(1995; 68 pages)
Annex 3. Report of the Working Group on Clinical Research Methodology for Acupuncture Aomori, Japan, 1-4 June 1994
The Working Group on Clinical Research Methodology for Acupuncture met in Aomori, Japan, from 1 to 4 June 1994. The main objective of the meeting was to develop guidelines for clinical research on acupuncture and to make recommendations on further collaboration and activity on clinical research of acupuncture.
The meeting was attended by 12 members from six Member States, one secretariat staff from the WHO Regional Office for the Western Pacific and three observers from Japan.
Dr Sung-Keel Kang was elected Chairman, Dr K. Segami, Vice-Chairman and Dr Daniel Eskinazi, Rapporteur. Dr S.T. Han, WHO’S Regional Director for the Western Pacific, delivered a speech during the closing ceremony.
The members presented their papers to review the current status of clinical research on acupuncture. The drafts of guidelines for clinical research on acupuncture were discussed extensively. The issues covered during the discussion included: the definition of terms used in the guidelines; organization of clinical research on acupuncture; ethical problems involved in the process of clinical research; research methods; and concepts expressed in the guidelines.
In the course of these discussions, the Working Group developed the guidelines for clinical research on acupuncture and made recommendations for promoting the dissemination of the guidelines. A summary of these recommendations follows:
1. Each interested Member State should develop a national programme that will be proactive and designed to make available: (a) safe and effective acupuncture through clinical research studies; and (b) unbiased information to the public to help guide patients’ preferences.
2. Interested Member States should specify a centre or centres of excellence in order to coordinate their country’s programmes.
3. Research education of interested acupuncturists and other health professionals should form an essential first step in developing a research culture within each Member State through: (a) dissemination of the guidelines for clinical research on acupuncture; (b) publication of the guidelines in book form, multilingually; and (c) development of a programme of clinical research methodology workshops in interested Member States based on the guidelines.
4. Each Member State should consider the ethical problems involved in the process of clinical research.
5. Information exchange should be assured among all interested parties.
6. Standard acupuncture nomenclature should be used (wherever possible) in all clinical research projects.
7. Detailed research strategies in relation to disease-oriented research proposals should be developed.
8. Cooperation between acupuncturists and other health care providers should be fostered.
9. The practice of acupuncture should receive an introduction in the medical education system.
10. The Working Group realizes that WHO may not have the necessary resources to directly implement all the recommendations outlined above. However, it is recommended that WHO should play the leading and coordinating role, and involve appropriate organizations and associations in implementing these recommendations.
Acupuncture has been practised in China for more than 2500 years. It was introduced to neighbouring countries like Japan, the Republic of Korea and Viet Nam early in the 6th century. Because of the wide indication of its therapeutic properties, the simplicity of its application, and its low cost and rapid results for treatment of many disorders, acupuncture has spread worldwide during the last 20 years.
Following the growing interest in acupuncture, clinical research on its effectiveness has been carried out by acupuncturists, clinicians and other researchers, particularly in east Asia. However, it is noted that the quality of research still varies considerably, and some difficulty in applying common scientific principles to clinical research on acupuncture has been experienced by many researchers.
In 1987, during its thirty-eighth session, the WHO Regional Committee for the Western Pacific adopted a resolution on traditional medicine which urged Member States to undertake research to evaluate the safety and efficacy of traditional medicine, based on the concepts of both modem and traditional medicines. The Scientific Group on Acupuncture which met in October 1989 in Geneva, recommended that WHO should play a role in consolidating guidelines on research methodology to ensure the comparability of results.
The WHO Regional Office for the Western Pacific (WHO/WPRO) has played an important role in the development of standard terminology and technology on traditional medicine, including acupuncture. The Working Group on Clinical Research Methodology for Acupuncture was constituted by the WHO Regional Office for the Western Pacific to review and finalize the Guidelines for Clinical Research on Acupuncture prepared by the Traditional Medicine Unit in WHO/WPRO. The Guidelines provide the basic principles and standards for preparing, conducting and evaluating clinical research on acupuncture. The Working Group met in Aomori, Japan from 1 to 4 June 1994.
The objectives of the meeting were as follows:
1. to review the current status of clinical research on acupuncture in the Region;
2. to discuss the methodology used for clinical research on acupuncture;
3. to review and finalize the guidelines for clinical research on acupuncture; and
4. to make recommendations on further collaboration and activities in the field of research on acupuncture.
The Working Group is composed of 12 temporary advisers and one member of the WHO Secretariat. Three observers from Japan also attended the meeting. The list of participants is shown in Annex 4.
Professor Sung-Keel Kang and Dr K. Segami were elected Chairman and Vice-Chairman of the Working Group. Dr Daniel Eskinazi was elected Rapporteur.
1.4 Opening ceremony
Owing to a previous commitment, Dr S.T. Han, Regional Director of the WHO Regional Office for the Western Pacific, was not able to attend the opening ceremony.
Dr Chen Ken, Medical Officer for Traditional Medicine, delivered the speech on behalf of Dr Han. During his speech, Dr Han pointed out that acupuncture has been widely recognized as a valuable and readily available means of health care and is effective, requiring only simple equipment and inexpensive medical techniques. However, he indicated that a lack of well-designed and conducted research on acupuncture has affected its acceptance. He reminded the Working Group that WHO considered research on acupuncture to be essential and the main purpose of WHO in developing guidelines for clinical research on acupuncture was to guide researchers in designing and conducting clinical research to improve the quality of research activities. He insisted that the criteria and theories of oriental philosophy reflected in acupuncture should be respected, and that the promotion of clinical research did not mean that acupuncture’s efficacy should be evaluated only according to the methodology used by modem medicine. He noted that the Working Group had the responsibility to finalize the first guidelines in the Region to be applied to clinical research on acupuncture.
During the opening ceremony, Mr Masaya Kitamura, Governor of Aomori Prefecture,Dr Hiroyuki Doi, Deputy Director, International Affairs Division of the Ministry of Health and Welfare, Japan and Dr Takayoshi Harada, Chairman of Aomori Medical Association, gave their welcome speeches.
The current status of clinical research on acupuncture and the methodology used for clinical evaluation of acupuncture were outlined in the working papers prepared by the members of the Working Group. The papers submitted are summarized below.
Dr Chen Ken indicated that WHO is aware of the value of acupuncture for maintaining health, and its possible potential contribution to WHO’S goal of health for all. In June 1977, WHO organized an Interregional Seminar on Acupuncture Moxibustion and Acupuncture Anaesthesia in Beijing, China In 1985 and 1987, two resolutions on traditional medicine were adopted by the Regional Committee for the Western Pacific, which formed the policy basis and programme direction of traditional medicine. After summarizing WHO’S programme activities in the field of acupuncture, he introduced the procedure of preparation of draft guidelines. The guidelines drafted by WPRO, were sent out to 20 experts from different countries both within and outside the Region, for comments. Based on the comments received by the Regional Office, the guidelines were revised several times. The Working Group was asked to discuss and finalize the guidelines.
Dr Eskinazi, Deputy Director, Office of Alternative Medicine, National Institute of Health (NIH), United States of America, informed the group that the NIH Office of Alternative Medicine (OAM) was created by the US Congress in October 1991 and is a permanent part of the NIH structure. It is currently located in the Office of the Director. Its mission is to evaluate any form of alternative medicine. Acupuncture is one of these “alternative medicines”. Thus far, OAM has taken essentially two approaches to research in acupuncture. First, it has funded a few research grants dealing with protocols evaluating the efficacy of acupuncture in dealing with specific medical conditions. Second, it has organized a conference with the cooperation of the Food and Drug Administration (FDA). The purpose of the conference was to present a thorough analysis of the acupuncture scientific literature to help FDA re-evaluate regulations. This re-evaluation may have a significant impact on the acceptance and patterns of acupuncture use in the United States.
Professor S.K Kang, College of Oriental Medicine, Kyung Hee University, Republic of Korea and Dr Y.S. Kim, Department of Acupuncture and Moxibustion, Kyung Hee University, Republic of Korea, summarized the clinical research on acupuncture covered in tile Republic of Korea. There are a number of clinical acupuncture reports detailing excellent improvements; however, they have not been conducted by controlled studies owing to their cultural background. Most of the patients do not want to be experimental subjects. Therefore, many of the acupuncture studies have been conducted by animal experimental trials in the Republic of Korea. Currently, many doctors are interested in the clinical research methodology for acupuncture. By reviewing and analysing clinical research papers taken from MEDLINE, the general issues in acupuncture research in the Republic of Korea may be divided into three parts: selection of point, mode of stimulation and determination of placebo group for acupuncture. It is recommended that the compromised form of control-placebo for acupuncture is carried on in clinical trials.
Dr Lewith, The Centre for the Study of Complementary Medicine, United Kingdom, re-examined the three areas which have encompassed the major part of clinical research into acupuncture: chronic pain, addiction (in particular smoking cessation), and the treatment of nausea and vomiting. Clarification of the findings, and of the different control conditions that have been used, suggests that point location is an important variable in the treatment of chronic pain and nausea, but not of addiction. These observations can be explained by postulating that different underlying mechanisms are involved in the treatment of different conditions: addictions may be mediated purely by opioid peptides, nausea by the autonomic system and a combination of both may be involved in chronic pain, together with local trigger point action. A hypothesis is presented which suggests that the closer one gets to a purely endorphin-mediated effect, the less relevant it is to think in terms of point location and the more misleading a real versus sham acupuncture model is in the context of a clinical trial. The hypothesis is necessarily speculative but it does provide a coherent theoretical framework which integrates neurophysiology, our current knowledge of clinical trials, and some aspects of traditional Chinese medicine.
Professor Meng Xian Kun, Director, Acupuncture Department, Dong Zhi Men Hospital, China, described the most commonly-used clinical research methods for acupuncture in China. They are: (1) clinical observation; (2) clinical experiment; and (3) summing-up of the clinical experience of famous acupuncturists. Clinical observation is still the dominant method employed in China, although, the academic value of observational studies varies greatly. He suggested that careful consideration should be given to selection of research topics, selection of cases, use of control groups, randomization, use of blind technique, application of treatment, evaluation of outcome and statistical analysis.
Dr K. Nishijo, Professor, Department of Acupuncture, Tsukuba College of Medical Technology and Nursing, Japan; Dr K. Segami, Executive Director and in charge of Deputy Director-General, Department of Health and Medical Services and Environmental Control, the Government of Aomori, Japan; Dr T. Shichido, Head, Information and Evaluation Group, Research Committee, Scientific Group, Society of Acupuncture, Japan and Dr K. Tsutani, Associate Professor, Department of Clinical Pharmacology, Division of Information and Science, Medical Research Institute, Tokyo Medical and Dental University, Japan, reviewed two bibliometrical studies on acupuncture and analysis of the controlled studies of acupuncture. A MEDLINE search reveals that a sharp increase of the number of acupuncture papers occurred in the early 1970s, and that about 300 papers are produced annually. Altogether, 3000 papers on acupuncture are found in MEDLINE, of which 30% are from China, 20% from the former Soviet Union, 10% from the United States, 10% from the United Kingdom, 3% from Germany and 2% from Japan. However, biased inclusion of journals in MEDLINE was noted. For instance, no journals on acupuncture and Japanese oriental medicine are indexed there. Japan Centra Revuo Medicine was searched in its CD-ROM format. About 2000 papers were found from 1987 to 1993, or an average of 300 papers annually. Most of the papers are on human beings, and published in journals of acupuncture or Japanese oriental medicine, but few are controlled studies. Most of them are descriptive studies, some combining laboratory evaluation, mechanism of action, treatment technique, discussions on meridian and discussions in clinics. A manual search revealed that 13 controlled trials have been conducted in Japan since 1966. There are, however, several problems in design, sample size, description of randomization, blinding and control, handling of drop-out cases and incorrect statistical analysis and interpretation (i.e. inappropriate conclusions in the light of data reported).
Professor Nguyen Tai Thu, Director, National Institute of Acupuncture, Viet Nam, introduced experiences in clinical use and research on acupuncture. During the past 30 years, acupuncture has been used to treat not only common diseases but also difficult cases. Acupuncture analgesia has been carried out for about 28 000 patients undergoing surgery.
Professor Zhuang Ding, Institute of Acupuncture and Moxibustion, China Academy of Traditional Medicine, China, reviewed the organization of clinical research on acupuncture in China, its current status and problems encountered during clinical research on acupuncture. In the last 40 years, a great deal of work has been done on clinical research on acupuncture in China and more than 20 000 articles have been published in various journals or presented at academic meetings. However, some researchers lack strict scientific training, and this can be identified in their reports. In some research reports, the observed patients were outpatients, who may still have been receiving other kinds of medical treatment without a control on them. Thus the observed therapeutic result was achieved through complicated treatment, not acupuncture alone. In other research, when the treating course lasted for several months, the number of patients who continued treatment was quite different from the number at the beginning. In another report, curative effect statistics included only those who continued their treatment, and not those who failed. Consequently, the statistics did not meet the requirements of medical statistics, although the survey was carried out in a statistical way. The high curative rate was therefore not solely the result of acupuncture.
The draft guidelines prepared by WPRO were used as the basic document for discussion.
The discussion was devoted to concepts expressed in the guidelines and to creating a sample outline of the guidelines.
In terms of concepts, it was agreed that no simple and methodological approach could cover all acupuncture research. Instead, methodologies need to be tailored to the questions asked. The notions of simple case prospective studies as well as that of outcome research were introduced and discussed. The purposes of conducting research for guiding physicians’ choices on the one hand and patients’ choices (which would also be reflected by choice due to ethnic background) on the other, were also discussed. It became clear that these two different demands could be best met by randomized controlled trials and by outcome research respectively.
It was agreed that it would be helpful to be very explicit and that a glossary should be included. In this context, the notion of randomization of sampling versus that of allocation was clarified.
After briefly debating whether a specific example (e.g. asthma) should be discussed, it was decided that only statements not referring to specific conditions should be made in the guidelines. However, examples should be randomly chosen to illustrate the various points covered in the final document.
Before closing the session, a tentative structure was adopted as a working model for the guidelines. This would include:
1. background on acupuncture;
2. the purpose of research and what constitutes research;
3. general considerations; and
4. research methodologies.
2.2.2 Specific issues
1. Research methods
This group considered the following issues in relation to research methodology:
a. Existing data on acupuncture have a cultural bias but form the essential first step of any research project.
b. Descriptive research outlines the uncontrolled effects of acupuncture with respect to:
- traditional medicinal systems;
- cultural aspects of each country’s health provision;
- the process or techniques of the acupuncture utilized; and
- outcomes (objective and subjective).
c. A clinical trial (CT) is one of the clinical research methods available. A clinical trial consists of four elements:
(i) it is carried out on human beings;
(ii) it has an evaluation purpose (efficacy and safety);
(iii) it is conducted intensively; and
(iv) it is a scientific experiment.
d. Randomized controlled clinical trials (RCTs) provide detailed outcome information. The problems and difficulties in relation to RCTs involving acupuncture are outlined by the group.
e. Outcome research analyses data retrospectively in relation to the clinical effects and cost-effectiveness of acupuncture with respect to other “possibly conventional” treatments.
f. Single case studies are analyses carried out prospectively on the effects of a planned treatment regimen on one individual.
New research strategies also need to be considered based on a realistic assessment of the cost and cultural and political environment in which health care operates. These include:
- pragmatic research that compares outcomes and cases of different treatment packages (conventional and traditional);
- development research (“fix, maintain, contain”) that allows us to develop a better understanding of cost and cost-effectiveness.
2. Outcome measurements in relation to research
The group agreed that research is needed to provide information about one or more of the following points:
d. preventive effects of acupuncture;
f. utility; and
Particular attention needs to be paid to:
a. cultural and ethnic factors that may promote research;
b. outcome measures designed to answer the questions raised by the hypothesis being tested;
c. statistical techniques relevant to the disease studied;
d. the assumptions made within a particular system of traditional medicine; and
e. the process of random allocation in relation to patient choice and outcome.
Proper understanding of terminology in clinical research such as randomization, blindness, placebo, validity, reliability and generalizability is most important in discussions on sound development of clinical research methodology for acupuncture.
The group agreed that a glossary with working definitions would be included in the Guidelines.
4. Ethical issues
Although fundamental human rights are fully recognized by the Working Group and should be respected in clinical research, including acupuncture research, there are different national interpretations in countries where acupuncture is officially recognized and those where acupuncture is not fully recognized.
In those countries where acupuncture has a long history, acupuncture practitioners as well as patients have a cultural barrier accepting the concept of ethical issues developed in the west, such as informed consent. In other countries where acupuncture is not yet recognized, to conduct clinical trial without informed consent is an abuse of human rights.
2.3 Field visit
The members of the Working Group visited Aomori Oriental Medical Hospital and the library affiliated with the hospital.
2.4 Closing ceremony
Dr S.T. Han, Regional Director of the WHO Regional Office for the Western Pacific, pointed out in his closing remarks’, that this was the first attempt to produce research guidelines for acupuncture, and it would enhance scientific research on acupuncture not only in the Western Pacific Region but Other parts of the world as well. He indicated that WHO supports scientific research on acupuncture; however, the experience obtained by its use over many years should not be ignored.He noted that the group had fulfilled the objectives of the Meeting and he assured the group that the Regional Office would continue its leading role in the promotion of the proper use of acupuncture.
On behalf of all participants, Dr Eskinazi acknowledged the effort and support of the WHO Regional Office for the Western Pacific in holding the Working Group Meeting and in developing the Guidelines for Clinical Research on Acupuncture.
3. Conclusions and recommendations
3.1.1 The Guidelines for Clinical Research on Acupuncture were finalized. The Working Group successfully fulfilled the task assigned to it.
3.1.2 As a valid and effective health care approach, acupuncture should be accepted by health service systems, even though the Working Group recognizes that further clinical research is required.
3.1.3 The consensus reached by the Working Group on social, cultural and ethical considerations and basic principles, methodologies used in clinical research on acupuncture and other related issues, are set out in the Guidelines for Clinical Research on Acupuncture. The recommendations of the Working Group are outlined below.
It is essential to develop a worldwide research culture through which acupuncture can be evaluated, thus providing the background for all the detailed recommendations within this report. The advent of a research-led decision-making process will be achieved by a process of continued education and development. It is recognized that this ideal will not occur immediately but we believe that a number of simple recommendations can be implemented which will, in time, begin this process. Further review of these recommendations will be required over a certain time.
3.2.1 Each interested Member State should develop a national programme that will be proactive and designed to make available:
1. acupuncture where it has been shown to be safe and effective through appropriate clinical research studies; and
2. unbiased information to the public to help guide patients’ preferences.
3.2.2 It is recommended that interested Member States specify a centre or centres of excellence to coordinate their country’s programmes.
3.2.3 The research education of interested acupuncturists and other health professionals would form an essential first step in developing a research culture within each Member State. In order to implement this general principle, a number of specific activities are recommended:
1. the widespread dissemination of the Guidelines for Clinical Research on Acupuncture. This can be effected by publication of hard copy, electronic publication, the active assistance of acupuncture associations on a worldwide basis and the active participation of medical schools and medical research establishments;
2. the publication of the Guidelines in book form, in various languages; and
3. the development of a programme of clinical research methodology workshops based on the Guidelines in interested Member States. The workshops should be designed to initiate a research culture that is practical and should be realistically tailored to the audience and also relevant to the local health care system. The effectiveness of the workshops will ultimately be reflected in the quality of published research.
3.2.4 The group recommends that each Member State should consider the ethical problems involved in the process of clinical research. Particular attention should be paid to patient safety, confidentiality, informed consent, and overall care as it applies in the cultural context of each Member State. Further studies should be conducted in relation to the ethical issues involved in clinical research on acupuncture. Consideration should be given to the different value systems that are involved in human rights such as social, cultural and historical issues.
3.2.5 Information is now frequently exchanged worldwide. Effective clinical research requires an international database of published research. The development of a unified and effective research database is essential. All too often, databases are underused. Therefore, an active programme of promotion and education must go hand-in-hand with database investment and development. Duplication of efforts should be avoided. Institutions such as the National Institute of Health and the databases available in the Institute of Information in the China Academy of Traditional Chinese Medicine, supported by WHO, should coordinate their efforts to make research databases available on a worldwide basis.
3.2.6 Standard acupuncture nomenclature should be used (wherever possible) in all clinical research projects. Further promotional activity in relation to the standardization of acupuncture technology and point location is recommended.
3.2.7 Detailed research strategies in relation to disease-oriented research proposals should be developed. This will require specific workshops that focus on particular illnesses defined by clear conventional or traditional diagnoses.
3.2.8 To foster cooperation between acupuncturists and other health care providers.
3.2.9 The group recommends the practice of acupuncture in the medical education system. This may involve a simple basic introduction as a first step that just outlines its mechanism, uses and abuses.
3.2.10 The Working Group realizes that WHO may not have the necessary resources to directly implement all the recommendations outlined above. However, it is recommended that WHO play a leadership and coordinating role, and involve appropriate organizations and associations in implementing these recommendations.