Research Guidelines for Evaluating the Safety and Efficacy of Herbal Medicines
(1993; 94 pages)
Table of Contents
View the documentFOREWORD
Open this folder and view contents1. INTRODUCTION
Open this folder and view contents2. GENERAL CONSIDERATIONS IN HERBAL MEDICINE RESEARCH
Open this folder and view contents3. RESEARCH STUDIES
Open this folder and view contents4. USING THE GUIDELINES
Close this folderANNEXES
View the documentANNEX 1. WORLD MEDICAL ASSOCIATION DECLARATION OF HELSINKI*
View the documentANNEX 2. REPORT OF THE MEETING OF THE WORKING GROUP ON THE SAFETY AND EFFICACY OF HERBAL MEDICINE (MANILA, 5 - 9 OCTOBER 1992)
View the documentANNEX 3. LIST OF MEMBERS, CONSULTANTS AND SECRETARIAT
View the documentNOTES
View the documentBIBLIOGRAPHY
View the documentSELECTED WHO PUBLICATIONS OF RELATED INTEREST
 

ANNEX 2. REPORT OF THE MEETING OF THE WORKING GROUP ON THE SAFETY AND EFFICACY OF HERBAL MEDICINE (MANILA, 5 - 9 OCTOBER 1992)

Summary

The Working Group on the Safety and Efficacy of Herbal Medicine met in Manila, Philippines, from 5 to 9 October 1992 The main objective of the meeting was to develop research guidelines for evaluating the safety and efficacy of herbal medicines and to make recommendations on further collaboration and activity on the safety and efficacy of herbal medicines.

The meeting was attended by 15 members from ten Member States, two consultants, two secretariat staff from the WHO Regional Office for the Western Pacific and one observer from Japan. Dr Nelia Cortes-Maramba was elected Chairperson, Dr G.N. Vaughan as Vice-Chairman, and Dr Kit Lam Chan and Professor Yun Cheong Kong as Rapporteurs. Dr S.T Han, WHO’s Regional Director for the Western Pacific, delivered addresses at both the opening and the closing ceremonies.

The members presented their papers to review the current status of research works on herbal medicine, and to introduce methodology used for evaluating the safety and efficacy of herbal medicines. The drafts of guidelines for evaluating safety and efficacy of herbal medicines were discussed extensively. The issues covered in the discussion included: the definition of terms used in the guidelines; the development of a coherent scheme for describing various herbal medicines and the plant substances from which they are formulated; the means of incorporating ethical considerations into the guidelines, the standards for non-clinical and clinical studies; the philosophical difficulties of evaluating herbal medicine remedies outside the system of medical thought in which they were developed; and the financial and technical difficulties liable to be encountered in carrying out the terms of the guidelines.

In the course of these discussions, the Working Group developed the research guidelines for evaluating the safety and efficacy of herbal medicines and made recommendations for promoting the dissemination of these guidelines. A summary of these recommendations follows:

(1) WHO and the Member States should help to promote the use of scientifically validated herbal medicines for the purpose of providing medical care in a cost-effective manner with the goal of validating claims for herbal medicines now in use and seeking collaborative solutions to common national and regional problems. In addition, programmes should be established to disseminate research on herbal medicine, not only to research workers, but to health planners and health care practitioners as well as students in the health care professions.

Member States are also encouraged to make national policies that encourage the rational use of herbal medicines and promote their safety and quality. In addition, national policies should be made to preserve the environment that provides valuable medicinal plants.

(2) WHO should disseminate these guidelines as widely as possible among Member States and their institutions concerned with herbal medicines to solicit their comments and recommendations, so that the guidelines can be revised and made as helpful as possible to each country in forming its own guidelines to meet its own specific needs.

Introduction

Humankind has used plants as therapeutic agents for thousands of years and continues to rely on them for health care, particularly in developing countries where they are usually prescribed by traditional medical practitioners who are respected members of the community. WHO has recognized the potential significance of the practice of traditional medicine, the therapeutic practices of which are based almost entirely on the use of traditional herbal remedies. Thus, resolutions have been adopted both by the World Health Assembly and the Regional Committee for the Western Pacific to encourage the appropriate development of traditional systems of medicine and to examine the therapeutic properties of their herbal remedies.

Approximately 40% of the world’s population lives in the countries served by the WHO Regional Office for the Western Pacific. This Office has actively examined how the resources of herbal medicines, which have a particularly rich tradition in many of its member countries, might be mobilized to help achieve the goal of health for all by the year 2000.

With a view to providing safe and effective herbal medicines and promoting research on herbal medicines for their scientific development, WHO constituted a Working Group on the Safety and Efficacy of Herbal Medicine which met from 5 to 9 October 1992, in Manila.

Objectives

The objectives of the meeting were as follows:

(1) to review the current status of attempts to evaluate the safety and efficacy of herbal medicines;

(2) to discuss the methodology for evaluating the safety and efficacy of herbal medicines,

(3) to outline principles and approaches to be used in developing guidelines for the safety and efficacy of herbal medicines; and

(4) to develop research guidelines for evaluating the safety and efficacy of herbal medicines and to make recommendations on further collaboration and activity on the safety and efficacy of herbal medicines.

Participants

The working group comprised 15 temporary advisers, two consultants and two members of the WHO secretariat. One observer from Japan also attended the meeting. The list of participants is in Annex 3.

Organization

Dr Nelia-Cortes-Maramba and Dr G. N. Vaughan were elected Chairperson and Vice-Chairman respectively of the Working Group and Dr Kit Lam Chan and Professor Yun Cheong Kong were elected as Rapporteurs.

Opening ceremony

Dr S.T. Han, Regional Director of the WHO Regional Office for the Western Pacific Region opened the meeting by pointing out how herbal medicines, which have contributed to human health for thousands of years, continue to do so, particularly in the Western Pacific Region where herbal medical traditions are particularly rich and still vital. He reminded the Working Group that WHO was fully aware of the continuing importance of herbal medicines for the health of a very large sector of the world’s population and that WHO encouraged the use of herbal medicines which have been proven to be safe and effective. He noted that the Working Group had the responsibility to develop the first guidelines in the Region to be applied to research on the evaluation of herbal medicines.

Proceedings

The Working Group recognized its task to develop Research Guidelines for Evaluating Herbal Medicines and was aided by working papers provided by the members of the Working Group and by draft guidelines provided by two consultants and members of the secretariat.

Presentation

The current status of research on herbal medicine in the Region and the methodology used for evaluating the safety and efficacy of herbal medicines were outlined by the members during the presentation of their working papers in the Meeting. The papers are summarized below:

Dr Chen Ken, WHO-WPRO Medical Officer, Traditional Medicine, gave a summary of various global and regional WHO resolutions regarding traditional medicine. He emphasized that the aim of WHO’s Traditional Medicine Programme is to promote the appropriate utilization of traditional medicine in relation to a country’s health care system, and reviewed WHO’s role in developing a comprehensive approach to herbal medicines that includes utilization and administration, inventory survey and conservation, training and research, cultivation and pharmaceutical production, legislation and registration.

In another paper, Dr Chen Ken reviewed the research carried out on herbal medicines within the Western Pacific Region. Such research was classified according to the materials examined, the disciplines involved and the purpose and place of research. The difficulties of carrying out research on the safety and efficacy of herbal medicines were also pointed out. These include inadequate technical facilities, financial shortages, and in some cases different approaches to problems as a result of different cultural and ethical norms. He outlined a set of principles for the development of research guidelines for evaluating the safety and efficacy of herbal medicine.

Mr Noriaki Shigeno, WHO-WPRO Scientist, Pharmaceutical, outlined the basic requirements for the quality control of both prescription drugs and non-prescription drugs and suggested that herbal medicines may be considered non-prescription drugs.

Dr Kit Lam Chan emphasized the importance of identifying the biologically active constituents of each plant which forms the composition of a herbal medicine preparation in order to explain the therapeutic properties of the preparation. He reviewed evidence of the value of the brine shrimp as a test system for screening for pharmacological activity prior to the use of more specific and sophisticated bioassays, and pointed out how KB cell cultures may provide preliminary insight into the therapeutic selectivity of plant materials and some measure of the difference between possible therapeutic activity and toxicity in the same host system.

Professor Byung Hoon Han pointed out the need for a systemic approach to, and the importance of evaluating the efficacy of herbal medicines, by both in vitro and in vivo studies. False-positive and false-negative results are inevitable in the in vitro assay systems owing to the wide distribution in plants of simple fatty acids, polyvalent organic acids, tannin and metallic ions. Professor Byung Hoon Han also pointed out that the registration for sale of herbal medicine preparations by the Korean Government relies almost completely on acceptance of a formulation that follows one of the classic traditional medicine texts.

Professor Hoang Bao Chau, reviewed the progress made at the Institute of Traditional Medicine of Viet Nam since 1960. The Institute has worked towards improving the safety and evaluating the efficacy of traditional drugs, and efforts have been made to standardize drugs and overcome toxicity In the period from 1990 to 1995, the Institute will focus on the safety and efficacy of some herbal medicine preparations with different functional groups as compared with total extracts. Measures taken to integrate studies from various non-clinical disciplines with clinical practice were also mentioned.

Dr Nam-Jae Kim presented the screening methodology for the biochemical and pharmacological evaluation of herbal medicines. He also summarized the present status of the role of herbal medicines in the health care system of the Republic of Korea. He proposed revising the terminology of traditional medicine into an integrated system that could readily be adapted to modern scientific terms, and which would be in accordance with pathological studies.

Professor Yun Cheong Kong focused on the measures that could improve the quality of both the crude plant materials and proprietary herbal medical products. He concluded that education of the public in the basic concepts of traditional medicine and principles guiding its diagnostic methods is the best way to enable people to make their own evaluation of traditional medical practitioners and of the safety and efficacy of the medicines they prescribe.

Dr Liao Fu-long suggested guidelines for the evaluation of the safety and efficacy of both crude and processed forms and preparations of herbal medicines. He also emphasized the importance of legislative and administrative policies in determining the approval of new herbal medicines.

Professor Lou Zhi-cen, presented a comprehensive scheme for the evaluation of the safety and efficacy of herbal medicines by considering standards for appropriate pharmacodynamic, toxicological and clinical investigations.

Dr Nelia Cortes-Maramba described the research activities conducted by the National Integrated Research Programme on Medicinal Plants in the Philippines and described a survey of 1207 traditional healers regarding their preparation of herbal medicines, the plants and their parts, the methods of processing, and the dose and frequency of administration for various indications. Pre-clinical studies have been carried out for 30 medicinal plants, and out of 270 plants tested 12 were found to have mutagenic activity.

Dr Motoyoshi Satake described the guidelines for the required types of pharmacological, pharmacokinetic, toxicological and clinical studies that have been developed to assure the quality of herbal medicines (Kampo) registered with the Japanese regulatory authorities. Kampo medicines in Japan are of two types: one, the traditional decoctions prepared from several varieties of chopped herbs, the other specific formulations of extracts compounded on an industrial scale by pharmaceutical manufacturers.

Professor S. Sotheeswaran reviewed the safety and efficacy of some of the plants used in the herbal medicines of the South Pacific and some of their pharmacological activities. He indicated that extracts of many of these medicinal plants have pharmacological properties that confirm their clinical use, such as herbs used to treat wounds that show antimicrobial activity. He also drew attention to the toxic compounds of some of these herbs which have not yet been fully appreciated and pointed out ways in which the actions of some traditional herbal medicines may interfere with the intended actions of modern drugs.

In the paper of Dr Bounhoong Southavong, the research activities of herbal medicine in Lao People’s Democratic Republic were presented. The Research Institute of Medicinal Plants was founded in 1976, and since then has begun to evaluate more than 200 species of newly discovered medicinal plants whose evaluation for safety and efficacy is a continuing activity of the Institute.

Dr Hiroyori Tosa addressed the problem of evaluating the safety and efficacy of Kampo prescriptions, particularly when physicians no longer understand the Kampo philosophy. To increase the accuracy of Kampo prescribing, he proposed that checklists of symptoms, signs, laboratory tests and other examinations should be created and their intensity graded systematically. Composite scores could then be created, which, with statistical analysis, could provide a clinical evaluation of the efficacy of Kampo prescriptions.

Dr G.N. Vaughan reviewed the guidelines and policies at the Therapeutic Goods Administration (TGA), the federal agency in Australia responsible for evaluating the quality, safety and efficacy of all drugs including herbal medicines. “Registration” drugs undergo intensive evaluation to ensure safety, quality and efficacy. “Listed” drugs, on the other hand, which apply to most herbal medicines, undergo an evaluation emphasizing only quality and safety. No therapeutic claims can be made for such drugs. All drugs, however, are subject to Good Manufacturing Practice (GMP).

Professor Wang Bao-qin described how herbal medicines are assessed in the People’s Republic of China. In the past five years, the Government has listed 120 commonly used crude herbal medicines for systematic investigation and strict quality assessment. It is of particular interest that pharmacodynamic studies show that several traditional multi-herbal prescriptions have a greater therapeutic effect than their individual components. Studies are also under way to develop and evaluate new herbal medicines.

Dr Haruki Yamada described his studies on pharmacologically active molecules in Japanese Kampo medicines which call attention to the pharmacological activity of the larger molecules in some of these prescriptions. Several pectic polysaccharides in the “Kampo” prescription, Juzen-Taiho-To, for example, have immunomodulating activity. Such studies support the conviction that attention in the study of classic herbal medicines should not be confined exclusively to compounds of low molecular weight.

Discussion

During the preparation of the guidelines, a number of issues were raised that received particular attention and required considerable discussion.

The definition of the term herbal medicines was accepted to refer to the remedy derived primarily from plant material taken by the patient, although it was recognized that such remedies are not always exclusively of plant origin and that the term herbal medicine can be used to refer to the system of medicine based on plant remedies rather than exclusively to the remedies themselves.

Another difficult problem was the development of a coherent scheme for describing various herbal medicines and the plant substances from which they are formulated. Such remedies come from many cultures and are often thousands of years old. The Working Group recognized, therefore, that there would probably be important exceptions to any scheme proposed, but hoped that its proposed definitions would be a helpful frame of reference that would not unjustly exclude any useful or potentially useful herbal medicine.

Although the Guidelines do not specifically raise the issue of financing the scientific evaluation of the safety and efficacy of herbal medicines, the issue of such financial support was repeatedly raised by members of the Working Group. All members of the Working Group recognized that the goals of the guidelines required research facilities, personnel and supplies that in turn required the necessary financial support.

In addition to general principles such as feasibility, reliability, repeatability and practicality, the following four points were considered by the members of the Working Group in relation to principles for developing research guidelines for evaluating the safety and efficacy of herbal medicine.

The Working Group wished to make clear the importance of ethical considerations relevant to both human and animal research and to the preservation of the environment that allows medicinal herbs to flourish, but wished to incorporate these considerations into the guidelines in a way that would be acceptable to all groups within the Region and elsewhere in the world.

The Working Group also recognized the difficulty of setting standards for non-clinical studies that might be too rigid on the one hand or too vague on the other, since in a sense the task of writing such guidelines forces the Group to solve the very difficult problem of defining “good science”.

Randomized, double-blind, placebo-controlled clinical trials have provided much useful information about drugs used in modern medicine, but their power lies in their ability to eliminate the biases that seem to beset the advocates of any therapy and that make it so difficult to distinguish a true therapeutic response from the variability inherent in clinical medicine. Similarly, statistical reasoning has helped the modern clinician to recognize that an apparent therapeutic success may merely be a chance occurrence. Thus the guidelines on clinical trials were formulated to show the importance of these principles of modern drug evaluation and not to thwart imaginative research protocols that find other ways of convincing the sophisticated observer that bias and chance results have not been confused with therapeutic effect.

Although the Working Group carried out its charge to develop guidelines on the evaluation of herbal medicines, its members were keenly aware of the philosophical difficulties of evaluating remedies used in traditional systems of medicine. This unfortunate philosophical paradox was also one of the reasons why several members of the Working Group felt so strongly that the philosophical rationale of traditional systems of medicine should be made available in the courses taken by students in the health professions and made available to the public as well.

Conclusions and recommendations

Conclusion

The consensus reached by the Working Group on principles, methodologies and technical considerations is set out in the Research Guidelines for Evaluating the Safety and Efficacy of Herbal Medicines which were developed during this meeting. The recommendations of the working group are outlined below.

Recommendations

The Working Group recommends that WHO and its Member States help to promote the use of scientifically validated herbal medicines for the purpose of providing medical care in a cost-effective manner.

To carry out this overall goal the following more specific recommendations are made:

1. Research on herbal medicines should be encouraged both by WHO and the individual Member States, with the goals of validating claims for herbal medicines now in use; encouraging the convergence of traditional and modern medicine; and providing collaborative solutions to common national and regional medical problems. When planning research projects on the medical value of herbal medicines, the value of this research as a basis for economic development should also be considered.

2. WHO should encourage the establishment of facilities for the dissemination of research and other information about research on herbal medicines with the goal of providing health care workers and planners with the latest information for use in their own countries and to encourage them to establish regional cooperation and collaboration towards the solution of common medical and educational problems. Facilities, which should be equipped with computers, CD-ROM and other modern information technology and stationed within one country should be made accessible to scientists and planners from other countries.

3 WHO and its Member States should foster programmes that enable students and practitioners in the health care professions to learn about traditional medicines and the benefits that herbal remedies can provide. Education of the public about herbal medicine will help in the selection of remedies of the highest standards.

4. All Member States should develop national policies to foster the rational use of herbal medicines including the development of standards for those products that may eventually result in national or regional formularies; and they should foster efforts both to preserve the environment which provides valuable medicinal plants and to increase knowledge about their own medicinal plants.

WHO should disseminate the Research Guidelines for Evaluating the Safety and Efficacy of Herbal Medicines as widely as possible among Member States and their institutions concerned with herbal medicines to solicit their comments and recommendations, particularly with regard to the value of these guidelines in helping each country to form its own guidelines.

WHO should help the Member States to develop and improve their national health policies on herbal remedies by taking steps to amend these guidelines periodically to reflect both technical and scientific advances and the experience of other Member States.

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