A systematic review of the quality of homeopathic pathogenetic trials published from 1945 to 1995
Received23 March 2006
revised26 June 2006
accepted06 November 2006
13 December 2017 (online)
Background The quality of information gathered from homeopathic pathogenetic trials (HPTs), also known as ‘provings’, is fundamental to homeopathy. We systematically reviewed HPTs published in six languages (English, German, Spanish, French, Portuguese and Dutch) from 1945 to 1995, to assess their quality in terms of the validity of the information they provide.
Methods The literature was comprehensively searched, only published reports of HPTs were included. Information was extracted by two reviewers per trial using a form with 87 items. Information on: medicines, volunteers, ethical aspects, blinding, randomization, use of placebo, adverse effects, assessments, presentation of data and number of claimed findings were recorded. Methodological quality was assessed by an index including indicators of internal and external validity, personal judgement and comments of reviewers for each study.
Results 156 HPTs on 143 medicines, involving 2815 volunteers, produced 20,538 pathogenetic effects (median 6.5 per volunteer). There was wide variation in methods and results. Sample size (median 15, range 1–103) and trial duration (mean 34 days) were very variable. Most studies had design flaws, particularly absence of proper randomization, blinding, placebo control and criteria for analysis of outcomes. Mean methodological score was 5.6 (range 4–16). More symptoms were reported from HPTs of poor quality than from better ones. In 56% of trials volunteers took placebo. Pathogenetic effects were claimed in 98% of publications. On average about 84% of volunteers receiving active treatment developed symptoms. The quality of reports was in general poor, and much important information was not available.
Conclusions The HPTs were generally of low methodological quality. There is a high incidence of pathogenetic effects in publications and volunteers but this could be attributable to design flaws. Homeopathic medicines, tested in HPTs, appear safe. The central question of whether homeopathic medicines in high dilutions can provoke effects in healthy volunteers has not yet been definitively answered, because of methodological weaknesses of the reports. Improvement of the method and reporting of results of HPTs are required.
References References to all included RCTs are available on-line at www.sciencedirect.com/homp/
- 1 Hahnemann S. Organon of Medicine. 6th edn. Los Angeles: J.P. Tarcher; 1982.
- 2 The Concise Oxford Dictionary of Current English. 9th edn. Oxford: Oxford University Press; 1990.
- 3 Dantas F. How can we get more reliable information from homoeopathic pathogenetic trials?. Br Hom J 1996; 85: 230-236.
- 4 Hahnemann S. Materia Medica Pura. 2v. London: Homoeopathic Publishing Co.; 1936.
- 5 Campbell A. Lycopodium from provings. Br Hom J 1981; 70: 94-99.
- 6 Campbell A. Rhus from provings. Br Hom J 1981; 70: 179-182.
- 7 Stolberg M. Die Homöopathie auf dem Prüfstein. Der erste Doppelblindversouch der Medizingeschichte im Jahr 1835. Münchener Medizinische Wochenschrift 1996; 138: 364-366.
- 8 The Medical Investigation Club of Baltimore. A Pathogenetic Materia Medica. Philadelphia: Boericke & Tafel, 1895.
- 9 Bellows HP. The Test Drug-Proving of the O. O. & L. Society : A Reproving of Belladonna Being an Experimental Study of the Pathogenic Action of that Drug Upon the healthy Human Organism. Boston: The O. O. & L. Society, 1906.
- 10 Hughes R. A Manual of Pharmacodinamics. 6th edn. London: Leath and Ross; 1912.
- 11 Dantas F., Fisher P. A systematic review of homoeopathic pathogenetic trials (‘provings’) published in the United Kingdom from 1945 to 1995. in: Ernst E., Hahn E.G. Homoeopathy: A Critical Appraisal. 1998. London: Butterworth-Heinemann; 69-97
- 12 Anello C., Fleiss J.L. Exploratory or analytic meta-analysis: should we distinguish between them?. J Clin Epidemiol 1995; 48: 109-116.
- 13 Hering C. Guiding Symptoms of our Materia Medica. 01 New Delhi: B. Jain Publishers; 1974.
- 14 Juni P., Altman D.G., Egger M. Systematic reviews in health care: assessing the quality of controlled clinical trials. BMJ 2001; 323: 42-46.
- 15 Sackett D.L. Bias in analytic research. J Chron Dis 1979; 32: 51-63.
- 16 Blackwell B., Bloomfield S.S., Buncher C.R. Demonstration to medical students of placebo responses and non-drug factors. Lancet 1972; 1: 1279-1282.
- 17 Fillmore M., Vogel-Sprott M. Expected effect of caffeine on motor performance predicts the type of response to placebo. Psychopharmacology 1992; 106: 209-214.
- 18 Drici M., Raybaud F., De Lunardo C., Iacono P., Gustovic P. Influence of the behaviour pattern on the nocebo response of healthy volunteers. Br J Clin Pharmacol 1995; 39: 204-206.
- 19 Sibille M., Deigat N., Olagnier V., Durand D.V., Levrat R. Adverse events in phase one studies: a study in 430 health volunteers. Eur J Clin Pharmacol 1992; 42: 389-393.
- 20 Reidenberg M.M., Lowenthal D.T. Adverse nondrug reactions. New Engl J Med 1968; 279: 678-679.
- 21 Dantas F. Incidência de efeitos patogenéticos não-farmacológicos e triviais numa amostra de estudantes de medicina. Rev Homeopatia 2004; 69: 5-10.
- 22 Flack J.M., Ensrud K.E., Mascioli S., Launer C.A., Svendsen K., Elmer P.J., Grimm Jr. R.H. Racial and ethnic modifiers of the salt-blood pressure response. Hypertension 1991; 17 (Suppl. 01) I115-I121.
- 23 Payer L. Medicine & Culture: Varieties of Treatment in the United States, England, West Germany, and France. New York: First Owl Books; 1996.
- 24 Tran C., Knowles S.R., Liu B.A., Shear N.H. Gender differences in adverse drug reactions. J Clin Pharmacol 1998; 38: 1003-1009.
- 25 Martin R.M., Biswas P.N., Freemantle S.N., Pearce G.L., Mann R.D. Age and sex distribution of suspected adverse drug reactions to newly marketed drugs in general practice in England: analysis of 48 cohort studies. Br J Clin Pharmacol 1998; 46: 505-511.
- 26 Schroyens F, Cecchi M, Saetonne MF et al. Homeopathic proving of Hydrogen. Proceedings of 54th International Congress of LMHI, Milan; 1996.
- 27 Sherr J. The Homeopathic Proving of Hydrogen. West Malvern: Dynamis School; 1992.
- 28 Schulz K.F., Chalmers I., Hayes R.J., Altman D.G. Empirical evidence of bias: dimensions of methodological quality associated with estimates of treatment effects in controlled trials. JAMA 1995; 273: 408-412.
- 29 Ioannidis J.P.A. Why most published research findings are false. PLoS Med 2005; 2 (08) e124
- 30 Green D.M. Pre-existing conditions, placebo reactions and “side effects”. Ann Int Med 1964; 60: 255-265.
- 31 Dantas F., Rampes H. Do homeopathic medicines provoke adverse effects? A systematic review. Br Hom J 2000; 89 (Suppl. 01) S35-S38.
- 32 Greenland S. Quality scores are useless and potentially misleading. Am J Epidemiol 1994; 140: 290-296.
- 33 Juni P., Witschi A., Bloch R., Egger M. The hazards of scoring the quality of clinical trials for meta-analysis. JAMA 1999; 282: 1054-1060.
- 34 Bhandari M., Richards R.R., Prague S., Schemitsch E.H. Quality in the reporting of randomized trials in surgery: is the Jadad scale reliable?. Control Clin Trials 2001; 22: 687-688.
- 35 Walach H., Sherr J., Schneider R., Shabi R., Bond A., Rieberer G. Homeopathic proving symptoms: result of a local, non-local or placebo process? A blinded, placebo-controlled pilot study. Homeopathy 2004; 93: 179-185.
- 36 Fisher P., Dantas F. Homeopathic pathogenetic trials of Acidum malicum and Acidum ascorbicum. Br Hom J 2001; 90: 118-125.
- 37 Signorini A., Lubrano A., Manuele G. et al. Classical and new proving methodology: Provings of Plumbum metallicum and Piper methysticum and comparison with a classical proving of Plumbum metallicum . Homeopathy 2005; 94: 164-174.
- 38 Brien S., Lewith G., Bryant T. Ultramolecular homeopathy has no observable clinical effects. A randomized, double-blind, placebo-controlled proving trial of Belladonna 30C. Br J Clin Pharmacol. 2003; 56: 562-568.
- 39 Riley D.S. Contemporary drug provings. J Am Inst Hom 1994; 87: 161-165.
- 40 Calabrese E.J. Paradigm lost, paradigm found: the re-emergence of hormesis as a fundamental dose response model in the toxicological sciences. Environ Pollut 2005; 138: 379-411.