MD, PhD, FMedSci, FSB, FRCP, FRCPEd

The recent meta-analysis by Mathie et al for non-individualised homeopathy (recently discussed here) identified just 3 RCTs that were rated as  ‘reliable evidence’. But just how rigorous are these ‘best’ studies? Let’s find out!

THE FIRST STUDY

The objective of the first trial was “to evaluate the efficacy of the non-hormonal treatment BRN-01 in reducing hot flashes in menopausal women.” Its design was that of a multicentre (35 centres in France), randomized, double-blind, placebo-controlled. One hundred and eight menopausal women, ≥50 years of age, were enrolled in the study. The eligibility criteria included menopause for <24 months and ≥5 hot flashes per day with a significant negative effect on the women’s professional and/or personal life. Treatment was either BRN-01 tablets, a registered homeopathic medicine [not registered in the UK] containing Actaea racemosa (4 centesimal dilutions [4CH]), Arnica montana (4CH), Glonoinum (4CH), Lachesis mutus (5CH), and Sanguinaria canadensis (4CH), or placebo tablets, prepared by Laboratoires Boiron according to European Pharmacopoeia standards [available OTC in France]. Oral treatment (2 to 4 tablets per day) was started on day 3 after study enrolment and was continued for 12 weeks. The main outcome measure was the hot flash score (HFS) compared before, during, and after treatment. Secondary outcome criteria were the quality of life (QoL) [measured using the Hot Flash Related Daily Interference Scale (HFRDIS)], severity of symptoms (measured using the Menopause Rating Scale), evolution of the mean dosage, and compliance. All adverse events (AEs) were recorded. One hundred and one women were included in the final analysis (intent-to-treat population: BRN-01, n = 50; placebo, n = 51). The global HFS over the 12 weeks, assessed as the area under the curve (AUC) adjusted for baseline values, was significantly lower in the BRN-01 group than in the placebo group (mean ± SD 88.2 ± 6.5 versus 107.2 ± 6.4; p = 0.0411). BRN-01 was well tolerated; the frequency of AEs was similar in the two treatment groups, and no serious AEs were attributable to BRN-01. The authors concluded that BRN-01 seemed to have a significant effect on the HFS, compared with placebo. According to the results of this clinical trial, BRN-01 may be considered a new therapeutic option with a safe profile for hot flashes in menopausal women who do not want or are not able to take hormone replacement therapy or other recognized treatments for this indication.

Laboratoires Boiron provided BRN-01, its matching placebo, and financial support for the study. Randomization and allocation were carried out centrally by Laboratoires Boiron. I would argue that the treatment time in this study was way too short for generating a therapeutic response. The evolution of the HFS in the two groups was assessed by analysis of the area under the curve (AUC) of the mean scores recorded weekly from each patient in each group over the duration of the study, including those at enrollment (before any treatment). I wonder whether this method was chosen only when the researchers noted that the HFS at the pre-defined time points did not yield a significant result or whether it was pre-determined (elsewhere in the methods section we are told that “The primary evaluation criterion was the effect of BRN-01 on the HFS, compared with placebo. The HFS was defined as the product of the daily frequency and intensity of all hot flashes experienced by the patient, graded by the women from 1 to 4 (1 = mild; 2 = moderate; 3 = strong; 4 = very strong). These data were recorded by the women on a self-administered questionnaire, assisted by a telephone call from a clinical research associate. Data were collected (i) during the first 2 days after enrolment and before any medication had been taken; (ii) then every Tuesday and Wednesday of each week until the 11th week of treatment, inclusive; and (iii) finally, every day of the 12th week of treatment.”). Two of the authors of this paper are employees of Boiron.

THE SECOND STUDY

The second trial was aimed at finding out “whether a well-known and frequently prescribed homeopathic preparation could mitigate post-operative pain.” It was a randomized, double-blind, placebo-controlled trial to evaluate the efficacy of the homeopathic preparation Traumeel S® in minimizing post-operative pain and analgesic consumption following surgical correction of hallux valgus. Eighty consecutive patients were randomized to receive either Traumeel tablets or an indistinguishable placebo, and took primary and rescue oral analgesics as needed. Maximum numerical pain scores at rest and consumption of oral analgesics were recorded on day of surgery and for 13 days following surgery. Traumeel was not found superior to placebo in minimizing pain or analgesic consumption over the 14 days of the trial, however a transient reduction in the daily maximum post-operative pain score favoring the Traumeel arm was observed on the day of surgery, a finding supported by a treatment-time interaction test (p = 0.04). The authors concluded that Traumeel was not superior to placebo in minimizing pain or analgesic consumption over the 14 days of the trial. A transient reduction in the daily maximum post-operative pain score on the day of surgery is of questionable clinical importance.

Traumeel is a mixture of 6 ingredients, 4 of which are in the D2 potency. Thus it neither is administered as a homeopathic remedy (no ‘like cures like’) nor is it highly diluted. In fact, it is not homeopathy at all but belongs to a weird offspring of homeopathy called ‘homotoxicology’ [this is an explanation from my book: Homotoxicology is a method inspired by homeopathy which was developed by Hans Heinrich Reckeweg (1905 – 1985). He believed that all or most illness is caused by an overload of toxins in the body. The toxins originate, according to Reckeweg, both from the environment and from the malfunction of physiological processes within the body. His treatment consists mainly in applying homeopathic remedies which usually consist of combinations of single remedies, because health cannot be achieved without ridding the body of toxins. The largest manufacturer and promoter of remedies used in homotoxicology is the German firm Heel.] The HEEL Company (Baden-Baden, Germany) provided funding for the performance and monitoring of this project, supplied the study medication and placebo, and prepared the randomization list. The positive outcome mentioned in the authors’ conclusion refers to a secondary endpoint. I would argue that the authors should not have noted it there and should have made it clear that the trial generated a negative result.

THE THIRD STUDY

Finally, the third of the 3 ‘rigorous’ studies “evaluated the effectiveness of the homeopathic preparation Plumbum Metallicum  (PM) in reducing the blood lead levels of workers exposed to this metal.” The Brazilian researchers recruited 131 workers to this RCT who took PM in the CH15 potency or placebo for 35 days (10 drops twice daily). Thereafter, the percentage of workers whose lead level had fallen by at least 25% did not differ between the groups, both on intention to treat and per protocol analyses. The authors concluded that PM “had no effect in this study in terms of reducing serum lead in workers exposed to lead.”

This study lacks a power calculation, and arguably the period might have been too short to show an effect. The trial was published in the journal HOMEOPATHY which, some might argue, has not the most rigorous of peer-review procedures.

CONCLUDING REMARKS

The third study seems the most rigorous by far, in my view. The other two trials are seriously under-whelming in several respects, primarily because we cannot be sure how much influence the commercial interests of the sponsor had on their findings. I am sure others will spot weaknesses in all three trials that I failed to see.

Mathie et al partly disagree with my assessment when they write in their paper: “We report separately our model validity assessments of these trials, evaluating consequently their overall quality based on a GRADE-like principle of ‘downgrading’ [14]: two trials [23, 25] rated here as reliable evidence were downgraded to ‘low quality’ overall due to the inadequacy of their model validity; the remaining trial with reliable evidence [24] was judged to have adequate model validity. The latter study [24] thus comprises the sole RCT that can be designated ‘high quality’ overall by our approach, a stark finding that reveals further important aspects of the preponderantly low quality of the current body of evidence in non-individualised homeopathy.”

References 23, 24 and 25 are Padilha (the paper on Plumbum Metallicum), Colau (the RCT on menopausal women) and Singer (the Traumeel trial) respectively. This means that – as per Mathie’s assessment – just the Colau study remains as the sole trial with ‘reliable evidence’ for non-individualised homeopathy.

What Mathie et al seem to forget entirely is that none of the 3 RCTs is a trial of homeopathy as defined by treatment according to the ‘like cures like’ principle. The authors of the second study acknowledge this fact by stating: “Homeopathic purists may find fault in the administration of a standardized combination homeopathic formula to all patients, based upon clinical diagnosis – as opposed to the individualized manner dictated by standard homeopathic practice.”

So, which ever way we look upon this evidence, we cannot possibly deny that the evidence for non-individualised homeopathy is rubbish.

26 Responses to Even the 3 ‘best’ studies of homeopathy are far from convincing

  • Looking for evidence of efficacy in non-individualised homeopathy is proving to be tiresome. By now, after so many of these studies have been completed, surely a clearly positive outcome for non-individualised homeopathy would have been noted, if this method of treatment worked?

    • correct – and the same applies for individualised homeopathy (http://edzardernst.com/2014/12/homeopaty-proof-of-concept-or-proof-of-misconduct/)

    • By now, after so many of these studies have been completed, surely a clearly positive outcome for non-individualised homeopathy would have been noted, if this method of treatment worked?

      That is correct.

      It also prompts this question: So why are homeopaths and their trade bodies (SoH, BHA, FoH, HRI, etc.) not enthusiastically, openly and publicly condemning any outfit (Boiron, Nelsons. Ainsworths, etc.) that touts non-individualised homeopathy?

      • Because the ‘method of treatment’ does work.
        Many folks (who have enough faith) do ‘feel better’.

        Of course there is no evidence the homeopathic pillules have any effect on any specific ailment, but the pillules are only one aspect of the ‘method’.
        The second element, dimension, the type I effects, are due to TLC.
        And just as a magician waves a wand, or a priest waves his hands in supplication when giving a blessing, or a hypnotist might use a swinging pendulum (a bit dated this), so homeopaths find that giving pillules enhances the placebo responses.

        My only beef is that few, if any, homeopaths tell patients that’s what they are up to – and certainly the trade bodies don’t. Patients do not give fully informed consent. That is unethical IMHO, and might be fraudulent.

        Princes Harry and William now openly acknowledge they have benefited from counselling. Their father is unable to be so open, and still ascribes the benefits he gains from counselling to inert pillules.
        Hey ho.

        • Dr. Rawlins, the problem is that you don’t know for certain that homeopathic remedies do not have a medicinal effect. (See: Robert Mathie’s study)

          Therefore, if it is not certainly known that remedies are pure placebos, why should homeopaths state that they are?

          You have not addressed this:
          Greg on Thursday 13 April 2017 at 06:53

          Dr Rawlins, please go through these comments and explain:

          10 April

          Greg: After a lifetime of investigating homeopathy, Edzard should be able to provide a concise ‘head of argument’ for the case against homeopathy. Perhaps he could also try to do this in a dispassionate scientific manner to support his prosecutorial rhetoric: homeopaths are ignorant, corrupt, charlatans, frauds, quacks, criminals, ‘kill your entire family’ (see your listed article above).

          What if his case is wrong? Perhaps he would not feel any sense of shame for insulting so many people?

          Dr Rawlins: ‘Homeopaths are ignorant, corrupt, charlatans, frauds, quacks, criminals.’
          What evidence is there that they are not?

          Greg: Dr Rawlins, I would not have thought of you as the type of person to jump into this with your statement:
          ‘Homeopaths are ignorant, corrupt, charlatans, frauds, quacks, criminals.’
          What evidence is there that they are not?

          What if the model and method of ‘investigating’ homeopathy is wrong? I have stated several times on this site that I consider the method (RCT) and model allopathic/clinical homeopathy used in most of the investigations into homeopathy are likely to fail P=F.

          If someone devises a way to test homeopathy properly and evidence of efficacy is found, what will you say then?

          Greg: Crimen injuria is a crime under South African common law, defined to be the act of “unlawfully, intentionally and seriously impairing the dignity of another. (Wikipedia)

          Does this law apply in the UK?

          11 April
          Dr Rawlins:
          I made no allegations.
          I was quoting another post.
          That is why my comment was in quotation marks.
          I have no idea whether any homeopath is ignorant, corrupt, a quack, charlatan, fraud or criminal.
          Do you?
          How do we tell?

          We are dealing here with probabilities and likelihoods, That’s why a proper scientific approach is necessary.
          Which is more likely, that homeopaths are ignorant, quacks or frauds – or that they have discovered a quite remarkable phenomenon which requires all current knowledge of natural sciences to be set aside?
          Which do you think more likely?

          Dr Rawlins: No – nor in SA either.
          Folks in the categories we are considering here have no dignity which can be impaired.

          End of quotes

          The conflicting statements in the text are:

          I have no idea whether any homeopath is ignorant, corrupt, a quack, charlatan, fraud or criminal.
          Folks in the categories we are considering here have no dignity which can be impaired.
          What evidence is there that they are not?

          These statements appear inconsistent, please would you clarify, thank you.

          • yes, you are a bit slow on the uptake!
            ” you don’t know for certain that homeopathic remedies do not have a medicinal effect”
            this shows your complete ignorance of important issues in medicine.
            IN CLINICAL MEDICINE, IT IS NOT ABOUT PROVING THAT SOMETHING DOES NOT WORK, BUT ABOUT USING STUFF THAT HAS BEEN PROVEN TO WORK.

  • Edzard,

    Just a general comment for you Edzard.

    What you are doing is so important. And I appreciate it so much and learned so much from you.

    Each and every of your blog post is a master class in critical thinking.

    Those who believe and/or practice in CAM should realize that science has no agenda. Any approach has no other way to prove its efficacy than following rigorous experimentation that “neutralizes” the minefield of biases that patient, practitioner and researcher alike falls prey to.

    Here are two quotes by great humans:

    The first principle is that you must not fool yourself — and you are the easiest person to fool.
    –Richard Feynman

    Belief can be a cosy shelter from the truth; it does not require much thinking; it hardly needs any learning, no changing of minds, etc. However, belief can never be a basis for good healthcare.
    –Edzard Ernst

  • Edzard, don’t you think Dr. Rawlins is able to answer the question himself?

  • Of course it is a blog and anyone can write comments on it; but, in my view, Dr. Rawlins’ statements are for him to answer.

  • I find Dr. Rawlins’ comments ‘weird’.

  • “Thus it neither is administered as a homeopathic remedy (no ‘like cures like’) nor is it highly diluted. In fact, it is not homeopathy at all ……”

    http://www.homeoint.org/books/boericmm/a.htm

    Read the homeopathic materia medica. It seems you have your own definition of homeopathy??????????????????.

  • Edzard

    I have not checked this dictionary. Plan to do so.

    You read of the book defines Berberis Aq Q, Nux Vom Q, Thuja O Q as not homeopathic remedies?

    • oh dear!
      do I need to explain even the basics of homeopathy to you?
      it is not the substance that makes a remedy homeopathic, it is the way it is used.
      NaCl is salt when I put it in my soup, and it is a homeopathic remedy when you give it to a patient.

      • Edzard

        “NaCl is salt when I put it in my soup, and it is a homeopathic remedy when you give it to a patient.”

        That is your knowledge of homeopathy? Even the first year student of homeopathy knows better.

        The remedies Nux Vom Q, Nux V 6, Nux V 30, 200, i M, 10 M, CM are ALL part of the homeopathic materia medica and used as such.

        • Iqbal Krishna said:

          The remedies Nux Vom Q, Nux V 6, Nux V 30, 200, i M, 10 M, CM are ALL part of the homeopathic materia medica and used as such.

          All of which contain strychnine. Or not, as the case may be.

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