Thursday, May 19, 2011
The healing art of homeopathy dates back several centuries, yet it remains controversial. A recently reported clinical trial demonstrated that homeopathic remedies were of no help for treating painful rheumatoid arthritis (RA), but benefits of the homeopathic consultation itself were substantial. Yet, there are serious deficiencies in this research that leave open the question of whether homeopathic remedies might be of value in treating RA.
Homeopathy is a form of complementary and alternative medicine (CAM) in which practitioners treat patients using highly diluted preparations of agents, either individually or in combination, that are believed to exert healing effects for specific disorders. It originated in the late 18th Century and, apart from assessing symptoms, homeopathic practitioners examine all aspects of a patient’s physical, psychological, and spiritual state during an extensive consultation to determine appropriate therapeutic remedies.
Most recently, a research team in the United Kingdom conducted a randomized, double-blind, placebo-controlled clinical trial (RCT) to assess whether benefits from adjunctive homeopathic interventions in patients with rheumatoid arthritis (RA) are due to the homeopathic consultation process, the prescribed homeopathic remedies, or both [Brien et al. 2011]. Writing in the journal Rheumatology, they report enrolling 83 patients — with active but stable RA and receiving conventional therapy for the disorder — in a trial conducted during 2008.
Participants, who were recruited from 3 secondary-care outpatient clinics in the UK, were randomly assigned to 24 weeks of treatment in 1 of 5 trial groups: 1) homeopathic consultation, plus either a. individualized homeopathy agents, b. complex homeopathy (a standard combination of agents), or c. placebo, or 2) no homeopathic consultation, plus either a. complex homeopathy, or b. placebo. It was expected that this elaborate design would be able to distinguish whether any beneficial effects were due to the consultation approach, to the homeopathic remedies utilized, or to both combined.
Primary outcomes included response to a standard composite measure of rheumatology treatment success (ACR20) and each patient’s monthly global assessment (GA) of health. Secondarily, the researchers assessed tender and swollen joints, disease severity, pain, weekly patient and physician GA, and inflammatory markers.
Among the 56 subjects who completed the treatment phase of the trial, there were no significant differences observed on either of the two primary outcome measures. While all homeopathic agents were relatively safe and without serious adverse events, there was no clear therapeutic effect due to type of remedy compared with placebo. However, participants receiving a homeopathic consultation, as opposed to those not having a consultation, experienced significantly large, clinically-relevant effects demonstrating improvements in secondary measures of disease activity, swollen joint count, current pain, weekly pain, weekly patient GA, and negative mood.
The researchers concluded that homeopathic consultations, but not homeopathic remedies themselves, are associated with clinically important benefits for patients with active but relatively stable RA. They claim that this is the first such study demonstrating the importance of the consultative process; however, they acknowledge that this may only be exerting a strong placebo effect. Although this would appear to repudiate the therapeutic value of homeopathic remedies, there are aspects of this trial that largely disclaim its validity.
COMMENTARY: Homeopathy is a therapeutic modality practiced worldwide, it is very popular among some patients, and it has withstood the test of time. Still, few therapies have attracted more controversy and debate.
While not going so far as to call homeopathy a hoax, scientists claim that homeopathic remedies are so highly dilute that specific therapeutic effects are biologically implausible. Yet, some observational studies have suggested that patients with certain ailments do improve after consulting a homeopath.
On the other hand, one assessment of systematic reviews of homeopathy concluded that there seem to be no specific health conditions that respond convincingly better to homeopathic treatment than to placebo or other control interventions [Ernst 2002]. Included in this assessment were 4 RCTs investigating homeopathy for migraine prophylaxis and 4 RCTs of the modality in treating osteoarthritis — all concluded that homeopathy was generally ineffective, beyond placebo effects. However, an assessment of 6 controlled trials of homeopathy for rheumatic conditions found that it was superior to placebo, but there were not enough trials for any specific condition to reach definitive conclusions.
The present trial by Brien et al. investigating homeopathy in RA is a model of excellent design, impeccable execution, and meticulous reporting. The fatal flaw, which makes this study so disappointing, is that too few subjects completed the trial for determining valid outcomes. The design, with 5 treatment groups, was ambitious to begin with. In their statistical power analysis, the researchers found they would need at least 22 participants per group to demonstrate a 30% difference in the primary ACR20 outcome measure (with 80% power at a 5% significance level).
The total number needed, 110, relies on an expectedly large effect size and is probably inadequate for such a complex design. At the outset, the researchers under-enrolled their trial with only 83 participants and, through attrition, they ended up with merely 14 to 16 subjects per group for analysis. They claimed that such small numbers still permitted sufficient power for analyses of some secondary outcome measures in comparing consultation versus no consultation groups. However, this may be overly optimistic and a misuse of statistics, since there is a point at which such small numbers of subjects in an ambitious design with multiple groups becomes a series of related case reports rather than a bona fide parallel-group RCT; both the internal and external validity and reliability of outcome data must be questioned.
Technical Example: An important measure for patient care would be pain relief afforded by a therapy. In this trial, outcomes on this variable had very wide, imprecise confidence intervals (CIs), as might be expected with such small numbers of subjects. All of the CIs for comparisons of homeopathic remedies versus placebo included the 0.0 null value of no difference and, thus, were statistically non-significant. The comparison of homeopathic consultation versus no consultation had a point estimate of 9.12 and 95% CI = 0.521 to 17.718 — a wide range but it excluded the null value and was statistically significant (P = 0.038) — and a moderate effect size of 0.481. However, even combined group sizes in a per protocol analysis included only 21 (consultation) and 19 (no consultation) subjects, which was still below the 22 subjects per group needed for even minimal statistical power. [For explanations of the various statistical concepts discussed here, see the UPDATES series on “Making Sense of Pain Research” here.]
Would more significant relationships have been found demonstrating homeopathic agent efficacy if groups were of much larger size? Very commonly, small studies are prone to a high degree of Type II (false negative) errors; that is, not detecting significant differences when they actually do exist. And, while the authors state, “…we consider these data to be rigorous and robust,” this may be wishful thinking, and they concede that their trial “was not designed to be definitive or prove the effectiveness of ultra-molecular [ie, homeopathic] medication….” It is regrettable that the outcomes of this otherwise excellent study cannot be trusted as valid or worthwhile, which leaves unanswered the question of whether or not homeopathic remedies might indeed be helpful for patients with RA.
What seems of most importance coming from this study is reaffirmation of the therapeutic value of a healthcare provider who incorporates empathy, sympathy, and holistic understanding in an unhurried consultation with the patient in pain. However, this is not a new insight. Although, such compassionate care may be disappearing from mainstream medicine and possibly becoming the purview of complementary and alternative medicine practitioners.
> Brien S, Lachance L, Prescott P, et al. Homeopathy has clinical benefits in rheumatoid arthritis patients that are attributable to the consultation process but not the homeopathic remedy: a randomized controlled clinical trial. Rheumatology. 2011;50(6):1070-1082 [article here].
> Ernst E. A systematic review of systematic reviews of homeopathy. Br J Clin Pharmacol. 2002;54(6);577-582 [available here].