British Journal of Clinical Pharmacology
Volume 54 Issue 6 Page 577 - December 2002
A systematic review of systematic reviews of homeopathy
E. Ernst
Homeopathy is a therapeutic method using preparations of substances whose effects when administered to healthy subjects correspond to the manifestations of the disorder (symptoms, clinical signs, pathological states) in the individual patient. The method was developed by Samuel Hahnemann (1755-1843) and is now practised throughout the world [1]. Homeopathy is based on two main principals [1-3]. According to the 'like cures like' principle, patients with particular signs and symptoms can be helped by a homeopathic remedy that produces these signs and symptoms in healthy individuals. According to the second principle, homeopathic remedies retain biological activity after repeated dilution and sucussion even when diluted beyond Avogadro's number.
Few therapies have attracted more debate and controversy than homeopathy. Throughout its 200-year history, critics have pointed out that its very principles fly in the face of science, while proponents have maintained that it is narrow minded to reject an overtly helpful approach to healing only because one cannot explain how it might work [2]. Similarly, proponents have quoted seemingly rigorous trials that suggest efficacy, while critics had little trouble citing equally rigorous studies that implied the opposite.
The existence of contradicting evidence is not unusual in therapeutics. One solution to resolve such contradictions is to conduct systematic reviews and meta-analyses of rigorous studies. In 1997, Linde et al. [3] did just that. The conclusions of this technically superb meta-analysis expressed the notion that homeopathic medicines are more than mere placebos. The authors also stated that no indication was identified in which homeopathy is clearly superior to placebo. Despite this and other caveats, homeopaths worldwide celebrated this publication as the ultimate proof of their treatment. Since then, a flurry of interest in homeopathy has emerged, and several further systematic reviews have been published. This article is an attempt to critically evaluate all such papers published since 1997 with a view to defining the clinical effectiveness of homeopathic medicines.
Literature searches were carried out in the following databases: Medline (via Pubmed), Embase, Amed, CISCOM (from inception to October 2001). The search terms used were homeopath . . . , homoeopath . . . , clinical trial, meta-analysis, systematic review, efficacy, effectiveness. In addition, other experts in the field (n = 5) were consulted and my own, extensive files were studied. The bibliographies of all articles thus located were scanned for further relevant references. No language restrictions were applied.
Only systematic reviews (including meta-analyses) of controlled clinical trials of homeopathy with human patients or volunteers were included. Non-systematic reviews, overviews, clinical trials and reviews of non-clinical investigations were excluded. All articles were evaluated by the present author. The following information was extracted from the original articles: inclusion/exclusion criteria, total sample size, assessment of methodological quality, results of meta-analyses, overall conclusion of the authors.
Six re-analyses of Linde et al.'s original meta-analysis [3] were located [4-9]. The results of these re-analyses demonstrate that the more rigorous trials are associated with smaller effect sizes which, in turn, render the overall effect insignificant [5, 6, 8]. One re-analysis suggests that the initial positive meta-analytic result [3] was largely due to publication bias [9], a notion that had been considered by the original authors but was rejected by them. Most notably, perhaps, the authors of the original meta-analysis [3] concluded that their re-analysis 'weakened the findings of their original meta-analysis' [6]. Collectively these re-analyses imply that the initial conclusions of Linde et al. [3] was not supported by critical evaluation of their data.
In addition, 11 independent systematic reviews were located [10-20]. Collectively the findings do not provide strong evidence in favour of homeopathy. With the exception of postoperative ileus [10] and influenza [17] there is no condition for which homeopathy is convincingly effective [10, 11, 13, 18-20]. Arnica, the most frequently tested homeopathic remedy, is not demonstrably different from placebo [12, 15]. One homeopathic remedy (oscillococcinum) was found to be superior to placebo as a treatment and prevention of influenza but the effect size was small and therefore of debatable clinical relevance [17]. Moreover, the volume of the evidence for oscillococcinum is small and therefore not fully conclusive. Our systematic review of various homeopathic medicines for postoperative ileus produced an overall positive result [10]. Yet several caveats need to be taken into account, most importantly the fact that the definitive study designed as a multicentre trial to replicate several of smaller studies failed to demonstrate a positive effect [10]. One independent review of all homeopathic RCTs regardless of indication or type of remedy yielded a positive result [16]. Yet the statistical approach to generate this result was of debatable validity and the authors are keen to point out that their overall result is weak and not sufficient for definitive recommendations.
Collectively these data do not provide sound evidence that homeopathic remedies are clinically different from placebos. However, the present analysis has several limitations that should be kept in mind when interpreting its conclusions. Even though a thorough search strategy was adopted, there is no absolute guarantee that all relevant articles were located. Many of the included reviews are from the present author's team, and this could have introduced bias. Finally the validity of conducting a systematic review of systematic reviews has its limitations; most importantly it does not create any information that was not available before.
The clinical evidence summarized above is not dissimilar from the preclinical data. Vickers recently conducted a systematic review of preclinical investigations of homeopathy [21]. Even though 120 papers could be included in the evaluation, this author found that lack of independent replications, serious methodological flaws, and contradictory results precluded any firm conclusion. This systematic review therefore casts considerable doubt on one of the main assumptions of homeopathy, namely that homeopathic remedies retain biological activity even when diluted beyond Avogadro's number.
Perhaps the most recent trial evidence, not yet included in systematic reviews, helps clarify the question whether homeopathic remedies are more than placebos. Since the publication of the systematic reviews, both positive, e.g. [22-24]. as well as negative clinical trials e.g. [25-27] have emerged. It seems therefore unlikely that these new findings would substantially change the results of any of the systematic reviews were they to be up-dated.
The recent observation of solute clusters in highly diluted water has been interpreted by several homeopaths as increasing the plausibility of homeopathy [28]. This novel finding requires independent replication. Furthermore, this observation (if confirmed) does not lend itself to explaining how solute clusters could have any effects on human health. Thus both the clinical evidence and the basic research underpinning homeopathy remain unconvincing.
If one accepts this conclusion, one might ask what its implications for future research may be. Two opposing views exist. One holds that the definitive trial of homeopathy should be conducted to once and for all settle the question [29]. The other states that 'new trials . . . are no longer a research priority' and advocates 'outcome studies to evaluate the individual treatment decisions . . . and compare outcomes to orthodox treatment' [30]. Such outcome studies exist. They are burdened with a myriad of methodological weaknesses, most importantly a proneness to selection bias, and usually report findings which are convincingly in favour of the homeopathic approach [31]. This could imply that the individualized, empathetic and time-intensive approach most homeopaths adopt to healthcare yields good clinical results. This emphasizes the importance of the therapeutic encounter and is in accordance with a wealth of information in this area [32]. It does not, however, answer the 'placebo question'. I insist that this question does require an answer - for the sake of scientific honesty and possibly in the name of clinical progress.
In conclusion, the hypothesis that any given homeopathic remedy leads to clinical effects that are relevantly different from placebo or superior to other control interventions for any medical condition, is not supported by evidence from systematic reviews. Until more compelling results are available, homeopathy cannot be viewed as an evidence-based form of therapy.
Conflict of interest: The author is a trained homeopath; he has no financial interests in this area.