- Email: [email protected]
Meta-analysis of homoeopathy trials
CORRESPONDENCE
that prospective observational studies containing clinical information were a research priority. Charlotte Paterson Warwick House Medical Centre, Holway Green, Taunton, Somerset TA1 2YJ, UK 1
2
3 4
Linde K, Clausius N, Ramirez G, et al. Are the clinical effects of homoeopathy placebo effects? A meta-analysis of placebocontrolled trials. Lancet 1997; 350: 834–43. Schon DS. The reflective practitioner: how professionals think in action. Aldershot: Arena, 1995. Vandenbroucke JP. Homoeopathy trials: going nowhere. Lancet 1997; 350: 824. Langman MJS. Homoeopathy trials: reason for good ones but are they warranted? Lancet 1997; 350: 825.
SIR—The conflict between observation and theory has raged ever since Bacon advocated the experimental method. Homoeopathic research epitomises this conflict; on the one hand, Klaus Linde and colleagues’ meta-analysis1 shows that the effects of homoeopathy are unlikely to be due to placebo, but on the other, Vandenbroucke2 refuses to accept this evidence “because it runs counter to current scientific theory”. Application of Bayesian theory could rationalise such conflict, and is invoked by Vandenbroucke only to be erroneously negated by assigning a prior belief value P(H) of 0 since “the infinite dilutions of the agents used cannot possibly produce any effect”. “Cannot possibly”—ie, to assign a P(H) of 0 as an a-priori position is incompatible with rational science and Bayesian theory. It is incorrect to suggest that there is no hypothesis from which to start. Not only do 42% of general practitioners refer patients for homoeopathy, but numerous hypotheses have been proposed by physicists.3 The physicists’ understanding of matter goes beyond the idea of discrete entities confined to one modality, which has yet to impart its full potential to biology. However speculative, these hypotheses serve to bring homoeopathy from metaphysical realms to those of physics.3,4 However, the arbitrary separation of science into fields has constrained such hypotheses to the domain of physics—meaning that doctors, medical scientists, and, evidently, epidemiologists remain ignorant of them. Hypotheses are, however, testable and some have been substantiated by Raman-laser, infrared absorbence, and nuclear magnetic resonance spectral analyses of homoeopathic preparations.3 Reproducible evidence is emerging that the electromagnetic nature of the homoeopathic signal can be received, digitised, and transferred. 3 Beyond human clinical studies, laboratory experiments have shown ultra high
366
dilution effects.3 With such hypotheses and data, a credible P(H) could rationally be assigned.3 To be sceptical is to be rational, but Vandenbroucke betrays this by suggesting that if Bayesian analysis should support homoeopathy, then Bayes’ theory should be abandoned. In other words if a phenomenon exists, but cannot be explained, it does not exist. Like many facing the seemingly absurd, he seems to be frog-hopping from pad to pad trying to find one which supports him. But none will. Such an attitude, blinded by dogma, almost robbed us of the discoveries of Galileo, Semmelweis, Pasteur, Einstein, and Bohr. Surely the argument must be for further research to be urgently undertaken because there is too much at stake to deride the evidence, too much evidence for it yet to be ignored, but not enough to decide one way or the other. Ultimately it may be found that homoeopathy does not have an effect above placebo, but progressing physicists’ hypotheses and additional evidence in favour of homoeopathy would lead science to uncharted territory, with far-reaching implications for medicine. The difficulty is what would constitute acceptable evidence, for if data such as those of Linde and colleagues continue to be insufficient to stimulate such research there are profound implications for the interpretation of controlled clinical trials in general.5 Aaron K Vallance, *Kim A Jobst
As a more constructive contribution to the debate, we have compiled data from trials of homoeopathy published after Linde and colleagues’ searches were completed (October, 1995). Linde and colleagues mention two such studies (both of which were negative), but we found four further publications reporting randomised controlled trials of homoeopathy.* These trials investigated the effects of various homoeopathic remedies in different indications; the only common factor is that none of them show any superiority of homoeopathy over placebo on prespecified outcome measures. Furthermore, a recent systematic review4 of seven controlled trials of homoeopathy for delayed-onset muscle soreness, a condition judged nonclinical by Linde and colleagues and not included in their meta-analysis, included three randomised controlled trials, all of which reported negative results for homoeopathy. The picture painted by Linde and colleagues’ excellent meta-analysis may well be slightly more positive for homoeopathy than recent published evidence implies. *References available from the author or The Lancet, on request.
*E Ernst, J Barnes Department of Complementary Medicine, Postgraduate Medical School, University of Exeter, Exeter EX2 4NT, UK e-mail: [email protected] 1
2
School of Medicine, Royal Free Hospital, London; and *University Department of Medicine and Therapeutics, Gardiner Institute, Western Infirmary, Glasgow G11 6NT, UK
3
1
4
2 3
4
5
Linde K, Clausius N, Ramirez G, et al. Are the clinical effects of homoeopathy placebo effects? A meta-analysis of placebocontrolled trials. Lancet 1997; 350: 834–43. Vandenbroucke JP. Homoeopathy trials: going nowhere. Lancet 1997; 350: 824. Vallance AK. Can biological activity be maintained at ultra-high dilution? An overview of homoeopathy, evidence and Bayesian philosophy. J Altern Complement Med 1998; 4: 49–76. Lo S-Y, Lo A, Chong LW, Tianzhang L, Hua LH, Geng X. Physical properties of water with IE structures. Modern Physics Letters B 1996; 10: 921–30. Editorial. Reilly’s challenge. Lancet 1994; 344: 1585.
SIR—Klaus Linde and colleagues1 should be congratulated on their methodologically rigorous meta-analysis and for restimulating the discussion on a perpetually controversial subject. Both accompanying commentaries2,3 are critical of the report, yet neither raises any argument not already considered by the investigators.
Linde K, Clausius N, Ramirez G, et al. Are the clinical effects of homeopathy placebo effects? A meta-analysis of placebocontrolled trials. Lancet 1997; 350: 834–43. Vandenbroucke JP. Homoeopathy trials: going nowhere. Lancet 1997; 350: 824. Langman MJS. Homoeopathy trials: reason for good ones but are they warranted? Lancet 1997; 350: 825. Ernst E, Barnes J. Are homoeopathic remedies effective for delayed onset muscle soreness? A systematic review of placebocontrolled trials. Perfusion 1998; 11: 4–8.
SIR—In his commentary1 on the metaanalysis by Klaus Linde and colleagues,2 Jan Vandenbroucke terms the study “completely state of the art”. Although this meta-analysis has been done with rigour and will stimulate discussion about the usefulness and efficacy of homoeopathy, its presentation is not sufficient. One should keep in mind that the publication of scientific work has two aims. First, the publication credits the work of the researcher and second, even more importantly, it should provide a sound basis for future research in the same field. Because a simple table with the primary results of the contributing trials has not been included, even the simplest additional questions the
THE LANCET • Vol 351 • January 31, 1998
that prospective observational studies containing clinical information were a research priority. Charlotte Paterson Warwick House Medical Centre, Holway Green, Taunton, Somerset TA1 2YJ, UK 1
2
3 4
Linde K, Clausius N, Ramirez G, et al. Are the clinical effects of homoeopathy placebo effects? A meta-analysis of placebocontrolled trials. Lancet 1997; 350: 834–43. Schon DS. The reflective practitioner: how professionals think in action. Aldershot: Arena, 1995. Vandenbroucke JP. Homoeopathy trials: going nowhere. Lancet 1997; 350: 824. Langman MJS. Homoeopathy trials: reason for good ones but are they warranted? Lancet 1997; 350: 825.
SIR—The conflict between observation and theory has raged ever since Bacon advocated the experimental method. Homoeopathic research epitomises this conflict; on the one hand, Klaus Linde and colleagues’ meta-analysis1 shows that the effects of homoeopathy are unlikely to be due to placebo, but on the other, Vandenbroucke2 refuses to accept this evidence “because it runs counter to current scientific theory”. Application of Bayesian theory could rationalise such conflict, and is invoked by Vandenbroucke only to be erroneously negated by assigning a prior belief value P(H) of 0 since “the infinite dilutions of the agents used cannot possibly produce any effect”. “Cannot possibly”—ie, to assign a P(H) of 0 as an a-priori position is incompatible with rational science and Bayesian theory. It is incorrect to suggest that there is no hypothesis from which to start. Not only do 42% of general practitioners refer patients for homoeopathy, but numerous hypotheses have been proposed by physicists.3 The physicists’ understanding of matter goes beyond the idea of discrete entities confined to one modality, which has yet to impart its full potential to biology. However speculative, these hypotheses serve to bring homoeopathy from metaphysical realms to those of physics.3,4 However, the arbitrary separation of science into fields has constrained such hypotheses to the domain of physics—meaning that doctors, medical scientists, and, evidently, epidemiologists remain ignorant of them. Hypotheses are, however, testable and some have been substantiated by Raman-laser, infrared absorbence, and nuclear magnetic resonance spectral analyses of homoeopathic preparations.3 Reproducible evidence is emerging that the electromagnetic nature of the homoeopathic signal can be received, digitised, and transferred. 3 Beyond human clinical studies, laboratory experiments have shown ultra high
366
dilution effects.3 With such hypotheses and data, a credible P(H) could rationally be assigned.3 To be sceptical is to be rational, but Vandenbroucke betrays this by suggesting that if Bayesian analysis should support homoeopathy, then Bayes’ theory should be abandoned. In other words if a phenomenon exists, but cannot be explained, it does not exist. Like many facing the seemingly absurd, he seems to be frog-hopping from pad to pad trying to find one which supports him. But none will. Such an attitude, blinded by dogma, almost robbed us of the discoveries of Galileo, Semmelweis, Pasteur, Einstein, and Bohr. Surely the argument must be for further research to be urgently undertaken because there is too much at stake to deride the evidence, too much evidence for it yet to be ignored, but not enough to decide one way or the other. Ultimately it may be found that homoeopathy does not have an effect above placebo, but progressing physicists’ hypotheses and additional evidence in favour of homoeopathy would lead science to uncharted territory, with far-reaching implications for medicine. The difficulty is what would constitute acceptable evidence, for if data such as those of Linde and colleagues continue to be insufficient to stimulate such research there are profound implications for the interpretation of controlled clinical trials in general.5 Aaron K Vallance, *Kim A Jobst
As a more constructive contribution to the debate, we have compiled data from trials of homoeopathy published after Linde and colleagues’ searches were completed (October, 1995). Linde and colleagues mention two such studies (both of which were negative), but we found four further publications reporting randomised controlled trials of homoeopathy.* These trials investigated the effects of various homoeopathic remedies in different indications; the only common factor is that none of them show any superiority of homoeopathy over placebo on prespecified outcome measures. Furthermore, a recent systematic review4 of seven controlled trials of homoeopathy for delayed-onset muscle soreness, a condition judged nonclinical by Linde and colleagues and not included in their meta-analysis, included three randomised controlled trials, all of which reported negative results for homoeopathy. The picture painted by Linde and colleagues’ excellent meta-analysis may well be slightly more positive for homoeopathy than recent published evidence implies. *References available from the author or The Lancet, on request.
*E Ernst, J Barnes Department of Complementary Medicine, Postgraduate Medical School, University of Exeter, Exeter EX2 4NT, UK e-mail: [email protected] 1
2
School of Medicine, Royal Free Hospital, London; and *University Department of Medicine and Therapeutics, Gardiner Institute, Western Infirmary, Glasgow G11 6NT, UK
3
1
4
2 3
4
5
Linde K, Clausius N, Ramirez G, et al. Are the clinical effects of homoeopathy placebo effects? A meta-analysis of placebocontrolled trials. Lancet 1997; 350: 834–43. Vandenbroucke JP. Homoeopathy trials: going nowhere. Lancet 1997; 350: 824. Vallance AK. Can biological activity be maintained at ultra-high dilution? An overview of homoeopathy, evidence and Bayesian philosophy. J Altern Complement Med 1998; 4: 49–76. Lo S-Y, Lo A, Chong LW, Tianzhang L, Hua LH, Geng X. Physical properties of water with IE structures. Modern Physics Letters B 1996; 10: 921–30. Editorial. Reilly’s challenge. Lancet 1994; 344: 1585.
SIR—Klaus Linde and colleagues1 should be congratulated on their methodologically rigorous meta-analysis and for restimulating the discussion on a perpetually controversial subject. Both accompanying commentaries2,3 are critical of the report, yet neither raises any argument not already considered by the investigators.
Linde K, Clausius N, Ramirez G, et al. Are the clinical effects of homeopathy placebo effects? A meta-analysis of placebocontrolled trials. Lancet 1997; 350: 834–43. Vandenbroucke JP. Homoeopathy trials: going nowhere. Lancet 1997; 350: 824. Langman MJS. Homoeopathy trials: reason for good ones but are they warranted? Lancet 1997; 350: 825. Ernst E, Barnes J. Are homoeopathic remedies effective for delayed onset muscle soreness? A systematic review of placebocontrolled trials. Perfusion 1998; 11: 4–8.
SIR—In his commentary1 on the metaanalysis by Klaus Linde and colleagues,2 Jan Vandenbroucke terms the study “completely state of the art”. Although this meta-analysis has been done with rigour and will stimulate discussion about the usefulness and efficacy of homoeopathy, its presentation is not sufficient. One should keep in mind that the publication of scientific work has two aims. First, the publication credits the work of the researcher and second, even more importantly, it should provide a sound basis for future research in the same field. Because a simple table with the primary results of the contributing trials has not been included, even the simplest additional questions the
THE LANCET • Vol 351 • January 31, 1998