Supplementary memorandum submitted by Professor Edzard Ernst
Following my oral evidence to the committee on Wednesday 25th November 2009 and having read the written evidence published that day, I am submitting this supplementary memo on the references made to systematic reviews.
The memorandum submitted by 'The British Homeopathic Association' (BHA) contains a section on "systematic reviews of randomised controlled trials" which requires clarification, particularly as numerous other submissions (e.g. those by Dr Lionel R Milgrom, Prof H Walach, Prof G Lewith, Dr Sara Eames, Society of Homeopaths, Complementary Medicine Research Group, Homeopathy Research Institute, Alliance of Registered Homeopaths, Homeopathy: Medicine for the 21st Century, European Central Council of Homeopaths) also allude to the subject of allegedly positive systematic reviews.
2. Comprehensive systematic reviews
The BHA state that 4 of a total of 5 comprehensive reviews reached positive conclusions. These reviews are (full references see submission of BHA):
1. Kleijnen et al, BMJ 19911
2. Boissel et al, 19962
3. Cucherat et al, Eur J Clin Pharm 20003
4. Linde et al, Lancet 19974
5. Shang et al, Lancet 20055
This statement is misleading for the following reasons:
1. The Kleijnen review1 is now 18 years old and thus outdated
2. Boissel et al2 merely combined p-values of the included studies. This article is now also outdated. Furthermore it is not unambiguously positive.
3. Cucherat et al3 is the publication of the Boissel document which was a EU-sponsored report.
4. Linde et al4 has been re-analysed by various authors, including Linde himself, and all of the 6 re-analyses (none of which were cited in the BHA's submission) have come out negative (see my previous submission to this committee).
5. Shang et al5 very clearly arrived at a devastatingly negative overall conclusion.
3. Systematic reviews focussing on particular medical conditions
The BHA cites 17 systematic review of which 5 allegedly "concluded there was positive evidence for homeopathy". These relate to the following conditions.
1. Childhood diarrhoea6
2. Post-operative ileus7
3. Seasonal allergic rhinitis (2 reviews)8;9
This statement is equally misleading for the following reasons:
1. Childhood diarrhoea; this
is a meta-analysis by the
2. Post-operative ileus; this is our own meta-analysis which included the important caveat that the only reliable trial of good quality in our meta-analysis was clearly negative.7
3. Seasonal allergic rhinitis; two reviews/meta-analyses by Wiesnauer8 as well as Taylor9 are analyses of the respective authors' own studies.
4. Vertigo; this is a meta-analysis of Vertigohel, a homeopathically diluted preparation which is administered not according to the philosophy of homeopathy but that of homotoxicology (humans are assumed to be poisoned by toxins, particularly those from pork meat consumption!)10
It seems crucial to stress that one main purpose of science in general and systematic reviews in particular is to insist on independent replication of results. Therefore systematic reviews of author x reviewing nothing but his or her own studies are complete nonsense.
4. Systematic reviews focussing on particular group of diagnoses
Here the BHA claim that 4 positive reviews exist. These relate to
2. Upper respiratory tract infections (2 reviews)12;13
3. Rheumatic diseases14
This statement is misleading for the following reasons:
1. Allergies. The Bellavite article (eCAM 2006)11 is (according to its authors) "a lecture series" not aimed to provided a meta-analysis. It clearly is not a systematic review of controlled clinical trials and includes uncontrolled studies.
2. Upper respiratory tract infections. The Bornhöft article (Forsch Komp Med 2006)12 is not a systematic review of controlled clinical trials but a 'Health Technology Assessment' that includes mostly uncontrolled data. The second Bellaviste article (eCAM 2006)13 has the same limitations as the first (see above).
3. Rheumatic disease. This review14 is based on a selection of the 5 'rheumatic' trials from Linde's Lancet meta-analysis (see above). Not enough trials in any specific rheumatic condition were available to allow firm conclusions. Furthermore, the data can be criticised on the same ground as Linde's original Lancet article (see above).
5. Systematic reviews omitted by the BHA
It should also be noted that the BHA's evidence omits several systematic reviews and meta-analysis which were published. My list is not necessarily complete and includes:
1. Ernst E. Are highly dilute homoeopathic remedies placebos? Perfusion 1998; 11: 291-292.
2. Morrison B, Lilford RJ, Ernst E. Methodological rigour and results of clinical trials of homoeopathic remedies. Perfusion 2000;13:132-138.
3. Ernst E, Pittler MH. Reanalysis of previous meta-analysis of clinical trials of homeopathy. J Clin Epidemiol 2000; 53: 1188.
4. Sterne J, Egger M, Smith, GD. Investigating
and dealing with publication and other biases. In Systematic Reviews in Healthcare: Meta-analysis in Context, eds
Egger M, Smith GD, Altman DG. Pp.189-208.
5. Ernst E. Classical homoeopathy versus conventional treatments: a systematic review. Perfusion 1999; 12: 13-15.
It is noteworthy that all of theses 5 "forgotten" systematic reviews must have been known to the BHA as there were cited in my "systematic review of systematic reviews" (Br J Pharmacol 2002),15 and that all of them arrived at negative conclusions.
6. Specific criticism of the Shang review5
Several submissions (e.g. those by the BHA, Dr Sara Eames and the European Central Council of Homeopaths) criticise specifically the review by Shang et al.5
· Dr Eames states that "all meta-analyses... have been broadly positive until the last one published by Shang et al in the Lancet". The details provided above clearly demonstrate that this is erroneous.
· The European Central Council of Homeopaths state that "7 out of 8... reviews/analyses found results in favour of homeopathy... The 8th study...Shang et al, has since been severely criticised..." Again, the details provided above here show this to be incorrect.
It is, of course, unsurprising that numerous homeopaths tried to find faults with the Shang meta-analysis. It is also clear to me that no such paper can ever be entirely free of limitations. Yet it is equally obvious that Shang et al5 does not stand alone: the vast majority of evaluations by independent experts failed to show that homeopathic remedies are different from placebo.15
(1) Kleijnen J, Knipschild P, Ter Riet G. Clinical trials of homoeopathy. BMJ 1991; 302:316-332.
(2) Boissel JP, Cucherat M, Haugh M, Gauthier E. Critical literature review on the effectiveness of homoeopathy: overview of the homoeopathic medicine trials. In: Homoeopathic Medicine Research Group, Report of the Commision of the European Communities, Directorate-General XII - Science, Research and Development E - RTD Actions: Life Sciences and Technologies - Mewdical 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. Eur J Clin Pharmacol 2000; 56:27-33.
(4) Linde K, Clausius N, Ramirez G, Melchart D, Eitel F, Hedges LV et al. Are the clinical effects of homoeopathy placebo effects? A meta-analysis of placebo-controlled trials. Lancet 1997; 350:834-843.
(5) Shang A, Huwiler-Muntener K, Nartey L, Juni P, Dorig S, Sterne JA 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.
(6) Jacobs J, Jonas WB, Jimenez-Perez M, Crothers D. Homeopathy for childhood diarrhea: combined results and metaanalysis from three randomized, controlled clinical trials. Pediatr Infect Dis J 2003; 22:229-234.
(7) Barnes J, Resch KL, Ernst E. Homeopathy for Postoperative Ileus. J Clin Gastroenterol 1997; 25:628-633.
(8) Wiesenauer M, Lüdtke R. A meta-analysis of the homeopathic treatment of pollinosis with Galphimia glauca. Forsch Komplementarmed Klass Naturheilkd 1996; 3:230-236.
(9) Taylor MA, Reilly D, Llewellyn-Jones RH, McSharry C, Aitchison TC. Randomised controlled trial of homoeopathy versus placebo in perennial allergic rhinitis with overview of four trial series. BMJ 2000; 321:471-476.
(10) Schneider B, Klein P, Weiser M. Treatment of vertigo with a homeopathic complex remedy comapred with usual treatments: a meta-analysis of clinical trials. Arzneimittelforschung 2005; 55:23-29.
(11) Bellavite P, Ortolani R, Pontarolo F, et al. Immunology and homeopathy. 4. Clinical studies - Part 2. eCAM 2006; 3:397-409.
(12) Bornhöft G, Wolf U, von Ammon K, Righetti M, Maxion-Bergemann S, Baumgartner S et al. Effectiveness, safety and cost-effectiveness of homeopathy in general practice - summarized health technology assessment. Forsch Komplementmed 2006; 13(Suppl2):19-29.
(13) Bellavite P, Ortolani R, Pontarolo F, et al. Immunology and homeopathy. 4. Clinical studies - Part 1. eCAM 2006; 3:293-301.
(14) Jonas WB, Linde K, Ramirez G. Homeopathy and rheumatic disease. Rheum Dis Clin North Am 2000; 26:117-123,x.
(15) Ernst E. A systematic review of systematic reviews of homeopathy. Br J Clin Pharmacol 2002; 54:577-582.