Table 1 Checklist of Items for Clinical Trial Registration of Traditional Chinese Medicine^a

1

Primary Registry and Trial Identifying Number

2

Date of Registration in Primary Registry

3

Secondary Identifying Numbers

Other identifiers besides the Trial Identifying Number allocated by the Primary Registry, if any. These include:

• The Universal Trial Number (UTN)

• Identifiers assigned by the sponsor (record Sponsor name and Sponsor-issued trial number (e.g. protocol number))

• Other trial registration numbers issued by other Registries (both Primary and Partner Registries in the WHO Registry Network, and other registries)

• Identifiers issued by funding bodies, collaborative research groups, regulatory authorities, ethics committees / institutional review boards, etc.

All secondary identifiers will have 2 elements: an identifier for the issuing authority (e.g. NCT, ISRCTN, ACTRN) plus a number.

There is no limit to the number of secondary identifiers that can be provided.

4

Source(s) of Monetary or Material Support

Major source(s) of monetary or material support for the trial (e.g. funding agency, foundation, company, institution).

Statement of whether any conflicts of interest exist.

5

Primary Sponsor

The individual, organization, group or other legal entity which takes responsibility for initiating, managing and/or financing a study. The Primary Sponsor is responsible for ensuring that the trial is properly registered. The Primary Sponsor may or may not be the main funder.

6

Secondary Sponsor(s)

Additional individuals, organizations or other legal persons, if any, that have agreed with the primary sponsor to take on responsibilities of sponsorship.

A secondary sponsor may have agreed to:

• take on all the responsibilities of sponsorship jointly with the primary sponsor; or

• form a group with the Primary Sponsor in which the responsibilities of sponsorship are allocated among the members of the group; or

• act as the Primary Sponsor’s legal representative in relation to some or all of the trial sites.

7

Contact for Public Queries

Email address, telephone number and postal address of the contact who will respond to general queries, including information about current recruitment status.

8

Contact for Scientific Queries

Responsibility for scientific leadership must be clearly assigned to a named Principal Investigator. The PI may delegate responsibility for dealing with scientific enquiries to a scientific contact for the trial. This scientific contact will be listed in addition to the PI. The contact for scientific queries must therefore include:

• Name and title, email address, telephone number, postal address and affiliation of the Principal Investigator, and;

• Email address, telephone number, postal address and affiliation of the contact for scientific queries about the trial (if applicable). The details for the scientific contact may be generic (that is, there does not need to be a named individual): e.g. a generic email address for research team members qualified to answer scientific queries.

9

Public Title

Title intended for the lay public in easily understood language.

10

Scientific Title

Scientific title of the study as it appears in the protocol submitted for funding and ethical review. Include trial acronym if available.

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.).

11

Countries of Recruitment

The countries from which participants will be, are intended to be, or have been recruited at the time of registration.

The research setting(s) or centre(s) from which participants will be, are being, or have been recruited at the time of registration.

12

Health Condition(s) or Problem(s) Studied

Primary health condition(s) or problem(s) studied (e.g., depression, breast cancer, medication error).

If the study is conducted on healthy human volunteers belonging to the target population of the intervention (e.g. preventive or screening interventions), enter the particular health condition(s) or problem(s) being prevented.

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).

13

Intervention(s)

For each arm of the trial record a brief intervention name plus an intervention description.

Intervention Name: For drugs use generic name; for other types of interventions provide a brief descriptive name.

For investigational new drugs that do not yet have a generic name, a chemical name, company code or serial number may be used on a temporary basis. As soon as the generic name has been established, update the associated registered records accordingly.

For non-drug intervention types, provide an intervention name with sufficient detail so that it can be distinguished from other similar interventions.

Intervention Description: Must be sufficiently detailed for it to be possible to distinguish between the arms of a study (e.g. comparison of different dosages of drug) and/or among similar interventions (e.g. comparison of multiple implantable cardiac defibrillators). For example, interventions involving drugs may include dosage form, dosage, frequency and duration.

If the intervention is one or more drugs, then use the International non-proprietary name for each drug if possible (not brand/trade names). For an unregistered drug, the generic name, chemical name, or company serial number is acceptable.

If the intervention consists of several separate treatments, list them all in a series, separated by commas (e.g. “low-fat diet, exercise”).

For controlled trials, the identity of the control arm should be clear. The control intervention(s) is/are the interventions against which the study intervention is evaluated (e.g. placebo, no treatment, active control). If an active control is used, be sure to enter in the name(s) of that intervention or enter “placebo” or “no treatment” as applicable. For each intervention, describe other intervention details (dose, duration, mode of administration, etc.).

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 that the formula is originally targeted.

• Acupuncture

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 criterion (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.

• Moxibustion

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.

13b. Descriptions of control group(s).

For interventions with the control group(s), descriptions of the control groups should include the following:

• For CHM formulas

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 or 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).

13c. Statement of the qualifications or experiences criteria of possible treatment providers, if applicable.

14

Key Inclusion and Exclusion Criteria

Inclusion and exclusion criteria for participant selection, including age and sex. Other selection criteria may relate to clinical diagnosis and co-morbid conditions; exclusion criteria are often used to ensure patient safety.

If the study is conducted on healthy human volunteers not belonging to the target population (e.g. a preliminary safety study), enter “healthy human volunteer”.

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.

15

Study Type

Study type consists of:

1. Type of study (interventional or observational)

2. Study design including:

Method of allocation (randomized/non-randomized)

Masking (is masking used and, if so, who is masked)

Assignment (single arm, parallel, crossover or factorial)

Purpose

3. Phase (if applicable)

For randomized trials: the allocation concealment mechanism and sequence generation will be documented.

16

Date of First Enrollment

Anticipated or actual date of enrolment of the first participant.

17

Sample Size

Sample Size consists of:

1. Number of participants that the trial plans to enrol in total.

2. Number of participants that the trial has enrolled.

18

Recruitment Status

Recruitment status of this trial:

1. Pending: participants are not yet being recruited or enrolled at any site

2. Recruiting: participants are currently being recruited and enrolled

3. Suspended: there is a temporary halt in recruitment and enrolment

4. Complete: participants are no longer being recruited or enrolled

5. Other

19

Primary Outcome(s)

Outcomes are events, variables, or experiences that are measured because it is believed that they may be influenced by the intervention.

The Primary Outcome should be the outcome used in sample size calculations, or the main outcome(s) used to determine the effects of the intervention(s). Most trials should have only one primary outcome.

For each primary outcome provide:

1. The name of the outcome (do not use abbreviations)

2. The metric or method of measurement used (be as specific as possible)

3. The timepoint(s) of primary interest

Outcome Name: Depression

Metric/method of measurement: Beck Depression Score

Timepoint: 18 weeks following end of treatment

If TCM-related outcome (e.g., Pattern outcome) involved, illustration of method of measurement in detail, if applicable.^c

20

Key Secondary Outcomes

Secondary outcomes are outcomes which are of secondary interest or that are measured at timepoints of secondary interest. A secondary outcome may involve the same event, variable, or experience as the primary outcome, but measured at timepoints other than those of primary interest.

As for primary outcomes, for each secondary outcome provide:

1. The name of the outcome (do not use abbreviations)

2. The metric or method of measurement used (be as specific as possible)

3. The timepoint(s) of interest

21

Ethics Review

The ethics review process information of the trial record in the primary register database. It consists of:

1. Status (possible values: Not approved, Approved, Not Available)

2. Date of approval

3. Name and contact details of Ethics committee(s)

22

Completion date

The date on which the final data for a clinical study were collected (commonly referred to as, “last subject, last visit”).

23

Summary Results

It consists of:

1. Date of posting of results summaries

2. Date of the first journal publication of results

3. URL hyperlink(s) related to results and publications

4. Baseline Characteristics: Data collected at the beginning of a clinical study for all participants and for each arm or comparison group. These data include demographics, such as age and sex, and study-specific measures.

5. Participant flow: Information to document the progress and numbers of research participants through each stage of a study in a flow diagram or tabular format.

6. Adverse events: An unfavorable change in the health of a participant, including abnormal laboratory findings, and all serious adverse events and deaths that happen during a clinical study or within a certain time period after the study has ended. This change may or may not be caused by the intervention being studied.

7. Outcome measures: A table of data for each primary and secondary outcome measure and their respective measurement of precision (eg a 95% confidence interval) by arm (that is, initial assignment of participants to arms or groups) or comparison group (that is, analysis groups), including the result(s) of scientifically appropriate statistical analyses that were performed on the outcome measure data, if any.

8. URL link to protocol file(s) with version and date

9. Brief summary

24

IPD sharing statement

Statement regarding the intended sharing of deidentified individual clinical trial participant-level data (IPD). Should indicate whether or not IPD will be shared, what IPD will be shared, when, by what mechanism, with whom and for what types of analyses. It consists of:

1. Plan to share IPD (Yes, No, Undecided)

2. Plan description

 A1

URL

The unique URL of the trial record in the primary registry database.

 B1

Lay Summary

Short description of the primary purpose and background of the study followed by a description of the included participants, interventions to be tested and outcomes to be measured. Include a brief statement of the study hypothesis. This should be written in language intended to be read and understood by the lay public.

Do not include the entire protocol; do not duplicate information recorded in other data elements.

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.

 B2

Approvals

Oversight entities that have approved the trial (or to which the trial has been submitted for approval). These include ethics committees and regulatory authorities. For each approving entity the name of the entity, the date and status of the approval should be reported.