Systematic Review and Meta-Analysis of Randomised, Other-than-Placebo Controlled, Trials of Individualised Homeopathic Treatment

Abstract

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.

Keywords

comparative effectiveness - explanatory trial - individualised homeopathic treatment - meta-analysis - pragmatic trial - randomised controlled trial - risk of bias - systematic review

Highlights

• 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.

Authors' Contributions

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.

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