MD, PhD, FMedSci, FSB, FRCP, FRCPEd

causation

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In a recent PJ article, Michael Marshall from the ‘Good Thinking Society’ asked “WHY ON EARTH IS THE NHS SPENDING EVEN A SINGLE PENNY ON HOMEOPATHY?”. A jolly good question, given the overwhelmingly negative evidence, I thought  – but one that must be uncomfortable to homeopaths. Sure enough, a proponent of homeopathy, Jeanette Lindsay from Glasgow, has objected to Marshall’s arguments in a short comment which is a fairly typical defence of homeopathy; I therefore take the liberty of reproducing it here (the 12 references in her text were added by me and refer to my footnotes below):

I wonder if people such as Michael Marshall (The Pharmaceutical Journal 2016;297:101), who would refuse [1] patients the option of NHS homeopathic treatment, have considered the plight of people failed by evidence-based medicine ? [2] Where are those with chronic, disabling conditions to turn when the medicines available on the NHS do not work, or worse, are positively harmful? [3]

Take the instance of a woman with multiple drug allergies who has no means of treating her severe inflammatory arthritis and no suitable analgesia. [4] It has been demonstrated that disease states with immune system involvement are particularly susceptible to the placebo effect but how does one induce this? Current thinking precludes treatment with placebo medicines but it so happens that homeopathic remedies would appear, from the results of clinical trials [5], to be a good substitute. [6] Used properly, there is a good chance that in this case homeopathic treatment may achieve a real therapeutic effect. [7]

Patients who cannot tolerate allopathic [8] treatment do not just go away because they cannot take the prescribed medicine. [9] They suffer and surely deserve a better range of options [10] than those provided by the current obsession with evidence-based medicine. [11] The availability of homeopathic treatment is important and should not be denied until better alternatives become commonplace. [12]

[1] Michael Marshall does not ‘refuse’ homeopathy on the NHS; that is not in his power. He merely questions whether NHS funds should not be spent on treatments that demonstrably do more good than harm.

[2] I am sure he as carefully considered such patients.

[3] Depending on the exact circumstances, such patients have many options: for instance, they could change their physician, have their diagnosis re-considered, or try a non-drug treatment.

[4] An allergy to one drug is rarely (I would even say never) associated with allergies to all drugs for any given condition. Even if this were the case, there are several non-drug treatments for arthritis or other diseases.

[5] I think this is fantasy; there is no good evidence from clinical trials to show that homeopathy is efficacious for either inflammatory or degenerative arthritis.

[6] Is this an admission that homeopathic remedies are placebos?

[7] I am not aware of sound evidence to support this statement.

[8] ‘Allopathic’ is a derogatory term introduced by Hahnemann to defame conventional medicine.

[9] I have never seen a patient who could not tolerate any prescription medicine. I suspect this is fantasy again.

[10] Patients deserve the optimal therapy available for their conditions – that is a therapy that demonstrably generates more good than harm. Homeopathy is clearly not in this category.

[11] An obsession? Yes, perhaps it is an obsession for some dedicated healthcare professionals to provide the best possible treatments for their patients. But the way it is put here, it sounds as though this was something despicable. I would argue that such an ‘obsession’ would be most commendable.

[12] For practically all conditions, symptoms, illesses and diseases that afflict mankind, better alternatives than homeopathy have been available since about 150 years.

It seems to me that Jeanette Lindsay has been harshly disappointed by conventional medicine. Perhaps this is why, one day, she consulted a homeopath and received the empathy, understanding and compassion that she needed to get better. Many homeopaths excel at these qualities; and this is the main reason why their patients swear by them, even though their remedies are pure placebos.

My advice to such patients is: find a physician who has time, empathy and compassion. They do exist! Once you have found such a doctor, you can benefit from the compassion and empathy just as you may have benefitted from the homeopath’s compassion and empathy. But in addition to these benefits (and contrary to what you got from your homeopath), you will also be able to profit from the efficacy of the treatments prescribed.

To put it simply: homeopaths can help patients via non-specific therapeutic effects; responsible physicians can help patients via non-specific therapeutic effects plus the specific effects of the treatments they prescribe.

 

WARNING: THIS MIGHT MAKE YOU LAUGH OUT LOUDLY AND UNCONTROLLABLY.

Deepak Chopra rarely publishes in medical journals (I suppose, he has better things to do). I was therefore intrigued when I saw a recent article of which he is a co-author.

The ‘study‘ in question allegedly examined the effects of a comprehensive residential mind–body program on well-being. The authors describe it as “a quasi-randomized trial comparing the effects of participation in a 6-day Ayurvedic system of medicine-based comprehensive residential program with a 6-day residential vacation at the same retreat location.” They included 69 healthy women and men who received the Ayurvedic intervention addressing physical and emotional well-being through group meditation and yoga, massage, diet, adaptogenic herbs, lectures, and journaling. Key components of the program include physical cleansing through ingestion of herbs, fiber, and oils that support the body’s natural detoxification pathways and facilitate healthy elimination; two Ayurvedic meals daily (breakfast and lunch) that provide a light plant-based diet; daily Ayurvedic oil massage treatments; and heating treatments through the use of sauna and/or steam. The program includes lectures on Ayurvedic principles and lifestyle as well as lectures on meditation and yoga philosophy. The study group also participated in twice-daily group meditation and daily yoga and practiced breathing exercises (pranayama) as well as emotional expression through a process of journaling and emotional support. During the program, participants received a 1-hour integrative medical consultation with a physician and follow-up with an Ayurvedic health educator.

The control group simply had a vacation without any of the above therapies in the same resort. They were asked to do what they would normally do on a resort vacation with the additional following restrictions: they were asked not to engage in more exercise than they would in their normal lifestyle and to refrain from using La Costa Resort spa services. They were also asked not to drink ginger tea or take Gingko biloba during the 2 days before and during the study week.

Recruitment was via email announcements on the University of California San Diego faculty and staff and Chopra Center for Wellbeing list-servers. Study flyers stated that the week-long Self-Directed Biological Transformation Initiative (SBTI) study would be conducted at the Chopra Center for Wellbeing, located at the La Costa Resort in Carlsbad, California, in order to learn more about the psychosocial and physiologic effects of the 6-day Perfect Health (PH) Program compared with a 6-day stay at the La Costa Resort. The study participants were not blinded, and site investigators and study personnel knew to which group participants were assigned.

Participants in the Ayurvedic program showed significant and sustained increases in ratings of spirituality and gratitude compared with the vacation group, which showed no change. The Ayurvedic participants also showed increased ratings for self-compassion as well as less anxiety at the 1-month follow-up.

The authors arrived at the following conclusion: Findings suggest that a short-term intensive program providing holistic instruction and experience in mind–body healing practices can lead to significant and sustained increases in perceived well-being and that relaxation alone is not enough to improve certain aspects of well-being.

This ‘study’ had ethical approval from the University of California San Diego and was supported by the Fred Foundation, the MCJ Amelior Foundation, the National Philanthropic Trust, the Walton Family Foundation, and the Chopra Foundation. The paper’s first author is director of research at the Chopra Foundation. Deepak Chopra is the co-founder of The Chopra Center for Wellbeing.

Did I promise too much?

Isn’t this paper hilarious?

Just for the record, let me formulate a short conclusion that actually fits the data from this ‘study’: Lots of TLC, attention and empathy does make some people feel better.

This is hardly something one needs to write home about; and certainly nothing to do a study on!

But which journal would publish such unadulterated advertising?

On this blog, I have mentioned the JACM several times before. Recently, I wrote about the new man in charge of it. I concluded stating WATCH THIS SPACE.

I think the wait is now over – this paper is from the latest issue of the JACM, and I am sure we all agree that the new editor has just shown us of what he is made and where he wants to take his journal.

Just as I thought that this cannot get any better, it did! It did so in the form of a second paper which is evidently reporting from the same ‘study’. Here is its abstract unaltered in its full beauty:

The effects of integrative medicine practices such as meditation and Ayurveda on human physiology are not fully understood. The aim of this study was to identify altered metabolomic profiles following an Ayurveda-based intervention. In the experimental group, 65 healthy male and female subjects participated in a 6-day Panchakarma-based Ayurvedic intervention which included herbs, vegetarian diet, meditation, yoga, and massage. A set of 12 plasma phosphatidylcholines decreased (adjusted p < 0.01) post-intervention in the experimental (n = 65) compared to control group (n = 54) after Bonferroni correction for multiple testing; within these compounds, the phosphatidylcholine with the greatest decrease in abundance was PC ae C36:4 (delta = -0.34). Application of a 10% FDR revealed an additional 57 metabolites that were differentially abundant between groups. Pathway analysis suggests that the intervention results in changes in metabolites across many pathways such as phospholipid biosynthesis, choline metabolism, and lipoprotein metabolism. The observed plasma metabolomic alterations may reflect a Panchakarma-induced modulation of metabotypes. Panchakarma promoted statistically significant changes in plasma levels of phosphatidylcholines, sphingomyelins and others in just 6 days. Forthcoming studies that integrate metabolomics with genomic, microbiome and physiological parameters may facilitate a broader systems-level understanding and mechanistic insights into these integrative practices that are employed to promote health and well-being.

Now that I managed to stop laughing about the first paper, I am not just amused but also puzzled by the amount of contradictions the second article seems to cause. Were there 65 or 69 individuals in the experimental group? Was the study randomised, quasi-randomised or not randomised? All of these versions are implied at different parts of the articles. It turns out that they randomised some patients, while allocating others without randomisation – and this clearly means the study was NOT randomised. Was the aim of the study ‘to identify altered metabolomic profiles following an Ayurveda-based intervention’ or ‘to examine the effects of a comprehensive residential mind–body program on well-being’?

I am sure that others will find further contradictions and implausibilites, if they look hard enough.

The funniest inconsistency, in my opinion, is that Deepak Chopra does not even seem to be sure to which university department he belongs. Is it the ‘Department of Family Medicine and Public Health, University of California, San Diego, La Jolla, CA.’ as indicated in the 1st paper or is it the ‘Department of Family and Preventive Medicine, University of California San Diego, La Jolla, California, USA’ as listed in the 2nd article?

Does he know from which planet he is?

 

After > 200 years of existence, homeopathy still remains unproven – in fact, most rational thinkers would call it disproven. Today only homeopaths doubt this statement; they work hard to find a water-tight proof that might show the doubters to be wrong.

What is better suited for this purpose than a few rigorous animal experiments?

Engystol® is a popular homeopathic product promoted as an anti-viral agent manufactured by Heel GmbH, Baden-Baden, Germany. In several in vivo and in vitro studies, it apparently affected an immune response. This new study was to “evaluate the innate and adaptive immuno-modulatory effects of oral Engystol® (1 or 10 tablets/L water consumed), prior to and post antigenic challenge in a mouse model with a well-characterized and clinically measureable immune system.”

The investigators first evaluated the murine immune response when oral Engystol® was given alone for 28 days. to mice. The animals were then challenged with an antigen-specific H5N1 HA vaccine while on Engystol® for an additional 33 days. Serum and supernatants from cultured splenic lymphocytes were collected and screened with a 32-cytokine panel. Serum vaccine epitope-specific IgG titers plus T cell and B cell phenotypes from splenic tissue were also evaluated.

The results showed that Engystol® alone did not alter immunity. However, upon vaccine challenge, Engystol® decreased CD4+/CD8+ ratios, altered select cytokines/chemokines, and anti-H5N1 HA IgG titers were increased in the group of mice receiving 10 tablet/L.

The authors concluded that “these data suggest that Engystol® can modulate immunity upon antigenic challenge.”

Engystol is being advertised as “a homeopathic preparation which has been scientifically proven to significantly reduce the duration and severity of symptoms during an acute viral infection and help protect from subsequent infections.” I was unable find good evidence for this claim and therefore have to assume that it is bogus. The only human trial I was able to locate was this one:

OBJECTIVE:

To compare the effects of a complex homeopathic preparation (Engystol; Heel GmbH, Baden-Baden, Germany) with those of conventional therapies with antihistamines, antitussives, and nonsteroidal antiinflammatory drugs on upper respiratory symptoms of the common cold in a setting closely related to everyday clinical practice.

DESIGN:

Nonrandomized, observational study over a treatment period of maximally two weeks.

SETTING:

Eighty-five general and homeopathic practices in Germany.

PARTICIPANTS:

Three hundred ninety-seven patients with upper respiratory symptoms of the common cold.

INTERVENTIONS:

Engystol-based therapy or common over-the-counter treatments for the common cold. Patients receiving this homeopathic treatment were allowed other short-term medications, but long-term use of analgesics, antibiotics, and antiinflammatory agents was not permitted. Patients were allowed nonpharmacological therapies such as vitamins, thermotherapies, and others.

MAIN OUTCOME MEASURES:

The effects of treatment were evaluated on the variables fatigue, sensation of illness, chill/tremor, aching joints, overall severity of illness, sum of all clinical variables, temperature, and time to symptomatic improvement.

RESULTS:

Both treatment regimens provided significant symptomatic relief, and this homeopathic treatment was noninferior in a noninferiority analysis. Significantly more patients (P < .05) using Engystol-based therapy reported improvement within 3 days (77.1% vs 61.7% for the control group). No adverse events were reported in any of the treatment groups.

CONCLUSION:

This homeopathic treatment may be a useful component of an integrated symptomatic therapy for the common cold in patients and practitioners choosing an integrative approach to medical care.

Let me comment on the human study first. It is an excellent example of the bias that can be introduced by non-randomization. The patients in the homeopathic group obviously were those who chose to be treated homeopathically. Consequently they had high expectations in this therapy. Consequently they reported better results than the control group. In other words the reported outcomes have nothing to do with the homeopathic remedy.

But what about the animal study? Animals, we hear so often, do not exhibit a placebo response. Does that render this investigation any more reliable?

The answer, I am afraid is no.

The animal study in question had no control group at all. Therefore a myriad of factors could have caused the observed result. This study is very far from a poof of homeopathy!

But even if the findings of the two studies had not been the result of bias and confounding, I would be more than cautious about viewing them as anything near conclusive. The reason lies in the nature of this particular homeopathic remedy.

Engystol® contains Vincetoxicum hirundinaria (D6), Vincetoxicum hirundinaria (D10), Vincetoxicum hirundinaria (D30), sulphur (D4) and sulphur (D10). In other words, it is one of those combination remedies which are not sufficiently dilute to be devoid of active molecules. Sulphur D4, for instance, means that the remedy contains one part of sulphur in 10 000 parts of diluent. It is conceivable, even likely that such a concentration might affect certain immune parameters, I think.

And my conclusion from all this?

The proof of homeopathy – if it ever came – would need to be based on investigations that are more rigorous than these two rather pathetic studies.

The aim of a new meta-analysis was to estimate the clinical effectiveness and safety of acupuncture for amnestic mild cognitive impairment (AMCI), the transitional stage between the normal memory loss of aging and dementia. Randomised controlled trials (RCTs) of acupuncture versus medical treatment for AMCI were identified using six electronic databases.

Five RCTs involving a total of 568 subjects were included. The methodological quality of the RCTs was generally poor. Participants receiving acupuncture had better outcomes than those receiving nimodipine with greater clinical efficacy rates (odds ratio (OR) 1.78, 95% CI 1.19 to 2.65; p<0.01), mini-mental state examination (MMSE) scores (mean difference (MD) 0.99, 95% CI 0.71 to 1.28; p<0.01), and picture recognition score (MD 2.12, 95% CI 1.48 to 2.75; p<0.01). Acupuncture used in conjunction with nimodipine significantly improved MMSE scores (MD 1.09, 95% CI 0.29 to 1.89; p<0.01) compared to nimodipine alone. Three trials reported adverse events.

The authors concluded that acupuncture appears effective for AMCI when used as an alternative or adjunctive treatment; however, caution must be exercised given the low methodological quality of included trials. Further, more rigorously designed studies are needed.

Meta-analyses like this one are, in my view, perfect examples for the ‘rubbish in, rubbish out’ principle of systematic reviews. This may seem like an unfair statement, so let me justify it by explaining the shortfalls of this specific paper.

The authors try to tell us that their aim was “to estimate the clinical effectiveness and safety of acupuncture…” While it might be possible to estimate the effectiveness of a therapy by pooling the data of a few RCTs, it is never possible to estimate its safety on such a basis. To conduct an assessment of therapeutic safety, one would need sample sizes that go two or three dimensions beyond those of RCTs. Thus safety assessments are best done by evaluating the evidence from all the available evidence, including case-reports, epidemiological investigations and observational studies.

The authors tell us that “two studies did not report whether any adverse events or side effects had occurred in the experimental or control groups.” This is a common and serious flaw of many acupuncture trials, and another important reason why RCTs cannot be used for evaluating the risks of acupuncture. Too many such studies simply don’t mention adverse effects at all. If they are then submitted to systematic reviews, they must generate a false positive picture about the safety of acupuncture. The absence of adverse effects reporting is a serious breach of research ethics. In the realm of acupuncture, it is so common, that many reviewers do not even bother to discuss this violation of medical ethics as a major issue.

The authors conclude that acupuncture is more effective than nimodipine. This sounds impressive – unless you happen to know that nimodipine is not supported by good evidence either. A Cochrane review provided no convincing evidence that nimodipine is a useful treatment for the symptoms of dementia, either unclassified or according to the major subtypes – Alzheimer’s disease, vascular, or mixed Alzheimer’s and vascular dementia.

The authors also conclude that acupuncture used in conjunction with nimodipine is better than nimodipine alone. This too might sound impressive – unless you realise that all the RCTs in question failed to control for the effects of placebo and the added attention given to the patients. This means that the findings reported here are consistent with acupuncture itself being totally devoid of therapeutic effects.

The authors are quite open about the paucity of RCTs and their mostly dismal methodological quality. Yet they arrive at fairly definitive conclusions regarding the therapeutic value of acupuncture. This is, in my view, a serious mistake: on the basis of a few poorly designed and poorly reported RCTs, one should never arrive at even tentatively positive conclusion. Any decent journal would not have published such misleading phraseology, and it is noteworthy that the paper in question appeared in a journal that has a long history of being hopelessly biased in favour of acupuncture.

Any of the above-mentioned flaws could already be fatal, but I have kept the most serious one for last. All the 5 RCTs that were included in the analyses were conducted in China by Chinese researchers and published in Chinese journals. It has been shown repeatedly that such studies hardly ever report anything other than positive results; no matter what conditions is being investigated, acupuncture turns out to be effective in the hands of Chinese trialists. This means that the result of such a study is clear even before the first patient has been recruited. Little wonder then that virtually all reviews of such trials – and there are dozens of then – arrive at conclusions similar to those formulated in the paper before us.

As I already said: rubbish in, rubbish out!

What a silly question! At least this is what most sceptics would say: if we are not sure that it works, we do not need to spend any thoughts on a potential mechanism!

However, in the realm of acupuncture, the potential mode of action remains a hotly debated and fundamentally relevant issue.

The TCM folks, of course, ‘knew’ all along how acupuncture works: it re-balances the life-forces yin and yang. This is a nice theory – it has but one disadvantage: it has no bearing whatsoever on reality. Vitalistic ideas such as this one have long been proven to be nothing but fantasy.

Meanwhile, several more plausible hypotheses have been developed, and hundreds of papers have been published on the subject. One recent article, for instance, suggests a range of mechanisms including microinjury, increased local blood flow, facilitated healing, and analgesia. Acupuncture may trigger a somatic autonomic reflex, thereby affecting the gastric and cardiovascular functions. Acupuncture may also change the levels of neurotransmitters such as serotonin and dopamine, thereby affecting the emotional state and craving… By affecting other pain-modulating neurotransmitters such as met-enkephalin and substance P along the nociceptive pathway, acupuncture may relieve headache. Acupuncture may affect the hypothalamus pituitary axis and reduce the release of the luteinizing hormone…

Another article states that the Western explanation for acupuncture effectiveness is based upon more than half a century of basic and clinical research, which identified the activation of sensory system and the subsequent activity-dependent regulation of neurotransmitters, neurohormones, and several classes of neuromodulators as plausible mechanism for the acupuncture‘s therapeutic properties. The regulation of neurotrophins’ expression and activity is one of the possible neurophysiological mechanisms underlying acupuncture‘s effects on neuropathic pain, nerve injury, neurodegeneration, and even in the regulation of gonadal functions…

Recently Burnstock proposed that mechanical deformation of the skin by needles and application of heat or electrical current leads to release of large amounts of ATP from keratinocytes, fibroblasts and other cells in skin; the ATP then occupies specific receptor subtypes expressed on sensory nerve endings in the skin and tongue; the sensory nerves send impulses through ganglia to the spinal cord, the brain stem, hypothalamus and higher centres; the brain stem and hypothalamus contain neurons that control autonomic functions, including cardiovascular, gastrointestinal, respiratory, urinogenital and musculo-skeletal activity. Impulses generated in sensory fibres in the skin connect with interneurons to modulate (either inhibition or facilitation) the activities of the motoneurons in the brain stem and hypothalamus to change autonomic functions; specifically activated sensory nerves, via interneurons, also inhibit the neural pathways to the pain centres in the cortex.

A brand-new article in the journal SCIENTIFIC AMERICAN puts the hypothesis in perspective:

…scientists have been studying a roster of potential biological pathways by which needling might relieve pain. The most successful of these efforts has centered on adenosine, a chemical believed to ease pain by reducing inflammation. A 2010 mouse study found that acupuncture needles triggered a release of adenosine from the surrounding cells into the extracellular fluid that diminished the amount of pain the rodents experienced. The mice had been injected with a chemical that made them especially sensitive to heat and touch. The researchers reported a 24-fold increase in adenosine concentration in the blood of the animals after acupuncture, which corresponded to a two-thirds reduction in discomfort, as revealed by how quickly they recoiled from heat and touch. Injecting the mice with compounds similar to adenosine had the same effect as acupuncture needling. And injecting compounds that slowed the removal of adenosine from the body boosted the effects of acupuncture by making more adenosine available to the surrounding tissue for longer periods. Two years later a different group of researchers went on to show that an injection of PAP, an enzyme that breaks other compounds in the body down into adenosine, could relieve pain for an extended chunk of time by increasing the amount of adenosine in the surrounding tissue. They dubbed that experimental procedure “PAPupuncture.”

Both sets of findings have excited researchers—and for good reason. The current options for treating pain are limited and rely mostly on manipulating the body’s natural pain-management system, known as the opioid system. Opioid-based painkillers are problematic for several reasons. Not only does their efficacy tend to wane over time, but they have been linked to an epidemic of addiction and overdose deaths across the U.S.—so much so that the Centers for Disease Control and Prevention has recently advised doctors to seriously restrict their use. The available nonopioid pain treatments are few; many of them require multiple injections or catheterization to work; and they often come with side effects, such as impaired movement. Adenosine offers an entirely new mechanism to exploit for potential treatments—one that may come with fewer side effects and less potential for addiction. What is more, adenosine can be made to circulate in the body for prolonged stretches. Pharmaceutical companies are actively investigating adenosine-related compounds as potential drugs.

But however promising adenosine may be as a treatment, the findings from this research do not prove that acupuncture itself “works.” For one thing, the researchers did not show that the release of adenosine was specific to acupuncture. Acupuncture needles might cause adenosine to flood the surrounding tissue, but so might a hard pinch, or applied pressure, or any number of other physical insults. In fact, both of the studies found that when adenosine was turned on in mouse tissue by other mechanisms, the pain response was equal to or better than the response generated by acupuncture. For another thing, the study results offered no support for the use of acupuncture to treat any of the other conditions for which the procedure is often advertised. A localized adenosine response may mitigate localized pain. That does not mean it can also cure insomnia or infertility.

It may well be that the reams of research scientists have done on acupuncture have lit the path toward improved understanding of—and eventually better treatments for—intractable pain. But it may also be time to take whatever bread crumbs have been laid out by that work and move on.

END OF QUOTE

As we see, there is no shortage of potential explanations as to HOW acupuncture works. The most plausible theory still is that it works largely or even exclusively via a placebo effect.

Due to this type of mechanistic research, acupuncture has gained much credibility. The question is, does it deserve it? In my view, it would be much more fruitful to first make sure THAT acupuncture works (beyond a placebo response) and, if so, for what conditions. The question HOW it works is unquestionably interesting but in the final analysis it probably is secondary.

The subject of placebo is a complex but fascinating one, particularly for those interested in alternative medicine. Most sceptics believe that alternative therapies rely heavily, if not entirely, on the placebo effect. Some alternative practitioners, when unable to produce convincing evidence that their treatment is effective, seem to have now settled to admitting that their therapy works (mostly or entirely) via a placebo effect. They the hasten to add that this is perfectly fine, because it is just an explanation as to how it works – a mechanism of action, in other words. Causing benefit via a placebo effect still means, they insist, that their therapy is effective.

In a previous post, I have tried to demonstrate that this belief is erroneous and where the notion comes from. It originates, I believe, from a mistaken definition of ‘effectiveness’: for many alternative practitioners ‘effectiveness’ encompasses the specific plus the non-specific (e. g. placebo) effects of their therapy. In real medicine, ‘effectiveness’ is the degree to which a treatment works under real life conditions.

The ‘alternative’ definition is, of course, incorrect but alternative practitioners stubbornly refuse to acknowledge this fact. Here are just two reasons why it cannot be right:

  • If it were correct, it would be hardly conceivable to think of a treatment that is NOT effective. Applied with empathy and compassion, virtually all treatments – however devoid of specific effects – will produce a placebo effect. Thus they will all be effective, and the term would be superfluous because ‘treatment’ would automatically mean ‘effective’. An ineffective treatment would, in other words, be a contradiction in terms.
  • If it were correct, any pharmaceutical or devices company could legally market ineffective drugs or gadgets and rightly claim (or even prove) that they are effective. Any such therapy could very easily be shown to generate a placebo-effect under the right circumstances; and as long as this is the case, it would be certifiably effective.

I do sympathise with alt med enthusiasts who find this hard or even impossible to accept. They see almost every day how their placebo-therapy benefits their patients. (It seems worth remembering that not just the placebo phenomenon but several other factors are involved in such outcomes – take, for instance, the natural history of the disease and the regression towards the mean.) And they might think that my arguments are nothing but a devious attempt do away with the beneficial power of the placebo.

The truth, however, is that nobody wants to do anything of the sort; we all want to help patients as much as possible, and that does, of course, include the use of the placebo effect. In clinical practice, we usually want to maximise the placebo effect where possible. But for this goal, we do not require placebo therapies. If we administer a specifically effective therapy with compassion, we undoubtedly also generate a placebo response. In addition, our patients would benefit from the specific effects of the prescribed therapy. Both elements are essential for an optimal therapeutic response, and I don’t know any conventional healthcare professionals who do not aim at this optimal outcome.

Giving just placebos will not normally generate an optimal outcome, and therefore it cannot truly be in the interest of the patient. It is also ethically problematic because it usually entails a degree of deception of the patient. Moreover, placebo effects are unreliable and usually of short duration. Foremost, they do not normally cure a disease; they may alleviate symptoms but they almost never tackle their causes. These characteristics hardly make placebos an acceptable choice for routine clinical practice.

The bottom line is clear and simple: a drug that is not better than placebo can only be classified as being ineffective. The same applies to all non-drug therapies. Double standards are not acceptable in healthcare. And the demonstration of a placebo effect does not turn an ineffective therapy into an effective one.

I know that many alternative practitioners do not agree with this line of thought – so, let’s hear their counter-arguments.

Alternative medicine has no shortage of research that suggests it to be effective. Almost invariably, however, one finds – when looking a bit more carefully at such investigations – that the positive conclusions are not warranted by the data. Here is an excellent, recent example:

This new study, authored by two Turkish nurses, was an RCT where the patients were randomly assigned to either an aromatherapy massage (n = 17), reflexology (n = 17) or the control group (n = 17). Aromatherapy massage was applied to both knees of subjects in group 1 for 30 minutes. Reflexology was administered to both feet of subjects in group 2 for 40 minutes during weekly home visits. The subjects of group 3, the control group, received no intervention.

Fifty-one subjects with rheumatoid arthritis were recruited from a university hospital rheumatology clinic in Turkey between July 2014 and January 2015 for this trial. Data were collected by personal information form, DAS28 index, Visual Analog Scale and Fatigue Severity Scale. Pain and fatigue scores were measured at baseline and within an hour after each intervention for 6 weeks.

Pain and fatigue scores significantly decreased in the aromatherapy massage and reflexology groups compared with the control group (p < .05). The reflexology intervention started to decrease pain and fatigue scores earlier than aromatherapy massage (week 1 vs week 2 for pain, week 1 vs week 4 for fatigue) (p < .05).

The authors concluded that aromatherapy massage and reflexology are simple and effective non-pharmacologic nursing interventions that can be used to help manage pain and fatigue in patients with rheumatoid arthritis.

I am sure that most readers have spotted the snag: the two interventions generated better outcomes than no therapy. It is quite simply wrong to assume that this outcome is specifically related to the two treatments. Both of these treatments are fairly agreeable and generate expectations, involve touch, attention and care. In my view, it is these latter factors which together have caused the better outcomes. And this is, of course, entirely unrelated to any specific effects of the two therapies.

This might well be trivial, but if such sloppy conclusions pollute the literature to the extend that they currently do in the realm of alternative medicine, it becomes important.

Yesterday, I wrote about a new acupuncture trial. Amongst other things, I wanted to find out whether the author who had previously insisted I answer his questions about my view on the new NICE guideline would himself answer a few questions when asked politely. To remind you, this is what I wrote:

This new study was designed as a randomized, sham-controlled trial of acupuncture for persistent allergic rhinitis in adults investigated possible modulation of mucosal immune responses. A total of 151 individuals were randomized into real and sham acupuncture groups (who received twice-weekly treatments for 8 weeks) and a no acupuncture group. Various cytokines, neurotrophins, proinflammatory neuropeptides, and immunoglobulins were measured in saliva or plasma from baseline to 4-week follow-up.

Statistically significant reduction in allergen specific IgE for house dust mite was seen only in the real acupuncture group. A mean (SE) statistically significant down-regulation was also seen in pro-inflammatory neuropeptide substance P (SP) 18 to 24 hours after the first treatment. No significant changes were seen in the other neuropeptides, neurotrophins, or cytokines tested. Nasal obstruction, nasal itch, sneezing, runny nose, eye itch, and unrefreshed sleep improved significantly in the real acupuncture group (post-nasal drip and sinus pain did not) and continued to improve up to 4-week follow-up.

The authors concluded that acupuncture modulated mucosal immune response in the upper airway in adults with persistent allergic rhinitis. This modulation appears to be associated with down-regulation of allergen specific IgE for house dust mite, which this study is the first to report. Improvements in nasal itch, eye itch, and sneezing after acupuncture are suggestive of down-regulation of transient receptor potential vanilloid 1.

…Anyway, the trial itself raises a number of questions – unfortunately I have no access to the full paper – which I will post here in the hope that my acupuncture friend, who are clearly impressed by this paper, might provide the answers in the comments section below:

  1. Which was the primary outcome measure of this trial?
  2. What was the power of the study, and how was it calculated?
  3. For which outcome measures was the power calculated?
  4. How were the subjective endpoints quantified?
  5. Were validated instruments used for the subjective endpoints?
  6. What type of sham was used?
  7. Are the reported results the findings of comparisons between verum and sham, or verum and no acupuncture, or intra-group changes in the verum group?
  8. What other treatments did each group of patients receive?
  9. Does anyone really think that this trial shows that “acupuncture is a safe, effective and cost-effective treatment for allergic rhinitis”?

In the comments section, the author wrote: “after you have read the full text and answered most of your questions for yourself, it might then be a more appropriate time to engage in any meaningful discussion, if that is in fact your intent”, and I asked him to send me his paper. As he does not seem to have the intention to do so, I will answer the questions myself and encourage everyone to have a close look at the full paper [which I can supply on request].

  1. The myriad of lab tests were defined as primary outcome measures.
  2. Two sentences are offered, but they do not allow me to reconstruct how this was done.
  3. No details are provided.
  4. Most were quantified with a 3 point scale.
  5. Mostly not.
  6. Needle insertion at non-acupoints.
  7. The results are a mixture of inter- and intra-group differences.
  8. Patients were allowed to use conventional treatments and the frequency of this use was reported in patient diaries.
  9. I don’t think so.

So, here is my interpretation of this study:

  • It lacked power for many outcome measures, certainly the clinical ones.
  • There were hardly any differences between the real and the sham acupuncture group.
  • Most of the relevant results were based on intra-group changes, rather than comparing sham with real acupuncture, a fact, which is obfuscated in the abstract.
  • In a controlled trial fluctuations within one group must never be interpreted as caused by the treatment.
  • There were dozens of tests for statistical significance, and there seems to be no correction for multiple testing.
  • Thus the few significant results that emerged when comparing sham with real acupuncture might easily be false positives.
  • Patient-blinding seems questionable.
  • McDonald as the only therapist of the study might be suspected to have influenced his patients through verbal and non-verbal communications.

I am sure there are many more flaws, particularly in the stats, and I leave it to others to identify them. The ones I found are, however, already serious enough, in my view, to call for a withdrawal of this paper. Essentially, the authors seem to have presented a study with largely negative findings as a trial with positive results showing that acupuncture is an effective therapy for allergic rhinitis. Subsequently, McDonald went on social media to inflate his findings even more. One might easily ask: is this scientific misconduct or just poor science?

I would be most interested to hear what you think about it [if you want to see the full article, please send me an email].

Reiki is one of the most popular types of ‘energy healing’. Reiki healers believe to be able to channel ‘healing energy’ into patients’ body thus enabling them to get healthy. If Reiki were not such a popular treatment, one could brush such claims aside and think “let the lunatic fringe believe what they want”. But as Reiki so effectively undermines consumers’ sense of reality and rationality, I feel I should continue informing the public about this subject – despite the fact that I have already reported about it several times before, for instance here, here, here, here, here and here.

A new RCT, published in a respected journal looks interesting enough for a further blog-post on the subject. The main aim of the study was to investigate the effectiveness of two psychotherapeutic approaches, cognitive behavioural therapy (CBT) and a complementary medicine method Reiki, in reducing depression scores in adolescents. The researchers from Canada, Malaysia and Australia recruited 188 adolescent depressed adolescents. They were randomly assigned to CBT, Reiki or wait-list. Depression scores were assessed before and after 12 weeks of treatments/wait list. CBT showed a significantly greater decrease in Child Depression Inventory (CDI) scores across treatment than both Reiki (p<.001) and the wait-list control (p<.001). Reiki also showed greater decreases in CDI scores across treatment relative to the wait-list control condition (p=.031).  Male participants showed a smaller treatment effects for Reiki than did female participants. The authors concluded that both CBT and Reiki were effective in reducing the symptoms of depression over the treatment period, with effect for CBT greater than Reiki.

I find it most disappointing that these days even respected journals publish such RCTs without the necessary critical input. This study may appear to be rigorous but, in fact, it is hardly worth the paper it was printed on.

The results show that Reiki produced worse results than CBT. That I can well believe!

However, the findings also suggest that Reiki was nevertheless “effective in reducing the symptoms of depression”, as the authors put it in their conclusions. This statement is misleading!

It is based on the comparison of Reiki with doing nothing. As Reiki involves lots of attention, it can be assumed to generate a sizable placebo effect. As a proportion of the patients in the wait list group are probably disappointed for not getting such attention, they can be assumed to experience the adverse effects of their disappointment. The two phenomena combined can easily explain the result without any “effectiveness” of Reiki per se.

If such considerations are not fully discussed and made amply clear even in the conclusions of the abstract, it seems reasonable to accuse the journal of being less than responsible and the authors of being outright misleading.

As with so many papers in this area, one has to ask: WHERE DOES SLOPPY RESEARCH END AND WHERE DOES SCIENTIFIC MISCONDUCT BEGIN?

A recent comment to a blog-post about alternative treatments for cancer inspired me to ponder a bit. I think it is noteworthy because it exemplifies so many of the comments I hear in the realm of alternative medicine on an almost daily basis. Here is the comment in question:

“Yes…it appears that the medical establishment have known for years that chemotherapy a lot of the time kills patients faster than if they were untreated…what’s more, it worsens a person’s quality of life in which many die directly of the severe effects on the endocrine, immune system and more…cancers often return in more aggressive forms metastasising with an increased risk of apoptosis. In other words it makes things worse whereas there are many natural remedies which not only do no harm but accumulating evidence points to their capacity to fight cancer…some of it is bullshit whilst some holds some truth!! So turning away from toxic treatments that kill towards natural approaches that are showing more hope with the backing of trials kinda reverses the whole argument of this article.”

The comment first annoyed me a bit, of course, but later it made me think and consider the differences between conspiracy theories, assumptions, opinions, evidence and scientific facts. Let’s tackle each of these in turn.

CONSPIRACY THEORIES

A conspiracy theory is an explanatory or speculative theory suggesting that two or more persons, or an organization, have conspired to cause or cover up, through secret planning and deliberate action, an event or situation typically regarded as illegal or harmful.

Part of the above comment bears some of the hallmarks of a conspiracy theory: “…the medical establishment have known for years that chemotherapy a lot of the time kills patients faster than if they were untreated…” The assumption here is that the conventional healthcare practitioners are evil enough to knowingly do harm to their patients. Such conspiracy theories abound in the realm of alternative medicine; they include the notions that

  • BIG PHARMA is out to kill us all in order to maximize their profits,
  • the ‘establishment’ is suppressing any information about the benefits of alternative treatments,
  • vaccinations are known to be harmful but nevertheless being forced on to our children,
  • drug regulators are in the pocket of the pharmaceutical industry,
  • doctors accept bribes for prescribing dangerous drugs
  • etc. etc.

In a previous blog-post, I have discussed the fact that the current popularity of alternative medicine is at least partly driven by the conviction that there is a sinister plot by ‘the establishment’ that prevents people from benefitting from the wonders of alternative treatments. It is therefore hardly surprising that conspiracy theories like the above are voiced regularly on this blog and elsewhere.

ASSUMPTION

An assumption is something taken for granted or accepted as true without proof.

The above comment continues stating that “…[chemotherapy] makes things worse whereas there are many natural remedies which not only do no harm but accumulating evidence points to their capacity to fight cancer…” There is not proof for these assertions, yet the author takes them for granted. If one were to look for the known facts, one would find the assumptions to be erroneous: chemotherapy has saved countless lives and there simply are no natural remedies that will cure any form of cancer. In the realm of alternative medicine, this seems to worry few, and assumptions of this or similar nature are being made every day. Sadly the plethora of assumptions or bogus claims eventually endanger public health.

OPINION

An opinion is a judgment, viewpoint, or statement about matters commonly considered to be subjective.

The above comment continues with the opinion that “…turning away from toxic treatments that kill towards natural approaches that are showing more hope with the backing of trials kinda reverses the whole argument of this article.” In general, alternative medicine is based on opinions of this sort. On this blog, we have plenty of examples for that in the comments section. This is perhaps understandable; evidence is usually in short supply, and therefore it often is swiftly replaced with often emotionally loaded opinions. It is even fair to say that much of alternative medicine is, in truth, opinion-based healthcare.

EVIDENCE

Evidence is anything presented in support of an assertion. This support may be strong or weak. The strongest type of evidence is that which provides direct proof of the truth of an assertion.

One remarkable feature of the above comment is that it is bar of any evidence. In a previous post, I have tried to explain the nature of evidence regarding the efficacy of medical interventions:

The multifactorial nature of any clinical response requires controlling for all the factors that might determine the outcome other than the treatment per se. Ideally, we would need to create a situation or an experiment where two groups of patients are exposed to the full range of factors (e. g. placebo effects, natural history of the condition, regression towards the mean), and the only difference is that one group does receive the treatment, while the other one does not. And this is precisely the model of a controlled clinical trial.

Such studies are designed to minimise all possible sources of bias and confounding. By definition, they have a control group which means that we can, at the end of the treatment period, compare the effects of the treatment in question with those of another intervention, a placebo or no treatment at all.

Many different variations of the controlled trial exist so that the exact design can be adapted to the requirements of the particular treatment and the specific research question at hand. The over-riding principle is, however, always the same: we want to make sure that we can reliably determine whether or not the treatment was the cause of the clinical outcome.

Causality is the key in all of this; and here lies the crucial difference between clinical experience and scientific evidence. What clinician witness in their routine practice can have a myriad of causes; what scientists observe in a well-designed efficacy trial is, in all likelihood, caused by the treatment. The latter is evidence, while the former is not.

Don’t get me wrong; clinical trials are not perfect. They can have many flaws and have rightly been criticised for a myriad of inherent limitations. But it is important to realise that, despite all their short-comings, they are far superior than any other method for determining the efficacy of medical interventions.

There are lots of reasons why a trial can generate an incorrect, i.e. a false positive or a false negative result. We therefore should avoid relying on the findings of a single study. Independent replications are usually required before we can be reasonably sure.

Unfortunately, the findings of these replications do not always confirm the results of the previous study. Whenever we are faced with conflicting results, it is tempting to cherry-pick those studies which seem to confirm our prior belief – tempting but very wrong. In order to arrive at the most reliable conclusion about the efficacy of any treatment, we need to consider the totality of the reliable evidence. This goal is best achieved by conducting a systematic review.

In a systematic review, we assess the quality and quantity of the available evidence, try to synthesise the findings and arrive at an overall verdict about the efficacy of the treatment in question. Technically speaking, this process minimises selection and random biases. Systematic reviews and meta-analyses [these are systematic reviews that pool the data of individual studies] therefore constitute, according to a consensus of most experts, the best available evidence for or against the efficacy of any treatment.

SCIENTIFIC FACTS

Scientific facts are verified by repeatable careful observation or measurement (by experiments or other means).

Some facts related to the subject of alternative medicine have already been mentioned:

  • chemotherapy prolongs survival of many cancer patients;
  • no alternative therapy has achieved anything remotely similar.

The comment above that motivated me to write this somewhat long-winded post is devoid of facts. This is just one more feature that makes it so typical of the comments by proponents of alternative medicine we see with such embarrassing regularity.

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