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Homeopathy, a tremendous opportunity for medicine!
European Journal of Internal Medicine 22 (2011) 117–123
Contents lists available at ScienceDirect
European Journal of Internal Medicine j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / e j i m
Letters to the Editor Homeopathy, a tremendous opportunity for medicine!
Keywords: Homeopathy Pharmacology Infinitesimal doses Clinical evidence Meta-analysis
In his article [1], Pandolfi denigrates homeopathy and its practitioners, and abusively generalising from the reports of just a few patients or physicians that he has come across! This attitude seems, to me, to be rather un-scientific. Personally, I do not recognise myself at all in his descriptions. Yet mine is a fairly privileged standpoint from which to testify to the situation of homeopathy, because I was born 63 years ago into a family that dedicated itself to this field. My father and my uncle, Jean and Henri Boiron, with degrees in science, gold and silver medallists at the Faculty of Pharmacy in Nancy, devoted their entire—fortunately long—lives to investigating all the scientific aspects of homeopathy (pharmacology, biology, physical–chemical, and clinical) alongside independent researchers, especially in a university setting. As a result of such efforts, over the past 70 years there has been a proliferation of scientific publications all over the world. I myself have established two scientific foundations, one in the United States, the “Boiron Research Foundation” (1982), the other in France, the “Fondation française pour la Recherche en Homéopathie” (1985), as part of the “Fondation de France”. I have also written a book in which I clearly reject sectarian attitudes, whether it be that of homeopathy or of allopathy: (“Il futuro dell'omeopatia” Edizione Tecniche Nuove 2004, “The future of homeopathy” Hatherleigh, in press). Here, then, are some corrections that I wish to make to the assertions of Pandolfi. First of all, homeopathy is an integral part of modern science; it is the fruit of some of the earliest studies in toxicology and pharmacology, embarked upon by its founder, Hahnemann. He decided to experiment, on himself and his friends, most of the remedies known in those times, from mercury or arsenic salts, to nux vomica and cinchona bark. It was during these systematic and utterly innovative trials that he discovered the “similitude” between the toxic properties of medicinal substances and their therapeutic potential. He used this recurrent observation as the basis for a new method of pharmacological investigation, whose foundations he set forth in a work published in 1796: “Essay on a new principle for ascertaining the curative powers of drugs”. Anyone reading this work will clearly perceive that Hahnemann was by no means a dreamer, but rather a rigorous pharmacologist, willing to test on himself the majority of substances that were administered to patients in those days.
Continuing a rigorous and objective exploration of this new screening method led him to discover a new pharmacology, that of infinitesimal dilutions. In fact, the use of substances with toxic properties similar to the patient's symptoms provokes, even at low doses, a pharmacological worsening that preannounces improvement or recovery, but which can nevertheless be bothersome. To counter this, Hahnemann increasingly diluted the original substances, to the point that we would today describe as “infinitesimal”, concerning which so much has been written in the past 200 years! This famous infinitesimal dose is not therefore a theory, but rather the awkward product of a series of observations and experimentations. Hahnemann was fully aware of the apparent incongruity of his discovery: even though Avogadro had not yet discovered his “magic number”, Hahnemann knew he was going beyond the theoretical molecular limit. In any case, it is not the clinical results of homeopathic medicine that pose a problem, or even their underlying scientific principles, but rather the infinitesimal dilution that poses a really difficult scientific question. Yet it is not enough to simply deny the truth of homeopathy to eliminate the problem which it poses; just as proving the clinical efficacy of these remedies is not enough to remove all doubts surrounding infinitesimals; and neither is it sufficient to prove the reality of infinitesimals from the standpoint of biology or physics, as we have done many times. There always remains this pressing question: how is it possible for such dilutions to produce a real physical, biological, pharmacological, clinical effect? For the time being, science does not give us any answers, but only some lines of thinking to follow. It is a matter of time. Advances in our understanding of the infinitesimally small, which is increasing every day and it will finally wash up at our homeopathic shores. For the time being, we have only to continue progressing in the fields of pharmacology, clinical practice, biology and epidemiology, whilst awaiting answers from physics, chemistry and mathematics. In his article, Pandolfi also deals with the question of meta-analysis of clinical trials of homeopathy. Not all of these are negative; on the contrary! This method of meta-analysis was employed by the opponents of homeopathy to demonstrate that it was nothing more than a placebo. As a matter of fact, the above meta-analysis unanimously proved the opposite. The one by Kleijnen et al. [2]: “the evidence of the clinical trials is positive”; that by Boissel et al. [3], in 1996, in a report to the European Commission: “the patients treated with homeopathy had greater beneficial effects than those who took the placebo”; that by Clausius et al. [4] in 1997,: “the results of this meta-analysis are not compatible with the hypothesis that the clinical effects of homeopathy are completely due to placebo”. If this had been an allopathic remedy successfully used for over two centuries, all these meta-analysis would have been sufficient to corroborate its use and earn it a medal. For homeopathy, however,
118
Letters to the Editor
these results were not accepted because this efficacy was not conceivable from a theoretical point of view. It was thus necessary to begin again, with a new meta-analysis, to prove, at last, that homeopathy was nothing but a placebo. This was attempted and published by Boissel et al. [3] in 2000. Unfortunately, this metaanalysis likewise yielded a positive outcome! “There is evidence that homeopathic remedies are more effective than placebos”. I can imagine the chagrin of those whose mission was to kill off homeopathy, and who instead saw that their efforts had only succeeded in boosting its credibility. Hence yet another attempt was made in 2005, with the publication of a pseudo meta-analysis by Shang et al. [5]. A careful and in-depth reading of this meta-analysis reveals that all the trials examined were randomized and placebo-controlled. Starting from the results, these are essentially the following: • In both groups (homeopathic and conventional publications) the great majority of clinical trials showed positive effects for the remedy versus the placebo. • An analysis of methodological quality was carried out, and the trials graded accordingly, based on criteria comprising the randomization method used, the blinding procedures (of physicians, patients and those who evaluated the result) and the type of data analysis. Only 21 homeopathic trials (19%) and even fewer, 9 (8%), trials of conventional medicine were judged to be of high quality. Nevertheless, taking all the trials together, the quality differences between homeopathy and conventional medicine were not significant. • In both groups, smaller trials and those of lower quality reported greater benefits compared to higher quality trials. Selecting, out of the higher quality studies, those with the largest number of patients, the odds ratio of homeopathy (8 trials) was 0.88 (95% CI 0.65–1.19) while that of conventional medicine (6 trials) was 0.58 (0.39–0.85). Based on this, the authors concluded that homeopathy is no different from a placebo! Finally! Unfortunately for them, the work of Shang et al. has been highly criticized for various reasons summarised in: Fisher et al. [6] in 2005; Ludtke and Rutten [7] in 2008; and Rutten and Stolper [8] in 2008. In reality, the results of this analysis essentially corroborate the previous meta-analysis of homeopathic trials, which have always found a prevalence of positive therapeutic effects. However the most questionable operation done by these Swiss authors on the collected data is that they extract, according to a further quantity criterion (studies with the largest number of cases among those in the high quality group) just 8 (eight!) homeopathic trials and 6 (six!) allopathic trials: comparing only these
very few studies, the authors reach the conclusion of the inefficacy of homeopathy. In other words, the analysis of the results, excluding 102 trials out of 110, was conducted in such a way as to reach an interpretation that confirms a preconceived conviction of inefficacy. Yet if he had read the meta-analysis by Ludtke and Rutten, he would have noticed a surprising observation: the negative results of Shang's work are influenced by a single trial on the prevention of muscular soreness in marathon runners. Why not put an end to this repeated and disgraceful anti-scientific denialism? All the more so because, with its hundreds of thousands of fatalities each year (Starfield [9]) and with just 11% of drugs whose effect appears to be clearly beneficial allopathy has no cause for arrogance or disdainfulness. It is high time for the two branches of pharmacological therapy— allopathy and homeopathy—to forge a sacred union in the service of patients, so as to finally find the key to curing diseases such as cancer, AIDS, heart disease, allergies and parasitoses. Homeopathy is ready to serve that cause.
References [1] Pandolfi M. Homeopathy: ex nihilo fit nihil. Eur J Intern Med 2010;21:147–8. [2] Klenijnen J, Knipschild P, Riet G. Clinical trials of homeopathy. BMJ 1991;302:316–23. [3] Boissel JP, Cucherat M, Gooch M, Haugh MC. Evidence of clinical efficacy of homeopathy. A meta-analysis of clinical trials. Eur J Pharmacol 2000;56:27–33. [4] Clausius N, Eitel F, Hedges VL, Jonas EB, Linde K, Melchart D, Ramirez G. Are the clinical effects of homoeopathy placebo effects? A meta-analysis of placebocontrolled trials. Lancet 1997;350:834–43. [5] Shang A, Huwiler-Müntener K, Nartey L, Jüni P, Dörig S, Sterne JA, et al. Are the clinical effects of homoeopathy placebo effects? Comparative study of placebocontrolled trials of homoeopathy and allopathy. Lancet 2005;366:726–32. [6] Fisher P, Berman B, Davidson J, Reilly D, Thompson T. Are the clinical effects of homoeopathy placebo effects? Lancet 2005;366:2082–3. [7] Lüdtke R, Rutten AL. The conclusions on the effectiveness of homeopathy highly depend on the set of analyzed trials. J Clin Epidemiol 2008;61:1197–204. [8] Rutten AL, Stolper CF. The 2005 meta-analysis of homeopathy: the importance of post-publication data. Homeopathy 2008;97:169–77. [9] Starfield B. Is US health really the best in the world? JAMA 2000;284:483–5.
Christian Boiron Boiron Group, Via Cassanese, 100, 20090 Segrate, Italy E-mail address: [email protected]. 13 September 2010
0953-6205/$ – see front matter © 2010 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved. doi:10.1016/j.ejim.2010.10.001
Refutable refutations For its past merits homeopathy deserves gratitude. In times of cruel and useless remedies this gentle cure provided solace to innumerable patients while sparing them additional suffering. As Boiron says [1], Hahnemann was a scientist in a modern sense, and homeopathy was born as an experimental science. Being so meritorious, and because of its respectable origin, homeopathy seems an unlikely object of preconceived hostility. Thus Boiron is probably wrong [1] when he imagines clinicians rejoicing over publications denying homeopathy a genuine therapeutic effect. If enmity is unjustified, scepticism is [2]. The reason is that after the birth of homeopathy (Hahnemann's “Organon” was published in 1810), science has advanced rapidly making discoveries in conflict with the tenets of this therapy. Avogadro's number is not something “magic”, as Boiron somewhat dismissively calls it [1], but a fundamental principle
of chemistry making the protracted dilutions of homeopathy meaningless in all aspects. And the uncompromising laws of thermodynamics, formulated after Hahnemann's death, deny credibility to other key principles of homeopathy such as the storing of information in solvents. Little wonder then, that reports of clinical efficacy of homeopathy are met with incredulity while trials showing ineffectiveness are easily accepted. This attitude is not due to a negative bias towards homeopathy supposedly present in the medical literature [3], but to the widespread awareness of the principle that implausible claims are not to be believed unless supported by strong evidence. This is not the case in the trials favourable to homeopathy where evidence is generally modest and often at the limit of statistical significance. It is in this context that the meta-analysis of Shang et al. published in “The Lancet” in 2005 [4] readily gained acceptance: it seemed to definitely confirm what was reasonable to expect, namely that the clinical effects of homeopathy are placebo effects.
Contents lists available at ScienceDirect
European Journal of Internal Medicine j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / e j i m
Letters to the Editor Homeopathy, a tremendous opportunity for medicine!
Keywords: Homeopathy Pharmacology Infinitesimal doses Clinical evidence Meta-analysis
In his article [1], Pandolfi denigrates homeopathy and its practitioners, and abusively generalising from the reports of just a few patients or physicians that he has come across! This attitude seems, to me, to be rather un-scientific. Personally, I do not recognise myself at all in his descriptions. Yet mine is a fairly privileged standpoint from which to testify to the situation of homeopathy, because I was born 63 years ago into a family that dedicated itself to this field. My father and my uncle, Jean and Henri Boiron, with degrees in science, gold and silver medallists at the Faculty of Pharmacy in Nancy, devoted their entire—fortunately long—lives to investigating all the scientific aspects of homeopathy (pharmacology, biology, physical–chemical, and clinical) alongside independent researchers, especially in a university setting. As a result of such efforts, over the past 70 years there has been a proliferation of scientific publications all over the world. I myself have established two scientific foundations, one in the United States, the “Boiron Research Foundation” (1982), the other in France, the “Fondation française pour la Recherche en Homéopathie” (1985), as part of the “Fondation de France”. I have also written a book in which I clearly reject sectarian attitudes, whether it be that of homeopathy or of allopathy: (“Il futuro dell'omeopatia” Edizione Tecniche Nuove 2004, “The future of homeopathy” Hatherleigh, in press). Here, then, are some corrections that I wish to make to the assertions of Pandolfi. First of all, homeopathy is an integral part of modern science; it is the fruit of some of the earliest studies in toxicology and pharmacology, embarked upon by its founder, Hahnemann. He decided to experiment, on himself and his friends, most of the remedies known in those times, from mercury or arsenic salts, to nux vomica and cinchona bark. It was during these systematic and utterly innovative trials that he discovered the “similitude” between the toxic properties of medicinal substances and their therapeutic potential. He used this recurrent observation as the basis for a new method of pharmacological investigation, whose foundations he set forth in a work published in 1796: “Essay on a new principle for ascertaining the curative powers of drugs”. Anyone reading this work will clearly perceive that Hahnemann was by no means a dreamer, but rather a rigorous pharmacologist, willing to test on himself the majority of substances that were administered to patients in those days.
Continuing a rigorous and objective exploration of this new screening method led him to discover a new pharmacology, that of infinitesimal dilutions. In fact, the use of substances with toxic properties similar to the patient's symptoms provokes, even at low doses, a pharmacological worsening that preannounces improvement or recovery, but which can nevertheless be bothersome. To counter this, Hahnemann increasingly diluted the original substances, to the point that we would today describe as “infinitesimal”, concerning which so much has been written in the past 200 years! This famous infinitesimal dose is not therefore a theory, but rather the awkward product of a series of observations and experimentations. Hahnemann was fully aware of the apparent incongruity of his discovery: even though Avogadro had not yet discovered his “magic number”, Hahnemann knew he was going beyond the theoretical molecular limit. In any case, it is not the clinical results of homeopathic medicine that pose a problem, or even their underlying scientific principles, but rather the infinitesimal dilution that poses a really difficult scientific question. Yet it is not enough to simply deny the truth of homeopathy to eliminate the problem which it poses; just as proving the clinical efficacy of these remedies is not enough to remove all doubts surrounding infinitesimals; and neither is it sufficient to prove the reality of infinitesimals from the standpoint of biology or physics, as we have done many times. There always remains this pressing question: how is it possible for such dilutions to produce a real physical, biological, pharmacological, clinical effect? For the time being, science does not give us any answers, but only some lines of thinking to follow. It is a matter of time. Advances in our understanding of the infinitesimally small, which is increasing every day and it will finally wash up at our homeopathic shores. For the time being, we have only to continue progressing in the fields of pharmacology, clinical practice, biology and epidemiology, whilst awaiting answers from physics, chemistry and mathematics. In his article, Pandolfi also deals with the question of meta-analysis of clinical trials of homeopathy. Not all of these are negative; on the contrary! This method of meta-analysis was employed by the opponents of homeopathy to demonstrate that it was nothing more than a placebo. As a matter of fact, the above meta-analysis unanimously proved the opposite. The one by Kleijnen et al. [2]: “the evidence of the clinical trials is positive”; that by Boissel et al. [3], in 1996, in a report to the European Commission: “the patients treated with homeopathy had greater beneficial effects than those who took the placebo”; that by Clausius et al. [4] in 1997,: “the results of this meta-analysis are not compatible with the hypothesis that the clinical effects of homeopathy are completely due to placebo”. If this had been an allopathic remedy successfully used for over two centuries, all these meta-analysis would have been sufficient to corroborate its use and earn it a medal. For homeopathy, however,
118
Letters to the Editor
these results were not accepted because this efficacy was not conceivable from a theoretical point of view. It was thus necessary to begin again, with a new meta-analysis, to prove, at last, that homeopathy was nothing but a placebo. This was attempted and published by Boissel et al. [3] in 2000. Unfortunately, this metaanalysis likewise yielded a positive outcome! “There is evidence that homeopathic remedies are more effective than placebos”. I can imagine the chagrin of those whose mission was to kill off homeopathy, and who instead saw that their efforts had only succeeded in boosting its credibility. Hence yet another attempt was made in 2005, with the publication of a pseudo meta-analysis by Shang et al. [5]. A careful and in-depth reading of this meta-analysis reveals that all the trials examined were randomized and placebo-controlled. Starting from the results, these are essentially the following: • In both groups (homeopathic and conventional publications) the great majority of clinical trials showed positive effects for the remedy versus the placebo. • An analysis of methodological quality was carried out, and the trials graded accordingly, based on criteria comprising the randomization method used, the blinding procedures (of physicians, patients and those who evaluated the result) and the type of data analysis. Only 21 homeopathic trials (19%) and even fewer, 9 (8%), trials of conventional medicine were judged to be of high quality. Nevertheless, taking all the trials together, the quality differences between homeopathy and conventional medicine were not significant. • In both groups, smaller trials and those of lower quality reported greater benefits compared to higher quality trials. Selecting, out of the higher quality studies, those with the largest number of patients, the odds ratio of homeopathy (8 trials) was 0.88 (95% CI 0.65–1.19) while that of conventional medicine (6 trials) was 0.58 (0.39–0.85). Based on this, the authors concluded that homeopathy is no different from a placebo! Finally! Unfortunately for them, the work of Shang et al. has been highly criticized for various reasons summarised in: Fisher et al. [6] in 2005; Ludtke and Rutten [7] in 2008; and Rutten and Stolper [8] in 2008. In reality, the results of this analysis essentially corroborate the previous meta-analysis of homeopathic trials, which have always found a prevalence of positive therapeutic effects. However the most questionable operation done by these Swiss authors on the collected data is that they extract, according to a further quantity criterion (studies with the largest number of cases among those in the high quality group) just 8 (eight!) homeopathic trials and 6 (six!) allopathic trials: comparing only these
very few studies, the authors reach the conclusion of the inefficacy of homeopathy. In other words, the analysis of the results, excluding 102 trials out of 110, was conducted in such a way as to reach an interpretation that confirms a preconceived conviction of inefficacy. Yet if he had read the meta-analysis by Ludtke and Rutten, he would have noticed a surprising observation: the negative results of Shang's work are influenced by a single trial on the prevention of muscular soreness in marathon runners. Why not put an end to this repeated and disgraceful anti-scientific denialism? All the more so because, with its hundreds of thousands of fatalities each year (Starfield [9]) and with just 11% of drugs whose effect appears to be clearly beneficial allopathy has no cause for arrogance or disdainfulness. It is high time for the two branches of pharmacological therapy— allopathy and homeopathy—to forge a sacred union in the service of patients, so as to finally find the key to curing diseases such as cancer, AIDS, heart disease, allergies and parasitoses. Homeopathy is ready to serve that cause.
References [1] Pandolfi M. Homeopathy: ex nihilo fit nihil. Eur J Intern Med 2010;21:147–8. [2] Klenijnen J, Knipschild P, Riet G. Clinical trials of homeopathy. BMJ 1991;302:316–23. [3] Boissel JP, Cucherat M, Gooch M, Haugh MC. Evidence of clinical efficacy of homeopathy. A meta-analysis of clinical trials. Eur J Pharmacol 2000;56:27–33. [4] Clausius N, Eitel F, Hedges VL, Jonas EB, Linde K, Melchart D, Ramirez G. Are the clinical effects of homoeopathy placebo effects? A meta-analysis of placebocontrolled trials. Lancet 1997;350:834–43. [5] Shang A, Huwiler-Müntener K, Nartey L, Jüni P, Dörig S, Sterne JA, et al. Are the clinical effects of homoeopathy placebo effects? Comparative study of placebocontrolled trials of homoeopathy and allopathy. Lancet 2005;366:726–32. [6] Fisher P, Berman B, Davidson J, Reilly D, Thompson T. Are the clinical effects of homoeopathy placebo effects? Lancet 2005;366:2082–3. [7] Lüdtke R, Rutten AL. The conclusions on the effectiveness of homeopathy highly depend on the set of analyzed trials. J Clin Epidemiol 2008;61:1197–204. [8] Rutten AL, Stolper CF. The 2005 meta-analysis of homeopathy: the importance of post-publication data. Homeopathy 2008;97:169–77. [9] Starfield B. Is US health really the best in the world? JAMA 2000;284:483–5.
Christian Boiron Boiron Group, Via Cassanese, 100, 20090 Segrate, Italy E-mail address: [email protected]. 13 September 2010
0953-6205/$ – see front matter © 2010 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved. doi:10.1016/j.ejim.2010.10.001
Refutable refutations For its past merits homeopathy deserves gratitude. In times of cruel and useless remedies this gentle cure provided solace to innumerable patients while sparing them additional suffering. As Boiron says [1], Hahnemann was a scientist in a modern sense, and homeopathy was born as an experimental science. Being so meritorious, and because of its respectable origin, homeopathy seems an unlikely object of preconceived hostility. Thus Boiron is probably wrong [1] when he imagines clinicians rejoicing over publications denying homeopathy a genuine therapeutic effect. If enmity is unjustified, scepticism is [2]. The reason is that after the birth of homeopathy (Hahnemann's “Organon” was published in 1810), science has advanced rapidly making discoveries in conflict with the tenets of this therapy. Avogadro's number is not something “magic”, as Boiron somewhat dismissively calls it [1], but a fundamental principle
of chemistry making the protracted dilutions of homeopathy meaningless in all aspects. And the uncompromising laws of thermodynamics, formulated after Hahnemann's death, deny credibility to other key principles of homeopathy such as the storing of information in solvents. Little wonder then, that reports of clinical efficacy of homeopathy are met with incredulity while trials showing ineffectiveness are easily accepted. This attitude is not due to a negative bias towards homeopathy supposedly present in the medical literature [3], but to the widespread awareness of the principle that implausible claims are not to be believed unless supported by strong evidence. This is not the case in the trials favourable to homeopathy where evidence is generally modest and often at the limit of statistical significance. It is in this context that the meta-analysis of Shang et al. published in “The Lancet” in 2005 [4] readily gained acceptance: it seemed to definitely confirm what was reasonable to expect, namely that the clinical effects of homeopathy are placebo effects.