the ethics of complementary and alternative medicine research: a case study of traditional chinese...

Monash Bioethic s Review Vol. 24 No . 3

ARTICLE

52 Ethics Committee Suppl ement

The ethics of complementary andalternative medicine research: a casestudy of Traditional Chinese Medicineat the University ofTechnology, SydneylCHRlS ZASLAWSKI

College of Traditional Chinese MedicineDepartment of Health SciencesUniversity of Technology, Sydney

SUSANNA DAVIS

Research Ethics ManagerResearch and Commercialisation OfficeUniversity of Technology, Sydney

ABSTRACTThis article considers various approaches used in complementaryand alternative medicine research, and discusses the challengesthat reviewing such research poses for Human Research EthicsCommittees. Drawing on our experience with the University ofTechnology Sydney HREC, we offer some suggestions about howethical principles governing conventional medical research can beapplied in the context of research in complementary and alternativemedicine. We argue that effective HREC review requires members togain familiarity with such research, which helps ensure that suchresearch is conducted rigorously and ethically.

IntroductionComplementary and alternative medicines (CAM) are being

increasingly used by the Australian public, as well as taught, studiedand researched in Australian universities and hospitals. If CAM is tobe subject to the same stringent requirements, such as safety andefficacy, as are expected for conventional medicine, this will inevitablylead to an increase in the number of CAM applications going beforeHuman Research Ethics Committees (HRECs) for approval. This canbe a new experience for many CAM practitioners, who may be unusedto operating within a Western research paradigm and who may find theprocess of seeking ethics approval daunting. This can also posedifficulties for HRECs if they are unfamiliar with the principles of CAM.Both parties will have to learn from one another if they are to fulfil theirobligations to the public and ensure that CAM is safe and effective.

Our experience in dealing with CAM applications within theUniversity of Technology, Sydney (UTS) HREC has been shaped overthe last 10 years , since the first application for ethical approval of anacupuncture trial. We have written this paper in the hope that it willbe of assistance to other HRECs who may be struggling with CAM

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research, as well as to CAM practitioners who might be similarlystruggling with the demands of ethics committees.

BackgroundPopulation surveys in both North America and Europe have

documented the increasing popularity of CAM within Westernsocieties.> A South Australian study conducted in 2000 found that 52%of the sample had used a non-medically prescribed alternativemedicine, whilst 24% had visited at least one alternative practitioner.If costs were extrapolated to the Australian population, the publicwould have expended $2 .3 billion on alternative therapies for the year2000, which was nearly four times the public contribution to allpharmaceuticals.3

This trend is reflected in the growing number of Australianuniversities that research and teach both undergraduate andpostgraduate programs in CAM. These include the 'University ofTechnology, Sydney (UTSj, the University of Western Sydney, VictoriaUniversity and the Royal Melbourne Institute of Technology, who allteach Traditional Chinese Medicine . In addition, Swinburne Universityof Technology and Southern Cross University have programs in CAM,whilst a number of other universities are considering the addition ofCAM programs to their course profile. Given the widespreadacceptance of CAM by the Australian public and the higher educationsector, there is a pressing need to set a research agenda for CAM andto integrate CAM practices into the Australian health care systemwhere found appropriate.

Types oCCAMOne of the first difficulties for an HREC to comprehend will be the

wide and diverse range of therapeutic approaches that distinguish CAMfrom conventional medicine. CAM, as defined by the National Centrefor Complementary and Alternative Medicine," is a diverse range of'medical and health care systems, practices, and products that are notpresently considered to be part of conventional medicine'. They areoften termed 'complementary' when used in conjunction withconventional medicine, and 'alternative' when used in place ofconventional medicine. For the most part they have not been validatedby accepted scientific standards even though some CAM practices,such as acupuncture or herbal medicine, have a history dating backmany centuries. The view of many practitioners of these long-standingpractices can be summarised as, 'we know it works, we just don't knowwhy'. 5

The National Institutes of Health have classified the majordomains of CAM into the following five categories. The first category,that of Alternative medical systems, includes such practices ashomeopathic medicine and naturopathic medicine, both of whichdeveloped in Western cultures; They also include systems of medicinethat developed in non-Western cultures such as Ayurveda, anindigenous system of healing originating in India, and Traditional

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Chinese Medicine (TCM). They are seen as complete systems of theorythat include diagnostic techniques as well as treatment approaches.

The second category concerns mind-body interventions which areused to enhance the mind's capacity to affect bodily function andsymptoms. They include such practices as meditation, prayer andmental healing. They have originated and been developed within bothWestern and non-Western cultures.

The third category, that of biological-based therapies, often usesubstances found in the environment. Examples of such therapiesinclude European and Chinese herbal medicine, functional foods andmegavitamin therapy.

The fourth category, that of manipulative- and body-basedmethods, involves the movement or manipulation of one or more partsof the body. This category includes practices such as chiropractic,osteopathy and massage.

The final category, that of energy therapies, purports to useenergy fields to affect the body. Examples include qigong, Reiki andtherapeutic touch, as well as the unconventional use of electromagneticfields such as pulsed fields, magnetic fields, or alternating current ordirect current fields (National Centre for Complementary andAlternative Medicine) .

Challenges for CAM practitionersSince the commencement of CAM research there has been

resistance to empirical research by certain factions of CAMpractitioners. CAM practitioners often argue that there is a clashbetween the scientific base of conventional medicine and the conceptsunderlying CAM. David Peters, a UK medical practitioner as well as ateacher and researcher of CAM, expresses this conflict when he writes:

Common themes in CAM which may be described as post­modernist include the incorporation of traditional and indigenousperspectives alongside the scientific language of psychology,biochemistry and sociology: the fragmentation of knowledge intodisjointed parts; and a distrust that science and technology willbring unproblematic progress .. . It appears to offer new ways ofrepresenting health and of addressing those concerns which seemto have been left outside biomedicine".vMost proponents of CAM argue that research methods are

'paradigm-specific' and that conventional research methodologies areinappropriate for CAM. They often contend that CAM interventions arecomplex and may use multiple interventions, with treatmentsindividualised for each patient, and that CAM interventions are oftenused to treat multifactorial, non-specific conditions, such as stress andfatigue, which are hard to measure."

In addition to the methodological issues related to CAM research,there also exists a deep mistrust by many CAM practitionersconcerning the possible integration of CAM practices into conventionalmedicine. CAM practitioners may fear that such research andintegration will destroy some of the fundamental principles of CAM and

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eventually lead to the total breakdown of its practice. Most CAMs, asalluded to earlier, are based on paradigms that have a knowledge basethat is distinct from conventional medicine / science. For exampie,Traditional Chinese Medicine practitioners speak of 'Liver Fire Blazing'as a diagnostic category, whilst in homeopathy, 'constitutional'homeopathic medicines are prescribed on the basis of particular typesof personality and general features, rather than syndromes.

Research approachesIt is our belief that many of these arguments can be resolved and

that many of the existing research methodologies are in factappropriate for CAM research. For example, pragmatic trials in whichthe whole system is assessed in its everyday clinical context addressmany of these issues." Randomised controlled trials can also bedesigned to incorporate multiple arms so that subjects can be double­screened, allowing matching of subjects according to CAM diagnosticprinciples as well as biomedical diseases. In addition, the use ofqualitative research methods would further enhance an understandingof CAM interventions and assist in the development of appropriateoutcome measures for CAM. These outcome measures could includeinstruments to measure not only physical disease and illness but alsoemotional and spiritual well-being, thus facilitating a broaderunderstanding of CAM's holistic approach to health.

This perspective, of using established research methodologies, isalso supported in Section 12 of the National Statement on EthicalConduct in Research Involving Humans. This section deals with theaffirmation of the importance of the clinical trial as the mostappropriate way to ascertain whether or not an intervention canimprove a person's health. It states: 'Any intervention, including so­called "natural" therapies and other forms of complementary medicine,can be tested in this way. Other related disciplines also conductresearch which involves similar ethical considerations to those raisedin clinical trials." (1999, Section 12, p. 35) .

The December 2002 HREC Bulletin Supplement, reporting on theAHEC National Workshop series on privacy, supported the adoption ofsimilar attitudes to CAM and conventional medicine research. TheSupplement raised the question, 'Does medical research include alliedhealth research or research into alternative medicine?' The responsewas, 'The little available guidance suggests a broad interpretation maybe adopted, so that research into allied health is likely to be regardedas included'. Although not directly responding to the question ofalternative medicine, we can again assume that CAM is to be perceivedas being similar to conventional medicine in this respect.

Challenges for BRECsWith such a diverse range of practices being incorporated under

the term 'CAM', it may be bewildering for HREC members to evaluateCAM research incorporating these ideas. Answers to questions aboutissues such as how much the members of the committee know of the

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CAM practice, what is known concerning the public usage of the CAM(especially in regard to safety and adverse reactions), and whether theproposed CAM intervention is the most effective treatment choice forthe proposed disease, will require an in-depth understanding of CAMby the HREC. Indeed, individual HREC members may feeluncomfortable when reviewing CAM claims and it is important that thecommittee as a whole do not impose inappropriate demands on theCAM practitioners.

UTS experienceWith the introduction of a Traditional Chinese Medicine course

into UTS, it became apparent that there would be a responsibility tocritically evaluate practices such as acupuncture and Chinese herbalmedicine. This responsibility would primarily lie with the CAMpractitioners employed to teach the course, but obviously theUniversity also had a responsibility to support research as well asteaching. This meant that there had to be a genuine engagementbetween CAM researchers and other elements of the University,including the HREC , to initiate a mutually informative and respectfuldialogue.

The UTS experience was facilitated by three external factors . Thefirst related to the fact that prior to the submission of the firstapplication, two HREC members had had positive experiences withacupuncture. The second related to the fact that both an acupunctureand a Chinese herbal medicine outpatients' clinic operate on campusand are well patronised by University staff ami students. This led to anacceptance of Traditional Chinese Medicine by the wider Universitycommunity. The third related to the historical background of the UTSHREC. Given that the UTS HREC was founded in late 1992 and it wasin 1995 that the first TCM application was submitted for ethicalapproval, the HREC was still in a formative stage of development. Ithas now been ten years since the first acupuncture application andsince then over twenty TCM applications have been approved. Thesethree factors have probably led to a willingness to be more supportiveand accepting of Traditional Chinese Medicine, and this hassubsequently resulted in a better understanding of CAM by the HRECand the University community.

When the first application for acupuncture research wassubmitted, the HREC asked for more background information onacupuncture and, in addition, more information on risk. This resultedin a better understanding of the practice of acupuncture by the HRECas well as the recognition by the research team of the ethical issues inquestion. As a result of the increased numbers of acupunctureapplications being submitted for ethical approval at UTS, the Universitythen decided to appoint an academic onto the committee, withknowledge of, and experience with, Traditional Chinese Medicine. Thisresulted in a form of peer assessment and was in accord with Section2 .6 (c) of the National Statement on Ethical Conduct in Research.

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Ethical issues for CAM researchAs with all research, the potential for harm is an ethical concern

for CAM research. If, as most CAM practitioners argue, CAM practiceshave therapeutic value, then there must also exist the possibility thatthey can do harm as well as good. For example, a number of herbalsubstances have been shown to influence drug metabolism. Recentstudies on St John's Wort, a popular herbal remedy for mild depressionand mood disorders, have demonstrated an effect on the activity of anenzyme (CYP3A4) . This enzyme is involved in metabolising more than50% of all drugs and has the potential to lower the activity of thesedrugs when administered simultaneously." Other Chinese herbs such asDan Shen and Dang Qui have been shown to increase the effects of warfarin.10

Alternatively, if CAMs do not have a therapeutic action, they maycause harm by preventing or delaying patients from receivingappropriate diagnoses and medical care. Furthermore, ineffective CAMwould incur an unnecessary financial cost to patients.

Another issue relates to the cultural basis of some forms of CAM.Given that a number of CAM systems have developed in non-Westerncultures, especially alternative medical systems such as TraditionalChinese Medicine and Ayurvedic medicine, consideration must be givento the cultural aspects concerning the research. A report by Ashcroft etal ' ' reviewed the implications of socio-cultural contexts regardingethical considerations associated with clinical trials. They found thatthere exist cultural issues relating to miscommunication regarding theconsent process, the importance of health behaviours and attitudes tohealth, disease and medicine, and compliance with randomisation. Asmore ethics committees have to consider cross-cultural research intoalternative systems of medicine, this may present difficulties whenreviewing and approving research, particularly if that research takesplace outside Australia. HRECs need to be flexible and keep pace withsuch challenges. Besides being familiar with the more traditionalmethods such as the randomised controlled trial commonly employedin medical research, HRECs need to be informed about a wider range ofresearch methods, such as ethnographic and cross cultural research.It is possible that hospital-based HRECs may have less familiarity withqualitative research methodology than other university-based HRECs,which have had to contend with a large variety of researchmethodologies including non-medical research. This can be resolvedby ensuring that the composition of an HREC is cross-disciplinary,with a strong external membership.

An important issue to consider in view of the ethical approval ofboth conventional and CAM research is nonmaleficence, the principleof protecting the subject through minimising risk and harm. Allresearch, especially pharmaceutically-based interventions, is requiredto have passed through a number of preliminary stages prior to theimplementation of a human clinical trial. These preliminary phasesinclude basic science research, cellular in-vitro studies and animalstudies, as well as Phase I and Phase II clinical trials which evaluatethe safety and provide preliminary information on efficacy and dosage.

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As can be seen from Figure 1, the historical evolutionary pathway forCAM has followed a different trajectory in comparison to conventionalmedicine.t- Conventional medicine has passed through a number ofchecks and gateways, so that by the time it reaches the Phase II and IIIstages of development, a certain level of safety has been established. Incontrast, most CAMs have been in usage in the community for varyingperiods of time and have not been subject to the same level of scrutinyregarding safety and efficacy as conventional medicine.

One possible option, especially in regard to biologically-basedsubstances such as manufactured herbs or vitamins, is to ascertaintheir status under the Therapeutic Goods Act 1989, as either a'registered'medicine (AustR) or a 'listed' medicine. (AustL) The AustRstatus pertains to medicines that can demonstrate safety, quality andefficacy against the proposed therapeutic claims, while the AustLstatus pertains to medicines that can demonstrate safety and qualitybut not efficacy. Most 'listed' medicines have not been subjected toPhase I or II clinical trials, where adverse effects would be noted, butnevertheless have been granted AustL status based on a number ofcriteria. These are that they contain only well known, establishedingredients, have a long history of use, and do not contain substancesthat are scheduled in the Standard for the Uniform Scheduling ofDrugs and Poisons.P Thus, an HREC can be assured that theexperimental substance that has been granted AustL status isrelatively safe despite not having undergone rigorous safetyrequirements.

The use of individual raw, unprocessed herbal SUbstances, as inthe case of Chinese herbal formulae, can be problematic as they are notcurrently regulated under the Therapeutic Goods Act 1989. 14 Justrecently the Commonwealth Government has supported the call for areview of the regulation of raw herbs, but until regulations are in place,HRECs may require CAM herbal researchers to submit herbalmonographs listing a toxicity profile for each individual herbalsubstance, or require that preceding Phase I and II dose-rangingstudies (which provide preliminary data on safety) are conducted beforegoing on to larger definitive Phase III clinical trials.

When assessing the safety of other non-biologically-based CAMsuch as acupuncture or chiropractic, one solution is to check whetherany reviews concerning adverse reactions or side-effects have beendocumented in the literature. For example, in the case of acupuncture,a number of systematic reviews as well as large-scale prospectivestudies have been published, detailing the type and frequency ofadverse effects of acupuncture. IS These can be used to inform theHREC of the relative safety of the intervention as well being helpful ininforming the participants through reference to these studies inconsent forms.

ConclusionIn summary, we believe that not only is it imperative that CAM

practitioners conduct rigorous and ethical research but also that

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HRECs are willing to engage with CAM practitioners in order to developan understanding of CAM practices. This has been the practice atUTS, and we believe that both the HREC and CAM researchers havebenefited from the interaction. Despite the diverse range of practicesand underlying theoretical frameworks incorporated under the termCAM, we contend they are subject to the same ethical considerations asconventional medicine research. A lack of familiarity with CAM or withethics approval processes should not blind either the ethics committeeor researchers to the fact that ethical issues, such as risk, safety,recruitment, consent, privacy and so on, are the same for all researchinvolving humans. 16

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An earlier draft of this paper was presented at Ethics in Human ResearchConference, April 2003, Canberra, ACT, which was convened by the National Healthand Medical Research CouncilEisenberg OM, Davis RB, Ettner SL, Appel S, Wilkey S, Van Rompay M and KesslerRC, 'Trends "in alternative medicine use in the United States, 1990-1997', TheJournal of the American Medical Association, vol, 280, no.18, 1998, pp. 1569-1575;Siahpush M, 'Postmode rn attitudes about health : a population-based exploratorystudy', Complementary Therapies in Medicine, vol, 7, 1997, pp. 164-169.MacLennan AH, Wilson DH, and Taylor, AW, 'The escalating cost s and prevalence ofalternative medicine', Preventative Medicine, vol. 35, 2002, pp. 166-173.National Centre for Complementary and Alternative Medicine , What isComplementary and Alternative Medicine?, 2005, available athttp:j jnccam.nih.gov jhealthjwhatiscam. [accessed December 152004),Kelner MJ, Boon H, Wellman B, and Welsh S , 'Com plemen tary and alternativegroups contemplate the need for effectiveness, safety and cost effectivenessresearch ', Complementary Therapies in Medicine, vol. 10 ,2002, pp. 235-239.Peters 0 , 'Is complementary medicine holistic?' in Vickers A (ed .), ExaminingComplementary Med icine, Cheltenham UK: Stanley Thomes Publishers 1998.Verhoef M, Casebeer AL and Hilsden RJ , 'As se s sing efficacy of complementarymedicine: adding qualitative research methods to the 'Gold Standard", Journal ofAlternative and Complementary Medicine, vol. 8 , no. 3 , 2002, pp. 275-28l.Resch KL, 'Pragm atic randomised controlled trials for complex therapies ',Forschende Komplementarmedizin, vol. 5, suppl 1, 1998, pp. 136-139.Soumyanath A, 'Botanicals-quality, efficacy, safety and drug interactions', in OkenBS (ed.), Complementary Therapies in Neurology. London: The Parthenon PublishingGroup, 2004.Izzo AA and Ernst E, 'Interactions between herbal medicines and prescribed drugs:a systematic review', Drugs, vol. 61 no. 15, 2001, pp. 2163-2175; Sorensen JM,'Herb-drug, food-drug, nutrient-drug, and drug-drug interactions: mechanismsinvolved and their medical implications', Journal of Alternative and ComplementaryMedicine, vol. 8 no. 3 , 2002, pp. 293-308.Ashcroft RE, Chadwick OW, Clark SRL , Edwards RHT, Frith L and Hutton JL,'Implica ti on s of socio-cultural contexts for the ethics of clinical trials', HealthTechnology Assessment, vol. l no. 9,1997, pp. 1-63.Eisenberg 0 , 'Complemen tary and integrative medical therapies: current status andfuture trends', International Scientific Conference on Complementary, Alternativeand Integrative Medicine Research, Boston, 2002.Therapeutic Goods Administration, Medicine Regulation and the TGA, September2004, available at http:j jwww.tga.gov.aujdocsjhtmljmedregs.htm#listed [accessedDecember 15 , 2004) .Therapeutic Goods Administration, Australian Government Response to theRecommendations of the Expert Committee on Complementary Medicines in th e

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Health System, March 2005, available a thttp://www.tga .gov.au /cm/cmresponse .htm [accessed June 1,2005).

MacPherson H , Thomas K, Walters S and Fitter M, 'A prospective survey of adverseevents and treatment reactions following 34,000 consultations with professionalacupuncturists', Complementary Therapies in Medicine, vol. 19, no. 2, 2001 , pp.93-102.Other references consulted for this article include: Australian Health EthicsCommittee, '2002 AHEC National workshop series - privacy questions & answers,8', HREC Bulletin No 8, HREC Bulletin Supplement, December 2002; National Healthand Medical Research Council , National Statement on Ethical Conduct in ResearchInvolving Humans, Canberra, 1998.

Monash Bioethics Review Vol. 24 No. 3 6 1 Ethics Committee Suppleme nt

Conventional medicine

Basic science

1Cellular in vitro

AnimallodelS

.tPhase I, II and III

1Cost effect iveness/health science

1Health policyReimbursementPolitics

1Change healthcaredelivery

Adapted from Eisenberg, 2002

Complementary and alternative medicine

EpidemiologyPopular demand

1Political support

clinicJtrialS, phaseII and III

Cost elctivenessHealth .science

.i.Animal studiesIn vitro

1Scientific acceptance

1Health policyReimbursementPolitics

1Change healthcaredelivery