Systematic reviews of RCTs

A number of reviews have evaluated the homeopathy research literature. An outline of the most important such papers is given here. Articles that have reviewed other CAM therapies as well as homeopathy have not been included.

Comprehensive reviews

The first systematic review was published in 1991.1 From its 105 trials with interpretable results, 81 indicated positive results, which included RCTs that received high quality ratings for randomisation, blinding, sample size, and other methodological criteria. The authors came to the conclusions: “Based on this evidence we would be ready to accept that homoeopathy can be efficacious, if only the mechanism of action were more plausible” and “the evidence presented in this review would probably be sufficient for establishing homoeopathy as a regular treatment for certain indications”.

In 1996 the Homeopathic Medicine Research Group (HMRG), a joint group of researchers in conventional medicine and homeopathy, was commissioned by the European Commission. The HMRG’s preliminary report contains an overview of clinical research in homeopathy, and identifies 184 controlled clinical trials. They selected the highest quality randomized placebo controlled trials, which included a total of 2,001 patients.2 A full report and update of this review, with at least two new trials added to the meta-analysis and a total of 2,579 patients, found “some evidence that homeopathic treatments are more effective than placebo” (P < 0.001); it concluded that “the strength of this evidence is low because of the low methodological quality of the trials”.3

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 89.4 The overall mean odds ratio for these 89 clinical trials was 2.45 (95% confidence interval 2.05–2.93) in favour of homeopathy (individualized treatment, single or complex homeopathic medicines, or isopathy). Even after correction for publication bias, the results 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 a subsequent analysis of the same data set, Linde and colleagues investigated the influence of indicators of methodological quality on study outcome and found that studies with higher-quality scores had less tendency to be positive than those with lower-quality scores.5After discarding the lower-quality trials, however, homeopathic treatment remained more effective than placebo – though less strikingly so than in their previous analysis. In both of Linde’s systematic reviews, insufficient evidence was found to draw conclusions about the efficacy of homeopathy for any specific medical condition.

A further review aimed to clarify the clinical effectiveness of homeopathy based on systematic reviews only.6 Seventeen review articles fulfilled the inclusion criteria, 6 of which related to re-analyses of Linde’s 1997 meta-analysis. This approach concluded that clinical evidence for homeopathy was lacking. In particular, there was no medical condition that responded convincingly better to homeopathic treatment than to placebo or other control interventions. However, a review of reviews can draw conclusions only about the reviews themselves, not the primary research publications on which they were based.

In 2005, Shang et al. published a meta-analysis comparing 110 placebo-controlled trials of homeopathy and 110 matched trials of conventional medicine.7 Homeopathy and conventional medicine showed a similar positive treatment effect overall. Twenty-one homeopathy trials and 9 in conventional medicine were judged ‘of higher 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 contrast with Linde et al. in 1997, 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 review has been criticised for its lack of transparency. The British Homeopathic Association has re-examined the data included in the Shang meta-analysis, and reports some novel facts about findings from the RCTs of individualised homeopathy.

A grant-funded programme of systematic reviews is providing a more relevant and up-to-date analysis of the research literature.

Systematic reviews with focus on specific clinical areas

The small number of original research papers, the differing criteria reviewers have used for data extraction, the disparate styles of homeopathy used, and the fact that a diverse range of medical conditions has been examined collectively, all restrict the value of formal comprehensive systematic review, such as those attempted by Linde’s and Shang’s groups. The problem of heterogeneity of medical condition has been avoided in 35 systematic reviews focused on RCTs of homeopathy in specific clinical areas.

Nine of these 35 reviews presented conclusions that were positive for homeopathy:
Allergies and upper respiratory tract infections 8,9
Childhood diarrhoea 10
Post-operative ileus 11
Rheumatic diseases 12
Seasonal allergic rhinitis (hay fever) 13–15 
Vertigo 16

Fourteen reviews were non-conclusive (often due to lack of high-quality evidence):
Anxiety 17
Cancer side-effects 18
Chronic asthma 19
Dementia 20
Depression 21
Fibromyalgia 22, 23
Induction of labour 24
Influenza treatment 25
Irritable bowel syndrome 26
Osteoarthritis 27
Psychiatric disorders 28
Rheumatoid arthritis 29
Seasonal allergic rhinitis (hay fever) 30 

Little or no evidence for homeopathy has been the conclusion in:
Ailments of childhood and adolescence 31
Attention deficit hyperactivity disorder 32
Cancer treatment 33
Delayed-onset muscle soreness 34
Eczema 35
Headache and migraine 36, 37
Influenza prevention 25
Insomnia 38, 39

Homeopathic Arnica has been the subject of three systematic reviews: one reached a negative conclusion;40 more recent reviews have been non-conclusive.41, 42

Some Cochrane reviews have recommended that, as well as randomized trials, there is a need for observational data to document the different methods of homeopathic prescribing and how patients respond. For example, McCarney, et al. (2004) commented that such data “will help to establish to what extent people respond to a ‘package of care’ rather than the homeopathic intervention alone”.19

References:

1. Kleijnen J, Knipschild P, ter Riet G. Clinical trials of homoeopathy British Medical Journal, 1991; 302: 316–323.

2. Boissel JP, Cucherat M, Haugh M, Gauthier E. Critical literature review on the effectiveness of homoeopathy: overview of data from homoeopathic medicine trials. In: Homoeopathic 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, Belgium, 1996.

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

4. Linde K, Clausius N, Ramirez G, et al. Are the clinical effects of homoeopathy placebo effects? A meta-analysis of placebo-controlled trials. Lancet, 1997; 350: 834–843.

5. Linde K, Scholz M, Ramirez G, et al. Impact of study quality on outcome in placebo controlled trials of homeopathy. Journal of Clinical Epidemiology, 1999; 52: 631–636.

6. Ernst E. A systematic review of systematic reviews of homeopathy. British Journal of Clinical Pharmacology, 2002; 54: 577–582.

7. Shang A, Huwiler-Muntener K, Nartey L, et al. Are the clinical effects of homoeopathy placebo effects? Comparative study of placebo-controlled trials of homoeopathy and allopathy. Lancet, 2005; 366: 726–732.

8. Bornhöft G, Wolf U, Ammon K, et al. Effectiveness, safety and cost-effectiveness of homeopathy in general practice – summarized health technology assessment. Forschende Komplementärmedizin, 2006; 13 Suppl 2: 19–29.

9. Bellavite P, Ortolani R, Pontarollo F, et al. Immunology and homeopathy. 4. Clinical studies – Part 1. Evidence-based Complementary and Alternative Medicine: eCAM, 2006; 3: 293–301.

10. Jacobs J, Jonas WB, Jimenez-Perez M, Crothers D. Homeopathy for childhood diarrhea: combined results and metaanalysis from three randomized, controlled clinical trials. Pediatric Infectious Disease Journal, 2003; 22: 229–234.

11. Barnes J, Resch K-L, Ernst E. Homeopathy for postoperative ileus? A meta-analysis. Journal of Clinical Gastroenterology, 1997; 25: 628–633.

12. Jonas WB, Linde K, Ramirez G. Homeopathy and rheumatic disease. Rheumatic Disease Clinics of North America, 2000; 26: 117–123.

13. Wiesenauer M, Lüdtke R. A meta-analysis of the homeopathic treatment of pollinosis with Galphimia glauca. Forschende Komplementärmedizin und Klassische Naturheilkunde, 1996; 3: 230–236.

14. Taylor MA, Reilly D, Llewellyn-Jones RH, et al. Randomised controlled trials of homoeopathy versus placebo in perennial allergic rhinitis with overview of four trial series. British Medical Journal, 2000; 321: 471–476.

15. Bellavite P, Ortolani R, Pontarollo F, et al. Immunology and homeopathy. 4. Clinical studies – Part 2. Evidence-based Complementary and Alternative Medicine: eCAM, 2006; 3: 397–409.

16. Schneider B, Klein P, Weiser M. Treatment of vertigo with a homeopathic complex remedy compared with usual treatments: a meta-analysis of clinical trials. Arzneimittelforschung, 2005; 55: 23–29.

17. Pilkington K, Kirkwood G, Rampes H, et al. Homeopathy for anxiety and anxiety disorders: A systematic review of the research. Homeopathy, 2006; 95: 151–162.

18. Kassab S, Cummings M, Berkovitz S, et al. Homeopathic medicines for adverse effects of cancer treatments (Cochrane Review). In: The Cochrane Library. Chichester, UK: John Wiley & Sons, Ltd. CD004845, 2009.

19. McCarney RW, Linde K, Lasserson TJ. Homeopathy for chronic asthma (Cochrane Review). In: The Cochrane Library. Chichester, UK: John Wiley & Sons, Ltd. CD000353, 2004.

20. McCarney R, Warner J, Fisher P, van Haselen R. Homeopathy for dementia (Cochrane Review). In: The Cochrane Library. Chichester, UK: John Wiley & Sons, Ltd. CD003803, 2004.

21. Pilkington K, Kirkwood G, Rampes H, et al. Homeopathy for depression: a systematic review of the research evidence. Homeopathy, 2005; 94: 153–163.

22. Perry R, Terry R, Ernst E. A systematic review of homoeopathy for the treatment of fibromyalgia. Clinical Rheumatology, 2010; 29:457–464.

23. Boehm K, Raak C, Cramer H, Lauche R, Ostermann T. Homeopathy in the treatment of fibromyalgia – A comprehensive literature-review and meta-analysis. Complementary Therapies in Medicine, 2014; 22: 731–742.

24. Owen JM, Green BN. Homeopathic treatment of headaches: A systematic review of the literature. Journal of Chiropractic Medicine, 2004; 3: 45–52.

24. Smith CA. Homoeopathy for induction of labour (Cochrane Review). In: The Cochrane Library. Chichester, UK: John Wiley & Sons, Ltd. CD003399, 2004.

25. Mathie RT, Frye J, Fisher P. Homeopathic Oscillococcinum® for preventing and treating influenza and influenza-like illness (Cochrane Review). In: The Cochrane Library. Chichester, UK: John Wiley & Sons, Ltd. CD001957, 2012.

26. Peckham EJ, Nelson EA, Greenhalgh J, Cooper K, Roberts ER, Agrawal A. Homeopathy for treatment of irritable bowel syndrome (Cochrane Review). In: The Cochrane Library, Chichester, UK: John Wiley & Sons, Ltd. CD009710, 2013.

27. Long L, Ernst E. Homeopathic remedies for the treatment of osteoarthritis: a systematic review. British Homeopathic Journal, 2001; 90: 37–43.

28. Davidson JR, Crawford C, Ives JA, Jonas WB (2011). Homeopathic treatments in psychiatry: a systematic review of randomized placebo-controlled studies. Journal of Clinical Psychiatry, 72: 795–805.

29. Saha, Koley M, Medhurst R. A meta-analysis of the randomized controlled trials of individualized homeopathy in rheumatoid arthritis. World Journal of Pharmacy and Pharmaceutical Sciences, 2013; 2: 2097-2117.

30. Ernst E. Homeopathic Galphimia glauca for hay fever: A systematic review of randomised clinical trials and a critique of a published meta-analysis. Focus on Alternative and Complementary Therapies, 2011; 16: 200–203.

31. Altunç U, Pittler MH, Ernst E. Homeopathy for childhood and adolescence ailments: systematic review of randomized clinical trials. Mayo Clinic Proceedings, 2007; 82: 69–75.

32. Coulter MK, Dean ME. Homeopathy for attention deficit/hyperactivity disorder or hyperkinetic disorder (Cochrane Review). In: The Cochrane Library. Chichester, UK: John Wiley & Sons, Ltd. CD005648, 2007.

33. Milazzo S, Russell N, Ernst E. Efficacy of homeopathic therapy in cancer treatment. European Journal of Cancer, 2006; 42: 282–289.

34. Ernst E, Barnes J. Are homoeopathic remedies effective for delayed-onset muscle soreness? – A systematic review of Placebo-controlled trials. Perfusion (Nürnberg), 1998; 11: 4–8.

35. Ernst E. Homeopathy for eczema: a systematic review of controlled clinical trials. British Journal of Dermatology, 2012; 166: 1170-1172.

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

37. Owen JM, Green BN. Homeopathic treatment of headaches: A systematic review of the literature. Journal of Chiropractic Medicine, 2004; 3: 45–52.

38. Cooper KL, Relton C. Homeopathy for insomnia: A systematic review of research evidence. Sleep Medicine Reviews 2010; 14: 329–337.

39. Ernst E. Homeopathy for insomnia and sleep-related disorders: A systematic review of randomised controlled trials. Focus on Alternative and Complementary Therapies, 2011; 16: 195–199.

40. Ernst E, Pittler MH. Efficacy of homeopathic arnica. A systematic review of placebo-controlled clinical trials. Archives of Surgery, 1998; 133: 1187–1190.

41. Lüdtke R, Hacke D. On the effectiveness of the homeopathic remedy Arnica montana. Wiener Medizinische Wochenschrift, 2005; 155: 482–490.

42. Iannitti T, Morales-Medina JC, Bellavite P, Rottigni V, Palmieri B. Effectiveness and safety of Arnica montana in post-surgical setting, pain and inflammation. American Journal of Therapeutics, 2014; Sep 17 [Epub ahead of print].

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