Experimental studies in homeopathic clinical research

Rigorous research projects of the highest scientific standards have been conducted and published in leading international medical journals over the last few decades. In many controlled clinical trials homeopathic treatment has proven its effectiveness.
 A number of reviews have evaluated the homeopathy research literature, the most important of them are described below.
A total of 142 randomised controlled trials (RCTs) in homeopathy have been published in good quality scientific journals: positive effects have been reported in 63 (44% of the total) and negative findings have been reported in 11 (8%), while 68 (48%) have not been conclusively positive or negative. That research is spread rather thinly over 80 different medical conditions, and there are only 28 conditions in which there has been at least two trials. Differing study designs and the small size of many trials means that there are few conditions where there has been an opportunity to achieve consistent results. Nevertheless, systematic reviews of RCTs in specific medical areas have been positive for homeopathy for example in hayfever, fibromyalgia, sinusitis and vertigo.
Four out of five major systematic reviews of RCTs in homeopathy have concluded that homeopathy has an effect greater than placebo. The fact that these meta-analyses showed some positive evidence for homeopathy is remarkable because meta-analyses are far from appropriate when trials are extremely heterogeneous (as in homeopathy) not only in results but also in the interventions and health conditions under study and when a therapeutic system works in some but not all indications. The Cochrane Handbook for Systematic Reviews recommends "Meta-analysis should only be considered when a group of trials is sufficiently homogeneous in terms of participants, interventions and outcomes to provide a meaningful summary".


Systematic reviews and meta-analyses of the whole homeopathic literature

The first systematic review of homeopathic research was published in the British Medical Journal in 1991. Of the 105 trials with interpretable results, 81 indicated positive results, which included RCTs that received high quality ratings for randomization, blinding, sample size, and other methodological criteria. The authors, three orthodox epidemiologists, came to the following conclusion: "The amount of positive evidence even among the best studies came as a surprise to us. Based on this evidence we would readily accept that homeopathy can be efficacious, if only the mechanism of action were more plausible". And "The evidence presented in his review would probably be sufficient for establishing homeopathy as a regular treatment for certain indications".
[Kleijnen J, Knipschild P, ter Riet G (1991). Clinical trials of homeopathy, British Medical Journal, 302: 316-323]

In 1996, a review by the European Commission Homeopathic Medicine Research Group, later published in a scientific journal (Cucherat), identified 184 controlled clinical trials. They selected the highest quality randomized placebo controlled trials, which included a total of 2,001 patients. Boissel used a rather unusual technique of combining p-values of the selected trials to answer the question: 'Does homeopathy have an effect?' and concluded that homeopathy was more effective than placebo (P < 0.001) though "the strength of this evidence is low because of the low methodological quality of the trials" (P = 0.082 for the highest quality sub-group of just 5 trials).

[Boissel JP, Cucherat M, Haugh M, Gauthier E (1996). Critical literature review on the effectiveness of homeopathy: overview of data from homeopathic medicine trials. In: Homeopathic Medicine Research Group, Report of the, Commission of the European Communities, Directorate-General XII – Science, Research and Development, Directorate E – RTD Actions: Life Sciences and Technologies – Medical Research, Brussels 1996; Chap.11: 195-210]

[Cucherat M, Haugh MC, Gooch M, Boissel JP (2000). Evidence of clinical efficacy of homeopathy – A meta-analysis of clinical trials. European Journal of Clinical Pharmacology, 56:27–33]


A meta-analysis published in The Lancet in 1997 included 186 placebo controlled studies of homeopathy, from which data for analysis could be extracted from 89. The overall mean odds ratio for these 89 clinical trials was 2.45 (95% confidence interval 2.05–2.93) in favour of homeopathy, which means that the chances of homeopathy giving benefit were 2 to 3 times greater than those of placebo. Even when considering a "worst-case" scenario in which only high-quality studies, of high or medium dilutions, published in MEDLINE-listed journals, and with predefined measures of primary outcome were analysed, the pooled odds ratio was 1.97 and remained statistically significant. The main conclusion was that the results "were not compatible with the hypothesis that the effects of homoeopathy are completely due to placebo". In further analysis, the authors clarified that higher quality trials were less likely to be positive than those of lower quality – which is comparable to the conclusion from similar analyses in conventional medicine –, though the difference from placebo remained statistically significant until analysis was restricted to just five trials. There was insufficient volume of evidence to enable conclusions to be drawn about what homeopathic treatment is effective in which diagnosis.
[Linde K, Clausius N, Ramirez G, Melchart D, Eitel F, Hedges LV, Jonas WB (1997) Are the clinical effects of homeopathy placebo effects? A meta-analysis of placebo-controlled trials. Lancet, 350: 834-843]
In 2005 an other review was published in The Lancet comparing 110 placebo controlled trials of homeopathy and 110 matched trials of conventional medicine. Homeopathy and conventional medicine showed a similar positive treatment effect overall. Twenty-one homeopathy trials and 9 in conventional medicine were judged of higher methodological quality. From these, the results of 14 unspecified "larger trials of higher quality" (8 homeopathy, 6 conventional medicine) were analysed. The mean odds ratio was 0.88 (95% CI, 0.65-1.19) for the 8 homeopathy trials, and 0.58 (95% CI, 0.39-0.85) for the 6 conventional medicine trials. In this study, in contrast with the 1997 review, an odds ratio less than 1.0 indicated an effect greater than placebo. The authors concluded there was "weak evidence for a specific effect of homoeopathic remedies, but strong evidence for specific effects of conventional interventions. This finding is compatible with the notion that the clinical effects of homoeopathy are placebo effects."
The authors' analysis has been criticised to be prone to selection bias, especially when the set of 21 high-quality trials was reduced to 8 trials with large patient numbers. Obviously, the results depend on how the threshold for "large" studies was defined from these 21 studies. The overall results – and the conclusions drawn from them – change depending on which subset of homeopathic trials is analysed. The choice of other meaningful subsets could lead to the opposite conclusion. For example, four of the 21 trials dealt with preventing or treating muscle soreness and an earlier systematic review already showed that homeopathic medicines are probably not helpful in this condition. When restricting the analysis to the remaining 17 trials an overall statistically significant effect can be found. In addition, there is no external criterion why a "large" trial should have N=98 or more patients as defined by the authors (apart from being able to include a statistically non-significant trial with a sample size of exactly 98). For example, if the data set was split at a threshold of N=66, the median sample size of all 110 homeopathic trials, there had been a significant effect in favour of homeopathy. Surprisingly, the authors themselves highlight – but dismiss – the fact that 8 trials of homeopathy in upper respiratory tract infections have strongly positive findings overall. Clearly, the conclusions by this group of scientists under the direction of Professor Matthias Egger, well known for his anti-homeopathy standpoint, are not so definite as they have been reported and discussed.
[Shang A, Huwiler-Muntener K, Nartey L, Juni P, Dorig S, Sterne JA, Pewsner D, Egger M (2005). Are the clinical effects of homoeopathy placebo effects? Comparative study of placebo-controlled trials of homoeopathy and allopathy. Lancet, 366:726–32].
[Lüdtke R, Rutten AL (2008) .The conclusions on the effectiveness of homeopathy highly depend on the set of analyzed trials. Journal of Clinical Epidemiology, 61:1197-1204]

[Rutten AL, Stolper CF (2008) The 2005 meta-analysis of homeopathy: the importance of post-publication data. Homeopathy, 97:169-177].

Systematic reviews and meta-analyses focused on specific medical conditions

The problem of heterogeneity of medical condition has been avoided in 17 systematic reviews focused on RCTs of homeopathy in 15 specific areas. The positive evidence for homeopathy is here more obvious: seven of 17 such reports to date have been positive for homeopathy:
- childhood diarrhoea
[Jacobs J, Jonas WB, Jimenez-Perez M, Crothers D (2003). Homeopathy for childhood diarrhea: combined results and metaanalysis from three randomized, controlled clinical trials. Pediatric Infectious Disease Journal, 22:229–234]
- influenza
[Vickers A, Smith C (2006). Homoeopathic Oscillococcinum for preventing and treating influenza and influenza-like syndromes (Cochrane Review). In: The Cochrane Library. Chichester, UK: John Wiley & Sons, Ltd. CD001957]

- post-operative ileus
[Barnes J, Resch K-L, Ernst E (1997). Homeopathy for postoperative ileus? A meta-analysis. Journal of ClinicalGastroenterology, 25:628–633]

- seasonal allergic rhinitis
[Wiesenauer M, Lüdtke R (1996). A meta-analysis of the homeopathic treatment of pollinosis with Galphimia glauca. Forschende Komplementärmedizin und Klassische Naturheilkunde, 3:230–236]

[Taylor MA, Reilly D, Llewellyn-Jones RH, McSharry C, Aitchison TC (2000). Randomised controlled trials of homoeopathy versus placebo in perennial allergic rhinitis with overview of four trial series. British Medical Journal, 321:471–476]

[Bellavite P, Ortolani R, Pontarollo F, Piasere V, Benato G, Conforti A (2006). Immunology and homeopathy. 4. Clinical studies – Part 2. Evidence-based Complementary and Alternative Medicine: eCAM, 3:397–409]

- vertigo
[Schneider B, Klein P, Weiser M (2005). Treatment of vertigo with a homeopathic complex remedy compared with usual treatments: a meta-analysis of clinical trials. Arzneimittelforschung, 55:23–29]
Eight of the other 10 reviews were non-conclusive.
[Ernst E, Barnes J (1998). Are homoeopathic remedies effective for delayed-onset muscle soreness? – A systematic review of placebo-controlled trials. Perfusion (Nürnberg), 11:4–8]

[Ullman D (2003). Controlled clinical trials evaluating the homeopathic treatment of people with human immunodeficiency virus or acquired immune deficiency syndrome. Journal of Alternative and Complementary Medicine, 9:133–141]

[McCarney RW, Linde K, Lasserson TJ (2004). Homeopathy for chronic asthma (Cochrane Review). In: The Cochrane Library. Chichester, UK: John Wiley & Sons, Ltd. CD000353]
[McCarney R, Warner J, Fisher P, van Haselen R (2004). Homeopathy for dementia (Cochrane Review). In: The Cochrane Library. Chichester, UK: John Wiley & Sons, Ltd. CD003803]
[Owen JM, Green BN (2004). Homeopathic treatment of headaches: A systematic review of the literature. Journal of Chiropractic Medicine, 3:45–52]

[Smith CA (2003). Homoeopathy for induction of labour (Cochrane Review). In: The Cochrane Library. Chichester, UK: John Wiley & Sons, Ltd. CD003399]

[Pilkington K, Kirkwood G, Rampes H, Fisher P, Richardson J (2005). Homeopathy for depression: a systematic review of the research evidence. Homeopathy, 94:153–163]

[Pilkington K, Kirkwood G, Rampes H, Fisher P, Richardson J (2006). Homeopathy for anxiety and anxiety disorders: A systematic review of the research. Homeopathy, 95: 151–162]
Two reviews were negative.
[Long L, Ernst E (2001). Homeopathic remedies for the treatment of osteoarthritis – A systematic review. British Homeopathic Journal, 90:37–43]

[Ernst E (1999). Homeopathic prophylaxis of headaches and migraine? A systematic review. Journal of Pain and Symptom Management, 18:353–357]

Some non-replicated RCTs positive for homeopathy

For other medical conditions, the published evidence is fragmentary: there are some non-replicated RCTs showing positive effects for homeopathy, e.g. in acute otitis media, attention deficit hyperactivity disorder (ADHD), fybromyalgia, stomatitis, chronic fatigue syndrome, sepsis, and post-partum bleeding.
[Jacobs J, Springer DA, Crothers D (2001). Homeopathic treatment of acute otitis media in children: a preliminary randomized placebo-controlled trial. Pediatric Infectious Disease Journal, 20:177–183]

[Frei H, Everts R, von Ammon K, Kaufmann F, Walther D, Hsu-Schmitz SF, Collenberg M, Fuhrer K, Hassink R, Steinlin M, Thurneysen A (2005). Homeopathic treatment of children with attention deficit hyperactivity disorder: a randomized, double blind, placebo controlled crossover trial. European Journal of Pediatrics, 164:758–767]

[Bell IR, Lewis DA 2nd, Brooks AJ, Schwartz GE, Lewis SE, Walsh BT, Baldwin CM (2004). Improved clinical status in fibromyalgia patients treated with individualized homeopathic remedies versus placebo. Rheumatology (Oxford), 43:577-582
[Oberbaum M, Yaniv I, Ben-Gal Y, Stein J, Ben-Zvi N, Freedman LS, Branski D (2001). A randomized, controlled clinical trial of the homeopathic medication Traumeel S in the treatment of chemotherapy-induced stomatitis in children undergoing stem cell transplantation. Cancer, 92:684–690]

[Weatherley-Jones E, Nicholl JP, Thomas KJ, Parry GJ, McKendrick MW, Green ST, Stanley PJ, Lynch SP (2004). A randomized, controlled, triple-blind trial of the efficacy of homeopathic treatment for chronic fatigue syndrome. Journal of Psychosomatic Research, 56:189–197]

[Frass M, Linkesch M, Banyai S, Resch G, Dielacher C, Lobl T, Endler C, Haidvogl M, Muchitsch I, Schuster E (2005). Adjunctive homeopathic treatment in patients with severe sepsis: a randomized, double-blind, placebo-controlled trial in an intensive care unit. Homeopathy, 94:75–80]

[Oberbaum M, Galoyan N, Lerner-Geva L, Singer SR, Grisaru S, Shashar D, Samueloff A (2005). The effect of the homeopathic remedies Arnica and Bellis perennis on mild postpartum bleeding – a randomized, double-blind, placebo-controlled study –preliminary results. Complementary Therapies in Medicine, 13:87–90]

On the other hand, there are some conditions for which trial evidence has been non-conclusive or negative.