MD, PhD, MAE, FMedSci, FRSB, FRCP, FRCPEd.

The indefatigable Robert Mathie has published another systematic review/meta-analysis, and yet again he failed to come up with a convincingly positive result. This new paper reviews randomised controlled trials (RCTs) of individualised homeopathic treatment (IHT) in which the control (comparator) group was other than placebo (OTP). Its stated aim was to determine the comparative effectiveness of IHT on health-related outcomes in adults and children for any clinical condition that has been the subject of at least one OTP-controlled trial. 

For each eligible trial, published in the peer-reviewed literature up to the end of 2015, the authors assessed its risk of bias (internal validity) using the Cochrane tool, and its relative pragmatic or explanatory attitude (external validity) using the 10-domain PRECIS tool. All RCTs were categorised according to whether they examined IHT as an alternative treatment (study design Ia), adjunctively with another intervention (design Ib), or compared with a no-intervention group (design II). For each RCT, the researchers identified a ‘main outcome measure’ to use in meta-analysis: ‘relative effect size’ was reported as odds ratio (OR; values >1 favouring homeopathy) or standardised mean difference (SMD; values < 0 favouring homeopathy).

Eleven RCTs, representing 11 different medical conditions, were eligible for inclusion in this systematic review. Five of the RCTs (four of which in design Ib) were judged to have pragmatic study attitude, two were explanatory, and four were equally pragmatic and explanatory. Ten trials were rated ‘high risk of bias’ overall: one of these, a pragmatic study with design Ib, had high risk of bias solely regarding participant blinding (a bias that is intrinsic to such trials); the other trial was rated ‘uncertain risk of bias’ overall. Eight trials had data that were extractable for meta-analysis: for 4 heterogeneous trials with design Ia, the pooled OR was statistically non-significant; collectively for three clinically heterogeneous trials with design Ib, there was a statistically significant SMD favouring adjunctive IHT; in the remaining trial of design 1a, IHT was non-inferior to fluoxetine in the treatment of depression.

The authors concluded that due to the low quality, the small number and the heterogeneity of studies, the current data preclude a decisive conclusion about the comparative effectiveness of IHT. Generalisability of findings is limited by the variable external validity identified overall; the most pragmatic study attitude was associated with RCTs of adjunctive IHT. Future OTP-controlled trials in homeopathy should aim, as far as possible, to promote both internal validity and external validity.

Considering that almost all of the authors are known proponents of homeopathy – Mathie himself is employed by the London-based ‘Homeopathy Research Institute’ – one has to applaud their rigour and enthusiasm in publishing negative findings about their trade. But why so complicated? I would have thought that a much simpler conclusion would have been clearer: THESE ANALYSES FAILED TO GENERATE EVIDENCE TO SUGGEST THAT HOMEOPATHY IS EFFECTIVE.

 

26 Responses to Homeopathy: yet another systematic review fails to prove its effectiveness

  • Surely, the burden of proof is always on the person making an assertion or proposition.
    So this paper proves homeopathy is not effective (or at any rate, the ‘remedies’ are not. The consultatoions no doubt are appreciated).

    Thank you Mr Mathie – at last!

  • While the methodology used by these authors was rigorous, I am still puzzled as to why the actual trials carried out by homeopaths are usually of such poor quality. Have they learned so little about study design and conduct?

  • “Some of the results are euphemistically formulated. Who does not know them, the endeavoured “conclusions”, which are often garnished with the call for “more research”? – I recently wrote in connection with the previous Mathie reviews. He now perpetuates his results, thanks for that.

  • Much comment about “internal validity” – one of Dana Ullman’s favourite phrases, and one which (as with so many things) he plainly misunderstands and misuses. Let’s see if he pops up here for a bit of witless yammering.

    • It is odd that the homeopathy acolytes never seem to cite any of Mathie’s recent papers. Can’t think why…

      Just in case they were unaware of them, here’s three of them with his conclusions:

      Individualised homeopathy (why do homeopaths seem to favour this?):

      Randomised placebo-controlled trials of individualised homeopathic treatment: systematic review and meta-analysis

      Medicines prescribed in individualised homeopathy may have small, specific treatment effects. Findings are consistent with sub-group data available in a previous ‘global’ systematic review. The low or unclear overall quality of the evidence prompts caution in interpreting the findings. New high-quality RCT research is necessary to enable more decisive interpretation.

      Non-individualised (eg the stuff that can be bought over the counter without seeing a homeop… Ah. I’ve just answered my question.):

      Randomised, double-blind, placebo controlled trials of non-individualised homeopathic treatment: systematic review and meta-analysis

      The quality of the body of evidence is low. A meta-analysis of all extractable data leads to rejection of our null hypothesis, but analysis of a small sub-group of reliable evidence does not support that rejection. Reliable evidence is lacking in condition-specific meta-analyses, precluding relevant conclusions. Better designed and more rigorous RCTs are needed in order to develop an evidence base that can decisively provide reliable effect estimates of non-individualised homeopathic treatment.

      And now his latest one – individualised homeopathy compared to treatments:

      Systematic Review and Meta-Analysis of Randomised, Other-than-Placebo Controlled, Trials of Individualised Homeopathic Treatment

      Due to the low quality, the small number and the heterogeneity of studies, the current data preclude a decisive conclusion about the comparative effectiveness of IHT. Generalisability of findings is limited by the variable external validity identified overall; the most pragmatic study attitude was associated with RCTs of adjunctive IHT. Future OTP-controlled trials in homeopathy should aim, as far as possible, to promote both internal validity and external validity.

  • Now that Ernst and others have found Dr. Robert Mathie to be an honest, thorough, and accurate reviewer of homeopathic research, it is time that you noted other quotes from his work…

    Not only have many individual studies found efficacy in homeopathic medicines, but also various systematic review or meta-analyses have likewise found that homeopathic medicines often conclude that the effects of homeopathic medicines are different than those of a placebo. A 2017 review of homeopathic research by Mathie, et al, published in Systematic Reviews confirmed a difference between the effects of homeopathic treatment and of placebo. In reviewing the “highest quality studies,” the researchers found that homeopathic patients were almost twice as likely to experience a therapeutic benefit as those given a placebo. Further, in reviewing a total of 22 clinical trials, the homeopathic patients experienced greater than 50% likelihood to have benefited from the homeopathic treatment than those given a placebo.

    This important review of clinical research also acknowledged that four of the five leading previous systematic reviews of homeopathic research found a benefit from homeopathic treatment over that of placebo:

    “Five systematic reviews have examined the RCT research literature on homeopathy as a whole, including the broad spectrum of medical conditions that have been researched and by all forms of homeopathy: four of these ‘global’ systematic reviews reached the conclusion that, with important caveats, the homeopathic intervention probably differs from placebo.”

    And in addition to the important work of Mathie, this NEW study published at NATURE.COM (!!!!!) provides extremely compelling evidence for the power of nanomedicines…and it is NO LONGER possible for skeptics of homeopathy to say that there is no evidence for the biological action and clinical efficacy of homeopathic medicines.

    This carefully conducted group of studies clearly show a significant effect from various doses of RHUS TOXICODENDRON, including doses beyond Avogadro’s number! However, anyone who reference Avoagadro’s number in relationship to homeopathy clearly doesn’t understand homeopathy OR conventional pharmacology (100% of skeptics fit into this category!). The nanoparticle work published in LANGMUIR compellingly show AND explain how nanodoses of homeopathic medicines persist in water solutions.

    Here’s the reference that will bring skeptics of homeopathy down on their knees and have them realize that homeopathy IS the “original nanomedicine,” and the field of nanomedicine and nanopharmacology are the wave of the future. They are NOT “the future” (because nanomedicines are only a part of the future…and they will be an important and even essential part of this future).

    https://www.nature.com/articles/s41598-018-31971-9

    • It will take a lot more than a small study in rats to get me on my knees. If this is the systematic review by Mathie et al that you mean, the conclusion is:

      “The quality of the body of evidence is low. A meta-analysis of all extractable data leads to rejection of our null hypothesis, but analysis of a small sub-group of reliable evidence does not support that rejection. Reliable evidence is lacking in condition-specific meta-analyses, precluding relevant conclusions.” Systematic Reviews 2017 6:63

      I could put it more succinctly: There is no robust evidence from this systematic review that homeopathy differs from placebo.

      I have to wonder why Mathie et al classed most of the studies as unreliable, but still extracted them.

    • Ullman said:

      Now that Ernst and others have found Dr. Robert Mathie to be an honest, thorough, and accurate reviewer of homeopathic research

      ROFL! Please try to keep up, Dana.

    • Dana. Your recycled idiocy becomes tiresome. It has been explained to you repeatedly exactly how and why Chikramine et al’s nanofloaty nonsense in Langmuir is a meaningless exercise in poking around at statistical noise and yet you continue to cite it at every opportunity. All this does is demonstrate your continuing stupidity.

    • In other words, excrementum ad libitum, excrementum ad “hocum” (pocum)

    • Dana, One afterthought on your nano-particles-theory: If nanoparticles are the agent to trigger the effects of homeopathy, this would rule out all other remedies that do not form nanopraticles in water but dissociate to ions, like Natrium chloratum for instance, wouldn’t it?

  • I would have thought that a much simpler conclusion would have been clearer: THESE ANALYSES FAILED TO GENERATE EVIDENCE TO SUGGEST THAT HOMEOPATHY IS EFFECTIVE.

    Would something like that count as a publication on one’s C.V.?

  • Yeah…those photos of nanoparticles of the 6 different metals can be considered “noise” OR they can be consider nanoparticles of the original 6 metals. Your denial of facts is a classic in showing non-acceptance of reality.

    And further, I’m impressed that YOU are somehow more informed than the reviewers at LANGMUIR which is published by the American Chemistry Society. You must be very very smart or simply complete full of bowel particles…we know which.

    • Not me, Dana. I’m just commenting on what all the chemists and scientists who have recognised the paper for the nonsense it is and have hence ignored its findings have said.

      Keep yelling your rubbish into the evidencial and factual void, Dana. Your foolish yabbering continues to amuse.

    • Dana, let’s be generous and assume that your nano-theory is correct. Could you be equally generous and answer the following question, please?:
      1) How does a nano-particle of coffee, for instance, affect the sleep centre in the brain to make the patient sleep? Or how does a nano-particle of the Berlin Wall or a duck liver affect anything at all in the human body?
      2) Most homeopathic remedies are consumed not as liquids but as ‘globuli’, i. e. tiny little pills made of lactose. They are prepared by dropping the liquid remedy on to them. The liquid subsequently evaporates. How is it that the information retained in the liquid does not evaporate with the diluent?
      3) The diluent usually is a water-alcohol mixture which inevitably contains impurities. In fact, a liquid C12 remedy most certainly contains dimensions more impurities than stock. These impurities have, of course, also been vigorously shaken, i. e. potentised. How can we explain that their ‘potency’ has not been beefed up at each dilution step? Would this not necessitate a process where only some molecules in the diluent are agitated, while all the rest remain absolutely still? How can we explain this fantastic concept?
      4) Some stock used in homeopathy is insoluble (for instance Berlin Wall). Such stock is not diluted but its concentration in the remedy is initially lowered by a process called ‘trituration’, a process which consists in grinding the source material in another solid material, usually lactose. I have granted you that potentisation works in the way you think. But how is information transferred from one solid material to another?
      5) Everything we drink is based on water containing molecules that have been inadvertently potentised in nature a million times and therefore should have hugely powerful effects on our bodies. How is it that we experience none of these effects each time we drink?
      I look forward to your reply.
      Many thanks.

      • Dear Edzard, You are normally a smart man, but somehow, whenever you think or write about homeopathy, it seems that you lose your intelligence. I’m not writing this to condemn you, but to simply report on the obvious observation.

        First, conventional material sciences research has verified that 6ppm of silica fall off the glass walls into water after it undergoes succussion (vigorous shaking of the water). This increased turbulence is known to increase the water pressure to substantial levels (the former head of Stanford’s dept of material sciences estimated it to be at 10,000 atmospheres!). Good research published in LANGMUIR has verified that nanodoses of a medicinal agent persists in water solutions, in part because the medicinal agent is pushed into the silica fragments. This research has confirmed that nanodoses of each original medicinal agent persists, according to 3 different types of spectroscopy.

        Conventional pharmacological research has shown that nanodoses are able to penetrate cell membranes and blood brain barriers with greater ease. Once inside the cell or brain, the body seems to recognize the intruder, and an immunlogical reaction is created.

        As for insolable substances, those substances undergo trituration (you KNOW this, though you love to pretend to be dumb). Trituration is done in porcelein, and just as silica from glass breaks off, a mixture of minerals break-off of porcelein and seem to serve as carriers to nanodoses. After a certain # of trituration, the medicinal substance is then placed in water and glass.

        In addition to what we know about nanodoses, Luc Montagnier’s work has found electromagnetic signals, which will not have any effect unless the organism is HYPERSENSITIVE to that substance’s signals. By finding a medicinal agent that has toxicological properties that match a person’s pathology, that patient then has a hypersensitive reaction to the medicine and an immunological reaction verifies this.

        The small doses that surround us on a daily basis do NOT undergo the unique homeopathic potentization process that creates highly reactive nanodoses. Is this so hard to understand? Have your brains returned. I hope so…I really hope so.

        And now, this new body of research published at Nature.com verifies the significant power of nanodoses.

        • sorry, but I am not smart enough to see how this answers my questions

        • Dana

          You don’t half come out with some shite. Will you please stop waffling about “nanomedicine”. Nanomedicine is A Thing involving measurable amounts of a substance which have a measurable effect. Not the nanofloaties and statistical noise which troubles the imaginations of you and your mates.

          Once again. Homeopathy is bollocks. It does nothing. If it worked as you imagine, trial after trial, whether underpowered or well-conducted, would be demonstrating its effectiveness unarguably and repeatedly. It’s had 200 years to show this. It hasn’t. It’s rubbish. Garbage. Nonsense. It attracts the deluded and the foolish such as yourself who wail and yarble, torturing data, science and logic in a vain attempt to verify their delusions, triumphantly flourishing the results of their corruptions of the scientific method to the utter indifference of those who retain a grasp of reality.

          200 years, Dana. 200 years. Carry on all you like. It won’t alter reality. Homopathy will continue to have no part in proper healthcare and those who rely upon it will continue to seek out proper medicine when they get properly ill. Either that or they’ll die.

          • Lenny, poor Lenny, By YOUR logic, conventional medical science would not dispense with the “many” drugs that have been “proven” to be effective…but alas, the vast majority of drugs, once “proven,” are then PROVEN to cause more HARM than good…and they are taken OFF the market. When you consider how much MONEY Big Pharma has, one would think that they would find “answers” but they only find PROFIT. Your logic is proven to be lacking.

          • the vast majority?
            Dana, are you feeling ok?

          • Have you been drinking, Dana?

        • Dana,

          Your explanations of a possible mechanism whereby homeopathy might work might be a good basis for a science fiction story. In science fiction, there are usually some basic premises which go against what we know, such as matter transporters, telepathy, faster-than-light travel, time travel, alien civilisations (that look human and speak English) etc., but the explanations in the story sound plausible enough (without digging too deeply) to allow the reader to suspend disbelief, and internally consistent enough to maintain that suspension of disbelief for long enough to enjoy the story.

          However much I might enjoy reading or watching science fiction, I would not like to base the management of any of my patients on it.

          Actually, some of your claims should be quite straightforward to test. There is nothing difficult or expensive about assaying for nanograms or nanomoles of a substance, so it should be quite easy to submit homeopathic drugs for analysis. Indeed, you are claiming that this has been done, and if you could provide more detailed references perhaps we could see whether this work has been independantly replicated and verified. Nor should it be too difficult to look for evidence of a hypersensitivity reaction or other immunological reaction to one of your agents. Have there been any studies of the effects of homeopathic preparations by immunologists?

          • Julian

            One of the unanswered questions which fundamentally destabilises Dana’s house of cards is how homeopathic remedies can be distinguished from one another. If we gave Dana some unlabelled remedies, he should, as you say, be able to analyse them according to the “nanodoses” they contain and tell us which is which.

            But he wouldn’t be able to. Because they contain nothing measurable of the original substance they purport to contain. Dana’s “nanodoses” are as imaginary as everything else to do with homeopathy’

            Dana will. of course, splutter and wave his hands in indignation at this. It will alter nothing.

            We will point and laugh.

          • Lenny,

            “One of the unanswered questions which fundamentally destabilises Dana’s house of cards is how homeopathic remedies can be distinguished from one another.”

            If his claims are true, a biological assay, perhaps…

        • Your money is well earned Mr. Ullman. This collage of delusions could convince almost any lay-customer. Good job! Just don’t fall for the crap you yourself are peddling. Be professional.

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