Monthly Archives: February 2013
Acupuncture remains a highly controversial treatment: its mechanism of action is less than clear and the clinical results are equally unconvincing. Of course, one ought to differentiate between different conditions; the notion that acupuncture is a panacea is most certainly nonsense.
In many countries, acupuncture is being employed mostly in the management of pain, and it is in this area where the evidence is perhaps most encouraging. Yet, even here the evidence from the most rigorous clinical trials seems to suggest that much, if not all of the effects of acupuncture might be due to placebo.
Moreover, we ought to be careful with generalisations and ask what type of pain? One very specific pain is that caused by aromatase inhibitors (AI), a medication frequently prescribed to women suffering from breast cancer. Around 50 % of these patients complain of AI-associated musculoskeletal symptoms (AIMSS) and 15 % discontinue treatment because of these complaints. So, can acupuncture help these women?
A recent randomised, sham-controlled trial tested whether acupuncture improves AIMSS. Postmenopausal women with early stage breast cancer, experiencing AIMSS were randomized to eight weekly real or sham acupuncture sessions. The investigators evaluated changes in the Health Assessment Questionnaire Disability Index (HAQ-DI) and pain visual analog scale (VAS). Serum estradiol, β-endorphin, and proinflammatory cytokine concentrations were also measured pre and post-intervention. In total, 51 women were enrolled of whom 47 were evaluable (23 randomized to real and 24 to sham acupuncture).
Baseline characteristics turned out to be balanced between groups with the exception of a higher HAQ-DI score in the real acupuncture group. The results failed to show a statistically significant difference in reduction of HAQ-DI or VAS between the two groups. Following eight weekly treatments, a significant reduction of IL-17 was noted in both groups. No significant modulation was seen in estradiol, β-endorphin, or other proinflammatory cytokine concentrations in either group. No difference in AIMSS changes between real and sham acupuncture was seen.
Even though this study was not large, it was rigorously executed and well-reported. As many acupuncturists claim that their treatment alleviates pain and as many women suffering from AM-induced pain experience benefit, acupuncture advocates will nevertheless claim that the findings of this study are wrong, misleading or irrelevant. The often remarkable discrepancy between experience and evidence will again be the subject of intense discussions. How can a tiny trial overturn the experience of so many?
The answer is: VERY EASILY! In fact, the simplest explanation is that both are correct. The trial was well-done and its findings are thus likely to be true. The experience of patients is equally true – yet it relies not on the effects of acupuncture per se, but on the context in which it is given. In simple language, the effects patients experience after acupuncture are due to a placebo-response.
This is the only simple explanation which tallies with both the evidence and the experience. Once we think about it carefully, we realise that acupuncture is highly placebo-genic:
It is exotic.
It is invasive.
It is slightly painful.
It involves time with a therapist.
It involves touch.
If anyone had the task to develop a treatment that maximises placebo-effects, he could not come up with a better intervention!
Ahhh, will acupuncture-fans say, this means that acupuncture is a helpful therapy. I don’t care how it works, as long as it does help. Did we not just cover this issues in some detail? Indeed we did – and I do not feel like re-visiting the three fallacies which underpin this sentence again.
During the last decade, Professor Claudia Witt and co-workers from the Charite in Berlin have published more studies of homeopathy than any other research group. Much of their conclusions are over-optimistic and worringly uncritical, in my view. Their latest article is on homeopathy as a treatment of eczema. As it happens, I have recently published a systematic review of this subject; it concluded that “the evidence from controlled clinical trials… fails to show that homeopathy is an efficacious treatment for eczema“. The question therefore arises whether the latest publication of the Berlin team changes my conclusion in any way.
Their new article describes a prospective multi-centre study which included 135 children with mild to moderate atopic eczema. The parents of the kids enrolled in this trial were able to choose either homeopathic or conventional doctors for their children who treated them as they saw fit. The article gives only scant details about the actual treatments administered. The main outcome of the study was a validated symptom score at 36 months. Further endpoints included quality of life, conventional medicine consumption, safety and disease related costs at six, 12 and 36 months.
The results showed no significant differences between the groups at 36 months. However, the children treated conventionally seemed to improve quicker than those in the homeopathy group. The total costs were about twice higher in the homoeopathic compared to the conventional group. The authors conclude as follows: “Taking patient preferences into account, while being unable to rule out residual confounding, in this long-term observational study, the effects of homoeopathic treatment were not superior to conventional treatment for children with mild to moderate atopic eczema, but involved higher costs“.
At least one previous report of this study has been available for some time and had thus been included in my systematic review. It is therefore unlikely that this new analysis might change my conclusion, particularly as the trial by Witt et al has many flaws. Here are just some of the most obvious ones:
Patients were selected according to parents’ preferences.
This means expectations could have played an important role.
It also means that the groups were not comparable in various, potentially important prognostic variables.
Even though much of the article reads as though the homeopaths exclusively employed homeopathic remedies, the truth is that both groups received similar amounts of conventional care and treatments. In other words, the study followed a ‘A+B versus B’ design (here is the sentence that best gives the game away “At 36 months the frequency of daily basic skin care was… comparable in both groups, as was the number of different medications (including corticosteroids and antihistamines)…”). I have previously stated that this type of study-design can never produce a negative result because A+B is always more than B.
Yet, at first glance, this new study seems to prove my thesis wrong: even though the parents chose their preferred options, and even though all patients were treated conventionally, the addition of homeopathy to conventional care failed to produce a better clinical outcome. On the contrary, the homeopathically treated kids had to wait longer for their symptoms to ease. The only significant difference was that the addition of homeopathy to conventional eczema treatments was much more expensive than conventional therapy alone (this finding is less than remarkable: even the most useless additional intervention costs money).
So, is my theory about ‘A+B versusB’ study-designs wrong? I don’t think so. If B equals zero, one would expect exactly the finding Witt et al produced: A+0=A. In turn, this is not a compliment for the homeopaths of this study: they seem to have been incapable of even generating a placebo-response. And this might indicate that homeopathy was not even usefull as a means to generate a placebo-response. Whatever interpretation one adopts, this study tells us very little of value (as children often grow out of eczema, we cannot even be sure whether the results are not simply a reflection of the natural history of the disease); in my view, it merely demonstrates that weak study designs can only create weak findings which, in this particular case, are next to useless.
The study was sponsored by the Robert Bosch Stiftung, an organisation which claims to be dedicated to excellence in research and which has, in the past, spent millions on researching homeopathy. It seems doubtful that trials of this caliber can live up to any claim of excellence. In any case, the new analysis is certainly no reason to change the conclusion of my systematic review.
To their credit, Witt et al are well aware of the many weaknesses of their study. Perhaps in an attempt to make them appear less glaring, they stress that “the aim of this study was to reflect the real world situation“.Usually I do not accept the argument that pragmatic trials cannot be rigorous – but I think Witt et al do have a point here: the real word tells us that homeopathic remedies are pure placebos!
The most common pronouncement regarding alternative medicine that I have heard over the years from consumers, health care professionals or decision makers with a liking of alternative medicine goes as follows: “I don’t care how it works, as long as it helps.”
At first glance, this argument seems reasonable, logic and correct; it would be foolish, perhaps even unethical, to reject an effective treatment simply because we fail to understand how its effectiveness comes about – this would not be pragmatic and it is not what we do in medicine: aspirin, for instance, was used and helped many patients long before we understood how it worked. However, once we consider the way this notion is regularly used to defend the use of unproven therapies, we see that, in this context, it is fallacious – in fact, if we dissect it carefully, we find that it crams three large fallacies in one tiny sentence.
The first thing we notice is that the argument combines two fundamentally different issues which really should be separate 1) the mechanism of action of a therapy and 2) its clinical effectiveness. The matter gets clearer, if we discuss it not in the abstract, but in relation to a concrete example: BACH FLOWER REMEDIES (BFRs). I could have selected many other alternative therapies but BFRs seem fine, particularly as they have so far received no mention on this blog.
Similar to homeopathic preparations, BFRs are so dilute that they do not contain any active ingredients to speak of (they differ from homeopathic preparations, however, in that they do not follow the ‘like cures like’ principle). Several clinical trials of BFRs have been published; collectively, their results show very clearly that the clinical effects of BFRs do not differ from those of placebo. (This does not stop manufacturers selling and consumers buying them; in fact, BFRs are a thriving business.)
The principles backing up BFRs are scientifically implausible, and even BFR-practitioners would probably admit that they have no scientifically defensible idea how their remedies work. Scientists might add that a mechanism of action of such highly dilute remedies is not just unknown but unknowable; there is no way to explain how they work without re-writing several laws of nature.
The overall situation is thus quite clear: BFRs are not effective and there is no plausible mechanism of action.Yet it is hard to deny that many patients feel better after having consulted a BFR-practitioner (or after self-medicating BFRs), and those satisfied customers often insist: “I don’t care how BFRs work, as long as they help me.”
As previously discussed, symptoms can improve for a range of reasons which are related to any specific therapeutic effect: the natural history of the condition, regression towards the mean, placebo-effects etc. Only rigorously controlled trials can tell us whether the therapy or other factors caused the clinical outcome; our perception alone cannot identify cause and effect.
The fact that thousands of patients swear by BFRs, does therefore not constitute proof for their efficacy. The explanation of the apparently different impressions from experience and the results of clinical trials is therefore simple: the empathetic encounter with a therapist and/or a placebo-effect and/or the natural history of the condition are perceived as helpful, while the BFRs are pure placebos.
Back to the notion “I don’t care how this therapy works, as long as it helps” – it turns out to be based on at least three misunderstandings all tightly woven together.
Firstly, it was not the treatment itself that helped, but something else (see above). To imply that the treatment worked is therefore a fallacy.
Secondly, the reference to an unknown mechanism of action is aimed at misleading the opponent: it distracts from the first fallacy (“the treatment is effective”) by super-imposing a second fallacy (that there might be a mechanism of action). Crucially it attempts to wrong-foot the opponent by implying: “you reject something useful simply because you cannot explain it; this is poor logic and even worse ethics – shame on you!”.
BFR-enthusiasts are bound to see all this quite differently. They will probably claim that a placebo-effect is also a plausible mechanism. “Surely” they might say “this means that BFRs are useful and should be widely employed”.
In proclaiming this, they turn the double-fallacy into a triple fallacy. What they forget is that we do not need a placebo to generate placebo-effects. An effective treatment administered with time, compassion and empathy will, of course, also generate a placebo-effect – what is more, it would generate a specific therapeutic effect on top of it. Thus the BFR are quite useless in comparison. There is rarely a good justification for using placebos in clinical routine.
In conclusion, the often-used and seemingly reasonable sentence “I don’t care how it works, as long as it is helpful turns out to be a package of fallacies when used to support the use of unproven treatments.
There are at least two dramatically different kinds of herbal medicine, and the proper distinction of the two is crucially important. The first type is supported by some reasonably sound evidence and essentially uses well-tested herbal remedies against specific conditions; this approach has been called by some experts RATIONAL PHYTOTHERAPY. An example is the use of St John’s Wort for depression.
The second type of herbal medicine. It entails consulting a herbal practitioner who takes a history, makes a diagnosis (usually according to obsolete concepts) and prescribes a mixture of several herbal remedies tailor-made to the characteristics of his patient. Thus 10 patients with the identical diagnosis (say depression) might receive 10 different mixtures of herbs. This is true for individualized herbalism of all traditions, e.g. Chinese, Indian or European, and virtually every herbalist you might consult will employ this individualized, traditional approach.
Many consumers know that, in principle, there is some reasonably good evidence for herbal medicine. They fail to appreciate, however, that this does only apply to (sections of) rational phytotherapy. So, they consult herbal practitioners in the belief that they are about to receive an evidence-based therapy. Nothing could be further from the truth! The individualised approach is not evidence-based; even if the individual extracts employed were all supported by sound data (which they frequently are not) the mixutres applied are clearly not.
And this is where the danger of traditional herbalism lies; over the years, herbalists have fooled us all with this fundamental misunderstanding. In the UK, they might even achieve statutory regulation on the back of this self-serving misconception. When this happens, we would have a situation where a completely unproven practice has obtained the same status as doctors, nurses and physiotherapists. If this is not grossly misleading for the consumer, I do not know what is!!!
Some claim that individualized herbalism cannot be tested in clinical trials. This notion can very easily be shown to be wrong: several such studies testing individualized herbalism have been published. To the dismay of traditional herbalists, their results fail to confirm that such treatments are effective for any condition.
Now a further trial has become available that importantly contributes to this knowledge-base. Its authors (all enthusiasts of individualized herbalism) randomized 102 patients suffering from hip or knee-osteoarthritis into two groups. The experimental group received tailor-made mixtures of 7 to 10 Chinese herbs which were traditionally assumed to be helpful. The control group took a mixture of plants known to be ineffective but tasting similar. After 20 weeks of treatment, there were no differences between the groups in any of the outcome measures: pain, stiffness and function. These results thus confirm that this approach is not effective. Not only that, it also carries more risks.
As individualized herbalism employs a multitude of ingredients, the dangers of adverse-effects and herb-drug interactions, contamination, adulteration etc. are bigger that those with the use of single herbal extracts. It seems to follow therefore that the risks of individualized herbalism do not outweigh its benefit.
My recommendations are thus fairly straight forward: if we consider herbal medicine, it is vital to differentiate between the two types. Rational phytotherapy might be fine – of course, depending on the remedy and the condition we are aiming to treat. Individualised or traditional herbalism is not fine; it is not demonstrably effective and has considerable risks. This means consulting a herbalist is not a reasonable approach to treating any human ailment. It also means that regulating herbalists (as we are about to do in the UK) is a seriously bad idea: the regulation of non-sense will result in non-sense!
Rigorous studies of homeopathy are a bit like gold dust; they are so rare that we see perhaps only one or two per year. It is therefore good news that very recently one such trial has been published.
This randomized, placebo-controlled study tested the efficacy of a complex homeopathic medicine, Cocculine, for chemotherapy-induced nausea and vomiting (CINV) in non-metastatic breast cancer patients treated by standard chemotherapy regimens.
Chemotherapy-naive patients with non-metastatic breast cancer scheduled to receive 6 cycles of chemotherapy were randomized to receive standard anti-emetic treatment plus either the complex homeopathic remedy or the matching placebo. The primary endpoint was nausea score measured after the 1st chemotherapy course.
In total, 431 patients were randomized: 214 to Cocculine (C) and 217 to placebo (P). Patient characteristics were well-balanced between the 2 arms. Overall, compliance to study treatments was excellent and similar between the 2 arms. A total of 205 patients (50.9%; 103 patients in the placebo and 102 in the homeopathy arms) had nausea scores > 6 indicative of no impact of nausea on quality of life during the 1st chemotherapy course. There was no difference between the 2 arms when primary endpoint analysis was performed by chemotherapy stratum; or in the subgroup of patients with susceptibility to nausea and vomiting before inclusion. In addition, nausea, vomiting and global emesis scores were not statistically different at any time between the two study arms.
The authors’ conclusions could not be clearer: “This double-blinded, placebo-controlled, randomised Phase III study showed that adding a complex homeopathic medicine (Cocculine) to standard anti-emetic prophylaxis does not improve the control of CINV in early breast cancer patients.”
COCCULINE is manufactured by Boiron and contains Cocculus indicus 4CH, Strychnos nux vomica 4CH, Nicotiana tabacum 4CH, Petroleum rectificatum 4CH aa 0,375 mg. Boiron informs us that “this homeopathic preparation is indicated in sickness during travelling (kinetosis). Preventive dosage is 2 tablets 3 times a day one day before departure and on the day of journey. Treatment dosage is 2 tablets every hour. The interval is prolonged in dependence on improvement. Dosage in children is the same as in adults. The tablets are left to dissolve in mouth or in a small amount of water.”
Homeopaths might argue that this trail did not follow the rules of classical homeopathy where treatments need to be individualised. This may be true but, in this case, they should campaign for all OTC homeopathy to be banned. As they do not do that, I suggest they live with yet another rigorous clinical trial demonstrating that homeopathic remedies are pure placebos.
If I had a pint of beer for every time I have been accused of bias against chiropractic, I would rarely be sober. The thing is that I do like to report about decent research in this field and I am almost every day looking out for new articles which might be worth writing about – but they are like gold dust!
“Huuuuuuuuh, that just shows how very biased he is” I hear the chiro community shout. Well let’s put my hypothesis to the test. Here is a complete list of recent (2013)Medline-listed articles on chiropractic; no omission, no bias, just facts (for clarity, the Pubmed-link is listed first, then the title in bold followed by a short comment in italics):
http://www.ncbi.nlm.nih.gov/pubmed/23360894
Towards establishing an occupational threshold for cumulative shear force in the vertebral joint – An in vitro evaluation of a risk factor for spondylolytic fractures using porcine specimens.
This is an interesting study of the shear forces observed in porcine vertebral specimen during maneuvers which might resemble spinal manipulation in humans. The authors conclude that “Our investigation suggested that pars interarticularis damage may begin non-linearly accumulating with shear forces between 20% and 40% of failure tolerance (approximately 430 to 860N”
http://www.ncbi.nlm.nih.gov/pubmed/23337706
Development of an equation for calculating vertebral shear failure tolerance without destructive mechanical testing using iterative linear regression.
This is a mathematical modelling of the forces that might act on the spine during manipulation. The authors draw no conclusions.
http://www.ncbi.nlm.nih.gov/pubmed/23324133
Collaborative Care for Older Adults with low back pain by family medicine physicians and doctors of chiropractic (COCOA): study protocol for a randomized controlled trial.
This is merely the publication of a trial that is about to commence.
http://www.ncbi.nlm.nih.gov/pubmed/23323682
Military Report More Complementary and Alternative Medicine Use than Civilians.
This is a survey which suggests that ~45% of all military personnel use some form of alternative medicine.
http://www.ncbi.nlm.nih.gov/pubmed/23319526
Complementary and Alternative Medicine Use by Pediatric Specialty Outpatients
This is another survey; it concludes that ” that CAM use is high among pediatric specialty clinic outpatients”
http://www.ncbi.nlm.nih.gov/pubmed/23311664
Extending ICPC-2 PLUS terminology to develop a classification system specific for the study of chiropractic encounters
This is an article on chiropractic terminology which concludes that “existing ICPC-2 PLUS terminology could not fully represent chiropractic practice, adding terms specific to chiropractic enabled coding of a large number of chiropractic encounters at the desired level. Further, the new system attempted to record the diversity among chiropractic encounters while enabling generalisation for reporting where required. COAST is ongoing, and as such, any further encounters received from chiropractors will enable addition and refinement of ICPC-2 PLUS (Chiro)”.
http://www.ncbi.nlm.nih.gov/pubmed/23297270
US Spending On Complementary And Alternative Medicine During 2002-08 Plateaued, Suggesting Role In Reformed Health System
This is a study of the money spent on alternative medicine concluding as follows “Should some forms of complementary and alternative medicine-for example, chiropractic care for back pain-be proven more efficient than allopathic and specialty medicine, the inclusion of complementary and alternative medicine providers in new delivery systems such as accountable care organizations could help slow growth in national health care spending”
http://www.ncbi.nlm.nih.gov/pubmed/23289610
A Royal Chartered College joins Chiropractic & Manual Therapies.
This is a short comment on the fact that a chiro institution received a Royal Charter.
http://www.ncbi.nlm.nih.gov/pubmed/23242960
Exposure-adjusted incidence rates and severity of competition injuries in Australian amateur taekwondo athletes: a 2-year prospective study.
This is a study by chiros to determine the frequency of injuries in taekwondo athletes.
The first thing that strikes me is the paucity of articles; ok, we are talking of just january 2013 but by comparison most medical fields like neurology, rheumatology have produced hundreds of articles during this period and even the field of acupuncture research has generated about three times more.
The second and much more important point is that I fail to see much chiropractic research that is truly meaningful or tells us anything about what I consider the most urgent questions in this area, e.g. do chiropractic interventions work? are they safe?
My last point is equally critical. After reading the 9 papers, I have to honestly say that none of them impressed me in terms of its scientific rigor.
So, what does this tiny investigation suggest? Not a lot, I have to admit, but I think it supports the hypothesis that research into chiropractic is not very active, nor high quality, nor does it address the most urgent questions.
