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Homeopathy and Evidence-Based Medicine: Back to the Future – Part I

Introduction

“Either homeopathy works or controlled trials don’t!”

—Scottish homeopath David Reilly at the 2001 Harvard Medical School Complementary and Integrative Medicine Conference.

Reilly based that assertion on his own series of four small studies of homeopathic treatments of hay fever, asthma, and allergic rhinitis, the outcomes of which had been inconsistent and largely subjective. (1) Later he explained that small-minded skeptics in “conventional medicine” assume “homeopathy doesn’t work because it can’t work,” a view echoed by conference host Dr. David Eisenberg, then the Director of the Center for Alternative Medicine Research and Education at Harvard Medical School (now of the Osher Center); these comments were met with appreciative laughter from the partisan audience. If such charges were valid, it would indeed be fortunate that Harvard Medical School, several other medical schools, and the National Center for Complementary and Alternative Medicine (NCCAM) are promoting homeopathy, both as a clinical method and as a topic worthy of research.

The inconvenient truth, however, is that for homeopathy and many other implausible health claims, Dr. Reilly was correct: controlled trials don’t work.

This will be a multi-part blog that develops that argument.† In so doing it will expose a major weakness of Evidence Based Medicine: that its calculus does not incorporate plausibility in a useful way. It will also offer examples of hazards that result from this problem.

History

The German Samuel Christian Hahnemann invented homeopathy in the late 18th century shortly before the proposal, by Avogadro, that would forever banish it to the realm of pseudoscience. In an effort to understand the widely-accepted efficacy of Peruvian Cinchona bark in the treatment of “intermittent [or ‘swamp’] fever,” Hahnemann took some himself:

“I took by way of experiment, twice a day, four drams of good China (Cinchona). My feet, finger ends, etc., at first became cold; I grew languid and drowsy, then my heart began to palpitate, and my pulse grew hard and small; intolerable anxiety, trembling, prostration, throughout all my limbs; then pulsation in the head, redness of my cheeks, thirst, and in short, all these symptoms which are ordinarily characteristic of intermittent fever, made their appearance, one after the other, yet without the peculiar chilly, shivering rigor, briefly, even those symptoms which are of regular occurrence and especially characteristic – as the dullness of mind, the kind of rigidity in all the limbs, but above all the numb, disagreeable sensation, which seems to have its seed in the periosteum, over every bone in the body – all these made their appearance. This paroxysm lasted two or three hours each time, and recurred if I repeated this dose, not otherwise; I discontinued it, and was in good health.” (2)

Hahnemann’s interpretation of this experience was that the elicitation of “symptoms which are ordinarily characteristic of intermittent fever” offered the key to the mechanism of action of the remedy. From this he deduced the “law” that gives homeopathy its name: the “law of similars.” This states that the best remedy for a condition is a substance that, when given to a healthy person, mimics the symptoms of the condition. Hahnemann’s singular experience with cinchona bark was the sole experimental basis for his first “law,” and it is still widely quoted in homeopathic literature that “Cinchona bark was to Hahnemann what the falling apple was to Newton and the swinging lamp to Galileo.” (3)

Science Intervenes

Later it was discovered that quinine, an ingredient of Cinchona bark, has a specific anti-malarial effect. (4) The mechanism of action has been elucidated, and it has nothing to do with “like cures like,” vitalism, “dynamism,” or any other process proposed by Hahnemann or his followers. Nor does it have to do with host defenses, even those that are real. Thus the very foundation of homeopathy has been definitively disproved. It has recently been proposed that Hahnemann’s own experience was a hypersensitivity reaction to quinine.(5)

Hahnemann’s conclusion was not so unreasonable for its time, when most therapeutic hypotheses were based more on tradition and folklore than on science. “Like cures like” was a variant of the “sympathetic magic” theme common to the folk medicine of many cultures. (6) Contemporary explanations for the effectiveness of cinchona bark, one of the few useful remedies of the day, had to do with its “astringency” and its “tonic effect on the stomach.” (7,8) Neither these theories nor Hahnemann’s were close to the truth, but they can be forgiven for a time when medical science lacked molecular theory, physiology, pharmacology, or the germ theory.

Armed with his imagined insight, Hahnemann set about to investigate the proper uses of the pharmaceuticals of his day, by a process he called “provings.” This he did by taking substances himself or feeding them to his family, and noting the subsequent “symptoms.” (9) Many of these agents, e.g., arsenic and mercury, were highly toxic. Hahnemann eventually decided that the less that was used, the better the outcome. This decision, fortunate as it was for his children, led Hahnemann to formulate his second law: the “law of infinitesimals.” This states that the more dilute a preparation is, the more potent. The series of dilutions and shakings (“succussions”) that characterizes the preparation of every homeopathic “remedy” is known as “potentizing.” Ultra-dilute solutions are claimed to aid the body’s “vital force.”

Typical homeopathic preparations are diluted 10¹²-1060 times. Thanks to Avogadro, it can be calculated that dilutions much beyond 10-23 contain nary a molecule of the original substance, or even any molecules of the diluent that had been in contact with the original substance, or any molecules of the diluent that had been in contact with that diluent, on ad infinitum. In addition, most completed “remedies” consist of a drop of diluent (water and/or alcohol) applied to a sugar pill and allowed to dry. Thus not only must any theory of action account for an increase in effect as the dilution approaches that at which none of the original substance remains, but it also must account for how such “memory” is amplified and transferred to multiple, further dilutions and ultimately retained by a sugar pill after the diluent has evaporated. It also must explain how the sugar pill lacks “memory” of any contaminants that may have been in contact with the diluent, among which must be every substance on the planet that has ever been in contact with water. Finally, such a remedy must act according to the first law of homeopathy, “like cures like,” the basis for which is known to be spurious.

The second “law” thus posits an incremental increase in the informational content of a preparation even as the original, purported source of that information, along with its fluid environment, progressively decreases to the point of nonexistence. This is incompatible with the facts of probability, of which information theory and the second law of thermodynamics are manifestations. Acceptance of Hahnemann’s own “second law” would require discarding evidence for the statistical nature of information decay that is tested and confirmed, in this era of electronics, countless times every millisecond. It would require overthrowing a universal law that Einstein called “the only physical theory…which I am convinced…will never be overthrown.” (10)

Next Week: “Symptoms,” “Provings” and More

References:
1) Taylor M A, Reilly D, Llewellyn-Jones R H, McSharry C, Aitchison T C, Lancaster T, and A Vickers. Randomised controlled trial of homoeopathy versus placebo in perennial allergic rhinitis with overview of four trial series. Commentary: Larger trials are needed. BMJ 2000; 321:471-476.
2) Quoted in Thomas WE. Hahnemann’s Allergy to Quinine. 1998. Accessed 1/08 at: http://web.archive.org/web/20030402035507/http://www.angelfire.com/va/quinine/allergy.html
3) Discussed in Thomas WE. Hahnemann’s Allergy to Quinine. Op cit.
4) Tracy JW and Webster LT. Drugs used in the chemotherapy of protozoal infections: malaria. In: Hardman JG, Limbird LE, Gilman AG. Goodman & Gilman’s The Pharmacological Basis of Therapeutics, 10th Edition. McGraw-Hill, New York 2001. pp. 1069-1095
5) Thomas WE. Hahnemann’s Allergy to Quinine (op cit.).
6) Stevens P. Magical thinking in complementary and alternative medicine. Skeptical Inquirer 25, 6: 32-37 (Nov/Dec 2001)
7) Thomas WE. Hahnemann’s Allergy to Quinine (op cit.).
8) Ransom S. Homoeopathy: What Are We Swallowing? Credence Publications. Uckfield, East Sussex, England 1999. P. 23.
9) Ransom S. Homoeopathy: What Are We Swallowing? Op cit. pp. 32-34,
10) Einstein A (1949), quoted in Harrison DM: Life, Emerging Structures, and the Second Law of Thermodynamics. Updated 2/2006. Accessed 12/07 at: http://www.upscale.utoronto.ca/GeneralInterest/Harrison/LifeEnergy/LifeAndThermo.html

……………………….

The Homeopathy Series:

  1. Homeopathy and Evidence-Based Medicine: Back to the Future – Part I
  2. Homeopathy and Evidence-Based Medicine: Back to the Future – Part II
  3. Homeopathy and Evidence-Based Medicine: Back to the Future–Part III
  4. Homeopathy and Evidence-Based Medicine: Back to the Future Part IV
  5. Homeopathy and Evidence-Based Medicine: Back to the Future Part V
  6. Harvard Medical School: Veritas for Sale (Part III)
  7. The Dull-Man Law
  8. Smallpox and Pseudomedicine

Posted in: Clinical Trials, Homeopathy, Science and Medicine

Leave a Comment (40) ↓

40 thoughts on “Homeopathy and Evidence-Based Medicine: Back to the Future – Part I

  1. PalMD says:

    What a great post! Thanks for a great start!

  2. drunkensci says:

    Looking forward to the follow up post. I love the fact that it’s been set up with the ridiculous history of homeopthy.

    DS

  3. braxtont says:

    I think a couple things could use a little clarification:

    “The inconvenient truth, however, is that for homeopathy and many other implausible health claims, Dr. Reilly was correct: controlled trials don’t work.

    This will be a multi-part blog that develops that argument. In so doing it will expose a major weakness of Evidence Based Medicine: that its calculus does not incorporate plausibility in a useful way. ”

    In the first quoted paragraph, you seem to be saying that trials, as a mechanism, do not work.

    In the second, I’m confused about the term “Evidence Based Medicine” — shouldn’t all medicine be evidence based, and why should there be a weakness with it? It seems like homepathy is “Evidence Free Medicine”.

  4. Harriet Hall says:

    Yes, this is confusing because current thinking about “EBM” tends to be confused. As currently conceived and practiced, EBM usually does not take plausibility into consideration, and it should. This has been exploited by proponents of nonscientific treatments: they think that if they can produce a randomized, placebo-controlled trial we will have to accept the results. Good scientists recognize that this is not enough, since even the best-designed studies can go awry. Good medicine should be based on ALL the evidence, including the evidence of basic science. Good science demands replication, consistency, and coherence with the entire body of scientific knowledge. Of course, something might not cohere because there might be a defect in the body of scientific knowledge that needs to be altered, but in that case the evidence would need to be incontrovertibly strong.

    EBM is often taken to mean simply that there is evidence to support a practice. We need a better term to denote a practice that is supported by a critical analysis of all the evidence, taking into consideration all available knowledge including the quality of the studies and prior probabilities.

  5. DrRandy says:

    “Thanks to Avogadro, it can be calculated that dilutions much beyond 10-23 contain nary a molecule of the original substance…”

    It depends on the original concentration. a 100M solution would have to be diluted to 10^-26 to achieve “null content”… I know you said “much beyond” – but actually, you have to go another 2-3 orders of magnitude past 10^-23 to ensure null content for most solutions.

  6. David Gorski says:

    The main authors of the blog have been having a bit of a–shall we say?–vigorous discussion of this issue with regard to EBM by e-mail. I will very likely do a post on this topic at some point, but I want to wait and see how Kimball completes his argument before doing so. I agree that prior probability based on basic science has to be considered in the context of clinical trials. I also agree that plausibility based on science tends to be seriously undervalued in EBM, although saying that it isn’t considered is overstating the case.

    In any case, I see a very real danger of going too far in the other direction in insisting on scientific “plausibility” too stringently before considering an intervention. After all, we often do not know enough about the physiologic mechanisms of a disease or therapy to rule out the efficacy of an intervention a priori, and an unexpected positive result in a clinical trial could provide the basis for new scientific understanding of disease and therapy. This is more likely to be true where there is at least something understood about a disease and its mechanism, but I would advise being very careful about being too willing to reject a hypothesis for a clinical trial a priori on basic science evidence alone. I very well may develop this concept in a future post, but not until after Kimball’s had his say.

    Of course, some therapies are so utterly, laughably implausible on a scientific basis alone that it is quite reasonable to provisionally reject them and to require evidence at least as compelling to convince us to consider them seriously as the existing basic scientific evidence and understanding that leads us to conclude that they cannot possibly work. That’s why my concern stated above doesn’t apply in the least bit to homeopathy, mainly because for homeopathy to be an effective therapy huge swaths of our understanding of chemistry, physics, and biology would have to be utterly wrong. For us to consider questioning all that science, at the very least there would have to be unequivocal and highly compelling clinical evidence that homeopathy could cure deadly diseases (or even just non-self-limited diseases). There ain’t no such evidence.

  7. qetzal says:

    Dr. Randy,

    A 100M solution is physically impossible under standard pressure & temperature. Pure water is 55.56 M (1000 g/L divided by 18 g/mol). Pure ethanol is only 17.2 M (789 g/L divided by 46 g/mol).

    I think it would be uncommon for the initial solution to contain the putative active substance at even 1M. Plus, I doubt homeopaths typically start with a full liter of solution, do they? I’m guessing 10 – 100 mL, meaning they start with at most 0.1 mole of substance in 5.56 moles of water. Take one part in 10^23 of that, and you have on average ~ 0.6 molecules of the starting substance and 33 molecules of the starting water.

    I think the original statement was pretty accurate, at least as regards the substance itself (although maybe not with regard to molecules that had been in contact with the substance).

  8. Noni Mausa says:

    I have always thought that homeopathy was a completely goofy practice. Having said that, I have friends who are dedicated to homeopathic treatment, in particular the wife who suffered for many years with eczema before moving from steroids and creams to homeopathic treatment. Now, there are many times when she has no evidence of eczema at all. she has undertaken about 15 years of homeopathic treatment controlling the eczema.

    Placebo? I don’t know. Obviously, the treatments make my friends happy, but I still think the idea is goofy and have politely refused their practitioners name and phone number.

    What clinics are doing in-depth research on the practice and results of using placebos? Considering the stuff is cheap, easily available, and almost free of side effects, you would think the medical world would be more interested.

    Noni

  9. PalMD says:

    Placebo is actively studied, but has been found wanting as a therapy in and of itself for a variety of reasons. First, there are ethical considerations, as you must deceive a person into thinking they are using an “active” treatment.
    Second, placebos are not predictable, and are rarely as effective as a comparable “real” treatment. This is why placebos make good controls…there is actually a difference to compare.

    See also http://www.ncbi.nlm.nih.gov/pubmed/16125589?ordinalpos=10&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
    Lancet. 2005 Aug 27-Sep 2;366(9487):726-32.

  10. To braxtont:
    Your confusion about the word “evidence” is justified, as my colleagues have explained. I will argue that the “evidence” in EBM is formally limited, for practical purposes, to the results of clinical trials. This is a bit of an exaggeration, as Dr. Gorsky notes, but it is real enough in some threads of the medical literature to result in absurd and hazardous consequences. Even well-designed and conducted clinical trials are not nearly powerful enough to threaten well-established facts of nature, even if we can conjure imaginary trials that are dramatic enough to make us wonder (and even in that imaginary scenario, the clinical trials themselves would not be the final arbiters; they would, at best, trigger new investigations in basic science that may or may not–the overwhelming likelihood is NOT–succeed in overthrowing principles as ironclad as the laws of thermodynamics). No such clinical trials exist, in homeopathy or any other area of clinical investigation: thus between the choices offered by Dr. Reilly, the correct answer will become clear.

    To DrRandy and quetzal:
    The key to the accuracy of my assertion was, as you suspected, “much beyond.” Homeopaths make it easy to gloss over such details by providing not merely 2-3 orders of magnitude more dilution, but 20-40 more and beyond. That also nicely dispenses with diluent molecules that had been in contact with the substance. Each new dilution brings its own contaminants, of course, but that is a different matter.

    KA

  11. Egle says:

    Fantastic! Can´t wait for the second part.

    By the way, I recently attended a South Americanm conference on traditional and alternative medicine, where, between perfectly decent scientific evidence for the medical properties of certain plants (with lots of false plant VS. pharmaceutical dichotomy well explained in the previous post) there was more than enough blabber about the utility of homeopathy. I actually asked whether there existed any scientific evidence, and was condemned for “not going beyond the Cartesian logic”. Not quite getting the vibrations, you see.

    It`s interesting how even the Deans of Faculties of Medicine in the most prestigious universities here in Peru (where I`m spending this year) are devout followers of alternative therapies such as homeopathy or even crystal healing, whatever that is. Apparently, it`s “outside the realm of science”.

    To Noni: am I correct in thinking that eczema often has a significant psychosomatic part? In which case, placebo sounds like an effective method of treatment.

  12. Alan Duncan says:

    Some have argued here that the term EBM is insufficiently narrow to admit plausibility and considerations of study quality as a guide to the interpretation and application of evidence.

    To the second point, a major component of most EBM curricula is the critical appraisal of the literature – what are the strengths and weakness of a study? did the investigators take adequate care to control for confounders? were the statistics applicable to the type of analysis? Increasingly, critical appraisal also involves looking for sources of “spin” – what was the funding source? did the investigator have to rely on heavily loaded composite end-points to show significance?

    Also to the second point about study quality, most high quality meta-analyses take into consideration study quality.

    Back to the issue of plausibility in interpreting evidence – it’s an interesting problem because most low plausibility studies don’t get funded; or are funded to a limited extent. I’ve been of the opinion that for interventions that are low risk and low cost, that little evidence is needed; but the higher the risk and/or the higher the cost, the stronger the evidence required. Maybe we should factor in plausibility…e.g. high cost, high risk, low plausibility needs higher quality evidence.

    Best wishes on the new blog. Keep up the good work.

  13. aditya1642 says:

    Hi Dr. Kimball,

    I have never, and will never believe in homeopathy. I have always found it to be a standing example of pseudoscience. But I have a friend who swears by it, and no amount of reasoning will change her mind.

    This is because she has had first hand experience. She suffers from Vitiligo and had resorted to taking treatment under homeopathy(Yes, even before trying out Scientific Medicine). But her improvement has been remarkable and I have seen it myself. Could the Placebo Effect be at work here? Can it be so strong? Or is there something more complex at work here?

    I am waiting for your future posts, especially one which discusses the negative effects of taking homeopathic medicines for such long periods of time. (I’m predicting you are going to write one on that!)

    Not only is this a great blog but also a much needed one in a world that is steadily forgetting the importance of science and that is oblivious to the beauty of the Scientific Method.

    Do keep up the good work!

  14. Alan Duncan says:

    aditya1642:

    A skeptical viewpoint would say that your friend’s improvement is more likely to be due to spontaneous improvement in her vitiligo (a known phenomenon) than to a mechanistically-implausible therapy.

    This is the weakness of n=1 observations. No blinding, no chance to see the untreated natural history of the disease.

    The harms of homeopathy are mostly economic, but probably also “opportunity risks” – harm caused by failure to apply effective therapies, where such therapies exist.

  15. My response of 1/5/08 contained an ambiguity. I have revised it (above).

  16. DaveCarlson says:

    Okay this is OT: Shouldn’t the title of this blog be “Science-based Medicine” instead of “Science Based Medicine?” Correct me if I’m wrong here, but is a hyphen needed there?

    Anyway, I can already tell that this is going to be a very interesting and informative blog; I’m definitely looking forward to reading more.

  17. Ex-drone says:

    I look forward to your discussion of using the term “EBM”. It could be worse. You could have used the odious term “allopathy”.

    In Canada, our version of NIH, Health Canada, has been infested by the So-called Complementary and Alternative Medicine (SCAM) community with the establishment of the Natural Health Products Directorate (NPHD), similar to NCCAM. As part of their initiative to regulate NHPs, they have implemented versions of the Drug Identification Number (DIN) for NHPs. Sadly, for homeopathic preparations, the number is called a DIN-HM, where HM stands for Homeopathic Medicine. Since when did homeopathic preparations become “medicine”? Unfortunately, with the SCAM community co-opting the term “medicine”, it has become necessary to resort to using the term “EBM” to clarify when you are referring to a scientifically rational concept.

  18. To Ex-drone:

    You’ll be pleasantly surprised, if troubled, by Part II of this homeo blog, which takes the term “allopathy” to task (it was, after all, coined by Hahnemann himself). Regarding the term “EBM,” it does not adequately describe the field of modern medicine. It describes a movement within modern medicine that has existed for only about 20 years (I am embarrassed to admit that several years ago, before I started noticing the absurdities of academic ‘CAM’ trials and reviews, I did use “EBM” once or twice in publications as a synonym for modern medicine). It was well-enough intentioned, but its limitations have become clear, at least to some of us. That’s a large part of what this blog will discuss.

    What is the appropriate term for modern medicine? My preference is “modern medicine.” Some prefer “science based medicine” (I suppose DaveCarlson may be right that a hyphen oughtta be there, at least insofar as the term is to be compared to “evidence-based medicine”). I like my choice only because there is more to good medicine than scientifically derived knowledge, techniques, therapies, and the rest. Not more in the sense of woowoo; more in the sense of communication and compassion, weighing decisions that aren’t always clear cut, considering family and other social issues that may impinge upon patients, dealing with issues that aren’t strictly “medical,” eg, health insurance (or lack thereof), conflicts between laws and patient care, conflicts between caring for individual patients and doing what’s best for the greater “public health,” and much more.

    Nevertheless, I’d never say “there is more to medicine than ‘mere’ scientifically derived knowledge…” Science is, by far, the most important basis for medical knowledge and medical ethics that we in modern medicine have. Simply explained, it is dishonest to ignore it or to dismiss it without a compelling reason. That’s why we bloggers may quibble slightly about the best term for the field, but not at all about the best term for this blog.

    KA

  19. PalMD says:

    I’m quite partial to “modern medicine”, as “science-based medicine” implies that there is a legitimate medical practice that isn’t science-based. However, as a name for a blog which examines the difference between scientific medicine and “other”, I think it’s great.

    I think that most of us who actually lay hands on patients realize that EBM is necessary but not sufficient for the practice of medicine. I think that many of the woo-meisters wish the whole idea would go away. They would like to believe that “the plural of testimonial is evidence.”

  20. allopath says:

    Great!

    So that means if someone is allergic to quinine then quinine used in minute doses can ‘desensitize’ the person to it or to other agents be it bacteria, etc.. that stimulate (produce) similar effects or symptoms in the body. Therefore homeopathy is analogous to allergology! It desensitizes! And Benvenistes ‘basophil degranulation’ experiment (which was purposefully twisted by magicians) proves the fact that it works even when diluted beyond molecules!

    And if we are allergic to onions then we use Allium cepa 30 (a succussed dilution of onion) every 30 minutes to stop the cold (or ‘allergy’ if you like) And it works every time! Never failed! Try it! ;)) “like cures like’!! Everyone knows the symptoms when cutting onions, match it with similar symptoms in a cold and apply the therapy. You will be amazed! Try it and prove homeopathy! The ‘hypersensitivity’ is very important in homeopathy. Thanks for raising the issue!

  21. allopath says:

    Hey guys

    but wait!

    there is more…….

    But what about prozac! (and multitude of other drugs) It supposedly “cures” depression, but it also ’causes’ depression. Does it mean that people are allergic to it? Hmmm :)) Could it possibly be the hypersensitivity reaction to it ! ;)

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