Februari 2010

GUIDELINES ON EFFICACY DATA REQUIREMENTS FOR

TRADITIONAL MEDICINE AND HEALTH SUPPLEMENT (TMHS)

Contents

1. General Considerations

2. Objectives

3. Efficacy Data Requirements

3.1 Efficacy Overview on Available Information/Knowledge

3.2 Efficacy Summary of the Intended Claim/s of the Ingredient/ Products in

Published Papers

3.3 Efficacy Study Requirements on Animal and /or Human (company

proprietary)

Thailand - Delete “/ or ”and “(company proprietary)”

Indonesia/Philippines/AAHSA: Suggested to delete (company proprietary) in the title, and
add “Proprietary …” in the text body. Please refer to the Clean Copy of this document.

4. References

5. Acronyms and Abbreviations

6. Glossary

7. Annexes
Annex I Principle of ICH-GCP

Annex II Clinical trial protocol and protocol amendment(s)

Annex III Risk Assessment Model and Risk Based ACTR model

Annex IV General Guidelines on Observational and Interventional Studies

Thailand - -in general, we agree with the content in this topic but the level of claim
should be the same as ASEAN guideline on claims for TM.
-it should be in checklist format.
-Normally clinical trials must follow international guideline. eg. WHO , ICH-GCP
so it is not necessary to attach Annex I , II , IV. However, if annex I is to be
attached to give all the related details.
-Annex III doesnot directly relate to guideline on efficacy.
Indonesia/AAHSA/Philippines –The main objective is to agree on the content
of this document. This Guidelines will be amended according to the latest and
adopted Claim Framework. Agree to delete Annex III..

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1. General Considerations
This set of guidelines is to be used as a part of the ASEAN Common Technical
Requirement (ACTR) for TMHS. Efficacy data submission is applicable, but not limited
to products with the following types of claims :
a. New claims for TMHS.
b. Medicinal claim or serious diseases/ disorder/conditions for TM
c. Claims for products that have been changed significantly in their constituent profile
from the classical TM.

This set of guidelines is to be used as a part of the ASEAN Common Technical

Requirement (ACTR) for TMHS. Efficacy data submission is only applicable to TM and
HS claims that are not regarded as well-documented and acceptable in accordance with
ASEAN Guidelines on Claims for TMHS. For details, please refer to 4.2 for HS claims
including Nutritional or General Claims, Functional Claims and Disease Risk Reduction Claims;
and 5.2 for TM including Traditional Health Use Claims; Traditional Treatment Claims and
Scientifically Established Treatment Claims in the ASEAN Guidelines on Claims for TMHS,
respectively.

This Guideline shall assure the substantiation of efficacy of TMHS. It is recommended to

refer to the ASEAN definition of TM and HS, ASEAN Guidelines on Claims for TMHS,
and other international guidelines in the Annexes I, II and III, if applicable.

Thailand - request the definition of 1. New claims for TM and 2.Medicinal claim and 3.
constituent profile should be clarified
Malaysia -- to clarify the meaning of new claim
Singapore -- The term “New claims for HS” needs to be defined more clearly in order to
minimise differences in interpretation. The terms “New Claims”, “Medicinal claim or
serious diseases/ disorder / conditions for TM”, and “Claims for products that have been
changed significantly in their constituent profile from the classical TM.” need to be
defined more clearly in order to minimise differences in interpretation. To consider
whether “New Claims” could be subsumed under “Medicinal claim or serious diseases/
disorder / conditions for TM”, and “Claims for products that have been changed
significantly in their constituent profile from the classical TM”. To discuss whether
“products have been changed significantly in their constituent profile from the classical
TM” could still be considered TM.

Indonesia/AAHSA/Philippines –Suggest to use the green text to replace the black one.
(Claim definitions and classifications should be aligned under ACTR & Guidelines
on Claims before further development of this Guidelines on Efficacy Data
Requirements.)
.
Efficacy data submission is not required for TMHS with well established claims.

Thailand - Add the reference to substantiate this type of claims are…….

Malaysia -- to define what is well established claims.) Is it referring to low & medium
level claim (Refer claims framework).

Indonesia/AAHSA/Philippines –Suggest to delete the above paragraph as the

information
It is already
is important stated
for herbal very clearly
medicines, in the first paragraph.
and particularly for those made from mixture herbal
products, that the requirements for proof of efficacy, including the documentation
required to support the indicated claims, should depend on the nature and level of the
indications. For the treatment of minor disorders, for nonspecific indications, or for

2
prophylactic uses, less stringent requirements (e.g. observational studies) may be
adequate to prove efficacy, especially when the extent of traditional use and the
experience with a particular herbal medicine and supportive pharmacological data are
taken into account.

Singapore - As claims on “prophylactic uses” could be used for varying levels/severity of

the medical conditions, reference should be made to the ASEAN Guidelines on Claims for
TM & HS on the respective levels of supporting evidence required.
Malaysia -- Observational studies are not enough to support efficacy / claim. Must be
intervention studies
Indonesia/AAHSA/Philippines – Agree with Singapore that reference should be made to
the ASEAN Guidelines on Claims for TM & HS on the respective levels of supporting
evidence required.

This Guideline shall assure the substantiation of efficacy of TMHS. It is recommended to

refer to the ASEAN definition of HS, Guideline on Claims, and other international
guidelines such as Guideline for Good Clinical Practice (see Annex I & Annex II) if
applicable.

Thailand - Change word “Guideline for Good Clinical Practice (see Annex I & 

Annex II)” to “international accepted guideline for conducting clinical trials”.

Indonesia/AAHSA/Philippines – Clear references should be given. Don not agree to

2.change, but agree to add the other international guidelines above. Please refer to the
Objectives
Clean Copy of this document.
This Guideline is to facilitate the product placement of TMHS within the ACTR
framework and set up minimum requirements for efficacy data submission in ASEAN
region. Additional efficacy data may be required when necessary.

Malaysia – Add “Additional efficacy data may be required when

necessary.”
Indonesia/AAHSA/Philippines –Agree

3.Indonesia
Efficacy–Data
Disagree to add “Additional efficacy data may be required
Requirements
when necessary.”
3.1 Efficacy Overview on Available Information/Knowledge
This overview includes all relevant efficacy information available from regulatory
agencies and all kinds of public literatures, e.g. all kinds of observational studies (see
Annex IV)

EFFICACY
TM
It is important for herbal medicines, and particularly for those made from mixture herbal
products, that the requirements for proof of efficacy, including the documentation
required to support the indicated claims, should depend on the nature and level of the
indications. For the treatment of minor disorders, for nonspecific indications, or for
prophylactic uses, less stringent requirements (e.g. observational studies) may be
adequate to prove efficacy, especially when the extent of traditional use and the
experience with a particular herbal medicine and supportive pharmacological data are
taken into account.

Any review/overview must be based on unambiguous identification and or

characterization of the constituents. A literature search must be performed. This should
include the general literature such as handbooks specific to the individual form of

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therapy, modern handbooks on phytotherapy, phytochemistry and pharmacognosy,
articles published in scientific journals, official monographs such as WHO monographs,
national monographs and other authoritative data related to TM and, if available, database
searches in online or offline databases , e.g. WHO adverse drug reaction database,
Medline, etc. Toxicological information on single ingredients should be assessed for its
relevance to the TM.

For herbal preparation, the searches should not only focus on the specific herbal
medicinal preparation, but should include different parts of the plant, related plant species
and information originating from chemotaxonomy.

The need for additional data or new tests should be considered in the light of the
Information requirements for new substances ingredients. Many of the tests required for
new substances may be replaced by documented experience. However, it should be
carefully considered if all the questions on toxicology raised for new substances
ingredients could be answered sufficiently and in a plausible way by the available
general knowledge. A specific focus should be given to effects that cannot be detected or
are very difficult to detect empirically, e.g. genotoxicity.

HS

This overview must be based on unambiguous identification and characterization of the

constituents in the products. A literature search must be performed. This should include
the general literature such as handbooks specific to the individual form of therapy,
modern handbooks on phytotherapy, phytochemistry and pharmacognosy, articles
published in scientific journals, official monographs such as WHO monographs, national
monographs or pharmacopoeia and other authoritative data related to HS and, if
available, database searches in online or offline databases etc. Efficacy information on
single ingredients as well as the combinations should be assessed for its relevance to the
HS products.

Thailand - Change “national monographs and other authoritative data” to

“national pharmacopoeia and authoritative reference texts” Reason :
should comply with ASEAN guideline on claim for TM and HS.
Indonesia/AAHSA/Philippines – Agree

For TMHS products containing of complex mixture of ingredients, the above-mentioned

overview could be should be carried out not only on the levels of individual
substances/ingredient with the understanding but also on the end products to of the
limitation that such an approach does not generally allow the assessment of possible
synergistic or antagonistic effects.

For herbal preparation, the searches should not only focus on the specific herbal
medicinal preparation, but should include different parts of the plant, related plant species
and information originating from chemotaxonomy.

3.2 Efficacy Summary of the Intended Claim/s of the Ingredient/ Products in

Published Papers
AAHSA suggested to use the green text below for 3.2

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 3.2 Summary of the Scientific Data Supporting the Intended Claim/s of the
Ingredients/ Products
3.2.1 Wording and description of the intended claim/s
3.2.2 Summary of the scientific data in the following format if applicable:

Type of Studies Study Product/Ingredient Animals Duration Key Limitation Information

(Animal or Design tested Dosage, or of Findings of the On the
Human) Adm. Route Subjects Treatment study Journals

3.3 Efficacy Study Requirements on Animal and /or Human (company proprietary)

Thailand - Delete “/ or ”and “(company proprietary)”

Indonesia/Philippines/AAHSA: Suggested to delete (company proprietary) in the title, and
add “Proprietary …” in the text body. Please refer to the Clean Copy of this document.

a.   New claims for TMHS
b.   Medicinal claim or serious diseases/ disorder/conditions for TM 
c.   Claims for products that have been changed significantly in their constituent 
profile from the classical TM. 
( Animal or/and Human study requirements will have to align the level of claims
according to Guidelines on Claims. This Guidelines can be developed further only
after the completion of the Guidelines on Claims.)
Proprietary animal and/or human studies are only required to substantiate the efficacy for
the following TM and HS claims:
a. For HS, Functional Claims and Disease Risk Reduction Claims that are not regarded as
well-documented acceptable claims under 4.2 in the ASEAN Guidelines on Claims for
TMHS
Singapore: Animal studies should be used only for pre-clinical data submission and should not be used
to demonstrate efficacy in humans
b.
According For
to TM,
the Traditional
most recentlyTreatment
presentedClaims
Claimsand Scientifically
Framework, Established
categories of Treatment
HS claimsClaims
have been
amended as “Nutritional or General”, “Functional” and “Disease Risk Reduction” claims, and the
that are not regarded as well-documented acceptable claims under 5.2 in the ASEAN
supporting evidence requirements have been updated to reflect these amendments. Hence this guideline
Guidelines
should be on Claims for TMHS
updated accordingly.
Thailand - Delete and Change to “Efficacy study requirements are based on the level of claim”. Please
refer to ASEAN guideline on claim for TM + HS or copy the contents in column 1 + 4 of ASEAN
guideline on claim (page 12 – 13)
Malaysia -- animal study is only acceptable for preclinical studies. ASEAN Claim Framework for
TMHS is not necessary to include in this guide since there is a separate guide for claim. Also the criteria
for efficacy study a & c, does not relate to the claims framework. Under the claims framework, for high
claim the compulsory evidence (scientific evidence) states to “refer to the ASEAN Guideline on
Efficacy” and not add the claims framework here)

Indonesia/Philippines/AAHSA:
1. Agree to remove the old version of ASEAN Claim Framework for TMHS and develop this part
of document according to the latest version of the Claim Framework.
2. Suggest to use the green text to replace the black one.
3. Animal studies will be acceptable when human study is not feasible, eg. TMHS for5protection
of liver damage by chemicals; relief of chronic physical fatigue – only animal model available.
4. AAHSA suggested to add the Basic Principles and Annex VI for this document.
Basic Principles for Animal and Human Studies to Substantiate TMHS Efficacy
 Animal and human studies must be designed according to generally recognized
scientific and pharmacological principles;
 Human studies are recommended to follow the ICH-GCP Principles and Clinical
trial protocol and protocol amendment(s) in Annex I and II respectively if
applicable.
General guidelines on observational and interventional human studies are stated in Annex
III.

Individual Study Report should include the information stated in Annex IV.

REFERENCE

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1. World Health Organization. Guidelines for good clinical practice (GCP) for trials on
pharmaceutical products, 1995:106–107;108–110 (WHO Technical Report Series,
No. 850).

2 The ICH Harmonized tripartite guideline: guideline for Good Clinical Practice,
International Conference on Harmonization of Technical Requirements for
Registration of Pharmaceuticals for Human Use, International Federation of
Pharmaceutical Manufacturers Associations, Geneva, Switzerland. Recommended for
adoption on 1 May 1996 by the ICH Steering Committee.

3. World Health Organization. General Guidelines for Methodologies on Research and

Evaluation of Traditional Medicine, 2000.

4. World Health Organization. Guidelines for the regulation of herbal medicines in the
South-East Asia Region, 2003.

5. Final Report of 4th ACCSQ TMHSPWG Meeting, December 2005

6. Final Report of 5th ACCSQ TMHSPWG Meeting, July 2006

7. Final Report of 8th ACCSQ TMHSPWG Meeting, November 2007

8. Final Report of 9th ACCSQ TMHSPWG Meeting, June 2008

9. Fourth Meeting of the ACCSQ TMHS Scientific Committee (ATSC); ASEAN

Claims Requirements for TMHS,13 January 2009, Bangkok, Thailand;

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8
Acronyms and Abbreviations

GCP Good Clinical Practice

ICH International Conference on Harmonisation
MRA Mutual Recognition Arrangement
SEARO WHO Regional Office for South-East Asia
TMHS Traditional Medicine and Health Supplement

Glossary

Good Clinical Practice (GCP)

A standard for design, conduct, performance, monitoring, auditing, recording, analysis,
and reporting of clinical trials that provides assurance that the data and reported results
are credible and accurate, and that the rights, integrity, and confidentiality of trial subjects
are protected.

Traditional Medicine
Any medicinal product for human use consisting of active ingredients derived from
natural sources (plants, animals and/or minerals) used in the system of traditional
practice. It t should not include any sterile preparation, vaccines, any substance derived
from human parts, any isolated and characterized chemical substances.

Health Supplement
A Health Supplement means any product that is used to supplement a diet and to
maintain, enhance and improve the healthy function of human body, it is presented in
dosage forms (to be administered) in small unit doses such as capsules, tablets, powder,
liquids and it shall not include any sterile preparations (i.e. injectable, eyedrops), and
contains one or more, or a combination of the following:
a. Vitamins, minerals, amino acids*, fatty acids, enzymes, probiotics and other
bioactive substances*
b. Substances derived from natural sources, including animal, mineral and botanical
materials in the forms of extracts, isolates, concentrates, metabolite
c. Synthetic sources of ingredients mentioned in (a) and (b) may only be used where
the safety of these has been proven.

It is presented in dosage forms (to be administered) in small unit doses such as capsules,
tablets, powder, liquids and it shall not include any sterile preparations (i.e. injectable,
eyedrops).

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 Annex I
THE PRINCIPLES OF ICH-GCP

Guidelines for Good Clinical Practice

1. Clinical trials should be conducted in accordance with the ethical principles that have
their origin in the Declaration of Helsinki, and that are consistent with GCP and the
applicable regulatory requirement(s).
2. Before a trial is initiated, foreseeable risks and inconveniences should be weighed
against the anticipated benefit for the individual trial subject and society. A trial
should be initiated and continued only if the anticipated benefits justify the risks.
3. The rights, safety, and well-being of the trial subjects are the most important
considerations and should prevail over interests of science and society.
4. The available nonclinical and clinical information on an investigational product
should be adequate to support the proposed clinical trial.
5. Clinical trials should be scientifically sound, and described in a clear, detailed
protocol.
6. A trial should be conducted in compliance with the protocol that has received prior
institutional review board (IRB)/independent ethics committee (IEC) approval/
favorable opinion.
7. The medical care given to, and medical decisions made on behalf of, subjects should
always be the responsibility of a qualified physician or, when appropriate, of a
qualified dentist.
8. Each individual involved in conducting a trial should be qualified by education,
training, and experience to perform his or her respective task(s).
9. Freely given informed consent should be obtained from every subject prior to clinical
trial participation.
10. All clinical trial information should be recorded, handled, and stored in a way that
allows its accurate reporting, interpretation and verification.
11. The confidentiality of records that could identify subjects should be protected,
respecting the privacy and confidentiality rules in accordance with the applicable
regulatory requirement(s).
12. Investigational products should be manufactured, handled, and stored in accordance
with applicable good manufacturing practice (GMP). They should be used in
accordance with the approved protocol.
13. Systems with procedures that assure the quality of every aspect of the trial should be
implemented.

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 Annex II
Clinical trial protocol and protocol amendment(s)

General information

1. Protocol title, protocol identifying number, and date. Any amendment(s) should also
bear the amendment number(s) and date(s).
2. Name and address of the sponsor and monitor (if other than the sponsor).
3. Name and title of the person(s) authorized to sign the protocol and the protocol
amendment(s) for the sponsor.
4. Name, title, address, and telephone number(s) of the sponsor’s medical expert for the
trial.
5. Name and title of the investigator(s) who is (are) responsible for conducting the trial,
and the address and telephone number(s) of the trial site(s).
6. Name, title, address, and telephone number(s) of the qualified physician, who is
responsible for all trial-site related medical decisions (if other than investigator).
7. Name(s) and address(es) of the clinical laboratory(ies) and other medical and/or
technical department(s) and/or institutions involved in the trial.

Background information

1. Name and description of the investigational product(s).

2. A summary of findings from non-clinical studies that potentially have clinical
significance and from clinical trials that are relevant to the trial.
3. Summary of the known and potential risks and benefits, if any, to human subjects.
4. Description of, and justification for, the route of administration, dosage, dosage
regimen, and treatment period(s).
5. A statement that the trial will be conducted in compliance with the protocol, GCP and
the applicable regulatory requirement(s).
6. Description of the population to be studied.
7. References to literature and data that are relevant to the trial, and that provide
background for the trial.

Trial objective and purpose

A detailed description of the objectives and the purpose of the trial.

Trial design

1. The scientific integrity of the trial and the credibility of the data from the trial depend
substantially on the trial design. A description of the trial design, should include: A
specific statement of the primary endpoints and the secondary endpoints, if any, to be
measured during the trial.
2. A description of the type/design of trial to be conducted (e.g. double-blind, placebo-
controlled, parallel design) and a schematic diagram of trial design, procedures and
stages.
3. A description of the measures taken to minimize/avoid bias, including:
(a) randomization
(b) blinding.
4. A description of the trial treatment(s) and the dosage and dosage regimen of the
investigational product(s). Also include a description of the dosage form, packaging,
and labeling of the investigational product(s).
5. The expected duration of subject participation, and a description of the sequence and
duration of all trial periods, including follow-up, if any.
6. A description of the “stopping rules” or “discontinuation criteria” for individual
subjects, parts of trial and entire trial.
7. Accountability procedures for the investigational product(s), including the
placebo(s) and comparator(s), if any.
8. Maintenance of trial treatment randomization codes and procedures for breaking
codes.

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9. The identification of any data to be recorded directly on the case report forms (i.e. no
prior written or electronic record of data), and to be considered to be source data.

Selection and withdrawal of subjects

1. Subject inclusion criteria.

2. Subject exclusion criteria.
3. Subject withdrawal criteria (i.e. terminating investigational product treatment/trial
treatment) and procedures specifying:
a) when and how to withdraw subjects from the trial/investigational product
treatment;
b) the type and timing of the data to be collected for withdrawn subjects; whether
and how subjects are to be replaced;
c) (d) the follow-up for subjects withdrawn from investigational product
treatment/trial treatment.

Treatment of subjects

1. The treatment(s) to be administered, including the name(s) of all the product (s), the
dose(s), the dosing schedule(s), the route/mode(s) of administration, and the treatment
period(s), including the follow-up period(s) for subjects for each investigational
product treatment/trial treatment group/arm of the trial.
2. Medication(s)/treatment(s) permitted (including rescue medication) and not permitted
before and/or during the trial.
3. Procedures for monitoring subject compliance.

Assessment of efficacy

1. Specification of the efficacy parameters.

2. Methods and timing for assessing, recording, and analysing of efficacy parameters.

Assessment of safety

1. Specification of safety parameters.

2. The methods and timing for assessing, recording, and analysing safety parameters.
3. Procedures for eliciting reports of and for recording and reporting adverse event and
inter-current illnesses.
4. The type and duration of the follow-up of subjects after adverse events.

Statistics

1. A description of the statistical methods to be employed, including timing of any

planned interim analysis(ses).
2. The number of subjects planned to be enrolled. In multi-centre trials, the numbers of
enrolled subjects projected for each trial site should be specified. Reason for choice of
sample size, including reflections on (or calculations of) the power of the trial and
clinical justification.
3. The level of significance to be used.
4. Criteria for the termination of the trial.
5. Procedure for accounting for missing, unused, and spurious data.
6. Procedures for reporting any deviation(s) from the original statistical plan (any
deviation(s) from the original statistical plan should be described and justified in
protocol and/or in the final report, as appropriate).
7. The selection of subjects to be included in the analyses (e.g. all randomized subjects,
all dosed subjects, all eligible subjects, evaluable subjects).

Direct access to source data/documents

The sponsor should ensure that it is specified in the protocol or other written agreement
that the investigator(s)/institution(s) will permit trial-related monitoring, audits,
institutional review board/independent ethics committee review, and regulatory
inspection(s), providing direct access to source data/documents.

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Quality control and quality assurance Ethics
Description of ethical considerations relating to the trial.

Data handling and record keeping

Financing and insurance

Financing and insurance if not addressed in a separate agreement.

Publication policy
Publication policy, if not addressed in a separate agreement.

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 Annex III
Risk Assessment Model and Risk Based ACTR Model

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 Annex III
General Guidelines on Observational & Interventional Human Studies

Observational study if applicable

There is no universally valid method for weighing categories of observational studies.

However, in general, observational studies include, in descending order of
persuasiveness, cohort (longitudinal) studies, case control studies, cross-sectional
studies, uncontrolled case series or cohort studies, time-series studies, ecological or
cross-population studies, descriptive epidemiology, and case reports.

Observational studies may be prospective or retrospective. In prospective studies,

investigators recruit subjects and observe them prior to the occurrence of the
outcome. In retrospective studies, investigators review the records of subjects and
interview subjects after the outcome has occurred. Retrospective studies are usually
considered to be more vulnerable to recall bias (error that occurs when subjects are
asked to remember past behaviors) and measurement error but are less likely to suffer
from the subject selection bias that may occur in prospective studies.

 Cohort studies compare the outcome of subjects who have received a specific
exposure with the outcome of subjects who have not received that exposure.
 In case-control studies, subjects with the disease are compared to subjects who do
not have the disease (control group). Subjects are enrolled based on their outcome
rather than based on their exposure.
 In cross-sectional studies, at a single point in time the number of individuals with
a disease who have received a specific exposure is compared to the number of
individuals without the disease who did not receive the exposure.
 Uncontrolled case series studies depict outcomes in a group without comparing to
a control group.
 Time-series studies compare outcomes during different time periods, e.g. whether
the rate of occurrence of a particular outcome during one five-year period
changed during a subsequent five-year period.
 In ecological studies, the rate of a disease is compared across different
populations. Investigators seek to identify population traits that may cause the
disease.
 Descriptive epidemiology refers to study designs that assess parameters related to
the frequency and distribution of disease in a population, such as the leading
cause of death.
 Case reports describe observations of a single subject or a small number of
subjects.

Interventional Study if applicable

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The “gold standard” of interventional human studies is the randomized controlled
clinical trial.

In a randomized controlled trial, subjects similar to each other are randomly assigned
either to receive the intervention or not to receive the intervention. As a result,
subjects who are most likely to have a favorable outcome independent of any
intervention are not preferentially selected to receive the intervention being studied
(selection bias). Bias may be further reduced if both the subjects and the researcher
who assesses the outcome does not know which subjects received the intervention
(blinding).

Randomized controlled clinical trials are not an absolute requirement to demonstrate

significant scientific agreement in all cases, but are considered the most persuasive
and given the most weight. A single large, well-conducted and controlled clinical trial
in some cases might provide sufficient evidence to establish a substance/product and
disease relationship, provided that there is no contradictory experimental studies and
a supporting body of evidence from other studies: observational or mechanistic
studies. A combination product containing several substances/vitamins/minerals
should showed evidence as a product, not based on results of trials on each
component. This approach is very important to assure that possibilities of interactions,
positive or negative, are assessed in the study.

In the case of a new herbal medicine, a new indication for an existing herbal
medicine, or a significantly different dosage form or route of administration, the
general principles and requirements for a human study should be very similar to those
which apply to conventional drugs, which are described in Annex I. In some cases,
however, the design of such studies must be adapted to deal with the particularities of
herbal medicines. Well-established, randomized controlled clinical trials provide the
highest level of evidence for efficacy. Such studies facilitate the acceptance of herbal
medicines in different regions and in people with different cultural traditions.
However, methods such as randomization and use of a placebo may not always be
possible as they may involve ethical issues as well as technical problems. For
example, it may be not possible to have a placebo control if the herbal medicine has a
strong or prominent smell or taste, as is the case for products containing certain
essential oils. In addition, patients who have been treated previously with the herbal
medicine under investigation that has a characteristic organoleptic property, cannot be
randomized into control groups. In the case of herbal medicines with a strong flavour,
placebo substances with the same flavour may have a similar function. In such cases,
it may be advisable to use a low dosage of the same herbal medicine as a control.
Alternatively, a positive control, such as well established treatment, can be used.

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 Annex IV
Information to be Included in Individual Study Reports

1. Identification of study
Researchers:
Research titles:
Location:
Source of funding:
Good Clinical Practice status/ ethical approval:

2. Objective(s) of the study

3. Description of the study materials and subjects including animals and population
( general population, sub-population with particular medical condition); and number
of subjects under studied; age range; gender; ethnicity and geographical region, ect.

4. Study design
Brief description of the methods used from sampling till analysis of results. This
should also include design information (for example, randomized control trials,
cohort studies, cross-sectional studies, meta-analysis).

5. Study results
Include all results supporting the proposed claims such as:
 Comparison of pre- and post-test values
 Levels of intake in order to deliver the function claimed
 Adverse effect reported, if any

6. Conclusions and Discussions

Describe the key findings of the studies that are in favour and not in favour for
substantiation of the proposed claim. Discuss on study limitation (eg. method of
randomization, blinding, case-control); risk of bias (eg. selective outcome reporting)
Consistency of results (eg. dose-response relationship); directness of evidence (eg.
differences in population, interventions, interpretation of results to demonstrate the
functions claimed) if applicable.

17