Scientific assessment
of the motion V-01

„Real patient protection:
end the advantages for homeopathy!”


Motion to the Federal Delegate Conference of Bündnis90/DieGrünen
[The German Green Party] on 15–17 November 2019 in Bielefeld


Dr. med. Harald J. Hamre, Dr. med. Helmut Kiene
Institute for Applied Epistemology and Medical Methodology at the Witten/Herdecke University
Zechenweg 6, 79111 Freiburg, Germany


Summary

The motion V-01 contains false and misleading statements on homeopathy. In this document the central statements of the motion are contrasted with the relevant scientific evidence:

1. Proof of efficacy of highly-diluted (homeopathically potentized) solutions
The statement "a change in the efficacy of a substanceas a result of so-called potentization is not detectable" is false. Effects of homeopathically potentized substances have been demonstrated in many laboratory experiments using various test procedures, and have also been confirmed in replication studies.

2. Efficacy in placebo-controlled clinical trials
The statement "lack of efficacy of homeopathic treatment beyond the placebo effect has been repeatedly demonstrated in very large and high-quality trials" is false. Efficacy has been found in many clinical trials and in corresponding meta-analyses, also in trials and meta-analyses of higher methodological quality.

3. "Dangers" of homeopathy
The statement regarding a "health risk of delayed treatment if homeopathic remedies are used instead of medications with pharmaceutical active ingredients to treat dangerous or chronic diseases" is based on speculative claims without evidence base and is therefore misleading. The failure to use necessary treatments is a general problem in medicine. Whether this problem is more common than usual in homeopathy is unclear. Evidence from case reports and comparative studies does not support this hypothesis.

There is a striking discrepancy: These statements are intended as a "commitment to a health policy based on scientific knowledge", but the actual evidence base is ignored, while unverified popular opinions are adopted.



1. Proof of efficacy of highly-diluted (homeopathically potentized) solutions

"In most cases, the manufacturing of a homeopathic remedy from a substance involves repeated dilutions of the substance with water or alcohol, followed by vigorous shaking after each dilution step (so-called potentization). A change in the efficacy of a substance as a result of so-called potentization is not detectable."

The statement "a change in the efficacy of a substance as a result of so-called potentization is not detectable" is false. Effects of homeopathically potentized substances have been demonstrated in many laboratory experiments using various test procedures and have also been confirmed in replication studies:

2007: In a systematic review of laboratory research (in vitro) with homeopathic high potencies, 67 experiments were assessed, a third of which were replications: three quarters of the experiments and even the replications showed high-potency effects [1].

2010: In a systematic review, 107 biochemical, immunological, cell biological and zoological experiments were evaluated for reproducibility: in half of these (53), replication studies showed comparable effects [2].

Currently published research shows high potencies to have positive and replicable effects, also in recent experiments of higher standards, using validated models [3,4,5,6,7].



2. Efficacy in placebo-controlled clinical trials

"The lack of efficacy of homeopathic treatment beyond the placebo effect has been repeatedly demonstrated in very large and high-quality trials."

The statement is false. Efficacy of homeopathic treatment beyond the placebo effect has been found in many clinical trials and in corresponding meta-analyses, even in trials of higher methodological quality.

Since 1996 six meta-analyses of randomized, placebo-controlled clinical trials of homeopathy (See: Explanations on the methodology of placebo-controlled randomized clinical homeopathy trials and their meta-analyses) for any indications in humans have been published, thereof three on any type of homeopathy (Boissel 1996 and Cucherat 2000 [8,9]), (Linde 1997 und 1999 [10,11]) (Shang et al 2005/Lüdtke 2008 [12,13]), two on individualized homeopathy (Linde 1998 [14]) (Mathie et al 2014 [15]), and one on non-individualized homeopathy (Mathie et al 2017 [16]).

All primary analyses of these six meta-analyses showed a positive treatment effect of homeopathy beyond placebo. The treatment effects were statistically significant in five of the six meta-analyses [9,10,14,15,16] while in the sixth meta-analysis [12] the statistical significance was not explicitly mentioned but seems likely when considering the other published data.

For all six meta-analyses sensitivity analyses regarding the methodological quality of the included trials were conducted. These analyses involved 1 to 9 study quality indicators in different combinations and with different scoring systems, resulting in a total of more than 50 sensitivity analyses. If we exclude sensitivity analyses using procedures or quality indicators that are not recommended (correction procedures based on funnel plot diagnostics [17,18], restriction to trials with a drop-out rate below a specific percentage [19]) or in which a quality indicator is incrementally modified without results changing from statistical significance to non-significance or vice versa, 19 sensitivity analyses remain.

In 7 of these 19 sensitivity analyses [9,10,11], only one single quality indicator was used; all 7 showed a significant positive treatment effect of homeopathy beyond placebo.

In 12 of the 19 sensitivity analyses, more than one quality indicator was used. All 12 analyses showed a positive treatment effect of homeopathy beyond placebo, the effect was statistically significant in nine analyses [10,11,13,15,16] and non-significant in three [11,14,16].

  • Three of the 12 sensitivity analyses had a low number of quality indicators (3 each). Nine of the 12 analyses had a high number of quality indicators (7 or 9); among these nine analyses, the treatment effect was significant in seven analyses [10,11,15,16] and non-significant in two [11,16].
  • Four of the 12 sensitivity analyses had particularly strict quality indicators. The treatment effect was significant in three of them [10,11], and non-significant in one [11].
  • Eight of the 12 sensitivity analyses belong to four meta-analyses from the period 1996-2008 [8,9,10,11,12,13,14] and four of the analyses belong to two meta-analyses from the period 2014-2017 [15,16]. In these 21 years, the methodological standards for meta-analyses have advanced. The newer standards also involve aspects other than the quality indicators. The two most recent meta-analyses (Mathie 2014 und 2017 [15,16]) were conducted according to newer quality standards: predefined analysis protocol, quality assessment of the trials using the Cochrane risk-of-bias appraisal tool, selection of main outcome measures from the trials for meta-analysis according to WHO recommendations, reporting compliant with PRISMA guidelines. Among the 4 sensitivity analyses from these two meta-analyses, the treatment effect was statistically significant in three analyses [15,16], and non-significant in one [16].

Summary: Meta-analyses of placebo-controlled trials on homeopathy for any indication show positive treatment effects of homeopathy beyond placebo (6 out of 6 meta-analyses) that are statistically significant (explicitly in 5 out of 6, likely in 6 out of 6 meta-analyses). When restricting the meta-analyses to trials with higher methodological quality, the positive treatment effects remain predominantly significant (16 out of 19 sensitivity analyses), even in analyses with a high number of quality indicators (7 out of 9 analyses) or with particularly strict criteria (3 out of 4 analyses) and in the meta-analyses following newer, improved standards (3 out of 4 analyses).



3. "Dangers" of homeopathy

"Some emphasize the health risk of delayed treatment if homeopathic remedies are used instead of medications with pharmaceutical active ingredients to treat dangerous or chronic diseases."

This statement is based on speculative claims with no basis of evidence and is therefore misleading.

Generally speaking, medical malpractice occurs in medicine, and patient compliance is not always ideal. The failure to use necessary therapy is a general problem in medicine. Whether or not this problem occurs more commonly when "homeopathic remedies are used" is an empirical question. Instead of speculations, we need to take a critical look at the actual evidence from, amongst others, comparative studies on homeopathic versus other treatment.

We found one systematic review of published case reports and case series, in which “harm ... associated with the use of homeopathy as a replacement of conventional treatments” was addressed [20]. For this topic, eight publications with a total of 16 patients were identified in the world literature. According to the authors of the review, a wide range of complications were caused by the use of homeopathy instead of conventional medicine. This is, however, not supported by the actual data. We checked the eight original publications for this topic: Only in one (!) of the 16 cases, complications from the non-use of an indicated medication in conjunction with use of homeopathic remedies could be reliably confirmed: One patient did not use previously poorly-tolerated malaria prophylaxis when travelling in an area with endemic malaria, and subsequently contracted malaria. Notably, the failure to use malaria prophylaxis can be a problem in travel medicine, also independently of homeopathy [21,22]).

Regarding the other 15 patients: In 6 cases there was definitely no homeopathic treatment at all or no non-use of conventional treatment. In 4 cases there was very probably no homeopathic treatment or the complications were not due to a lack of effective treatment but very likely caused by dietary restrictions in infants. In 5 cases it was unclear whether the alleged “homeopathic” treatment or the treatment by alleged "homeopaths" involved any actual homeopathic remedies.

In comparative studies of homeopathic vs conventional treatment and placebo, respectively (various indications: randomized trials 23,24,25], observational studies [26,27,28,29,30,31,32,33]) adverse effects or complications from homeopathic treatment were comparably frequent [23,24,25,26,28,30,31,32,33] or significantly less frequent ([27,29] + adults in [28]) than under conventional treatment or placebo.


Conclusion and comments

The three claims examined here:
  • effects of potentization are supposedly not detectable,
  • lack of efficacy of homeopathic treatment beyond the placebo effect has supposedly been demonstrated several times,
  • homeopathic treatmentis said to pose health risks from delayed use of conventional treatment,

are false or misleading. The relevant facts have been presented above.

There is a striking discrepancy: These statements are intended as a "commitment to a health policy based on scientific knowledge", but the actual evidence base is ignored, while unverified popular opinions are adopted.

Freiburg, 8. November 2019

Dr. med. Harald J. Hamre
Dr. med. Helmut Kiene

This motion was written for the International Academy of Science in Homeopathy and Integrative Medicine, Berlin. English translation of the original German text, finalized by the authors.







Literature

  1. Witt CM, Bluth M, Albrecht H, Weisshuhn TE, Baumgartner S, Willich SN. The in vitro evidence for an effect of high homeopathic potencies - a systematic review of the literature. Complement Ther Med 2007; 15(2): 128-38.
  2. Endler P, Thieves K, Reich C, et al. Repetitions of fundamental research models for homeopathically prepared dilutions beyond 10(-23): a bibliometric study. Homeopathy 2010; 99(1): 25-36.
  3. Baumgartner S. Stand der Grundlagenforschung in der Homöopathie. Der aktuelle Stand der Forschung zur Homöopathie: Versorgungsforschung, randomisierte kontrollierte klinische Studien, Meta-Analysen, Grundlagenforschung. Köthen (Anhalt): Wissenschaftliche Gesellschaft für Homöopathie; 2016: 43-50.
  4. Harrer B. Replication of an experiment on extremely diluted thyroxine and highland amphibians. Homeopathy 2013; 102(1): 25-30.
  5. Majewsky V, Scherr C, Arlt SP, et al. Reproducibility of effects of homeopathically potentised gibberellic acid on the growth of Lemna gibba L. in a randomised and blinded bioassay. Homeopathy 2014; 103(2): 113-26.
  6. Jäger T, Wurtenberger S, Baumgartner S. Effects of homeopathic preparations of Mercurius corrosivus on the growth rate of severely mercury-stressed duckweed Lemna gibba L. Homeopathy 2019; 108(2): 128-38.
  7. Doesburg P, Andersen JO, Scherr C, Baumgartner S. Empirical investigation of preparations produced according to the European Pharmacopoeia monograph 1038. Eur J Pharm Sci 2019; 137: 104987.
  8. Boissel JP, Cucherat M, Haugh M, Gauthier E. Critical literature review on the effectiveness of homoeopathy: overview of data from homoeopathic medicine trials. Homoeopathic Medicine Research Group, Report of the Commission of the European Communities, Directorate-General XII - Science, Research and Development, Directorate E - RTD Actions: Life Sciences and Technologies - Medical Research. Brussels; 1996: 195-210.
  9. Cucherat M, Haugh MC, Gooch M, Boissel JP. Evidence of clinical efficacy of homeopathy. A meta-analysis of clinical trials. HMRAG. Homeopathic Medicines Research Advisory Group. Eur J Clin Pharmacol 2000; 56(1): 27-33.
  10. Linde K, Clausius N, Ramirez G, et al. Are the clinical effects of homoeopathy placebo effects? A meta-analysis of placebo-controlled trials. Lancet 1997; 350: 834-43.
  11. Linde K, Scholz M, Ramirez G, Clausius N, Melchart D, Jonas WB. Impact of study quality on outcome in placebo-controlled trials of homeopathy. J Clin Epidemiol 1999; 52(7): 631-6.
  12. Shang A, Huwiler-Muntener K, Nartey L, et al. Are the clinical effects of homoeopathy placebo effects? Comparative study of placebo-controlled trials of homoeopathy and allopathy. Lancet 2005; 366(9487): 726-32.
  13. Lüdtke R, Rutten AL. The conclusions on the effectiveness of homeopathy highly depend on the set of analyzed trials. J Clin Epidemiol 2008; 61(12): 1197-204.
  14. Linde K, Melchart D. Randomized controlled trials of individualized homeopathy: a state-of-the-art review. Journal of alternative and complementary medicine (New York, NY) 1998; 4(4): 371-88.
  15. Mathie RT, Lloyd SM, Legg LA, et al. Randomised placebo-controlled trials of individualised homeopathic treatment: systematic review and meta-analysis. Syst Rev 2014; 3: 142.
  16. Mathie RT, Ramparsad N, Legg LA, et al. Randomised, double-blind, placebo-controlled trials of non-individualised homeopathic treatment: systematic review and meta-analysis. Systematic reviews 2017; 6(1): 63.
  17. Sterne JA, Egger M, Smith GD. Systematic reviews in health care: Investigating and dealing with publication and other biases in meta-analysis. BMJ 2001; 323(7304): 101-5.
  18. Lau J, Ioannidis JP, Terrin N, Schmid CH, Olkin I. The case of the misleading funnel plot. Bmj 2006; 333(7568): 597-600.
  19. Higgins JPT, Thomas J, Chandler J, et al., editors. Cochrane Handbook for systematic reviews of interventions. 2. ed. Chichester: John Wiley & Sons; 2019.
  20. Posadzki P, Alotaibi A, Ernst E. Adverse effects of homeopathy: a systematic review of published case reports and case series. International journal of clinical practice 2012; 66(12): 1178-88.
  21. Kwon HY, Lee H, Im JH, et al. Determinants of compliance of travelers with vaccination and malaria prophylaxis at a travel clinic. Journal of Korean medical science 2019; 34(33): e217.
  22. Rodrigues KMP, Costa A, Santoro-Lopes G. Adherence to malaria prophylaxis among travelers from a middle-income country. Revista da Sociedade Brasileira de Medicina Tropical 2019; 52: e20190014.
  23. Stub T, Musial F, Kristoffersen AA, Alraek T, Liu J. Adverse effects of homeopathy, what do we know? A systematic review and meta-analysis of randomized controlled trials. Complement Ther Med 2016; 26: 146-63.
  24. Frass M, Friehs H, Thallinger C, et al. Influence of adjunctive classical homeopathy on global health status and subjective wellbeing in cancer patients - A pragmatic randomized controlled trial. Complement Ther Med 2015; 23(3): 309-17.
  25. Macias-Cortes EC, Llanes-Gonzalez L, Aguilar-Faisal L, Asbun-Bojalil J. Individualized homeopathic treatment and fluoxetine for moderate to severe depression in peri- and postmenopausal women (HOMDEP-MENOP study): a randomized, double-dummy, double-blind, placebo-controlled trial. PloS one 2015; 10(3): e0118440.
  26. Friese KH, Kruse S, Lüdtke R, Moeller H. The homoeopathic treatment of otitis media in children - comparisons with conventional therapy. Int J Clin Pharmacol Ther 1997; 35(7): 296-301.
  27. Riley D, Fischer M, Singh B, Haidvogl M, Heger M. Homeopathy and conventional medicine: an outcomes study comparing effectiveness in a primary care setting. J Altern Complement Med 2001; 7(2): 149-59.
  28. Haidvogl M, Riley DS, Heger M, et al. Homeopathic and conventional treatment for acute respiratory and ear complaints: a comparative study on outcome in the primary care setting. BMC Complement Altern Med 2007; 7: 7.
  29. Schneider C, Schneider B, Hanisch J, van Haselen R. The role of a homoeopathic preparation compared with conventional therapy in the treatment of injuries: an observational cohort study. Complement Ther Med 2008; 16(1): 22-7.
  30. Witt CM, Lüdtke R, Willich SN. Homeopathic treatment of children with atopic eczema: a prospective observational study with two years follow-up. Acta Derm Venereol 2009; 89(2): 182-3.
  31. Pomposelli R, Piasere V, Andreoni C, et al. Observational study of homeopathic and conventional therapies in patients with diabetic polyneuropathy. Homeopathy 2009; 98(1): 17-25.
  32. Roll S, Reinhold T, Pach D, et al. Comparative effectiveness of homoeopathic vs. conventional therapy in usual care of atopic eczema in children: long-term medical and economic outcomes. PLoS One 2013; 8(1): e54973.
  33. Rossignol M, Begaud B, Engel P, et al. Impact of physician preferences for homeopathic or conventional medicines on patients with musculoskeletal disorders: results from the EPI3-MSD cohort. Pharmacoepidemiology and drug safety 2012; 21(10): 1093-101.