Clinical Trials of Classical Homeopathy: Reflections on Appropriate Research Designs
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THE JOURNAL OF ALTERNATIVE AND COMPLEMENTARY MEDICINE Volume 9, Number 1, 2003, pp. 105–111 © Mary Ann Liebert, Inc. Clinical Trials of Classical Homeopathy: Reflections on Appropriate Research Designs MENACHEM OBERBAUM, M.D., M.F.Hom., 1 GEORGE VITHOULKAS, 2 ROBBERT VAN HASELEN, M.Sc. 3 ABSTRACT The growing popularity of complementary medicine has been accompanied by a call for con- trolled clinical studies to examine the efficacy and validity of its various methods. The difficul- ties encountered in applying the evaluation methods of conventional medicine to complemen- tary medicine are the result of the different paradigms underlying these two methods of medicine, and the differences in the healing process. This paper attempts to bridge the gap be- tween these two approaches and to suggest a possibility to use conventional research method- ology in clinical studies of classical homeopathy. Two methods are described. One is the ran- domization into a placebo or a treatment group after an individual remedy is chosen for each patient. This method requires an experienced homeopath and is reproducible only by the same homeopath in the same population. On the other hand, the expected success rate will be high. Another method is prescribing and treating according to so-called keynotes, a set of symptoms known to respond to a particular remedy that must be present in a patient in order to elicit a reaction from the remedy. This method is more suitable to a conventional design of a clinical study and is reproducible by anyone. Yet the expected success rate is much lower. Some gen- eral design issues that may have a particular impact on clinical trials of classical homeopathy are discussed, including the need for sufficiently powered trials to detect relatively small effects, strategies to deal with patient preference and embracing the use of “active-control” pragmatic trial designs. INTRODUCTION cacy and validity of the disciplines of comple- mentary medicine (Glass, 1997; Fontanarosa uring the past few years, complementary and Lundberg, 1998). Dand alternative medicine (CAM) has seen Most forms of CAM differ from conventional an increase in use (Eisenberg et al., 1993, 1998; medicine in their basic paradigm. A good ex- Fisher and Ward, 1994) and interest (Astin et ample is homeopathy. Conventional medicine al., 1998; Fontanarosa and Lundberg, 1998; sees a disease as a sum of symptoms common Hopper and Cohen, 1998). With this revival, to all pathologic conditions carrying the same there is also a growing demand for well-per- name of the disease. In contrast, classical home- formed clinical studies that examine the effi- opathy sees a disease as a pathologic condition 1The Institute of Research on Complementary Medicine and The Center of Integrated Complementary Medicine, Shaare Zedek Medical Center, Jerusalem, Israel. 2The International School of Classical Homeopathy, Alonisos, Greece. 3The Royal London Homoeopathic Hospital, Great Ormond Street, London, UK. 105 106 OBERBAUM ET AL. specific to a certain person (Hahnemann, 1994; 3.Clinical trials of classical homeopathy, Kent, 1991), an internal disease (Hahnemann, which is considered the genuine unadapted 1994) manifested by the sum of symptoms form of homeopathy. (Hahnemann, 1994) mental, emotional, and physical (Taylor et al., 2000) exhibited by the Whereas the rules for clinical trials with com- patient. As such, every sick person suffers from plexes and isotherapy could be the same as for a unique disease, and the goal is to prescribe conventional trials, this paper principally refers individually tailored remedies in order to stim- to classical homeopathy and indirectly to other ulate self-healing or cure at the broadest possi- forms of CAM where treatment is highly indi- ble level. In conventional medicine it is there- vidualized. fore possible to examine the influence of a Ignoring the major basic differences between b-blocker on a group of hypertensive patients, homeopathy and conventional medicine can but it is not possible to do the same with a lead to failure in planning clinical trials (Senn, homeopathic remedy. Furthermore, the dy- 1997) and misinterpretation of the results. For namics of the curative process differ. Whereas example, initial symptom aggravation can be a hypertensive patient might (or might not) re- misinterpreted as failure. Such initial aggrava- act with a decrease in blood pressure after re- tions have been observed in clinical homeopa- ceiving a conventional antihypertensive drug, thy for more than 200 years, and a recent the end point of the homeopathic remedy will placebo-controlled trial indicated that initial be reached in a more complicated way. The pa- aggravations are likely to be more than a no- tient’s symptoms might be aggravated initially cebo response and are associated with a sub- (Vithoulkas, 1980), the symptoms may disap- sequent favorable outcome (Shipley, 1983). pear, old symptoms may reappear (Vithoulkas, This paper attempts to raise some important 1980), or the patient may need to change reme- points and suggests certain requirements for dies (Hahnemann, 1994; Kent, 1993b; clinical studies in homeopathy, especially clas- Vithoulkas, 1980) until a cure is achieved. sical homeopathy. Keeping them in mind while A commentary in the Archives of Internal Med- planning such clinical studies will result in icine (Ernst and Kaptchuk, 1996) called for more fewer pitfalls, and facilitate the necessary valid research in homeopathy, putting aside for the evaluation of the efficacy of classical home- moment its implausibility. Accepting the need opathy and other highly individualized types for more clinical trials of homeopathy, we of CAM. would like to make the case that some modifi- cations of the conventional requirements for clinical studies are required, particularly in IMPLICATIONS OF MAIN PRINCIPLES studies using classical homeopathy (and in- OF CLASSICAL HOMEOPATHY FOR THE deed other types of CAM) where treatment is DESIGN OF CLINICAL TRIALS highly individualized. For instance, the evalu- ation of the outcome should take into account One of the main principles of homeopathy, factors such as initial aggravation of the dis- if not the most important one, is the need ease, the appearance and disappearance of old for individualization (Hahnemann, 1994; symptoms, and the need to change remedies. Vithoulkas, 1980). The patient has to be char- In order to avoid confusion it should be acterized by qualities and symptoms that are noted that there are three possible types of clin- unique, and that differ from those of other pa- ical trials of homeopathy: tients suffering from the same clinical disease. Contrary to conventional medicine, “idiosyn- 1.Clinical trials of complexes (mixture of crasy” is a crucial element in this form of ther- homeopathic dilutions, usually low dilu- apy. Modified for homeopathy, “idiosyncrasy” tions, targeting one specific disease). is defined as the complex of mental, emotional, 2.Clinical trials of isotherapy (dilutions of the and physical pathologic peculiarities of the pa- pathologic agent, targeting one specific dis- tient. There is no possibility of using a specific ease). remedy for a specific indication. For all the CLASSICAL HOMEOPATHY 107 above reasons there are two possible methods a certain cluster of symptoms that patients of structuring a homeopathic clinical study. exhibit respond to a particular remedy. Only These approaches are evaluated in hierarchical preselected patients showing these “group order. keynote symptoms” would participate in such a study. The keynotes have to be selected by an Unrestricted prescribing experienced homeopath or panel of home- opaths, and modified for different nosological The best method, if we do not want to re- entities. strict the possibilities, would be for an experi- An example of such keynote prescribing is a enced practitioner to assess every case in the clinical trial of the homeopathic treatment of study and determine which remedy is indi- premenstrual syndrome (PMS) with the rem- cated for each case. After the determination of edy Lachesis in patients who exhibit the fol- the indicated remedies, the patients would be lowing cluster of symptoms (Yakir, 2001): randomly assigned to either a placebo or treat- ment group. This method, however, requires a 1.Amelioration of the PMS as soon as the skilled homeopath in order to demonstrate the blood flow starts. full therapeutic possibilities of classical home- 2.Sensitivity to heat. opathy. In addition to being logistically com- 3.Aggravation of the symptoms on falling plex, this kind of study is truly reproducible asleep. only by the same homeopath within the same 4.Sensitivity to the touch of the throat and/or population. A change of the treating home- intolerance of the pressure of a tight collar. opath will change the results, for the better or worse, depending on his or her skills. There- All patients with these symptoms would be fore, from the point of view of reproducibility, randomly assigned to receive either Lachesis or this technique is not optimally suited for a clas- placebo. sical conventional design for clinical trials in Because the practice of using keynotes in a homeopathy. On the other hand, this kind of clinical experiment is not common, and there study will yield the best results. are no generally accepted keynotes for partic- Aside from the expertise of the homeopath, ular indications in the homeopathic literature, the indication and the severity of the pathol- the keynote selection process would be pio- ogy will also determine the success rate. Based neering, and would have to be based on on our experience, the pathologic conditions extensive experience. Only an experienced for which the best results would be expected homeopath or a panel of experienced home- include (from 1 to 7 in descending order): opaths would be suitable for the selections of the keynote symptoms. 1.Frontal and (less so) maxillary sinusitis. 2.Early stages of chronic and acute liver dis- eases. APPROPRIATE METHODS: 3.Infertility (female factor). FURTHER CONSIDERATIONS 4.Epilepsy (grand mal) in children and (less successfully) in adults.