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Papers, listed by lead author: K-L


Kainz, J.T., Kozel, G., Haidvogl, M., Smolle, J., (1996) Homoeopathic versus placebo therapy of children with warts on the hands: a randomized, double-blind clinical trial Dermatology Vol. 193 no. 4 pp. 318-20

“CONCLUSION: There was no apparent difference between the effects of homoeopathic therapy and placebo in children with common warts under the conditions of this study”

Links: [abstract pubmed]

Kaptchuk, T.J., Kelley, J.M., Conboy, L.A., Davis, R.B., Kerr, C.E., Jacobson, E.E., Kirsch, I., Rosa N Schyner, R.N., Bong Hyun Nam, B.H., Nguyen, L.T. Park, M., Rivers, A.L., McManus,C., Kokkotou, E., Drossman, D.A., Goldman, P., Lembo, A.J., (2008) Components of placebo effect: randomised controlled trial in patients with irritable bowel syndrome British Medical Journal Vol. 336 pp. 999-1003 [permalink]

Objective: To investigate whether placebo effects can experimentally be separated into the response to three components—assessment and observation, a therapeutic ritual (placebo treatment), and a supportive patient-practitioner relationship... in patients with irritable bowel syndrome.

“...  For three weeks either waiting list (observation), placebo acupuncture alone (“limited”), or placebo acupuncture with a patient-practitioner relationship augmented by warmth, attention, and confidence (“augmented”). At three weeks, half of the patients were randomly assigned to continue in their originally assigned group for an additional three weeks.

“... The proportion of patients reporting adequate relief showed a similar pattern: 28% on waiting list, 44% in limited group, and 62% in augmented group... The same trend in response existed in symptom severity score... and quality of life

“... Conclusion: Factors contributing to the placebo effect can be progressively combined in a manner resembling a graded dose escalation of component parts. Non-specific effects can produce statistically and clinically significant outcomes and the patient-practitioner relationship is the most robust component.

A comparison of three groups of patients with IBD – one was an observation-only group, one had placebo acupuncture carried out in an impersonal way and the third had placebo acupuncture carried out with warmth and empathy. The second group did better than the first. The third group though, scored much higher in all the end points than the second, indicating warmth, empathy etc can enhance the placebo response.

Links: [Abstract - BMJ]:[HTML - BMJ]:[PDF - BMJ]:[Abstract - Pubmed]:[Full text, Pubmed Central]

Kim, L.S., Riedlinger, J.E., Baldwin, C.M., Hilli, L., Khalsa, S.V., Messer, S.A. and Waters, R.F., (2005) Treatment of Seasonal Allergic Rhinitis Using Homeopathic Preparation of Common Allergens in the Southwest Region of the US: A Randomized, Controlled Clinical Trial Annals of Pharmacotherapy Vol. 39 no. 4 pp. 617-624

A paper which is described most eloquently by apgaylard as “small” - less than 50 participants per arm - means this trial is woefully underpowered to test a treatment for a condition with somewhat subjective signs and vague endpoints. Also the remedy used was far too concentrated to qualify as a standard homeopathic remedy and would have been likely to contain measurable quantities of pollen at a strength used routinely in conventional immunotherapy.

And the fact that the statistical analysis was highly questionable was even admitted by the authors.

All in all this is a paper, the conclusions of which are very much to be sniffed at.

Links: [abstract, annals of pharmacotherapy]
Responses: [apgaylard]:

Kleijnen, J., Knipschild, P and ter Riet, G., (1991) Clinical trials of homoeopathy BMJ Vol. 9 no. 302 pp. 316-323

"OBJECTIVE - To establish whether there is evidence of the efficacy of homoeopathy from controlled trials in humans...

CONCLUSIONS - 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."

Links: [abstract - pub med]:[abstract - BMJ]:[full text - BMJ, pdf]

This rather aged paper is one of the homeopathic “usual suspects” that get trotted out at every opportunity by homeopathic apologists. As proof of the effectiveness of homeopathy it is pretty flimsy, one would doubt whether the results would be able to fight their way out of a damp paper bag in order to defend the cause, really, this one ought to be able to retire gracefully. Still, it is some of the best evidence they’ve got, so let’s have a look at it.

What the homeopaths say: Proponents tend to cherry pick a few of the more favourable remarks from the body of this meta-analysis while conveniently ignoring others. A popular quote is "The amount of positive evidence even among the best studies came as a surprise to us. Based on this evidence we would be ready to accept that homoeopathy can be efficacious, if only the mechanism of action were more plausible.". “Boo, hiss!” shriek the homeopaths, “they know it works but they can’t bring themselves to admit it”. When, however, the explanatory " assume that an infinitesimally diluted substance in an alcoholic solution has pharmacological effects would mean that essential concepts of modern physics would have to be dismissed." is mentioned it all goes quiet and the only sound that can be heard is that of homeopaths with fingers in ears going “La, la, la, can’t hear you”.

In fact not having a plausible mode of action is an almost insurmountable hurdle for homeopathy. This isn't just someone commenting on say, a new antibiotic telling people "we haven't found out how it works yet but we've got a few ideas from the way others do and we have a set route which the investigation will take". It isn't just somebody with a vested interest in the status quo nit picking that "if it isn't 'science' then it can't work, no matter what the evidence says", although that this remark is simply prejudice is what homeopaths would like us to believe. Homeopathy's mechanism isn't just unknown it is, in any practical sense of the word, impossible. This is according to not just "essential concepts of modern physics" but to virtually every other branch of science as well - chemistry, biology, electromagnetics, you name it. If homeopathy were to be proved effective it would contradict most of known science at the most basic of levels - how is it that only homeopaths have noticed this gaping chasm of ignorance, and why aren't they able to prove it?

When considering homeopathy in this way something called the 'simplicity principle' applies. This is really a philosophical version of every day 'common sense', which has ancient roots going back at least to Occam (Sehon, 2010) and, in a nutshell, means that any evidence that homeopathy works must be massively convincing - orders of magnitude more so than for our antibiotic. Needless to say performing only slightly better than a sugar tablet in a few questionable trials doesn't come anywhere close.

Another favourite out of context remark from this paper is "The evidence presented in this review would probably be sufficient for establishing homoeopathy as a regular treatment for certain indications." while declining to mention that the authors had called into question much of that same evidence as a result of questionable methodologies, for example, "Double blinding... has to be checked by asking the patients in which group they believe that they were in during the trial... It is easy to state that a trial was double blind, but patients have many ways to break the code. This might explain small differences in favour of homoeopathy. Double blinding was not checked in any trial of homoeopathy." or bias, for example "When talking to authors of trials we identified at least six trials for which no manuscript had been submitted for publication. It is difficult to discover the true reasons for failure to submit an article for publication, but we think that the (possibly negative) results may have been an important factor in these cases.".

An important section is worth mentioning as it seems to be generally ignored in the process of wildly optimistic ‘spin’ is Kleijnen’s reference to an even older stalwart claimed, to this day, to offer proof positive for the effectiveness of homeopathy but which turns out to be nothing more than just another example of pro-homeopathic wishful thinking, casting doubt on even the purported positive evidence in the rest of the review:

“A trial of very high quality was that of the Groupe de Recherches et d'Essais Cliniques en Homeopathie, initiated by the French Ministry for Social Affairs and performed by a group consisting of regular and homoeopathic researchers (Mayaux 1998). After the earlier publication of several trials in which homoeopathy was shown to decrease the time to recovery of bowel movements after abdominal surgery, this hypothesis was retested in a rigorous trial comparing four groups of 150 patients (two groups were treated with opium C15 and raphanus C5, one group with indistinguishable placebo, and one group was not treated). No differences at all were found. Will more of such trials for other indications show the same results and refute the existing evidence?

So, the final verdict (and remember, this is one of the best pieces of evidence homeopaths can offer to support their case) is that the conclusion says it all, if you can interpret past the inevitable qualifiers: "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".

I'll translate - "poor trial quality and possible bias means there is no evidence that homeopathy works" - keep it simple, that's the motto of RationalVetMed. Yet another negative trial!

Klocke, P., Ivemeyer, S., Heil, F., Walkenhorst, M., Notz, C., (2007) Treatment of bovine sub-clinical mastitis with homeopathic remedies. Paper at: 3rd QLIF Congress: Improving Sustainability in Organic and Low Input Food Production Systems, University of Hohenheim, Germany, March 20-23

Considering the positive results of homeopathic therapy of bovine mastitis, the presented study should evaluate the effects of two standardized homeopathic methods in sub-clinical mastitis using a prospective randomized double-blind placebo control study design. A number of 124 dairy cows from 17 herds with increased somatic cell count were selected and randomly associated to 5 treatment groups. Two groups received a peroral therapy with (a) a homeopathic combination over 5 days and (b) a single treatment with a homeopathic nosode (Tuberculinum). To each treatment group a placebo control group was established with the same treatment frequency. A fifth group served as an untreated control. The bacteriological cure rate after 4 and 8 weeks was 28% and the total cure rate additionally regarding a normalized somatic cell count was 14% and 18%, respectively. There was no significant effect by the remedies at all. The cow somatic cell count over three months after treatment showed no significant difference in the five groups. Standardized homeopathic combinations and Tuberculinum nosodes are not able to control sub-clinical mastitis during lactation.

Mastitis, even in its mild form where the only indication there is a problem is an increased number of cells (somatic cell count) in the milk, is a serious, painful and commercially important disease of the dairy cow. This paper, presented at the 3rd congress of Quality Low Input Food (QLIF - allegedly "Improving sustainability in organic and low input food production systems") which was run in parallel with the 9th German Scientific Conference on Organic Agriculture, might have been expected to put as positive spin as possible on the virtues of homeopathy in treating this common condition.

But, after an upbeat first sentence, things go downhill rapidly until the final conclusion which is that homeopathy and nosodes are incapable of controlling mastitis and, yet again, performed no better than a blank placebo. Quelle surprise! Another nail in the coffin for the organic farming movement which makes a virtue out of witholding useful and safe drugs from sick animals.

Links: [full text, organic eprints]:[pdf, organic eprints]

Klopp, R., Niemer, W., Weiser, M., (2005) Microcirculatory effects of a homeopathic preparation in patients with mild vertigo: an intravital microscopic study Microvascular Research Vol. 69, nos. 1–2, pp.10–16

Testing the homeopathic preparation Vertigoheel, only the abstract of this paper is available online and it makes no mention of blinding or randomisation, leaving the reader to guess about how reliable the conclusion “The data support a pharmacological effect on microcirculation from the treatment” actually is. Even the British Homeopathic Association admits the trial is non-randomised while, at the same time, claiming it is good evidence in favour of homeopathy - they really do want it both ways!

Links: [abstract, science direct]


Lewith, G.T., Watkins, A.D., Hyland, M.E., Shaw, S., Broomfield, J.A., Dolan, G., et al., (2002) Use of ultramolecular potencies of allergen to treat asthmatic people allergic to house dust mite: double blind randomised controlled clinical trial. British Medical Journal Vol.  324 pp. 1-5

Links: [abstract pubmed]:[full text BMJ]:[full text pdf BMJ]:[full text pubmed central]

"... 242 people with asthma and positive results to skin prick test for house dust mite; 202 completed clinic based assessments, and 186 completed diary based assessments.

Intervention: After a four week baseline assessment, participants were randomised to receive oral homoeopathic immunotherapy or placebo and then assessed over 16 weeks with three clinic visits and diary assessments every other week...

Results: There was no difference in most outcomes between placebo and homoeopathic immunotherapy...

Conclusion: Homoeopathic immunotherapy is not effective in the treatment of patients with asthma...

Discussion: This randomised placebo controlled trail shows that homoeopathic immunotherapy is no better than placebo for the treatment of people with asthma who are allergic to house dust mite. Previous studies have suggested that homoeopathy is efficacious in the treatment of rhinitis and possibly asthma. Our study was substantially larger than any of the earlier studies and included a wider range of outcome measures. We found no evidence of difference measures between placebo and homoeopathy in our primary outcome at the end of the study..."

So, there we have it, a good, strong trial, which knocks the spots off any previous efforts and shows (yet again) that treatment with homeopathy is the same as treatment with a blank sugar tablet. There are the usual indignant huffings and puffings from homeopaths (who, of course have a vested interest) about how unfair the whole thing was and it doesn’t count because homeopaths didn’t get to design it and they reckon this was a study of isopathy rather than homeopathy (still just sugar tablets though!). But this is just the usual reasons homeopaths trot out when the evidence doesn’t suit their preconceptions, yet utterly ignore when they get the results they want. For example, have a look at the much smaller but broadly similar trial carried out by Reilly 1994, which also used diluted allergens to treat respiratory allergies in the same way as Leweth et al. 2002. You won’t find any complaints from homeopaths about whether this paper employed proper homeopathy or not though, since a hint of a favourable result was squeezed out of the poor unfortunate statistics after due pummelling. And that makes everything OK in the smoke and mirrors world of homeopathy.

Linde, K., Jonas, W.B., Melchart, D., Worku, F,. Wagner, H. and Eitel, F., (1994) Critical review and meta-analysis of serial agitated dilutions in experimental toxicology Human Experimental Toxicology Vol.13, no. 7 pp. 481-92

Links: [abstract, pubmed]

Linde, K., et al (1997) Are the clinical effects of homoeopathy placebo effects? A meta-analysis of placebo-controlled trials Lancet Vol. 350 no. 9081 pp. 834-843 *

BACKGROUND: Homeopathy seems scientifically implausible, but has widespread use. We aimed to assess whether the clinical effect reported in randomised controlled trials of homeopathic remedies is equivalent to that reported for placebo.

INTERPRETATION: 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.

What the homeopaths say: Despite the authors’ conclusion “we found insufficient evidence from these studies that homeopathy is clearly efficacious for any single clinical condition” the ENHR comment is ridiculously up-beat: “Result: significantly in favour of homeopathy... This meta-analysis included 186 placebo-controlled studies of homeopathy published until mid-1996, of which data for analysis could be extracted from 89. The overall odds ratio... means that the chances that homeopathy would benefit the patient were 2.45 times greater than placebo. When considering just those trials of high quality... and with predefined primary outcome measures, the pooled odds ratio was 1.97 and significant. Even after correction for publication bias the results remained significant. The main conclusion was that the results "were not compatible with the hypothesis that the effects of homeopathy are completely due to placebo". If the result of new trials were to show no difference between homeopathy and placebo, we would have to add 923 trials with no effect with 118 patients in each in order to balance the two.

Unfortunately however for the homeopaths two subsequent re-analyses (Linde et al, 1999 (below) and Ernst and Pittler, 2000) found that the statistics in this study were flawed and the interpretation of the results had been wildly over-optimistic.  Edzard Ernst reported "the reanalysis of Linde et al. can be seen as the ultimate epidemiological proof that homeopathic remedies are, in fact, placebos." and Linde himself stated, following a fresh look at the data, “We conclude that in the study set investigated, there was clear evidence that studies with better methodological quality tended to yield less positive results." As a further criticism of homoeopathic trials in general he states "in these trials homeopathy was mainly used for mild and chronic conditions for which there are few objective outcome measures."

So, this paper is out of date, has deeply flawed statistics and has been superceded by two subsequent re-analyses both of which found against homeopathy. Damningly, in 2005, its authors said in a Lancet article, “Our 1997 meta-analysis has unfortunately been misused by homoeopaths as evidence that their therapy is proven.“.

Jump back to the “Usual suspects” page for the next devastating weapon in the homeopathic arsenal of damp squibs...

Links: [abstract - pub med]:[full text - Lancet]

Resonses: [Bandolier]:[Ernst and Barnes - comment in Lancet]:[CRD DARE analysis]:[Edzard Ernst blog]

Linde, K. and Melchart, D., (1998) Randomized controlled trials of individualized homeopathy: a state-of-the-art review. J Altern Complement Med. Vol. 4 no.4 pp371-88.

“... when the analysis was restricted to the methodologically best trials no significant effect was seen...

“The results of the available randomized trials suggest that individualized homeopathy has an effect over placebo. The evidence, however, is not convincing because of methodological shortcomings and inconsistencies.”

Links: [abstract - pub med]

So, the better the quality of the trial the less likely it is to suggest that homeopathy works! No wonder homeopaths seem to prefer to publish poor-quality trials.

Linde, K., Scholz, M., Ramirez, G., et al., (1999) Impact of study quality on outcome in placebo controlled trials of homeopathy J Clin Epidemiol  Vol. 52 pp. 631–6

"We investigated the influence of indicators of methodological quality on study outcome in a set of 89 placebo-controlled clinical trials of homoeopathy in three different ways... Studies that were explicitly randomized and were double-blind as well as studies scoring above the cut-points yielded significantly less positive results than studies not meeting the criteria. In the cumulative meta-analyses, there was a trend for increasing effect sizes when more studies with lower-quality scores were added... We conclude that in the study set investigated, there was clear evidence that studies with better methodological quality tended to yield less positive results..."

Links: [abstract - pub med]
Responses: [Bandolier]

This is a reinterpretation of the lead author’s earlier work (Linde 1997, above) which completely overturned the, albeit weak, evidence of the original conclusion in favour of homeopathy and reported that the better the quality of the trial, the worse the results were for homeopathy. Homeopaths are always very keen to quote the Linde 1997 paper as irrefutable proof of how highly effective homeopathy is, but always seem to forget the Linde 1999 one - strange that!

Linde, K., and Jonas, W., (2005) Are the clinical effects of homoeopathy placebo effects? Lancet, Vol. 366, no. 9503, pp. 2081 - 2082 (this article is a response to Shang et al 2005)

Links: [full text, Lancet]
Responses: [Shang et al (authors' response)]

Lloyd, S., and Martin, S.A., (2006) Controlled trial on the effects of radionic healing and anthelmintics on faecal egg counts in horses Veterinary Record Vol. 158, pp. 734-737

No evidence was obtained to demonstrate that radionic healing reduced the faecal egg counts (FECs) of equine strongyles. In year 2, the group 2 horses (radionic healing) were compared directly with the horses receiving no treatment (group 1) and there were no significant differences in FEC between the two groups. In year 1 they could not be compared with untreated horses, but horses receiving occasional anthelmintic treatments occasionally had significantly lower FECs.

Links: [citation, Veterinary Record]

A mysterious black box, connected to the patient by invisible lines of energy no matter where either party is located on the planet; diagnosis and treatment both performed by interrogating a “witness” (e.g. a piece of hair or a drop of blood); answers to clinical questions relayed via a swinging pendulum or a sticky pad. This is a completely bonkers mode of “treatment” which makes voodoo look mainstream and shouldn’t have required all the expense and inconvenience of a trial to tell any rational person that it had absolutely no effect on disease whatsoever.