Back in August 2005, the Lancet published an interesting meta-analysis on homeopathy. The
full free text of this article is not available on the web, but if you can find a copy it is
well worth reading.
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Are the clinical effects of homoeopathy placebo effects? Comparative study of
placebo-controlled trials of homoeopathy and allopathy. Shang A, Huwiler-Muntener K,
Nartey L, Juni P, Dorig S, Sterne JA, Pewsner D, Egger M. Lancet 2005: 366(9487); 726-32.
[Medline]
[Abstract]
The researchers identified 110 placebo controlled homeopathy trials and matched them with
110 placebo controlled conventional-medicine trials. Both sets of trials showed that smaller
studies showed stronger effects. Both also showed that lower quality studies showed stronger
effects. But when the analysis was restricted to large trials of high quality, the effect of
conventional medicine was still statistically significant (odds ratio 0.58, 95% CI 0.39 to
0.85) but the effect of homeopathy was not (odds ratio 0.88, 95% CI 0.65 to 1.19).
The critics of this meta-analysis raise some interesting objections, and you can read some
of them in the in correspondence section of the December 17, 2005 issue of the Lancet. A
common complaint, voiced in the
letter by Harald Walach, Wayne Jonas, and George Lewith is that the type of homeopathy
testing in clinical trials is very different from that used in the real world. They also
argue that the comparison of homeopathy and conventional medicine is an apples to oranges
comparison.
Second, the six studies of conventional interventions are, by comparison, highly
selected. The substances assessed within them have gone through the four clinical
pharmacological stages of drug testing. Most newly developed pharmaceuticals do not make
it to the last stage of large, multicentre phase IV trials. Therefore the allopathy
trials chosen by Shang and colleagues tested medications that had already been largely
proven to be efficacious, whereas most homoeopathy trials start from a far less
systematic and rigorous evidence base. There have, after all, been very few
placebo-controlled randomised trials in homoeopathy, which is why there is an absence of
evidence. We are only just beginning to understand how to research homoeopathy and
complementary medicine in general. This seems to be an argument for more research, not
less.
I don't find this argument compelling. If homeopathy uses a lot of things that would not
survive the four clinical pharmacological stages of drug testing, then a large portion of
homeopathy, as it is currently practiced, is ineffective. If anything, this statement
supports the use of Evidence Based Medicine since the practice of conventional medicine to
test new therapies and, when indicated, adopt them in place of older therapies appears to
lead to superior results.
The authors also argue that the placebo effect is stronger in homeopathy studies than in
conventional medicine. They don't present any evidence for this statement other than pointing
out that the placebo effect can vary substantially.
Two other sets of authors criticize the published meta-analysis for leaving out important
details, such as the studies that were excluded from analysis. The authors do correct this in
their reply in the December 17 issue and point to a web site (www.ispm.ch)
with those details.
One of the letters referred to the crossword analogy of Susan Haack, which is worth
quoting here:
The clues [of the crossword] are the analogue of experiential evidence,
already-completed entries the analogue of background information. How reasonable an
entry in a crossword is depends upon how well it is supported by the clue and any other
already intersecting entries; how reasonable, independently of the entry in question,
those other entries are; and how much of the crossword has been completed. An empirical
proposition is more or less warranted depending on how well it is supported by
experiential evidence and background beliefs; how secure the relevant background beliefs
are, independently of the proposition in question; and how much of the relevant evidence
the evidence includes. How well evidence supports a proposition depends on how much the
addition of the proposition in question improves its explanatory integration. There is
such a thing as supportive-but-less-than-conclusive evidence, even if there is no
formalizable inductive logic.
This quote comes from the interesting publication
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Alternative medicine: a "mirror image" for scientific reasoning in conventional medicine.
Vandenbroucke JP, de Craen AJ. Ann Intern Med 2001: 135(7); 507-13.
[Abstract]
[PDF]
A far sharper criticism of the Lancet study was published by Domenico Mastrangelo and
Cosimo Lore.
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The growth of a lie and the end of "conventional" medicine. Mastrangelo D, Lore C.
Med Sci Monit 2005: 11(12); SR27-31.
[Medline]
[Abstract]
[PDF]
The authors argue that it is a mistake to compare homeophathy to a placebo because:
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the real nature of the placebo effect is unknown;
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it has never been explained in terms of interactions between molecules and hence must
be based on 'immaterial' interactions, if any (something like the 'vital force' in
homeopathy);
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'immaterial', and hence non-measurable, interactions are commonly discarded as
unproven by conventional medicine. On the other hand, this is the subject of the current
dispute between homeopathy and conventional medicine;
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nevertheless, conventional medicine looks at the placebo effect as something 'real'.
As a matter of fact, controlled clinical trials are commonly planned to include a
'control' group of patients to be treated with 'sugar pills' and therefore the placebo
effect, although mysterious and unexplainable, is still an integral part of the culture
of conventional medicine. It would be good to know why homeopathy should not be treated
in the same way;
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in spite of all the above, the placebo still has a curative effect since it refers to
people cured by the administration of a 'sugar pill' instead of an active drug.
They then go on to ask
Should we still consider the placebo as a sort of unwanted effect of treatment, or
would it perhaps be wiser and more advisable to try to better understand its nature and,
eventually, exploit it to reduce the incidence of adverse or fatal drug reactions?
Many proponents of alternative medicine are fascinated by the placebo effect because it
provides evidence of a mind-body interaction that might support and explain the efficacy of
their medical approaches. But quite honestly, hitching your wagon to the placebo star will
probably lead you nowhere. The placebo effect is an amalgam of different effects, such as the
self limiting nature of many diseases, the regression to the mean effect, observer bias, and
so forth. A major meta-analysis of placebo effects demonstrated that in many situations, a
placebo arm of a study does not differ from a "no treatment" arm.
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Is the placebo powerless? An analysis of clinical trials comparing placebo with no
treatment. Hrobjartsson A, Gotzsche PC. N Engl J Med 2001: 344(21); 1594-602.
[Medline] [Abstract]
[Full text]
[PDF]
Mastrangelo and Lore then attack the controlled clinical trial (CCT):
The Lancet campaign against homeopathy was launched by experts on controlled
clinical trials and it is therefore based on the unproven assumption that the CCT
methodology is reliable, repeatable, accurate, and infallible. This is simply not true.
In 1991, Dr. Harris L. Coulter [10], in his book 'The Controlled Clinical Trial: An
Analysis', reported that 'CCT cannot guarantee drug safety and efficacy because the
theoretical requirements of CCT are both unrealistic and unscientific'. This point of
view was more recently confirmed by scientists who reported that there is no evidence
for large-scale CCTs other than the vested interests of the pharmaceutical industry to
defy sound arguments which demonstrate that the methodology of these studies is deeply
flawed.
As support for the last sentence, these authors cite an article by James Penston:
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Large-scale randomised trials--a misguided approach to clinical research. Penston J.
Med Hypotheses 2005: 64(3); 651-7.
[Medline]
I have not yet read this article, but I have read the book by Dr. Penston
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Fiction and Fantasy in Medical Research: The Large Scale Randomised Trial. Penston J,
/ FPJ (2003) London, England: London Press. ISBN: 0954463617.
[BookFinder4U link]
which appears to make much the same claim. I disagree with Dr. Penston's pessimistic
assessment of medical research and have commented on it elsewhere (see the link to my other
weblog entry at the bottom).
All research has flaws, and it is a mistake to think that only unflawed research can
produce useful information. The trick is to recognize the difference between a trivial flaw
and an important flaw and to discern when a flaw becomes so serious that it makes the
research findings unusable.
The authors then point out some recent examples of commercial influences and fraud in
medical research.
With this picture in mind, the reader may now evaluate more objectively the
clinical and scientific relevance of the methodology behind CCTs and finally understand
why large collections of such investigations, as performed in meta-analyses, would only
lead to confusing, uncertain, and misleading conclusions.
The authors also point out that the tendency of a CCT to examine a single treatment for a
single disease limits its ability to examine the efficacy of homeopathy.
Let us suppose that a pharmaceutical company has to test the efficacy (and safety)
of the new drug 'ASA' (acetylsalicylic acid) in the treatment of fever. According to CCT
methodology, one would simply select a group of patients with fever, assign them,
through the process of 'randomization', to either the active drug (ASA) or a placebo
treatment, and look for differences in response. Hence: one disease (or symptom) ' one
treatment. Homeopathy, in contrast, teaches us that fever may manifest differently in
different individuals and it may depend on several diverse causes. Therefore, homeopathy
will use Aconitum to treat a fever with sudden onset, Arsenicum Album for a feverish,
anxious, and fidgety child, Belladonna for a feverish child who has chills and a flushed
and heated face and body, Bryonia for fever with strong thirst, Chamomilla for fever
associated with teething, Ferrum Phosphoricum for moderate fever, Gelsemium for the
child who sustains a fever and whose whole body feels achy and flushed, Mercurius
solubilis for the feverish child with offensive-smelling breath, body, stool, and/or
urine, etc., continuing with a list of tens or maybe hundreds of different remedies,
each with a single and extremely specific indication. It is easy to see that limiting
the homeopathic treatment to one remedy for a single indication, with no further
specification, would inevitably end up destroying the essence of homeopathic treatment
itself, thus resulting in ineffective treatment.
It is indeed true that the CCT ends up focusing too often on single treatments for single
diseases, but it is very easy to design a CCT that will test homeopathy in an individualized
approach. Send any patient with a fever to a homeopathic practitioner. Get an individualized
prescription and have it filled by a different practitioner who dispenses either the
indicated homeopathic solution or a placebo based on a random number table. The patient
returns to the original homeopathic practitioner for a blinded evaluation of the
effectiveness of the individualized treatment.
While the CCT does not deserve to rest untested and unchallenged at the top of the
research hierarchy, it still does better than Mastrangelo and Lore claim it does. A good
balanced review of the limitations of the CCT in testing alternative medicine appears in
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Evaluating complementary medicine: methodological challenges of randomised controlled
trials. Mason S, Tovey P, Long AF. Bmj 2002: 325(7368); 832-4.
[Medline] [Full text]
[PDF]
and I comment extensively on this article as well as the much more negative viewpoint of
Dr. Penston on another one of my weblog entries:
