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Clinical trials overview

Systematic reviews of homeopathy clinical trials

There have been six global systematic reviews (SRs) of clinical trials on homeopathy that assessed all types of homeopathic treatment for all available medical conditions together in one paper1-6. Of these SRs, 5 included meta-analysis1-5, whilst 1 (the 2015 NHMRC review)6 did not.

Findings of the 5 SRs with meta-analyses

  • Four SRs were positive – suggesting that there was some evidence of an effect of homeopathy beyond placebo, but more high quality research would be needed to reach definitive conclusions1-4
  • One SR was negative – concluding that homeopathy had no effect beyond placebo5.

Original conclusions from the 5 meta-analysesLess

  • Kleijnen et al. 1991: ‘At the moment the evidence of clinical trials is positive but not sufficient to draw definitive conclusions because most trials are of low methodological quality and because of the unknown role of publication bias. This indicates that there is a legitimate case for further evaluation of homoeopathy, but only by means of well performed trials.’1
  • Linde et al. 1997: ‘The results of our meta-analysis are not compatible with the hypothesis that the clinical effects of homeopathy are completely due to placebo. However, we found insufficient evidence from these studies that homeopathy is clearly efficacious for any single clinical condition. Further research on homeopathy is warranted provided it is rigorous and systematic.’ 2
  • Linde et al. 1999: ‘We conclude that in the study set investigated, there was clear evidence that studies with better methodological quality tended to yield less positive results.’3
  • Cucherat et al. 2000: ‘There is some evidence that homeopathic treatments are more effective than placebo; however, the strength of this evidence is low because of the low methodological quality of the trials. Studies of high methodological quality were more likely to be negative than the lower quality studies. Further high quality studies are needed to confirm these results.’4
  • Shang et al. 2005: ‘Biases are present in placebo-controlled trials of both homoeopathy and conventional medicine. When account was taken for these biases in the analysis, there was weak evidence for a specific effect of homoeopathic remedies, but strong evidence for specific effects of conventional interventions. This finding is compatible with the notion that the clinical effects of homoeopathy are placebo effects.’5

Limitations of these studies 

It is remarkable that the negative Shang et al. 2005 meta-analysis continues to be cited widely by opponents of homeopathy, despite only covering data up to 2003, being contradictory to the remainder of the evidence base of this type, and the serious scientific concerns regarding its reliability.

All five of these global SRs are now out of date – with the first review by Kleijnen et al. being 27 yrs old1 and Shang et al.5 being 13 yrs old.

Although the most current overview – the Australian NHMRC report6 – was published in 2015, this study only includes individual trials up 2010 (captured within SRs published up to 3 Jan 2013). The NHMRC report has also attracted international criticism for its flawed methodology.

Recent developments in homeopathy systematic reviews 

Since 2013, overviews and SRs of the clinical evidence base in homeopathy have made significant progress in the form of Dr Robert Mathie’s comprehensive review programme, which is nearing completion. What distinguishes these more recent SRs from the global studies above, is the consistent use of a contemporary, rigorous methodology and making clear distinctions between homeopathy type and comparator.

Dr Mathie’s programme includes four planned SRs with meta-analysis, each covering all clinical conditions, but with appropriate separation into treatment types and comparators i.e. whether homeopathic treatment is individualised or not, and whether the control group is placebo or ‘other than placebo’.

Making these distinctions in the homeopathy clinical trial evidence base is crucial as it prevents inappropriate combined analysis of unrelated homeopathic treatments. In conventional medicine, no SR or meta-analysis would combine the results of trials assessing completely different treatments e.g. antibiotics, antihistamines and hormone replacement therapy, in order to answer the question, ‘Does conventional medicine work?’. Yet, this approach has repeatedly – and completely inappropriately – been used to address the question, ‘Does homeopathy work?’.

Similarly, in homeopathy research, results from trials testing individualised homeopathic treatment provided by an expert homeopathic practitioner, should not be analysed along with trials testing over-the-counter preparations containing multiple remedies.

Individualised homeopathic treatment 

The first SR and meta-analysis in the Mathie et al. programme of work, published in 2014, found that homeopathic medicines, when prescribed during individualised treatment, are 1.5- to 2.0-times more likely to have a beneficial effect than placebo.7 

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Read HRI’s brief summary of Mathie et al.’s study or listen to Robert Mathie presenting his findings at the HRI Rome 2015 conference:

Crucially, this 2014 paper was not included in the NHMRC’s 2015 review of the evidence, as it was published one year later than the cut off for their literature search (up to 3 Jan 2013).

And it was not included or considered by the European Academies Scientific Advisory Council (EASAC) when producing their 2017 position statement on homeopathy. We have yet to ascertain the reasoning behind EASAC’s total exclusion of the most recent and robust study of individualised homeopathic treatment – other than they had no intention of presenting a fair and balanced assessment of the clinical evidence.

Similarly, the most recent 2018 paper by Mathie et al. looked at pragmatic trials of individualised homeopathic treatment compared to no treatment, another treatment or as an adjunctive treatment. While only 11 eligible trials were identified, the most promising results were shown for IHT as an adjunct to usual care (3 studies: pooled SMD -0.26; 95% CI -0.47 to -0.05)8.

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Listen to Robert presenting his findings at the HRI Malta 2017 conference.

Taken together, this pair of SRs of individualised homeopathic treatment provide the most robust and up to date assessment of the key question, ‘Does homeopathy work when provided in an individualised way by a trained practitioner?’. The answer is clearly ‘yes’, individualised homeopathy is distinct from placebo.

Non-individualised homeopathic treatment 

The evidence for non-individualised homeopathic treatment (NIHT) is also promising, but less clear. The study by Mathie et al.9 published in 2017 included 75 double blind, randomised placebo controlled clinical trials of non-individualised homeopathic treatment for a broad range of conditions. For the 54 trials with extractable data for meta-analysis, the results showed a small beneficial effect for non-individualised homeopathic treatment that was statistically significantly different from placebo (SMD -0.33; 95% CI -0.44 to -0.21).

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However, this pooled overall result only partially withstood rigorous sensitivity analysis according to study ‘reliability’; the trend remained in favour of homeopathy but lost significance when the data was reduced to 3 studies (out of 54) considered by Mathie et al. to be the most ‘reliable’ (SMD -0.18; -0.46 to 0.09). Additional meta-analyses were performed on 18 different sub-groups of trials including sample size, potency, acute/chronic conditions etc: statistically significant results were found in favour of homeopathy for 16 of these 18 sub-groups. Despite these positive trends, the overall quality of the evidence prevented decisive conclusions and the need for more high-quality trials of NIHT versus placebo is clear.

Summary

The most recent SRs and M-A of homeopathy can be summarised as follows.

It is clear from these recent and robust SRs that much work is still needed to expand and consolidate the current clinical trial evidence base in homeopathy – especially in other-than-placebo pragmatic trials. However, such rigorous SRs and meta-analyses help to focus future research efforts on areas of most promise, and encourage use of study design that will generate meaningful and useful results. This is the approach that HRI takes to supporting progress in homeopathy research.

ReferencesLess

  1. Kleijnen, J., Knipschild, P. & ter Riet, G. Clinical trials of homeopathy. BMJ, 1991; 302: 960 | PubMed
  2. Linde, K. et al. Are the clinical effects of homeopathy placebo effects? A meta-analysis of placebo-controlled trials. Lancet, 1997; 350:834–843 | PubMed
  3. Linde, K. et al. Impact of study quality on outcome in placebo-controlled trials of homeopathy. J. Clin. Epidemiol., 1999; 52: 631–636 | PubMed
  4. Cucherat, M., Haugh, M. C., Gooch, M. & Boissel, J. P. Evidence of clinical efficacy of homeopathy. A meta-analysis of clinical trials. HMRAG. Homeopathic Medicines Research Advisory Group. Eur. J. Clin. Pharmacol., 2000; 56: 27–33 | PubMed
  5. Shang A, Huwiler-Muntener K, Nartey L, et al. Are the clinical effects of homeopathy placebo effects? Comparative study of placebo-controlled trials of homeopathy and allopathy. Lancet, 2005; 366: 726–732 | PubMed
  6. Australian National Health and Medical Research Council (NHMRC) 2015 Homeopathy Review | Link
  7. Mathie RT et al. Randomised placebo-controlled trials of individualised homeopathic treatment: systematic review and meta-analysis. Systematic Reviews, 2014; 3: 142
 | Full text
  8. Mathie RT et al. Systematic Review and Meta-Analysis of Randomised, Other-than-Placebo Controlled, Trials of Individualised Homeopathic Treatment. Homeopathy, 2018; 107(4): 229-243 |Full text
  9. Mathie RT et al. Randomised, double-blind, placebo-controlled trials of non-individualised homeopathic treatment: systematic review and meta-analysis. Systematic Reviews, 2017; 6(1):63 | Full text

2-There isn’t a single RCT_shutterstock_100245305 adjusted

2-There isn’t a single RCT_shutterstock_100245305 adjusted