MD, PhD, FMedSci, FRSB, FRCP, FRCPEd

bias

Guest Post by Jan Willem Nienhuys

The so-called Swiss government report of 2011 on homeopathy was actually an expanded translation of a 2006 book, which in itself was an expanded version of a document submitted to a Swiss committee (PEK) in charge of evaluation of alternative medicine. It has been severely criticised. A summary of criticisms with links can be found on the RationalWiki item to which we may add the Zeno’s Blog. I present here the results of my scrutiny of chapter 10 (1), although I base my report on the original German edition.

This chapter by itself shows a familiar result: the better the investigation, the less evidence in favor of homeopathy it shows. It shows also how homeopaths systematically distort unfavorable results by mispresenting them. Chapter 10 deals with clinical investigations of homeopathy. The authors restrict their attention to an odd assortment of diseases such as acute rhinitis, allergic rhinitis, allergic asthma, sinusitis, adenoid vegetations, pharyngitis, tonsillitis, influenza-like infection and otitis media, together denoted as ‘upper respiratory tract infections/allergic reactions’ or URTI/A for short.

The number of papers reviewed is very small. The authors looked at much more than randomized clinical trials. Apparently their search did not extend further than 2003, but then they might have found over 150 papers, of which about one third double blind randomized trials that compared how well highly diluted homeopathy and placebo cured one of the indicated diseases. They managed to miss 25 papers mentioned in earlier meta-analyses and about four papers that are summarized in Pubmed.

Among the papers they missed is an extremely strong support for the claim ‘homeopathy works for URTI/A’. For example Riverón-Garrote et al. (2) did a placebo controlled double blind randomized clinical trial of homeopathy (apparently individualised) for asthma. Of about 33 verum patients 32 improved, whereas of about 30 placebo patients only 4 improved. The so-called p-value for such a result is less than 10–11. One wonders why this result wasn’t published in Science or Nature, but only in an obscure Spanish language homeopathic journal. Maybe the paper was excluded because it didn’t state that it was about allergic asthma, but note that in about three quarters of all asthma some kind of allergy is implicated.

Of course this pales in comparison to the paper by Friese and Zabalotnyi (3). Again a double blind randomised clinical trial with 72 sinusitis sufferers for both verum and placebo. But here 71 out of 72 verum patients were free of complaints after three weeks, or at least improved, whereas this was the case for only 8 of the placebo patients. Fisher’s Exact Test gives p = 2.47 times 10-29 (one tailed). A remarkable result, because it is well known that over 80% of sinusitis cases cures spontaneously within two weeks. Maybe placebos are dangerous in the hands of homeopaths. Again one wonders why Friese and Zabalotnyi didn’t share the Nobel prize in, say, 2008, and why it is necessary at all to meticulously analyse papers in which homeopathy shows a marginal advantage.

Instead, Maxion-Bergemann et al. include in their survey a paper by Bahemann (4). We quote the summary of the paper from the internet: ‘In homeopathic practice, Kalium bromatum is known as a remedy in the case of paranoid delusions, e. g. if someone suffers from the delusion of being the object of divine revenge, of being damned, or of being pursued. It is also a very important remedy in the case of nocturnal fears in children as well as in the case of convulsions, when they are hereditary, when they occur in childbed, or during teething. The following case demonstrates the successful treatment of a severe mononucleosis after studying the Materia medica.’ Mononucleosis isn’t even mentioned in the list given that specifies URTI/A. Maybe it was included because one of the symptoms of mononucleosis is a sore throat. Apparently the mononucleosis patient was given Kalium Bromatum (Maxion-Bergemann et al. state that it is Kalium Chromatum 200C, presumably Chromatum and Bromatum don’t differ too much to bother) because of something remarkable the patient said during the anamnesis. The reason for giving Kalium bromatum 200C in cases of paranoia might be that an overdose of bromide can induce psychoses. The homeopathic Materia Medica contains quite a few ‘symptoms’ from accidental poisonings reported in old medical literature; potassium bromide was liberally used in the nineteenth century for the calming of seizure and nervous disorders, according to Wikipedia.

More impressive in the list of 13 RCTs of Maxion-Bergemann are two of the largest ‘homeopathic’ trials known, namely of the remedy Oscillococcinum. These trials cannot be taken seriously. The first one, by Ferley et al. (5), has one glaring fault. They started with 478 ‘influenza’-patients (237 verum), tried to make 149 family physicians note down when the patients recovered, and then elected to restrict their attention to the 63 patients (39 verum) that recovered within 48 hours and therefore probably didn’t have flu at all. Coincidentally this was the only possibility out of 14 that gave a ‘significant’ result: correctly computed, p is just below 0.05. (Ferley et al. based their computation on 462 patients with 228 verum and applied a chi-squared test without continuity correction). It is hardly credible that they set this 48-hour criterion in advance, because even if the remedy worked, the risk of having too few subjects to get a significant result would have been considerable. But if one picks out one result among many possibilities, one should correct for multiple outcome. So the Ferley et al. investigation is at most an exploratory result in need of independent confirmation.

This ‘confirmation’ was undertaken soon afterwards, namely in the beginning of 1991, but the results were only published in 1998 and cannot be found on Pubmed (6). In this paper the definitions are somewhat different, but Papp et al. report that of 334 patients (167 verum) a total of 57 (32 verum) were cured in 48 hours. Now 25 versus 32 is not remarkable at all. One doesn’t need any elaborate computation for this. Calculation gives p=0.4. So one might think that the Ferley hypothesis was soundly refuted. But Papp et al. used something they call ‘the Krauth test’, probably some kind of automated post hoc fishing trip to select the best criteria to distinguish the placebo and verum groups. They claim that this ‘test’ gives p=0.0028. They specifically refer to ‘the null hypothesis (the number of patients free of symptoms after 48 hours is equal in both treatment groups)’, so their computation is wrong. The most remarkable thing about Papp et al. is that nobody seems to have to have noticed the large discrepancy between what the numbers say and the claim of the paper.

Another paper with ‘positive’ results is the 1994 study of Reilly et al. (7), number 28 in Maxion-Bergemann et al. The group of Reilly investigated allergic diseases treated by what they called homeopathy. The typical Reilly experiment consists of administering a highly diluted causative agent such as pollen or house dust mite or cat hairs or bird feathers to persons suffering from pollen allergy (seasonal rhinitis) or allergic asthma. However for true homeopathy one uses a substance that has been the subject of a so-called proving, and the remedy is chosen of the totality of all patient ‘symptoms’ – including things like sleeping position and fear of thunderstorms – sufficiently matches the symptoms of the proving. Let me call Reilly’s method ultra-isopathy. Reilly was already discussing this study on a symposium in 1990, but that paper is not clear. It is about 28 asthma patients, and only 24 were analysed. This small number in itself is already reason enough not to consider it. The main analysis was by comparing a subjective measure of wellbeing, the Visual Analog Scale (VAS). Here we find a significant difference (p=0.003) in favor of ultra-isopathy. However, in the small print we see that change in the very important FEV1-value (Forced Expiratory Volume in 1 second) was non-significant (p=0.08) but this refers only to the 18 patients that took such a test before and after the experiment.

Reilly attracted more attention with his first experiment in this vein (8). He started out with 79 patients in both the verum and the placebo group. The treatment was ultradiluted grass pollen for hay fever. The analysis was only about 56 verum and 52 placebo (in a diagram 53 placebo are shown). Such a large dropout (32%) is not good. On basis of the VAS-scores Reilly found p=0.02. VAS is only an ordinal scale and it is not at all clear that one person’s 60 mm means the same as another person’s 60 mm, and also not that two patients with respectively 40 mm and 80 mm together can be considered as equivalent to two other patients with 60 mm each. If we distinguish only better / equal / worse, then the numbers for the verum group were 34 / 9 / 13 and for the placebo group 27 / 5 / 21. One can analyse this in various ways: as a 3 by 2 contingency table (p=0.15), or as a 2 by 2 table, namely by joining the middle group either to the right (p=0.10) or to the left (p=0.34). In this manner the difference is less impressive.

Maxion-Bergemann et al. collected 29 articles. I take the liberty of removing from these everything that is not a double blind RCT that compares how well highly diluted homeopathy and placebo cures an URTI/A disease. We also remove all research with 50 or less patients. The more or less openly fraudulent or at least grossly mistaken Oscillococcinum trials I also leave out. In order of appearance we have then Wiesenauer 1985 (9) [8] Reilly 1986 (8) [6] Wiesenauer 1989 (10) [10] De Lange-de Klerk 1994 (11) [1] Aabel 2000 (12) [4] Jacobs 2001 (13) [22] Friese 2001 (14) [24] Lewith 2002 (15) [25] White 2003 (16) [29] The square brackets refer to the numbering in Maxion-Bergemann et al. A short review of these nine articles follows.

Wiesenauer 1985: one standard remedy for hayfever. Randomised 213 patients, analysed only 164. “no statistical significance was achieved” says the abstract on Pubmed. Reilly 1986: this we have discussed already. Ultra-isopathy for hayfever. Randomised 158 patients, analysed 108. Statistically significant, but barely so. Wiesenauer 1989: four groups, each with their own standard remedy or placebo for sinusitis, 152 patients. “There was no remarkable difference in the therapeutic success among the investigated homeopathic drug combinations nor between the active drugs and placebo”, according to the abstract in Pubmed De Lange-de Klerk 1994: this research was reported more extensively in the lead author’s dissertation (17). Individualised homeopathy for recurrent URTI in children. 175 children were randomised and 170 analysed after following them for a year. 128 different remedies/potencies were prescribed and all together 1042 different prescriptions were handed out. The result was a non-significant difference between homeopathy and placebo. One striking aspect of this investigation is that only after all computations were done, it was revealed which of the two groups was the placebo group and which the verum group. So the author or her thesis advisors deliberately made it impossible to fall for the temptation to start a fishing expedition in the data after the code was completely broken. See also Pubmed. Aabel 2000: ultra-isopathy for birch pollen allergy. Strictly speaking this investigation shouldn’t be in this short list because it was partly prophylactic. From Pubmed: “Surprisingly, the verum treated patients fared worse than the placebo group”. No measure of statistical significance is mentioned. Remarkably this article is preceded by a similar article (18) that Maxion-Bergemann et al. apparently weren’t able to locate. Jacobs 2001: 75 children with otitis media were treated with individualised homeopathy or placebo. Pubmed: “differences were not statistically significant”. It seems that Jacobs has indulged in a fishing trip because she mentions a “significant decrease in symptoms at 24 and 64 h after treatment in favor of homeopathy”. But that is wrong. Significance only can have a meaning if it refers to a single outcome that was planned before any patients were seen. Just picking out two results out of many and stating they are ‘significant’ betrays a fundamental ignorance of research methodology. Friese 2001: this article is also published elsewhere (19), at least the numbers are exactly the same according to Pubmed. 97 children randomized for either individual homeopathic treatment or placebo treatment of adenoid vegetations, 82 analysed. Apparently these 82 comprised 41 placebo and 41 verum, and of these 12 and 9 respectively required an operation in the end. This allegedly corresponds to p=0.64, “These results show no statistical significance.” Incidentally, this is the same Friese as reference 3. Lewith 2002: again ultra-isopathy, now for asthma, 242 patients randomised, 202 completed all clinical assessments. The full article can be accessed via Pubmed and elsewhere. The main conclusion is “Homoeopathic immunotherapy is not effective in the treatment of patients with asthma.” The authors notice that the averages in both groups behave somewhat erratic, and they have no explanation for this. White 2003: individualised homeopathy compared to placebo for 96 children with asthma, who are followed for 12 months. The conclusion is that there is no evidence that this kind of homeopathy is better than placebo. In other words, out of nine investigations only one (Reilly 1986) obtains a barely significant result.

But the interpretation of Maxion-Bergemann et al. is totally different: “If only the placebo-controlled, randomized trials with the highest EBM evidence are considered, 12 of 16 trials show a positive result for the homeopathically treated group (significantly positive 8/16 and trend 4/16).” Even in the more restricted subset of nine discussed above they are overly optimistic. They mark Wiesenauer (1985), De Lange-de Klerk (1994), Jacobs (2001) as showing a ‘trend for homeopathy’ and Lewith (2002) is even marked ‘significant’. The meticulous and high quality research of De Lange (1993, 1994) is judged ‘trend for homeopathy’.

In case of De Lange it seems clear where this judgement comes from. De Lange had several outcomes (number of sick periods, total duration of sick periods, sum of all dayscores etc., and all these showed roughly the same small non-significant difference in favor of homeopathy. This is not really strange, because these outcomes all measure about the same phenomenon. It is not remarkable that there is a small difference between the averages of the two groups that can only be noticed if the children are followed for a full year. There is not even the beginning of a reason that this has anything to do with the treatment. For example the homeopathy group had ‘significantly’ less pets at home. This might serve as an explanation why they as a group were slightly less sick. One might also speculate that this was retroactively caused by the homeopathic treatment. This is not really more improbable than highly diluted stuff (more than 95% D6 and higher) having an effect.

By convention ‘statistically significant’ is the lower limit where weak conclusions such as ‘worth investigating further’ can be justified, and we repeat: only if it refers to a single outcome measure or endpoint chosen before any data collection has started. De Lange chose recurrent URTI because homeopathy was reputed to be most effective for this type of complaints, especially after investigations such as those of Reilly (1986). If following 170 children for a full year cannot show a clear advantage, then that is simply a negative result. In the case of Lewith the ‘significant for homeopathy’ is probably based on partial results such as that in week 3 ‘homeopathy’ fared better in the asthma VAS. One can just as well point to week 16 where the FEV1 of the placebo group seems much better than in the homeopathy group.

Maxion-Bergemann et al. seem to have been singularly inept in collecting papers on homeopathic trials, and for no apparent reason they decided to look also at a large number of case reports and investigations without control group or blinding, even after investigators as early as 1991 have remarked that henceforth only well designed large double blind RCTs were worth considering. If we restrict our attention to the properly blinded controlled investigations, we see the same thing as in other meta-analyses of homeopathy: there is lots of rubbish in favor of homeopathy, but the good trials say plainly and clearly: homeopathy is ineffective, precisely what can be predicted from the fact that there is nothing in it.

Homeopaths nowadays have a lot to say about RCTs and how they prove homeopathy. RCTs are subtle and complicated scientific tools. It is somewhat strange to see how homeopaths resolutely ignore two centuries of basic science but then argue their cause on the basis of complicated statistics.

Homeopathy is an assortment of wildly different practices and theories. We have seen ultra-isopathy, individualised homeopathy and the practice of giving one standardised remedy for one diagnosis without asking too many personal details from the patient. These standard remedies are often branded mixtures of highly diluted ‘classical’ homeopathy, quite contrary to the opinions of homeopathy’s inventor Hahnemann. There are many more variants of homeopathy and the homeopaths themselves cannot agree which are the correct ones.

Moreover, if a treatment or trial doesn’t work out, then a number of additional hypotheses about homeopathy can be invoked, which is what Maxion-Bergemann et al. do. Homeopathic remedies supposedly are counteracted by lots of regular medications and even by strong tasting or smelling food, such as coffee, parsley, garlic and peppermint. Hahnemann even disapproved of reading in bed and long afternoon naps and prolonged suckling of infants (Organon, section 260). Poor performance of homeopathy can be blamed on something called ‘initial aggravation’ or else on lack of experience of the poorly performing homeopath.

But that these factors are relevant at all is unknown, just like there is no proof at all for the similia principle, nor for the hundred thousands or even millions of ‘symptoms’ associated with highly diluted materials in the homeopathic Materia Medica. If homeopaths really want scientists to share homeopathic beliefs, they should not think up lame excuses for ‘failed’ tests, but for starters they might try to present proofs for all or at least some of their ‘symptoms’. They don’t try very hard and in so far it has been tried, it also has failed (20).

I would like to thank Willem Betz for helpful remarks.

I am a retired mathematician with no other interest than a desire to promote science.

References

1. Stefanie Maxion-Bergemann, Gudrun Bornhöft, Denise Bloch, Christina Vogt-Frank, Marco Righetti, André Thurneysen. (2011) Clinical Studies on the Effectiveness of Homeopathy for URTI/A (Upper Respiratory Tract Infections and Allergic Reactions) in: Homeopathy in Healthcare – Effectiveness, Appropriateness, Safety, Costs. G. Bornhöft and P.F. Mattheiesen (eds.), Berlin etc., Springer 2011, p. 18-157.

2. Riverón-Garrote, M., Fernandez-Argüelles, R.; Morán-Rodríquez, F.; Campistrou-Labaut, J.L. (1998) Ensayo clínico controlado aleatorízado del tratamiento homeopático del asma bronquial, Boletín Mexicano de Homepatía 1998; 31(2):54-61.

3. Friese, K.-H., Zabalotnyi, D.I. (2007) Homöopathie bei akuter Rhinosinusitis, Eine doppelblinde, placebokontrollierte Studie belegt die Wirksamkeit und Verträglichkeit eines homöopathischen Kombinationsarzneimittels, HNO 55(4):271-277.

4. Bahemann A. (2002) Kalium bromatum bei infektiöser Mononukleose. Zeitschrift für Klassische Homöopathie 46:232–233.

5. Ferley J.P., Zmirou D., D’Adhemar D., Balducci F. (1989). A controlled evaluation of a homoeopathic preparation in the treatment of influenza like syndromes. British Journal of Clinical Pharmacology 27:329-335.

6. Papp R., Schuback G., Beck E., Burkard G., Bengel J., Lehrl S., Belon P. (1998). Oscillococcinum in patients with influenza-like syndromes: a placebo-controlled double-blind evaluation. British Homeopathic Journal 87:69-76.

7. Reilly, D.T., Taylor, M.A., Beattie, N.G.M., Campbell, J.H., McSharry C., Aitchison T.C., Carter R., Stevenson R. (1994) Is evidence for homoeopathy reproducible?, Lancet 1994 344:1601-1606.

8. Reilly, D.T., Taylor, M.A., McSharry, C., Aitchison, T. (1986) Is Homoeopathy a Placebo Response?, Controlled Trial of Homoeopathic Potency – With Pollen in Hayfever as Model, Lancet II.2:881-886.

9. Wiesenauer, M., Gaus, W. (1985) Double-blind Trial Comparing the Effectiveness of Galphimia Potentisation D6 (Homoeopathic Preparation), Galphimia Dilution 10-6 and Placebo on Pollinosis, Arzneimittelforschung 35(11):1745-1747.

10. Wiesenauer M, Gaus W, Bohnacker U, Häussler S (1989) Wirksamkeitsprüfung von homöopathischen Kombinationspräparaten bei Sinusitis: Ergebnisse einer randomisierten Doppelblindstudie unter Praxisbedingungen. Arzneimittelforschung 39:620-625.

11. de Lange-de Klerk E.S.M., Blommers J., Kuik D.J., Bezemer P.D., Feenstra L. (1994). Effects of homoeopathic medicines on daily burden of symptoms in children with recurrent upper respiratory tract infections. BMJ 309:1329-1332.

12. Aabel, S. (2000) No beneficial effect of isopathic prophylactic treatment for birch pollen allergy during a low-pollen season, A double-blind, placebo-controlled clinical trial of homeopathic Betula 30c. British Homeopathic Journal 89(4):169-173.

13. Jacobs, J., Springer, D.A., Crothers, D. (2001) Homeopathic treatment of acute otitis media in children, A preliminary randomized placebo-controlled trial. The Pediatric Infectious Disease Journal 20(2):177-183.

14. Friese K.H., Feuchter U., Lüdtke R., Moeller H. (2001) Results of a randomised prospective double-blind trial on the homeopathic treatment of adenoid vegetations. European Journal of General Practice 7:48-54.

15. Lewith, G.T., Watkins, A.D.; Hyland, M.E.; Shaw, S.; Broomfield, J.A.; Dolan, G.; Holgate, S.T. (2002) Use of ultramolecular potencies of allergen to treat asthmatic people allergic to house dust mite: double blind randomised controlled clinical trial, BMJ 324:520-523.

16. White, A., Slade, P.; Hunt, C.; Hart, A.; Ernst, E. (2003) Individualised homeopathy as an adjunct in the treatment of childhood asthma, A randomised placebo controlled trial. Thorax 58(4):317-321

17. Lange-de Klerk, E.S.M. de, Effects of homoeopathic medicines on children with recurrent upper respiratory tract infections. Vrije Universiteit Amsterdam, 1993 (Dissertation).

18. Aabel, S., Laerum, E.; Dölvik, S.; Djupesland, P. (2000) Is homeopathic ‘immunotherapy’ effective?, A double-blind, placebo-controlled trial with the isopathic remedy Betula 30c for patients with birch pollen allergy. British Homeopathic Journal 89(4):161-168.

19. Friese K.-H., Feuchter U., Möller H. (1997). Die homöopathische Behandling von adenoiden Vegetationen. HNO; 45:618–624.

20. Brien S., Lewith G., Bryant, T. (2003) Ultramolecular homeopathy has no observable clinical effects. A randomized, double-blind, placebo-controlled proving trial of Belladonna 30C.

A recent meta-analysis evaluated the efficacy of acupuncture for treatment of irritable bowel syndrome (IBS) and arrived at bizarrely positive conclusions.

The authors state that they searched 4 electronic databases for double-blind, placebo-controlled trials investigating the efficacy of acupuncture in the management of IBS. Studies were screened for inclusion based on randomization, controls, and measurable outcomes reported.

Six RCTs were included in the meta-analysis, and 5 articles were of high quality.  The pooled relative risk for clinical improvement with acupuncture was 1.75 (95%CI: 1.24-2.46, P = 0.001). Using two different statistical approaches, the authors confirmed the efficacy of acupuncture for treating IBS and concluded that acupuncture exhibits clinically and statistically significant control of IBS symptoms.

As IBS is a common and often difficult to treat condition, this would be great news! But is it true? We do not need to look far to find the embarrassing mistakes and – dare I say it? – lies on which this result was constructed.

The largest RCT included in this meta-analysis was neither placebo-controlled nor double blind; it was a pragmatic trial with the infamous ‘A+B versus B’ design. Here is the key part of its methods section: 116 patients were offered 10 weekly individualised acupuncture sessions plus usual care, 117 patients continued with usual care alone. Intriguingly, this was the ONLY one of the 6 RCTs with a significantly positive result!

The second largest study (as well as all the other trials) showed that acupuncture was no better than sham treatments. Here is the key quote from this trial: there was no statistically significant difference between acupuncture and sham acupuncture.

So, let me re-write the conclusions of this meta-analysis without spin, lies or hype: These results of this meta-analysis seem to indicate that:

  1. currently there are several RCTs testing whether acupuncture is an effective therapy for IBS,
  2. all the RCTs that adequately control for placebo-effects show no effectiveness of acupuncture,
  3. the only RCT that yields a positive result does not make any attempt to control for placebo-effects,
  4. this suggests that acupuncture is a placebo,
  5. it also demonstrates how misleading studies with the infamous ‘A+B versus B’ design can be,
  6. finally, this meta-analysis seems to be a prime example of scientific misconduct with the aim of creating a positive result out of data which are, in fact, negative.

Homeopathy is a deeply puzzling subject for many observers. Perhaps it gets a little easier to understand, if we consider the three main perspectives on homeopathy. For the purpose of this post, I take the liberty of exaggerating, almost caricaturizing, these perspectives in order to contrast them as clearly as possible.

THE SCEPTICS’ PERSPECTIVE

Sceptics take a brief look at the two main assumptions which underpin homeopathy (like cures like and potentiation/dilution/water memory) and henceforward are convinced that homeopathic remedies are pure placebos. Homeopathy flies in the face of science; if homeopathy is right, several laws of nature must be wrong, they love to point out. As this is most unlikely, they reject homeopathy outright, usually even without looking in any detail at what homeopaths consider to be evidence in support of their trade. If sceptics are forced to consider a positive study of homeopathy, they know before they have seen it that its results are wrong – due to an error caused by chance, faulty study design or fabrication. The sceptics’ conclusion on homeopathy: it is a placebo-therapy, no doubt about it; and further investment into research is a waste of scarce resources which must be stopped.

THE BELIEVERS’ PERSPECTIVE

The believers in homeopathy know from experience that homeopathy works. They therefore feel that they have no choice but to reject almost every word the sceptics might tell them. They cling on to the gospel of Hahnemann and elaborate on the modern but vague theories that might support the theoretical assumptions of homeopathy. They point to positive clinical trials and outcome studies, to 200 years of experience, and to the endorsement of homeopathy by VIPs. When confronted with the weaknesses of their arguments, they find even weaker ones, such as ‘much of conventional medicine is also not based on good evidence, and the mechanism of action of many mainstream drugs is also not fully understood’. Alternatively, they employ the phoniest argument of them all: ‘even if it works via a placebo effect, it still helps patients and therefore is a useful therapy’. When even this fails, they tend to resort to ad hominem attacks against their opponents. The believers’ conclusion on homeopathy: it is unquestionably a valuable type of therapy regardless of what anyone else might say; research is merely needed to confirm their belief.

THE PERSPECTIVE OF THE ADVOCATES OF EVIDENCE-BASED MEDICINE (EBM)

The perspective of EBM-advocates is pragmatic; they simply say: “show me the evidence!” If the majority of the most reliable clinical trials of homeopathic remedies (or anything else) suggests an effect beyond placebo, they conclude that they are effective. If that is not the case, they doubt the effectiveness. If the evidence is highly contradictory or incomplete, they are likely to advocate more rigorous research. Advocates of EBM are usually not all that concerned by the lack of plausibility of the interventions they evaluate. If it works, it works, they think – and if a plausible mechanism is currently not available, it might be found in due course. The advocates of EBM have no preconceived ideas about homeopathy. Their conclusion on homeopathy goes exactly where the available best evidence leads them.

COMMENT

The arguments and counter-arguments originating from the various perspectives would surely continue for another 200 years – unless, of course, two of the three perspectives merge and arrive at the same or very similar conclusions. And this is precisely what has now happened. As I have pointed out in a recent post, the most thorough and independent evaluation of homeopathy according to rigorous EBM-standards has concluded that “the evidence from research in humans does not show that homeopathy is effective for treating the range of health conditions considered.”

In other words, two of the three principal perspectives have now drawn conclusions which are virtually identical: there is a consensus between the EBM-advocates and the sceptics. This isolates the believers and renders their position no longer tenable. If we furthermore consider that the believers are heavily burdened with obvious conflicts of interest, while the other two groups are by definition much more independent and objective, it appears more and more as though homeopathy is fast degenerating into a cult characterised by the unquestioning commitment and unconditional submission of its members who are too heavily brain-washed to realize that their fervour has isolated them from the rational sections of society. And a cult is hardly what we need in heath care, I should think.

It seems to me therefore that these intriguing developments might finally end the error that homeopathy represented for nearly 200 years.

Progress at last?

Recently, I have been invited by the final year pharmacy students of the ‘SWISS FEDERAL INSTITUTE OF TECHNOLOGY ZURICH‘ to discuss alternative medicine with them. The aspect I was keen to debate was the issue of retail-pharmacists selling medicines which are unproven or even disproven. Using the example of homeopathic remedies, I asked them how many might, when working as retail-pharmacists, sell such products. About half of them admitted that they would do this. In real life, this figure is probably closer to 100%, and this discrepancy may well be a reflection of the idealism of the students, still largely untouched by the realities of retail-pharmacy.

In our discussions, we also explored the reasons why retail-pharmacists might offer unproven or disproven medicines like homeopathic remedies to their customers. The ethical codes of pharmacists across the world quite clearly prohibit this – but, during the discussions, we all realised that the moral high ground is not easily defended against the necessity of making a living. So, what are the possible motivations for pharmacists to sell bogus medicines?

One reason would be that they are convinced of their efficacy. Whenever I talk to pharmacists, I do not get the impression that many of them believe in homeopathy. During their training, they are taught the facts about homeopathy which clearly do not support the notion of efficacy. If some pharmacists nevertheless were convinced of the efficacy of homeopathy, they would obviously not be well informed and thus find themselves in conflict with their duty to practice according to the current best evidence. On reflection therefore, strong positive belief can probably be discarded as a prominent reason for pharmacists selling bogus medicines like homeopathic remedies.

Another common argument is the notion that, because patients want such products, pharmacists must offer them. When considering it, the tension between the ethical duties as a health care professional and the commercial pressures of a shop-keeper becomes painfully obvious. For a shop-keeper, it may be perfectly fine to offer all products which might customers want. For a heath care professional, however, this is not necessarily true. The ethical codes of pharmacists make it perfectly clear that the sale of unproven or disproven medicines is not ethical. Therefore, this often cited notion may well be what pharmacists feel, but it does not seem to be a valid excuse for selling bogus medicines.

A variation of this theme is the argument that, if patients were unable to buy homeopathic remedies for self-limiting conditions which do not really require treatment at all, they would only obtain more harmful drugs. The notion here is that it might be better to sell harmless homeopathic placebos in order to avoid the side-effects of real but non-indicated medicines. In my view, this argument does not hold water: if no (drug) treatment is indicated, professionals have a duty to explain this to their patients. In this sector of health care, a smaller evil cannot easily be justified by avoiding a bigger one; on the contrary, we should always thrive for the optimal course of action, and if this means reassurance that no medical treatment is needed, so be it.

An all too obvious reason for selling bogus medicines is the undeniable fact that pharmacists earn money by doing so. There clearly is a conflict of interest here, whether pharmacists want to admit it or not – and mostly they fail to do so or play down this motivation in their decision to sell bogus medicines.

Often I hear from pharmacists working in large chain pharmacies like Boots that they have no influence whatsoever over the range of products on sale. This perception mat well be true. But equally true is the fact that no health care professional can be forced to do things which violate their code of ethics. If Boots insists on selling bogus medicines, it is up to individual pharmacists and their professional organisations to change this situation by protesting against such unethical malpractice. In my view, the argument is therefore not convincing and certainly does not provide an excuse in the long-term.

While discussing with the Swiss pharmacy students, I was made aware of yet another reason for selling bogus medicines in pharmacies. Some pharmacists might feel that stocking such products provides an opportunity for talking to patients and informing them about the evidence related to the remedy they were about to buy. This might dissuade them from purchasing it and could persuade them to get something that is effective instead. In this case, the pharmacist would merely offer the bogus medicine in order to advise customers against employing it. This strategy might well be an ethical way out of the dilemma; however, I doubt that this strategy is common practice with many pharmacists today.

With all this, we should keep in mind that there are many shades of grey between the black and white of the two extreme attitudes towards bogus medicines. There is clearly a difference whether pharmacists actively encourage their customers to buy bogus treatments (in the way it often happens in France, for instance), or whether they merely stock such products and, where possible, offer responsible, evidence-based advise to people who are tempted to buy them.

At the end of the lively but fruitful discussion with the Swiss students I felt optimistic: perhaps the days when pharmacists were the snake-oil salesmen of the modern era are counted?

There is much debate about the usefulness of chiropractic. Specifically, many people doubt that their chiropractic spinal manipulations generate more good than harm, particularly for conditions which are not related to the spine. But do chiropractors treat such conditions frequently and, if yes, what techniques do they employ?

This investigation was aimed at describing the clinical practices of chiropractors in Victoria, Australia. It was a cross-sectional survey of 180 chiropractors in active clinical practice in Victoria who had been randomly selected from the list of 1298 chiropractors registered on Chiropractors Registration Board of Victoria. Twenty-four chiropractors were ineligible, 72 agreed to participate, and 52 completed the study.

Each participating chiropractor documented encounters with up to 100 consecutive patients. For each chiropractor-patient encounter, information collected included patient health profile, patient reasons for encounter, problems and diagnoses, and chiropractic care.

Data were collected on 4464 chiropractor-patient encounters between 11 December 2010 and 28 September 2012. In most (71%) cases, patients were aged 25-64 years; 1% of encounters were with infants. Musculoskeletal reasons for the consultation were described by patients at a rate of 60 per 100 encounters, while maintenance and wellness or check-up reasons were described at a rate of 39 per 100 encounters. Back problems were managed at a rate of 62 per 100 encounters.

The most frequent care provided by the chiropractors was spinal manipulative therapy and massage. The table shows the precise conditions treated

Distribution of problems managed (20 most frequent problems), as reported  by chiropractors

Problem group No. (%) of recorded diagnoses* (n = 5985) Rate per 100 encounters (n = 4417) 95% CI ICC
Back problem 2757 (46.07%) 62.42 (55.24–70.53) 0.312
Neck problem 683 (11.41%) 15.46 (11.23–21.30) 0.233
Muscle problem 434 (7.25%) 9.83 (6.64–14.55) 0.207
Health maintenance or preventive care 254 (4.24%) 5.75 (3.24–10.22) 0.251
Back syndrome with radiating pain 215 (3.59%) 4.87 (2.91–8.14) 0.165
Musculoskeletal symptom or complaint, or other 219 (3.66%) 4.96 (2.39–10.28) 0.350
Headache 179 (2.99%) 4.05 (2.87–5.71) 0.053
Sprain or strain of joint 167 (2.79%) 3.78 (2.30–6.22) 0.115
Shoulder problem 87 (1.45%) 1.97 (1.37–2.83) 0.022
Nerve-related problem 62 (1.04%) 1.40 (0.72–2.75) 0.072
General symptom or complaint, other 51 (0.85%) 1.15 (0.22–6.06) 0.407
Bursitis, tendinitis or synovitis 47 (0.79%) 1.06 (0.71–1.60) 0.011
Kyphosis and scoliosis 47 (0.79%) 1.06 (0.65–1.75) 0.023
Foot or toe symptom or complaint 48 (0.80%) 1.09 (0.41–2.87) 0.123
Ankle problem 46 (0.77%) 1.04 (0.40–2.69) 0.112
Osteoarthrosis, other (not spine) 39 (0.65%) 0.88 (0.51–1.53) 0.023
Hip symptom or complaint 35 (0.58%) 0.79 (0.53–1.19) 0.006
Leg or thigh symptom or complaint 35 (0.58%) 0.79 (0.49–1.28) 0.012
Musculoskeletal injury 33 (0.55%) 0.75 (0.45–1.24) 0.013
Depression 29 (0.48%) 0.66 (0.10–4.23) 0.288

These findings are impressive in that they suggest that most Australian chiropractors treat non-spinal conditions for which there is no evidence that the most frequently used interventions are effective. The treatments employed are depicted in this graph:
Distribution of techniques and care provided by chiropractors, with 95% CI


[Activator = hand-held spring-loaded device that delivers an impulse to the spine. Drop piece = chiropractic treatment table with a segmented drop system which quickly lowers the section of the patient’s body corresponding with the spinal region being treated. Blocks = wedge-shaped blocks placed under the pelvis.

Chiro system = chiropractic system of care, eg, Applied Kinesiology, Sacro-Occipital Technique, Neuroemotional Technique. Flexion distraction = chiropractic treatment table that flexes in the middle to provide traction and mobilisation to the lumbar spine.]

There is no good evidence I know of demonstrating these techniques to be effective for the majority of the conditions listed in the above table.

A similar bone of contention is the frequent use of ‘maintenance’ and ‘wellness’ care. The authors of the article comment: The common use of maintenance and wellness-related terms reflects current debate in the chiropractic profession. “Chiropractic wellness care” is considered by an indeterminate proportion of the profession as an integral part of chiropractic practice, with the belief that regular chiropractic care may have value in maintaining and promoting health, as well as preventing disease. The definition of wellness chiropractic care is controversial, with some chiropractors promoting only spine care as a form of wellness, and others promoting evidence-based health promotion, eg, smoking cessation and weight reduction, alongside spine care. A 2011 consensus process in the chiropractic profession in the United States emphasised that wellness practice must include health promotion and education, and active strategies to foster positive changes in health behaviours. My own systematic review of regular chiropractic care, however, shows that the claimed effects are totally unproven.

One does not need to be overly critical to conclude from all this that the chiropractors surveyed in this investigation earn their daily bread mostly by being economical with the truth regarding the lack of evidence for their actions.

As promised in the last post, I will try to briefly address the issues which make me uncomfortable about the quotes by Anthony Campbell. Readers will recall that Campbell, an ex-director of what was arguably the most influential homeopathic hospital in the world and a long-time editor of the journal HOMEOPATHY, freely admitted that homeopathy was unproven and its effects were most likely not due to any specific properties of the homeopathic remedies [which are, in fact, pure placebos] but largely rely on non-specific effects.

I agree with much that Campbell wrote but I disagree with one particular implication of his conclusions:Homeopathy has not been proved to work but neither has it been conclusively disproven….” and “…it is impossible to say categorically that all the remedies are without objective effect…”

This is an argument, we hear from proponents of alternative medicine with unfailing regularity:MY TREATMENT MAY NOT BE SUPPORTED BY GOOD SCIENCE [BECAUSE GOOD SCIENCE IS EXPENSIVE, AND WE CANNOT AFFORD IT] BUT IT HAS NOT BEEN DISPROVEN EITHER – AND, AS LONG AS IT IS NOT DISPROVEN, NOBODY SHOULD STOP US USING IT”

Campbell does not explicitly draw this latter conclusion but he certainly implies it. In his book, he explains that, even though homeopathic remedies probably are placebos, homeopathy does a lot of good through the placebo effect and through its spiritual aspects. And that is, in his view, sufficient reason to employ it for healing the sick. The very last sentence of his book reads: “Love it or loathe it, homeopathy is here to stay”

So the implication is there: alternative therapies can be as bizarre, nonsensical, implausible, unscientific or idiotic as they like, if we scientists cannot disprove them, they must be legitimate for general use. But there are, of course, two obvious errors in this line of reasoning:

  1. Why on earth should scientists waste their time and resources on testing notions which are clearly bonkers? It is hard to imagine research that is less fruitful than such an endeavour.
  2. Disproving homeopathy [or similarly ridiculous treatments] is a near impossibility. Proving a negative is rarely feasible in science.

In the best interest of patients, responsible health care has to follow an entirely different logic: we must consider any treatment to be unproven, while it is not supported with reasonably sound evidence for effectiveness; and in clinical routine, we employ mostly such treatments which are backed by sound evidence, and we avoid those that are unproven. In other words, whether homeopathy or any other medicine is unproven or disproven is of little practical consequence: we try not to use either category.

While I applaud Campbell’s candid judgement regarding the lack of effectiveness of homeopathic remedies, I feel the need to finish his conclusion for him giving it a dramatically different meaning: Homeopathy has not been proved to work but neither has it been conclusively disproven; this means that, until new evidence unambiguously demonstrates otherwise, we should classify homeopathy as ineffective – and this, of course, applies not just to homeopathy but to ALL unproven interventions.

These days, there is so much hype about alternative cancer treatments that it is hard to find a cancer patient who is not tempted to try this or that alternative medicine. Often it is employed without the knowledge of the oncology team, solely on the advice of non-medically qualified practitioners (NMPs). But is that wise? The aim of this survey was to find out.

Members of several German NMP-associations were invited to complete an online questionnaire. The questionnaire explored areas such as the diagnosis and treatment, goals for using complementary/alternative medicine (CAM), communication with the oncologist, and sources of information.

Of a total of 1,500 members of the NMP associations, 299 took part in this survey. The results show that the treatments employed by NMPs were heterogeneous. Homeopathy was used by 45% of the NMPs, and 10% believed it to be a treatment directly against cancer. Herbal therapy, vitamins, orthomolecular medicine, ordinal therapy, mistletoe preparations, acupuncture, and cancer diets were used by more than 10% of the NMPs. None of the treatments were discussed with the respective physician on a regular basis.

The authors concluded from these findings that many therapies provided by NMPs are biologically based and therefore may interfere with conventional cancer therapy. Thus, patients are at risk of interactions, especially as most NMPs do not adjust their therapies to those of the oncologist. Moreover, risks may arise from these CAM methods as NMPs partly believe them to be useful anticancer treatments. This may lead to the delay or even omission of effective therapies.

Anyone faced with a diagnosis of CANCER is understandably keen to leave no stone unturned to bring about a cure of the disease. Many patients thus go on to the Internet and look what alternative options are on offer. There they find virtually millions of sites advertising thousands of bogus cancer ‘cures’. Others consult their alternative practitioners and seek help. This new survey shows yet again that the advice they receive is dangerous. In fact, it might well be even more dangerous than the results imply: the response rate of the survey was dismal, and I fear that the less responsible NMPs tended not to reply.

None of the treatments listed above can cure cancer. For instance, homeopathy, the most popular alternative cancer treatment in Germany, will have no effect whatsoever on the natural history of the disease. To claim otherwise is criminally irresponsible.

But far too many patients are unaware of the evidence and of the dangers of being misled by bogus claims. What we need, I think, is a major campaign to get the word out. It would be a campaign that saves lives!

Dutch neurologists recently described the case of a 63-year-old female patient presented at their outpatient clinic with a five-week history of severe postural headache, tinnitus and nausea. The onset of these symptoms was concurrent with chiropractic manipulation of the cervical spine which she had tried because of cervical pain.

Cranial MRI showed findings characteristic for intracranial hypotension syndrome. Cervical MRI revealed a large posterior dural tear at the level of C1-2. Following unsuccessful conservative therapy, the patient underwent a lumbar epidural blood patch after which she recovered rapidly.

The authors conclude that manipulation of the cervical spine can cause a dural tear and subsequently an intracranial hypotension syndrome. Postural headaches directly after spinal manipulation should therefore be a reason to suspect this complication. If conservative management fails, an epidural blood patch may be performed.

Quite obviously, this is sound advice that can save lives. The trouble, however, is that the chiropractic profession is, by and large, still in denial. A recent systematic review by a chiropractor included eight cases of intracranial hypotension (IH) and concluded that case reports on IH and spinal manipulative therapy (SMT) have very limited clinical details and therefore cannot exclude other theories or plausible alternatives to explain the IH. To date, the evidence that cervical SMT is not a cause of IH is inconclusive. Further research is required before making any conclusions that cervical SMT is a cause of IH. Chiropractors and other health practitioners should be vigilant in recording established risk factors for IH in all cases. It is possible that the published cases of cervical SMT and IH may have missed important confounding risk factors (e.g. a new headache, or minor neck trauma in young or middle-aged adults).

Instead of distracting us from the fact that chiropractic can lead to serious adverse events, chiropractors would be well-advised to face the music, admit that their treatments are not risk-free and conduct rigorous research with a view of minimizing the harm.

The news that the use of Traditional Chinese Medicine (TCM) positively affects cancer survival might come as a surprise to many readers of this blog; but this is exactly what recent research has suggested. As it was published in one of the leading cancer journals, we should be able to trust the findings – or shouldn’t we?

The authors of this new study used the Taiwan National Health Insurance Research Database to conduct a retrospective population-based cohort study of patients with advanced breast cancer between 2001 and 2010. The patients were separated into TCM users and non-users, and the association between the use of TCM and patient survival was determined.

A total of 729 patients with advanced breast cancer receiving taxanes were included. Their mean age was 52.0 years; 115 patients were TCM users (15.8%) and 614 patients were TCM non-users. The mean follow-up was 2.8 years, with 277 deaths reported to occur during the 10-year period. Multivariate analysis demonstrated that, compared with non-users, the use of TCM was associated with a significantly decreased risk of all-cause mortality (adjusted hazards ratio [HR], 0.55 [95% confidence interval, 0.33-0.90] for TCM use of 30-180 days; adjusted HR, 0.46 [95% confidence interval, 0.27-0.78] for TCM use of > 180 days). Among the frequently used TCMs, those found to be most effective (lowest HRs) in reducing mortality were Bai Hua She She Cao, Ban Zhi Lian, and Huang Qi.

The authors of this paper are initially quite cautious and use adequate terminology when they write that TCM-use was associated with increased survival. But then they seem to get carried away by their enthusiasm and even name the TCM drugs which they thought were most effective in prolonging cancer survival. It is obvious that such causal extrapolations are well out of line with the evidence they produced (oh, how I wished that journal editors would finally wake up to such misleading language!) .

Of course, it is possible that some TCM drugs are effective cancer cures – but the data presented here certainly do NOT demonstrate anything like such an effect. And before such a far-reaching claim is being made, much more and much better research would be necessary.

The thing is, there are many alternative and plausible explanations for the observed phenomenon. For instance, it is conceivable that users and non-users of TCM in this study differed in many ways other than their medication, e.g. severity of cancer, adherence to conventional therapies, life-style, etc. And even if the researchers have used clever statistical methods to control for some of these variables, residual confounding can never be ruled out in such case-control studies.

Correlation is not causation, they say. Neglect of this elementary axiom makes for very poor science – in fact, it produces dangerous pseudoscience which could, like in the present case, lead a cancer patient straight up the garden path towards a premature death.

When we talk about conflicts of interest, we usually think of financial concerns. But conflicts of interests also extend to non-financial matters, such as strong beliefs. These are important in alternative medicine – I would even go as far as to claim that they dominate this field.

My detractors have often claimed that this is where my problem lies. They are convinced that, in 1993, I came into the job as PROFESSOR OF COMPLEMENTARY MEDICINE with an axe to grind; I was determined or perhaps even paid to show that all alternative medicine is utter hocus-pocus, they say. The truth is that, if anything, I was on the side of alternative medicine – and I can prove it. Using the example of homeopathy, I have dedicated an entire article to demonstrate that the myth is untrue – I was not closed-minded or out to ditch homeopathy (or any other form of alternative medicine for that matter).

What then could constitute my ‘conflict of interest’? Surely, he was bribed, I hear them say. Just look at the funds he took from industry. Some of those people have even gone to the trouble of running freedom of information requests to obtain the precise figures for my research-funding. Subsequently they triumphantly publish them and say: Look he got £x from this company and £y from that firm. And they are, of course, correct: I did receive support from commercially interested parties on several occasions. But what my detractors forget is that these were all pro-alternative medicine institutions. More importantly, I always made very sure that no strings were attached with any funds we accepted.

Our core funds came from ‘The Laing Foundation’ which endowed Exeter University with £ 1.5 million. This was done with the understanding that Exeter would put the same amount again into the kitty (which they never did). Anyone who can do simple arithmetic can tell that, to sustain up to 20 staff for almost 20 years, £1.5 million is not nearly enough. There must have been other sources. Who exactly gave money?

Despite utterly useless fundraising by the University, we did manage to obtain additional funds. I managed to receive support in the form of multiple research fellowships, for instance. It came from various sources; for instance, manufacturers of herbal medicines, Boots, the Pilkington Family Trust (yes, the glass manufacturers).

A hugely helpful contributor to our work was the sizable number (I estimate around 30) of visitors from abroad who came on their own money simply because they wanted to learn from and with us. They stayed between 3 months and 4 years, and importantly contributed to our research, knowledge and fun.

In addition, we soon devised ways to generate our own money. For instance, we started an annual conference for researchers in our field which ran for 14 successful years. As we managed everything on a shoestring and did all the organisation ourselves, we made a tidy profit each year which, of course, went straight back into our research. We also published several books which generated some revenue for the same purpose.

And then we received research funding for specific projects, for instance, from THE PRINCE OF WALES’ FOUNDATION FOR INTEGRATED HEALTH, a Japanese organisation supporting Jorhei Healing, THE WELCOME TRUST, the NHS, and even a homeopathic company.

So, do I have a conflict of interest? Did I take money from anyone who might have wanted to ditch alternative medicine? I don’t think so! And if I tell you that, when I came to Exeter in 1993, I donated ~£120 000 of my own funds towards the research of my unit, even my detractors might, for once, be embarrassed to have thought otherwise.

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