medicine practitioners or other trained professionals) and if there will be any special arrangements for Pattern outcome(s) evaluation (e.g., patient diary with series of symptoms and signs).
Optional data items for collection by the registries
B1: Lay Summary.
TCM extension item: Provide a brief statement regarding the specific TCM intervention for a TCM Pattern, a Western medicine–defined disease, or a Western medicine–defined disease with a specific TCM Pattern, as well as a short description of relevant rationale and selection principle of the utilized TCM intervention(s) with references.
This item is an optional data item for registry collection in WHO TRDS (v.1.3.1), which is not included in the required 24 items. Most registries, however, have individually included relevant registration items regarding “lay summary” of the trial. Different registries use different names. For example, ClinicalTrials.gov (registry of the United States) includes two items, “Brief Summary” and “Detailed Description”, which are related to the B1 item (Lay summary). Specifically, this item involves three reporting aspects: 1) study objective/hypothesis; 2) study background/rationale; and 3) description of participants, interventions, comparisons and outcomes (PICO). In our previous review, it was found that, of 2,955 TCM interventional trial registrations, 2,844 (96.2%) trials reported the study purpose, 1,644 (55.6%) trials provided a short description of PICO, and 972 (32.9%) reported the study background/rationale, particularly based on TCM theories 
Firstly, the objectives or hypotheses are the questions that the trial is designed to answer . Whether the TCM intervention(s) targets a Western medicine–defined disease, a Pattern, or a Western medicine–defined disease with a specific Pattern should be clarified, and then readers can easily understand which conditions and treatments are targeted in the trial. Secondly, the background and underlying rationale of the research question can help readers to understand the significance of the trial. For a better understanding of TCM trials, it is recommended that the TCM rationale for selecting the TCM intervention(s) for a targeted disease and Pattern, as well as the therapeutic principles about both the Pattern and intervention should be provided, if applicable. To make this part concise, a literature review or relevant references could be cited. Thirdly, a brief description of the PICO must be clearly presented; this will facilitate application of the trial results in the future clinical practice. Regarding the description of TCM interventions and Patterns, easily understood layman’s language is recommended.