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Systematic Review and Meta-Analysis of Randomised, Other-than-Placebo Controlled, Trials of Individualised Homeopathic TreatmentFunding The systematic review programme has been supported by a grant from the Manchester Homeopathic Clinic.
23 March 2018
06 June 2018
18 August 2018 (online)
Background This study focuses on randomised controlled trials (RCTs) of individualised homeopathic treatment (IHT) in which the control (comparator) group was other than placebo (OTP).
Aims To determine the comparative effectiveness of IHT on health-related outcomes in adults and children for any clinical condition that has been the subject of at least one OTP-controlled trial. For each study, to assess the risk of bias and to determine whether its study attitude was predominantly ‘pragmatic’ or ‘explanatory’.
Methods Systematic review. For each eligible trial, published in the peer-reviewed literature up to the end of 2015, we assessed its risk of bias (internal validity) using the seven-domain Cochrane tool, and its relative pragmatic or explanatory attitude (external validity) using the 10-domain PRECIS tool. We grouped RCTs by whether they examined IHT as an alternative treatment (study design Ia), adjunctively with another intervention (design Ib), or compared with a no-intervention group (design II). For each RCT, we identified a ‘main outcome measure’ to use in meta-analysis: ‘relative effect size’ was reported as odds ratio (OR; values >1 favouring homeopathy) or standardised mean difference (SMD; values < 0 favouring homeopathy).
Results Eleven RCTs, representing 11 different medical conditions, were eligible for study. Five of the RCTs (four of which in design Ib) were judged to have pragmatic study attitude, two were explanatory, and four were equally pragmatic and explanatory. Ten trials were rated ‘high risk of bias’ overall: one of these, a pragmatic study with design Ib, had high risk of bias solely regarding participant blinding (a bias that is intrinsic to such trials); the other trial was rated ‘uncertain risk of bias’ overall. Eight trials had data that were extractable for analysis: for four heterogeneous trials with design Ia, the pooled OR was statistically non-significant; collectively for three clinically heterogeneous trials with design Ib, there was a statistically significant SMD favouring adjunctive IHT; in the remaining trial of design 1a, IHT was non-inferior to fluoxetine in the treatment of depression.
Conclusions Due to the low quality, the small number and the heterogeneity of studies, the current data preclude a decisive conclusion about the comparative effectiveness of IHT. Generalisability of findings is limited by the variable external validity identified overall; the most pragmatic study attitude was associated with RCTs of adjunctive IHT. Future OTP-controlled trials in homeopathy should aim, as far as possible, to promote both internal validity and external validity.
Keywordscomparative effectiveness - explanatory trial - individualised homeopathic treatment - meta-analysis - pragmatic trial - randomised controlled trial - risk of bias - systematic review
• This systematic review focuses on randomised controlled trials (RCTs) of individualised homeopathic treatment (IHT) in which the control (comparator) group was other than placebo.
• For each eligible trial, risk of bias was assessed using Cochrane methods, and its relative pragmatic or explanatory attitude was approximated using the PRECIS tool.
• Eleven RCTs, representing 11 different medical conditions, were eligible for inclusion.
• Ten RCTs were rated ‘high risk of bias’; the other trial was rated ‘uncertain risk of bias’.
• Only five RCTs were judged to have pragmatic study attitude.
• Quantitative data extraction did not yield a decisive conclusion about the comparative effectiveness of IHT.
RTM devised and led the study, developed the study protocol and contributed to all facets of the work. SU-Z helped to develop the study protocol, co-assessed trials for risk of bias, contributed to data interpretation and edited the manuscript. PV helped to develop the study protocol, co-assessed trials for pragmatic/explanatory study attitude, contributed to data interpretation and edited the manuscript. ERR helped to develop the study protocol, contributed to data interpretation and edited the manuscript. ESB contributed to statistical analysis and data interpretation and edited the manuscript. LAL helped to develop the study protocol, contributed to data interpretation and edited the manuscript. JRTD helped to develop the study protocol, contributed to data interpretation and edited the manuscript. All authors have applied the normal high standards of scientific method in the conduct of the work and of complete and transparent reporting in the write-up of the manuscript; they have all read and approved the submitted manuscript.
- 1 Swayne J. International Dictionary of Homeopathy. Edinburgh: Churchill Livingstone; 2000
- 2 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
- 3 Mathie RT, Ramparsad N, Legg LA. , et al. Randomised, double-blind, placebo-controlled trials of non-individualised homeopathic treatment: systematic review and meta-analysis. Syst Rev 2017; 6: 63
- 4 Jacobs J, Jonas WB, Jiménez-Pérez M, Crothers D. Homeopathy for childhood diarrhea: combined results and metaanalysis from three randomized, controlled clinical trials. Pediatr Infect Dis J 2003; 22: 229-234
- 5 Taylor MA, Reilly D, Llewellyn-Jones RH, McSharry C, Aitchison TC. Randomised controlled trial of homoeopathy versus placebo in perennial allergic rhinitis with overview of four trial series. BMJ 2000; 321: 471-476
- 6 Schneider B, Klein P, Weiser M. Treatment of vertigo with a homeopathic complex remedy compared with usual treatments: a meta-analysis of clinical trials. Arzneimittelforschung 2005; 55: 23-29
- 7 Ernst E, Barnes J. Are homoeopathic remedies effective for delayed-onset muscle soreness? A systematic review of placebo-controlled trials. Perfusion (Nürnberg) 1998; 11: 4-8
- 8 Ernst E. Homeopathic prophylaxis of headaches and migraine? A systematic review. J Pain Symptom Manage 1999; 18: 353-357
- 9 Ernst E. Homeopathy for insomnia and sleep-related disorders: a systematic review of randomised controlled trials. Focus Altern Complement Ther 2011; 16: 195-199
- 10 Smith CA. Homoeopathy for induction of labour. Cochrane Database Syst Rev 2004; CD003399
- 11 Mathie RT, Frye J, Fisher P. Homeopathic Oscillococcinum® for preventing and treating influenza and influenza-like illness. Cochrane Database Syst Rev 2015; 1: CD001957
- 12 Long L, Ernst E. Homeopathic remedies for the treatment of osteoarthritis: a systematic review. Br Homeopath J 2001; 90: 37-43
- 13 Kleijnen J, Knipschild P, ter Riet G. Clinical trials of homoeopathy. BMJ 1991; 302: 316-323
- 14 Boissel JP, Cucherat M, Haugh M, Gauthier E. Critical literature review on the effectiveness of homoeopathy: overview of data from homoeopathic medicine trials. In: Homoeopathic Medicine Research Group Report. Commission of the European Communities' Directorate-General XII – Science, Research and Development, Directorate E – RTD Actions: Life Sciences and Technologies – Medical Research. Brussels: Commission of the European Communities; 1996
- 15 Linde K, Clausius N, Ramirez G. , et al. Are the clinical effects of homeopathy placebo effects? A meta-analysis of placebo-controlled trials. Lancet 1997; 350: 834-843
- 16 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: 631-636
- 17 Cucherat M, Haugh MC, Gooch M, Boissel JP. ; Homeopathic Medicines Research Advisory Group. Evidence of clinical efficacy of homeopathy. A meta-analysis of clinical trials. Eur J Clin Pharmacol 2000; 56: 27-33
- 18 Shang A, Huwiler-Müntener 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: 726-732
- 19 Ernst E. Classical homeopathy versus conventional treatments: a systematic review. Perfusion (Nürnberg) 1999; 12: 13-15
- 20 Treweek S, Zwarenstein M. Making trials matter: pragmatic and explanatory trials and the problem of applicability. Trials 2009; 10: 37
- 21 Bornhöft G, Maxion-Bergemann S, Wolf U. , et al. Checklist for the qualitative evaluation of clinical studies with particular focus on external validity and model validity. BMC Med Res Methodol 2006; 6: 56
- 22 Thorpe KE, Zwarenstein M, Oxman AD. , et al. A pragmatic-explanatory continuum indicator summary (PRECIS): a tool to help trial designers. J Clin Epidemiol 2009; 62: 464-475
- 23 Mathie RT, Ulbrich-Zürni S, Viksveen P. , et al. Systematic review and meta-analysis of randomised, other-than-placebo (OTP) controlled, trials of individualised homeopathic treatment (IHT): Study protocol. Version 1.2; 21 April 2017. Available at: https://www.hri-research.org/hri-research/learning-more-from-existing-evidence/systematic-review-programme/
- 24 Mathie RT, Hacke D, Clausen J, Nicolai T, Riley DS, Fisher P. Randomised controlled trials of homeopathy in humans: characterising the research journal literature for systematic review. Homeopathy 2013; 102: 3-24
- 25 Baker DG, Myers SP, Howden I, Brooks L. The effects of homeopathic Argentum nitricum on test anxiety. Complement Ther Med 2003; 11: 65-71
- 26 Higgins JPT, Altman DG. Assessing risk of bias in included studies. In: Higgins JPT, Green S. , eds. Cochrane Handbook for Systematic Reviews of Interventions; Version 5.1.0. The Cochrane Collaboration; 2011. . Chapter 8
- 27 Hewitt CE, Torgerson DJ, Miles JNV. Is there another way to take account of non-compliance in randomized controlled trials?. Can Med Assoc J 2007; 175: 347-348
- 28 Higgins JPT, Deeks JJ, Altman DG. Special topics in statistics. In: Higgins JPT, Green S. , eds. Cochrane Handbook for Systematic Reviews of Interventions; Version 5.1.0. The Cochrane Collaboration; 2011. . Chapter 16
- 29 Sedgwick P. Equivalence trials. BMJ 2013; 346: f184
- 30 Sedgwick P. What is a non-inferiority trial?. BMJ 2013; 347: f6853
- 31 Deeks JJ, Higgins JPT, Altman DG. Analysing data and undertaking meta-analyses. In: Higgins JPT, Green S. , eds. Cochrane Handbook for Systematic Reviews of Interventions; Version 5.1.0. The Cochrane Collaboration; 2011. . Chapter 9
- 32 Chinn S. A simple method for converting an odds ratio to effect size for use in meta-analysis. Stat Med 2000; 19: 3127-3131
- 33 Schünemann HJ, Oxman AD, Vist GE. , et al. Interpreting results and drawing conclusions. In: Higgins JPT, Green S. , eds. Cochrane Handbook for Systematic Reviews of Interventions; Version 5.1.0. The Cochrane Collaboration; 2011. . Chapter 12
- 34 Manchanda RK, Nair KRJ, Varanasi R. , et al. A randomized comparative trial in the management of alcohol dependence: individualized homoeopathy versus standard allopathic treatment. Indian J Res Homeopathy 2016; 10: 172-181
- 35 Viksveen P, Relton C, Nicholl J. Depressed patients treated by homeopaths: a randomised controlled trial using the “cohort multiple randomised controlled trial” (cmRCT) design. Trials 2017; 18: 299
- 36 Sedgwick P. Explanatory trials versus pragmatic trials. BMJ 2014; 349: g6694
- 37 Weatherley-Jones E, Thompson EA, Thomas KJ. The placebo-controlled trial as a test of complementary and alternative medicine: observations from research experience of individualised homeopathic treatment. Homeopathy 2004; 93: 186-189
- 38 Verhoef MJ, Lewith G, Ritenbaugh C, Boon H, Fleishman S, Leis A. Complementary and alternative medicine whole systems research: beyond identification of inadequacies of the RCT. Complement Ther Med 2005; 13: 206-212
- 39 Ernst E, Lee MS. A trial design that generates only “positive” results. J Postgrad Med 2008; 54: 214-216
- 40 Mathie RT, Roniger H, Van Wassenhoven M. , et al. Method for appraising model validity of randomised controlled trials of homeopathic treatment: multi-rater concordance study. BMC Med Res Methodol 2012; 12: 49