You may recall, we have dealt with the JCAM many times before; for instance here, here, here and here. Now they have come out with another remarkable paper. This study – no, the authors called it a ‘pilot study’ – was to compare the efficacy of Emotional Freedom Techniques (EFT) with that of Cognitive-Behavioral Therapy (CBT) in reducing adolescent anxiety. Sixty-three American high-ability students in grades 6–12, ages 10–18 years, who scored in the moderate to high ranges for anxiety on the Revised Children’s Manifest Anxiety Scale-2 (RCMAS-2) were randomly assigned to one of three groups:
- CBT (n = 21),
- EFT (n = 21),
- or waitlist control (n = 21).
EFT is an alternative therapy that incorporates acupoint stimulation. Students assigned to the CBT or EFT treatment groups received three individual sessions of the identified protocols from trained graduate counseling, psychology, or social work students enrolled at a large northeastern research university. The RCMAS-2 was used to assess preintervention and postintervention anxiety levels in participants.
EFT participants showed significant reduction in anxiety levels compared with the waitlist control group with a moderate to large effect size. CBT participants did not differ significantly from the EFT or control.
The authors concluded that EFT is an efficacious intervention to significantly reduce anxiety for high-ability adolescents.
They also state in their abstract that EFT is an evidence-based treatment for anxiety…
Are you happy with these conclusions?
Are you convinced that this trial lends itself to establish efficacy of anything?
Are you impressed with the trial design, the sample size, etc?
Are you sure that EFT is plausible, credible or evidence-based in any way?
If you look up EFT, you will find that there is a surprising amount of papers on it. Most of them have one thing in common: they were published in highly dubious journals. The field does not inspire trust or competence. The authors of the study state that EFT is an easily implemented strategy that uses such techniques as awareness building, exposure, reframing of interpretation, and systematic desensitization, while teaching the participant to self-stimulate protocol-identified acupoints (i.e., acupuncture points) by tapping. The effectiveness of acupuncture for treating anxiety has been well documented. Rather than using acupuncture needles, EFT relies on the manual stimulation of the acupoints. A recent meta-analysis indicated that interventions using acupoint stimulation had a moderate effect size (Hedge’s g = −0.66 95% CI [−0.99, −0.33]) in reducing symptoms. In EFT, the client stimulates the protocol-identified acupoints by tapping on them. Preliminary studies have suggested that tapping and other alternative ways of stimulating acupuncture points to be as effective as acupuncture needling. The EFT protocol and identified acupoints that were used in this study are the ones recommended for research purposes by the Association for Comprehensive Energy Psychology…
Wikipedia tells us that “Emotional Freedom Techniques (EFT) is a form of counseling intervention that draws on various theories of alternative medicine including acupuncture, neuro-linguistic programming, energy medicine, and Thought Field Therapy (TFT). It is best known through Gary Craig’s EFT Handbook, published in the late 1990s, and related books and workshops by a variety of teachers. EFT and similar techniques are often discussed under the umbrella term “energy psychology”. Advocates claim that the technique may be used to treat a wide variety of physical and psychological disorders, and as a simple form of self-administered therapy. The Skeptical Inquirer describes the foundations of EFT as “a hodgepodge of concepts derived from a variety of sources, [primarily] the ancient Chinese philosophy of chi, which is thought to be the ‘life force’ that flows throughout the body.” The existence of this life force is “not empirically supported”. EFT has no benefit as a therapy beyond the placebo effect or any known-effective psychological techniques that may be provided in addition to the purported “energy” technique. It is generally characterized as pseudoscience and it has not garnered significant support in clinical psychology.”
A recent systematic review of EFT concluded that “there were too few data available comparing EFT to standard-of-care treatments such as cognitive behavioral therapy, and further research is needed to establish the relative efficacy of EFT to established protocols.”
Notwithstanding these and many other verdicts on EFT, we now are asked to agree with the new study that EFT IS EFFICACIOUS.
Is this a joke?
They want us to believe this on the basis of a PILOT STUDY? Such studies are not even supposed to test efficacy! (Yet the authors of the trial state that this study was designed to meet the American Psychological Association (APA) Division 12 quality control criteria and the Consolidated Standards for Reporting Trials (CONSORT) criteria. I have to admit, they could have fooled me!)
No, it is not a joke, it is yet another nonsense from the ‘The Journal of Complementary and Alternative Medicine’ which, in my view, should henceforth be called THE JOURNAL OF ALTERNATIVE FACTS (JAF).
We have discussed the risks of (chiropractic) spinal manipulation more often than I care to remember. The reason for this is simple: it is an important subject; making sure that as many consumers know about it will save lives, I am sure. Therefore, any new paper on the subject is likely to be reported on this blog.
Objective of this review was to identify characteristics of 1) patients, 2) practitioners, 3) treatment process and 4) adverse events (AE) occurring after cervical spinal manipulation (CSM) or cervical mobilization. Systematic searches were performed in 6 electronic databases. Of the initial 1043 studies, 144 studies were included.
They reported 227 cases. 117 cases described male patients with a mean age of 45 (SD 12) and a mean age of 39 (SD 11) for females. Most patients were treated by chiropractors (66%) followed by non-clinicians (5%), osteopaths (5%), physiotherapists (3%) and other medical professions. Manipulation was reported in 95% of the cases (mobilisations only in 1.7%), and neck pain was the most frequent indication.
Cervical arterial dissection (CAD) was reported in 57% of the cases and 46% had immediate onset symptoms; in 2% onset of symptoms took for more than two weeks. Other complications were disc rupture, spinal cord swelling and thrombus. The most frequently reported symptoms included disturbance of voluntary control of movement, pain, paresis and visual disturbances.
In most of the reports, patient characteristics were described poorly. No clear patient profile, related to the risk of AE after CSM, could be extracted. However, women seem more at risk for CAD.
The authors concluded that there seems to be under-reporting of cases. Further research should focus on a more uniform and complete registration of AE using standardized terminology.
I do not want to repeat what I have stated in previous posts on this subject. So,let me just ask this simple question: IF THERE WERE A DRUG MARKTED FOR NECK PAIN BUT NOT SUPPORTED BY GOOD EVIDENCE FOR EFFICACY, DO YOU THINK IT WOULD BE ON THE MARKET AFTER 227 CASES OF SEVERE ADVERSE EFFECTS HAD BEEN DESCRIBED?
I think the answer is NO!
If we then consider the huge degree of under-reporting in this area which might bring the true figure up by one or even two dimensions, we must ask: WHY IS CERVICAL MANIPULATION STILL USED?
‘The use of a harmless alternative therapy is not necessarily wrong. Even if the treatment itself is just a placebo, it can help many patients. Some patients feel better with it, and it would be arrogant, high-handed and less than compassionate to reject such therapies simply because they are not supported by sufficient scientific evidence’.
How often have I heard this notion in one or another form?
I hear such words almost every day.
Arguments along these lines are difficult to counter. Any attempt to do so is likely to make us look blinkered, high-handed and less than compassionate.
Yet we all – well almost all – know that the notion is wrong. Not only that, it can be dangerous.
I will try to explain this with a concrete example of a patient employing a harmless alternative remedy with great success… until… well, you’ll see.
The patient is a married women with two kids. She is well known to her doctor because she has suffered from a range of symptoms for years, and the doctor – despite extensive tests – could never find anything really wrong with her. He knows about his patient’s significant psychological problems and has, on occasion, been tempted to prescribe tranquilizers or anti-depressants. Before he does so, however, he tells her to try Rescue Remedies@ (homeopathically diluted placebos from the range of Bach Flower Remedies). The patient is generally ‘alternatively inclined’, seems delighted with this suggestion and only too keen to give it a try.
After a couple of weeks, she reports that the Rescue Remedies (RR) are helping her. She says she can cope much better with stressful situations and has less severe and less frequent headaches or other symptoms. As she embarks on a long period of taking RR more or less regularly, she becomes convinced that the RR are highly effective and uses them whenever needed with apparent success. This goes on for months, and everyone is happy: the patient feels she has finally found a ‘medication that works’, and the doctor (who knows only too well that RR are placebos) is pleased that his patient is suffering less without needing real medication.
Then, a few months later, the patient notices that the RR are becoming less and less effective. Not only that, she also thinks that her headaches have changed and are becoming more intense. As she has been conditioned to believe that the RR are highly effective, she continues to take them. Her doctor too agrees and encourages her to carry on as before. But the pain gets worse and worse. When she develops other symptoms, her doctor initially tries to trivialise them, until they cannot be trivialised any longer. He eventually sends her to a specialist.
The patient has to wait a couple of weeks until an appointment can be arranged. The specialist orders a few tests which take a further two weeks. Finally, he diagnoses a malignant, possibly fast growing brain tumour. The patient has a poor prognosis but nevertheless agrees to an operation. Thereafter, she is paralysed on one side, needs 24-hour care, and dies 4 weeks post-operatively.
The surgeon is certain that, had he seen the patient several months earlier, the prognosis would have been incomparably better and her life could have been saved.
I suspect that most seasoned physicians have encountered stories which are not dissimilar. Fortunately they often do not end as tragically as this one. We tend to put them aside, and the next time the situation arises where a patient reports benefit from a bogus treatment we think: ‘Even if the treatment itself is just a placebo, it might help. Some patients feel better with it, and it would be arrogant, high-handed and less than compassionate to reject this ‘feel-good factor’.
I hope my story might persuade you that this notion is not necessarily correct.
If you are unable to make your patient feel better without resorting to quackery, my advice is to become a pathologist!!!
Yes, homeopaths are incredibly fond of the notion that homeopathy has been proven to work in numerous population studies of outbreaks of infectious diseases. The argument is bound to come up in any discussion with a ‘well-informed’ homeopathy fan. Therefore, it might be worth addressing it once and for all.
This website offers a fairly good summary of what homeopaths consider to be convincing evidence. It also provides links to the original articles which is valuable for all who want to study them in full detail. I will therefore present the crucial passage here unchanged.
START OF QUOTE
By the end of year 2014, there have been 19 papers published on Epidemiological studies on 7 epidemic diseases (scarlet fever, typhus fever, Cholera, Dengue, meningococcal, influenza and Leptospirosis) in 11 peer-reviewed (beyond year 1893) journals in evidence of Homeopathy including 2 Randomised Controlled Trials.
1. Samuel Hahnemann, “The Cure and prevention of scarlet fever”, Zeitschrift für Praktischen Medizin (Journal of Practical Medicine), 1801, Republished in Lesser Writings. B.Jain Publishing, New Delhi
Preventive use of homeopathy was first applied in 1799 during an epidemic of scarlet fever in Königslütter, Germany, when Dr. Hahnemann prescribed a single dose of Belladonna, as the remedy of the genus epidemicus to susceptible children in the town with more than 95% success rate. In this paper, he also specified how the Belladonna has to be potentised to 1/24,000,000 dilution. His recommended dose of Belladonna was 0.0416 nanograms to be repeated every 72 hrs. This is the first recorded nano dose of medicine used in treatment of any disease . It was another 125 years before Gladys Henry and George Frederick developed a vaccine for scarlet fever in 1924.
2. Samuel Hahnemann, “Scarlet fever and Purpura miliaris, two different diseases”, Zeitschrift für Praktischen Medizin, vol. 24, part. 1, 1806
3. Samuel Hahnemann, “Observations on scarlet fever”, Allgemeine Reichanzeiger (General Reich Gazette), No. 160, Germany, 1808
4. Samuel Hahnemann, “Reply to a question about the prophylactic for scarlet fever”, Zeitschrift für Praktischen Medizin, vol. 27, part. 4, p. 152-156, 1808
5. Samuel Hahnemann, “Treatment of typhus & fever at present prevailing”, Allgemeine Reichanzeiger, No. 6, Jan. 1814.
6. Hufeland, Prophylactic powers of Belladonna against Scarlet Fever , The Lancet, 1829
The proper use of belladonna has, in most cases, prevented infection. Numerous observations have shown that, by the general use of belladonna, epidemics of scarlet fever have actually been arrested. In those few instances where the use of belladonna was insufficient to prevent infection, the disease has been invariably slight. The Prussian (German Empire) Government ordered the use of the prophylactic during all scarlet fever epidemics
7. Samuel Hahnemann, “Cure and prevention of Asiatic cholera”, Archiv für die homöopathische Heilkunst (Archives for the Homoeopathic Healing Art), Vol. 11, part 1, 1831.
Cuprum 30c once every week as preventive medicine
8. Samuel Hahnemann, “On the contagiousness of cholera”. British Homoeopathic Journal, Vol. 7, 1849
9. Samuel Hahnemann, “Appeal to Thinking Philanthropists Respecting the Mode of Propagation of the Asiatic Cholera”, 20 pages, 1831. Republished in British Homoeopathic Journal, Oct 1849.
He said, “On board ships – in those confined spaces, filled with mouldy watery vapours, the cholera-miasm finds a favourable element for its multiplication, and grows into an enormously increased brood of those excessively minute, invisible, living creatures, so inimical to human life, of which the contagious matter of the cholera most probably consists millions of those miasmatic animated beings, which, at first developed on the broad marshy banks or the tepid Ganges– on board these ships, I say, this concentrated aggravated miasm kills several of the crew …” .
It was another 59 years (1890) before Koch saw these organisms, and later on orthodox medicine gave them the name ‘germs’
10. Charles Woodhull Eaton, The Facts about Variolinum, Transactions of the American Institute of Homoeopathy, 1907
2806 patients were treated prophylactically with Variolinum 30 (a nosode) for prevention of smallpox in Iowa. Of the 547 patients definitely exposed, only 14 developed the disease. Efficacy rate of 97.5%
11. Taylor Smith A, Poliomyelitis and prophylaxis British Homoeopathic Journal, 1950
In 1950 during an epidemic of poliomyelitis, Dr Taylor Smith of Johannesburg, South Africa protected 82 people with homoeopathic Lathyrus sativus. Of the 82 so immunised, 12 came into direct contact with disease. None were infected.
12. Oscillococcinum 200c in the treatment of influenza during epidemic in France from 1984-1987, British Journal of Clinical Pharmacology (1989)
A DBRPCT, Oscillococcinum 200c taken twice daily for 5 days significantly increased the rate of cure within two days (n=487, 237 treated and 241 on placebo), absence of symptoms at 48 hours, relative risk estimate significantly favour homeopathy (p=0.048), no pain and no fever (p=0.048), recovery rate (headache, stiffness, articular pain, shivering reduction) at 48 hours better in homeopathy group (p=0.032)
13. Bernard Leary, Cholera 1854 Update, British Homoeopathic Journal, 1994
Sir William Wilde, the well-known allopathic doctor of Dublin, which in his work entitled “Austria and its Institutions”, wrote: “Upon comparing the report of the treatment of Cholera in the Homeopathic hospital testified to by two allopathic medical inspectors appointed by Government with that of the treatment of the same disease in the other hospitals of Vienna during the same period the epidemic of 1836, it appeared that while two-thirds of the cases treated by Dr. Fleischmann the physician of the Homeopathic hospital, recovered, two-thirds of those treated by the ordinary methods in the other hospitals died.”
14. Meningococcinum – its protective effect against meningococcal disease, Homeopathy Links, 2001 (2001)
A total of 65,826 people between the ages of 0–20 were immunised homeopathically to protect against meningococcal disease while 23,532 were not. Over a year period, 4 out of 65,826 protected homeopathically developed meningococcal infection. 20 out of 23,532 not protected developed meningococcal infection. Based on the infection rate in the unprotected group, 58 cases of infection could have been expected in the homeopathically protected group. Instead, there were only four cases of meningococcal infection. Statistical analysis showed that homeopathic immunisation offered 95% protection in the first six months and 91% protection over the year against meningococcal disease. 
15. Contribution of homeopathy to the control of an outbreak of dengue epidemic in Macaé, Rio de Janeiro, Brazil in 2007-8 , International Journal of High Dilution Research, 2008
In a campaign ‘Homeopathy campaign against dengue’ by Brazilian Govt, “156,000 doses of homeopathic remedy were freely distributed in April and May 2007 to asymptomatic patients and 129 doses to symptomatic patients treated in outpatient clinics, according to the notion of genus epidemicus . The remedy used was a homeopathic complex against dengue containing Phosphorus 30c, Crotalus horridus 30c and Eupatorium perfoliatum 30c. The incidence of the disease in the first three months of 2008 fell 93% by comparison to the corresponding period in 2007, whereas in the rest of the State of Rio de Janeiro there was an increase of 128%.”
16. Marino R. Eupatorium perfoliatum 30c for the Dengue Epidemics in Brazil in 2007. International Journal of High Dilution Research, 2008
In May 2001, prophylactic use of Eupatorium perfoliatum 30c single dose was given during a dengue outbreak to 40% of residents in the most highly affected neighbourhood which resulted in significant decrease in dengue incidence by 81.5% (p<0.0001) when compared with those neighbourhoods that did not receive homeopathic prophylaxis.
17. Bracho et. al. Application of 200C potency of bacteria for Leptospirosis epidemic control in Cuba 2007-8 (2010)
Conducted by the Finlay Institute, a vaccines producer in Cuba gave 2.308562 million (70% of the target population above the age of 1 year) people in Cuba given two doses (1 dose=5 drops) of 200C potency of a nosode prepared from Leptospirosis bacteria, each (7-9 days apart), for protection against Leptospirosis (fever+jaundice+ inflammation in kidney+enlargement of spleen) with 84% decrease in disease incidence and only 10 reported cases. Dramatic decrease in morbidity within two weeks and zero morbidity of hospitalised patients, non-treated (8.8 millions) area saw an increase in number of cases from 309 cases in 2007 to 376 in 2008 representing a 21% increase. The cost of homeopathic immunization =1/15th of conventional vaccine.
18. Effect of individualized homoeopathic treatment in influenza like illness, Indian Journal of Research in Homeopathy (2013)
A multicenter, single blind, randomized, placebo controlled study to evaluate the effect of homoeopathic medicines in the treatment of Influenza like illness and to compare the efficacy of LM (50 millisimal) potency vis-à-vis centesimal (C) potency. In LM group (n=152), C group (n=147) or placebo (n=148) group. The study revealed the significant effect of individualized homoeopathic treatment in the patients suffering from ILI with no marked difference between LM and Centesimal groups. The medicines which were commonly prescribed were: Arsenic album, Bryonia alba, Rhus tox., Belladonna, Nux vomica, Sepia, Phosphorus, Gelsemium, Sulphur, Natrum mur. and Aconitum napellus. 
19. Reevaluation of the Effectiveness of Homoeoprophylaxis Against Leptospirosis in Cuba in 2007-8, Journal of Evidence-based Complementary & Alternative Medicine (2014)
The results support the previous conclusions that homoeoprophylaxis can be used to effectively immunize people against targeted infectious diseases such as leptospirosis.
 Iman Navab, Lives saved by Homeopathy in Epidemics and Pandemics, https://drnancymalik.wordpress.com/2013/01/23/epidemics-and-pandemics/
 Reshu Agarwal, Natural History of Disease and Homeopathy at different levels of Intervention, http://www.homeorizon.com/homeopathic-articles/homeopathic-philosophy/disease-history
 Homoeopathy- Science of Gentle Healing, Deptt. of AYUSH, Ministry of Health & Family Welfare, Govt, of India, 2013, http://www.ccrhindia.org/Dossier/content/page22.html
 Conversation with David Little, http://hpathy.com/homeopathy-papers/conversations-with-david-little/
 Nancy Malik, Principles of Homeopathy Explained, 2015, https://drnancymalik.wordpress.com/article/homeopathy-explained/
 Nancy Malik, Recent Advances in Nanoparticle Research in Homeopathy, Homeopathy 4 Everyone, Vol.12, Issue 6, 18 June 2015, http://hpathy.com/scientific-research/recent-advances-in-nanoparticle-research-in-homeopathy/
 Samuel Hahnemann, “Appeal to Thinking Philanthropists Respecting the Mode of Propagation of the Asiatic Cholera”, 20 pages, 1831, Translated by R E Dudgeon, M.D. in The Lesser Writings of Samuel Hahnemann, 1851, B Jain Publishers, reproduced edition, 2002, p. 758
 Fran Sheffield, Homeoprophylaxis: Human Records, Studies and Trials, 2014, http://homeopathyplus.com/Homeoprophylaxis-Human-Records-Studies-Trials.pdf
 Homoeopathy in Flu-like Illness- Factsheet, Central Council for Research in Homoeopathy, Deptt. of AYUSH, Ministry of Health & Family Welfare, Govt, of India, 2015, http://ccrhindia.org/pdf/swineflu.pdf
END OF QUOTE
Whenever I read articles of this nature, I get a little embarrassed. It seems obvious to me that the authors of such reviews have done some ‘research’ and believe strongly in the correctness in what they write. It embarrasses me to see how such people, full of good will, can be so naïve, ignorant and wrong. They clearly fail to understand several crucial issues. To me. this seems like someone such as me lecturing others about car mechanics, quantum physics or kite flying. I have no idea about these subjects, and therefore it would be idiotic to lecture others about them. But homeopaths tend to be different! And this is when my embarrassment quickly turns into anger: articles like the above spread nonsense and misguide people about important issues. THEY ARE DANGEROUS! There is little room for embarrassment and plenty of room for criticism. So, let’s criticise the notions advanced above.
In my recent book, I briefly touched upon epidemics in relation to homeopathy:
Epidemics are outbreaks of disease occurring at the same time in one geographical area and affecting large number of people. In homeopathy, epidemics are important because, in its early days, they seemed to provide evidence for the notion that homeopathy is effective. The results of homeopathic treatment seemed often better than those obtained by conventional means. Today we know that this was not necessarily due to the effects of homeopathy per se, but might have been a false impression caused by bias and confounding.
This tells us the main reason why the much-treasured epidemiological evidence of homeopaths is far from compelling. The review above does not mention these caveats at all. But it is lousy also for a whole host of other reasons, for instance:
- The text contains several errors (which I find too petty to correct here).
- The list of studies is the result of cherry-picking the evidence.
- It confuses what epidemiological studies are; RCTs are certainly not epidemiological studies, for instance.
- It also omits some of the most important epidemiological studies suggesting homeopathy works.
- It cites texts that are clearly not epidemiological studies.
- Several studies are on prevention of illness rather than on treatment.
- Some studies do not even employ homeopathy at all.
In the typical epidemiological case/control study, one large group of patients [A] is retrospectively compared to another group [B]. By large, I mean with a sample size of thousands of patients. In our case, group A has been treated homeopathically, while group B received the treatments available at the time. It is true that several of such reports seemed to suggest that homeopathy works. But this does by no means prove anything; the result might have been due to a range of circumstances, for instance:
- group A might have been less ill than group B,
- group A might have been richer and therefore better nourished,
- group A might have benefitted from better hygiene in the homeopathic hospital,
- group A might have received better care, e. g. hydration,
- group B might have received treatments that made the situation not better but worse.
Because these are RETROSPECTIVE studies, there is no way to account for these and many other factors that might have influenced the outcome. This means that epidemiological studies of this nature can generate interesting results which, in turn, need testing in properly controlled studies where these confounding factors are adequately controlled for. Without such tests, they are next to worthless for recommendations regarding clinical practice.
As it happens, the above author also included two RCT in the review (these are NOT epidemiological studies, as I already mentioned). Let’s have a quick look at them.
The first RCT is flawed for a range of reasons and has been criticised many times before. Even its authors state that “the result cannot be explained given our present state of knowledge, but it calls for further rigorously designed clinical studies.” More importantly, the current Cochrane review of Oscillococcinum, the remedy used in this study, concluded: “There is insufficient good evidence to enable robust conclusions to be made about Oscillococcinum® in the prevention or treatment of influenza and influenza-like illness.”
The second RCT is equally flawed; for instance, its results could be due to the concomitant use of paracetamol, and it seems as though the study was not double blind. The findings of this RCT have so far not been confirmed by an independent replication.
What puzzles me most with these regularly voiced notions about the ‘epidemiological evidence’ for homeopathy is not the deplorable ineptitude of those who promote them, but it is this: do homeopaths really believe that conventional medics and scientists would ignore such evidence, if it were sound or even just encouraging? This assumes that all healthcare professionals (except homeopaths) are corrupt and cynical enough not to follow up leads with the potential to change medicine for ever. It assumes that we would supress knowledge that could save the lives of millions for the sole reason that we are against homeopathy or bribed by ‘BIG PHARMA’.
Surely, this shows more clearly than anything else how deluded homeopaths really are!!!
A new joint position statement of the Italian Society of Diabetology (SID) and of the Italian Society for the Study of Arteriosclerosis (SISA) has recently been published. In the context of this blog, it seems relevant enough for its summary to be reproduced here:
Evidence showed that LDL-cholesterol lowering is associated with a significant cardiovascular risk reduction. The initial therapeutic approach to hypercholesterolaemia includes dietary modifications but the compliance to recommendations is often inadequate. Some dietary components with potential cholesterol-lowering activity are present in small amounts in food. Therefore, in recent years the use of “nutraceuticals” (i.e., nutrients and/or bioactive compounds with potential beneficial effects on human health) has become widespread. Such substances may be added to foods and beverages, or taken as dietary supplements (liquid preparations, tablets, capsules). In the present manuscript, the cholesterol-lowering activity of some nutraceuticals (i.e. fiber, phytosterols, soy, policosanol, red yeast rice and berberine) will be discussed along with: 1) the level of evidence on the cholesterol-lowering efficacy emerging from clinical trial; 2) the possible side effects associated with their use; 3) the categories of patients who could benefit from their use.
Based on the current literature, the cholesterol-lowering effect of fiber, phytosterols and red yeast rice is consistent and supported by a good level of evidence. Over berberine, there is sufficient evidence showing significant cholesterol-lowering effects, although the results come from studies carried out almost exclusively in Asian populations. Data on the effects of soy are conflicting and, therefore, the strength of recommendation is quite low. The evidence on policosanol is inconclusive.
Although health benefits may arise from the use of nutraceuticals with cholesterol-lowering activity, their use might be also associated with possible risks and pitfalls, some of which are common to all nutraceuticals whereas others are related to specific nutraceuticals.
END OF QUOTE
Many advocates of alternative medicine are highly sceptical of the value of statins. Yet, it seems clear that statins exert considerably larger effects on our lipid profile than nutraceuticals. So, why not use the treatment that is best documented and most efficacious? One answer could lie in the well-known adverse effects of statins. However, can we be sure that nutraceuticals are devoid of serious side-effects? I am not sure that we can: statins have been fully investigated, and we therefore are well-informed about their risks. Nutraceuticals, by contrast, have not been monitored in such detail, and their safety profile is therefore not as well-understood.
Other advocates of alternative medicine argue that cholesterol (I use the term simplistically without differentiating between the ‘good and bad’ cholesterol) has been hyped by the pharmaceutical industry and is, in truth, not nearly as important a risk factor as we have been led to believe. This line of thought would consequently deny the need to lower elevated cholesterol levels and therefore negate the need for cholesterol-lowering treatments. This stance may be popular, particularly in the realm of alternative medicine, but, to the best of my knowledge, it is erroneous.
Obviously, the first line treatment for people with pathological lipid profiles is the adoption of different life-styles, particularly in terms of nutrition. This may well incorporate some of the nutraceuticals mentioned above. If that strategy is unsuccessful in normalizing our blood lipids – and it often is – we should consider the more effective conventional medications; and that unquestionably includes statins.
I do not expect that everyone reading these lines will agree with me, yet, after studying the evidence, this is my honest conclusion – and NO, I am not paid or otherwise rewarded by the pharmaceutical industry or anyone else!
One of the questions I hear frequently is ‘HOW CAN I BE SURE THIS STUDY IS SOUND’? Even though I have spent much of my professional life on this issue, I am invariably struggling to provide an answer. Firstly, because a comprehensive reply must inevitably have the size of a book, perhaps even several books. And secondly, to most lay people, the reply would be intensely boring, I am afraid.
Yet many readers of this blog evidently search for some guidance – so, let me try to provide a few indicators – indicators, not more!!! – as to what might signify a good and a poor clinical trial (other types of research would need different criteria).
INDICATORS SUGGESTIVE OF A GOOD CLINICAL TRIAL
- Author from a respected institution.
- Article published in a respected journal.
- A clear research question.
- Full description of the methods used such that an independent researcher could repeat the study.
- Randomisation of study participants into experimental and control groups.
- Use of a placebo in the control group where possible.
- Blinding of patients.
- Blinding of investigators, including clinicians administering the treatments.
- Clear definition of a primary outcome measure.
- Sufficiently large sample size demonstrated with a power calculation.
- Adequate statistical analyses.
- Clear presentation of the data such that an independent assessor can check them.
- Understandable write-up of the entire study.
- A discussion that puts the study into the context of all the important previous work in this area.
- Self-critical analysis of the study design, conduct and interpretation of the results.
- Cautious conclusion which are strictly based on the data presented.
- Full disclosure of ethics approval and informed consent,
- Full disclosure of funding sources.
- Full disclosure of conflicts of interest.
- List of references is up-to-date and includes also studies that contradict the authors’ findings.
I told you this would be boring! Not only that, but each bullet point is far too short to make real sense, and any full explanation would be even more boring to a lay person, I am sure.
What might be a little more fun is to list features of a clinical trial that might signify a poor study. So, let’s try that.
WARNIG SIGNALS INDICATING A POOR CLINICAL TRIAL
- published in one of the many dodgy CAM journals (or in a book, blog or similar),
- single author,
- authors are known to be proponents of the treatment tested,
- author has previously published only positive studies of the therapy in question (or member of my ‘ALT MED HALL OF FAME’),
- lack of plausible rationale for the study,
- lack of plausible rationale for the therapy that is being tested,
- stated aim of the study is ‘to demonstrate the effectiveness of…’ (clinical trials are for testing, not demonstrating effectiveness or efficacy),
- stated aim ‘to establish the effectiveness AND SAFETY of…’ (even large trials are usually far too small for establishing the safety of an intervention),
- text full of mistakes, e. g. spelling, grammar, etc.
- sample size is tiny,
- pilot study reporting anything other than the feasibility of a definitive trial,
- methods not described in sufficient detail,
- mismatch between aim, method, and conclusions of the study,
- results presented only as a graph (rather than figures which others can re-calculate),
- statistical approach inadequate or not sufficiently detailed,
- discussion without critical input,
- lack of disclosures of ethics, funding or conflicts of interest,
- conclusions which are not based on the results.
The problem here (as above) is that one would need to write at least an entire chapter on each point to render it comprehensible. Without further detailed explanations, the issues raised remain rather abstract or nebulous. Another problem is that both of the above lists are, of course, far from complete; they are merely an expression of my own experience in assessing clinical trials.
Despite these caveats, I hope that those readers who are not complete novices to the critical evaluation of clinical trials might be able to use my ‘warning signals’ as a form of check list that helps them to tell the chaff from the wheat.
Hyperthyroidism is, so I am told, a frequent veterinary problem, particularly in elderly cats. Homeopathic treatment is sometimes used to treat this condition. One article even provided encouraging details based on 4 case-reports. All 4 cats showed resolution of clinical signs; three attained normal thyroid hormone levels. The authors concluded that homeopathic and complementary therapies avoid the potential side effects of methimazole and surgical thyroidectomy, they are less costly than radioactive iodine treatment, and they provide an option for clients who decline conventional therapies.
Yes, you guessed correctly: such a paper can only be published in the journal ‘HOMEOPATHY‘, respectable journals would not allow such conclusions based on 4 case-reports. They don’t permit inferences as to cause and effect. We have no idea what would have happened to these animals without homeopathy – perhaps they would have fared even better!
What we need is a proper controlled trial. The good news is that such a study has just been published. This double-blinded, placebo-controlled randomised trial was aimed at testing the efficacy of individualised homeopathy in the treatment of feline hyperthyroidism. Cats were randomised into two treatment arms. Either a placebo or a homeopathic treatment was given to each cat blindly.
After 21 days, the T4 levels, weight (Wt) and heart rate (HR) were compared with pre-treatment values. There were no statistically significant differences in the changes seen between the two treatment arms following placebo or homeopathic treatment, or between the means of each parameter for either treatment arm before and after placebo or homeopathic treatment. In a second phase of the study, patients in both treatment arms were given methimazole treatment for 21 days and T4, Wt and HR determined again. Subsequently, statistically significant reductions were noted in T4 (P<0.0001) and HR (P=0.02), and a statistically significant increase was observed in Wt (P=0.004).
The authors concluded that the results of this study failed to provide any evidence of the efficacy of homeopathic treatment of feline hyperthyroidism.
So, homeopathy does not work – not in humans nor in animals. This statement, backed by solid facts, proves all those wrong who cannot resist uttering the notion that HOMEOPATHY CANNOT BE A PLACEBO BECAUSE IT WORKS IN ANIMALS.
And we have seen the evidence for the correctness of this fact so often (for instance here, here, here and here) that I feel embarrassed to say it again: highly diluted homeopathic remedies are placebos. As soon as we adequately control for placebo and other non-specific effects in properly controlled studies, the alleged effects, reported in anecdotes and other uncontrolled studies, simply disappear.
We have repeatedly discussed the risks of chiropractic spinal manipulation (see, for instance here, here and here). Some chiropractors seem to believe that using a hand-held manipulator, called ‘activator’, better controls the forces used on the spine and therefore is safer. This recent paper raises doubts on this hypothesis.
A neurosurgeon from Florida published the case-report of a 75-year-old active woman who presented to a local hospital emergency room with a 3-day history of the acute onset of severe left temporal headache, initially self-treated with non-steroidals, to which they were resistant. Additional complaints included some vague right eye blurring of vision and a mild speech disturbance. Her primary-care physician had ordered an outpatient MRI, which was interpreted as showing a small sub-acute left posterior temporal lobe haemorrhage. He then referred her to the emergency room where she was categorized as a “stroke alert” and evaluated according to the hospital “stroke-alert” protocol.
There was no prior history of migraine, but some mild treated hypertension. The patient subsequently gave a history of chronic neck and back pain, but no headache, for which she had intermittently received chiropractic adjustments. Her current problem started after an activator treatment to the base of the left side at the junction of the skull with the upper cervical spine. She became concerned enough a few days later, because of the persistence of unremitting headache, to contact her primary-care physician. The patient was not taking any anticoagulants or antiplatelet agents and had a relatively unremarkable past medical and surgical history. Although she did not have a formal visual field examination or an ophthalmology consultation, she was found to have an incomplete right homonymous hemi-anopsia on clinical exam by the neurologist.
Based on MRI characteristics, the haemorrhage was determined to be primarily subarachnoid and displacing but not involving any brain parenchyma, and without any extra-axial component. After a 4-day hospitalization for evaluation and observation, the patient was discharged, neurologically improved in terms of visual and speech symptoms as well as headache complaints, to outpatient follow-up. She has remained well with resolution of imaging abnormalities and no reoccurrence of symptoms.
The authors explain how difficult it is to prove specific causation in such cases. It is frequently inferred by epidemiological reasoning or evidence. While there are other potential causes of the haemorrhage that occurred in this case, none is as or more likely than the activator stimulus. In support of the activator as the cause of the haemorrhage, the symptoms began almost immediately after the activator treatment (a temporal relationship), the area to which the activator was applied is almost directly superficial to the area of haemorrhage (a spatial relationship), the anatomic location of this haemorrhage is statistically unusual for any underlying and/or preexisting conditions, including stroke. The MRI confirmed that there was no infarction underlying the area of haemorrhage. The MRA disclosed no dissections or vascular lesions present. The only mechanisms left are trauma or cryptic vascular lesion that ruptured, obliterated itself, and occurred coincident to the activator stimulus. Although Activator stimulus is not high energy, it nonetheless was targeted to the cervico-occipital junction, an area where neural tissue is among the most vulnerable and least protected and closest to the skin (as opposed to the lower cervical or any of the thoracic or lumbar spine). There are many articles that make reference to minor or trivial head injury as a likely cause of intracranial haemorrhage.
The author concluded that he was unable to find a single documented case in which a brain hemorrhage in any location was reported from activator treatment. As such, this case appears to represent the first well-documented and reported brain hemorrhage plausibly a consequence of activator treatment. In the absence of any relevant information in the chiropractic or medical literature regarding cerebral hemorrhage as a consequence of activator treatment, this case should be instructive to the clinician who is faced with a diagnostic dilemma and should not forget to inquire about activator treatment as a potential cause of this complication. Our case had a benign course, but we do not rule out a more serious or potentially dangerous clinical course or adverse outcome. This is of heightened concern in the elderly and/or those with treatment-induced coagulopathy or platelet inhibition.
In light of all of the difficulties inherent in linking chiropractic treatments, including activator treatments, with serious neurological events, it is very possible that intracranial hemorrhage is far more frequent than reported. Several articles comment on the likelihood that complications of this type are almost certainly underreported. Most of the incidents mentioned in case series or surveys had never been previously reported. Neurologists, neurosurgeons, and chiropractors should be more vigilant both in the application and evaluation of these methods in all patients who report new neurologic-type symptoms following a manipulation (including an activator application) to the occiput or the cranio-cervical junction.
I think that case-report speaks for itself.
Chiropractors will, of course, argue (yet again) that:
- conventional treatments cause much more harm,
- spinal manipulation is highly effective,
- such complications are extreme rarities,
- the risk/benefit profile of spinal manipulation is positive,
- some studies have failed to show a risk of spinal manipulation,
- case-reports cannot establish causality.
We have rehearsed these arguments ad nauseam on this blog. The bottom line is well-expressed in the above conclusions: it is very possible that intracranial hemorrhage is far more frequent than reported. And that obviously applies to all other types of complications after chiropractic treatments.
Acupuncture is often recommended as a treatment for shoulder pain, but its effectiveness is far from proven. A new study has just been published; but does it change this uncertainty?
A total of 227 patients with subacromial pain syndrome were recruited to this RCT. The patients were allocated to three groups who received either A) group exercise, B) group exercise plus acupuncture or C) group exercise plus electro-acupuncture. The primary outcome measure was the Oxford Shoulder Score. Follow-up was post treatment, and at 6 and 12 months. Data were analysed on intention-to-treat principles with imputation of missing values.
Treatment groups were similar at baseline. All treatment groups demonstrated improvements over time. Between-group estimates were, however, small and non-significant.
The authors concluded that neither acupuncture nor electro-acupuncture were found to be more beneficial than exercise alone in the treatment of subacromial pain syndrome.
Well, that was to be expected!… I hear the rationalists amongst us exclaim.
Actually, I am not so sure.
One could easily have expected that the acupuncture groups (B and C) show a significant advantage over group A.
Because acupuncture is a ‘theatrical placebo’, a ritual that impresses patients and thus impacts on results, particularly on subjective outcomes like pain. If the results had shown a benefit for acupuncture + exercise (groups B and C) versus exercise alone (group A), what would we have made of it? Acupuncture fans would surely have claimed that it is evidence confirming acupuncture’s effectiveness. Sceptics, on the other hand, would have rightly insisted that it demonstrates nothing of the sort – it merely confirms that placebo effects can affect clinical outcomes such as pain.
As it turned out, however, this trial results happened to indicate that these placebo-effects can be so small that they fail to reach the level of statistical significance.
I think there is one noteworthy message here: RCTs with such a design (no adequate control for placebo effects) can easily generate false-positive results (in this case, this did not happen, but it was nevertheless a possible outcome). Such studies are popular but utterly useless: they don’t advance our knowledge one single iota. If that is so, we should not waste our resources on them because, in the final analysis, this is not ethical. In other words, we must stop funding research that has little or no chance of advancing our knowledge.
This new RCT was embargoed until today; so, I had to wait until I was able to publish my comments. Here are the essentials of the study:
The Swedish investigators compared the effect of two types of acupuncture versus no acupuncture in infants with colic in public child health centres (CHCs). The study was designed as a multicentre, randomised controlled, single-blind, three-armed trial (ACU-COL) comparing two styles of acupuncture with no acupuncture, as an adjunct to standard care. Among 426 infants whose parents sought help for colic and registered their child’s fussing/crying in a diary, 157 fulfilled the criteria for colic and 147 started the intervention.
Parallel to usual care, study participants visited the study CHC twice a week for 2 weeks. Thus, all infants received usual care plus 4 extra visits to a CHC, during which parents met a nurse for 20–30 min and were able to discuss their infant’s symptoms. Together these were considered to represent gold standard care. The nurse listened, and gave evidence-based advice and calming reassurance. Breastfeeding mothers were encouraged to continue breastfeeding. At each visit, the study nurse carried the infant to a separate treatment room where they were left alone with the acupuncturist for 5 min.
The acupuncturist treated the baby according to group allocation and recorded the treatment procedures and any adverse events. Disposable stainless steel 0.20×13 mm Vinco needles (Helio, Jiangsu Province, China) were used. Infants allocated to group A received standardised MA at LI4. One needle was inserted to a depth of approximately 3 mm unilaterally for 2–5 s and then withdrawn without stimulation. Infants allocated to group B received semi-standardised individualised acupuncture, mimicking clinical TCM practice. Following a manual, the acupuncturists were able to choose one point, or any combination of Sifeng, LI4 and ST36, depending on the infant’s symptoms, as reported in the diary. A maximum of five insertions were allowed per treatment. Needling at Sifeng consisted of 4 insertions, each to a depth of approximately 1 mm for 1 s. At LI4 and ST36, needles were inserted to a depth of approximately 3 mm, uni- or bilaterally. Needles could be retained for 30 seconds. De qi was not sought, therefore stimulation was similarly minimal in groups A and B. Infants in group C spent 5 min alone with the acupuncturist without receiving acupuncture.
The effect of the two types of acupuncture was similar and both were superior to gold standard care alone. Relative to baseline, there was a greater relative reduction in time spent crying and colicky crying by the second intervention week (p=0.050) and follow-up period (p=0.031), respectively, in infants receiving either type of acupuncture. More infants receiving acupuncture cried <3 hours/day, and thereby no longer fulfilled criteria for colic, in the first (p=0.040) and second (p=0.006) intervention weeks. No serious adverse events were reported.
The authors concluded that acupuncture appears to reduce crying in infants with colic safely.
Notice that the investigators are cautious and state in the abstract that “acupuncture appears to reduce crying…” Their conclusions from the actual article are, however, quite different; here they state the following:
Among those initially experiencing excessive infant crying, the majority of parents reported normal values once the infant’s crying had been evaluated in a diary and a diet free of cow’s milk had been introduced. Therefore, objective measurement of crying and exclusion of cow’s milk protein are recommended as first steps, to avoid unnecessary treatment. For those infants that continue to cry >3 hours/day, acupuncture may be an effective treatment option. The two styles of MA tested in ACU-COL had similar effects; both reduced crying in infants with colic and had no serious side effects. However, there is a need for further research to find the optimal needling locations, stimulation and treatment intervals.
Such phraseology is much more assertive and seems to assume acupuncture caused specific therapeutic effects. Yet, I think, this assumption is not warranted.
In fact, I believe, the study shows almost the opposite of what the authors conclude. Both minimal and TCM acupuncture seemed to reduce the symptoms of colic compared to no acupuncture at all. I think, this confirms previous research showing that acupuncture is a ‘theatrical placebo’. The study was designed without an adequate placebo group. It would have been easy to use some form of sham acupuncture in the control group. Why did the authors not do that? Heaven knows, but one might speculate that they were aiming for a positive result – and what better way to ensure it than with a ‘no treatment’ control group?
There are, of course, numerous other flaws. For instance, Prof David Colquhoun FRS, Professor of Pharmacology at University College London, criticised the study because of its lousy statistics:
START OF QUOTE
“It is truly astonishing that, in the 21st century, the BMJ still publishes a journal devoted to a form of pre-scientific medicine which after more than 3000 trials has still not been able to produce convincing evidence of efficacy1. Like most forms of alternative medicine, acupuncture has been advocated for a vast range of problems, and there is little evidence that it works for any of them. Colic has not been prominent in these claims. What parent would think that sticking needles into their baby would stop it crying? The idea sounds bizarre. It is. This paper certainly doesn’t show that it works.
“The statistical analysis in the paper is incompetent. This should have been detected by the referees, but wasn’t. For a start, the opening statement, ‘A two-sided P value ≤0.05 was considered statistically significant’ is simply unacceptable in the light of all recent work about reproducibility. Still worse, Table 1 uses the description ‘statistical tendency towards significance (p=0.051–0.1)’.
“Worst of all, Table 1 reports 24 different P values, of which three are (just) below 0.05. Yet no correction has been used for multiple comparisons. This is very bad practice. It’s highly unlikely that, if the proper correction had been done, any of the results would have given a type 1 error rate below 5%.
“Even were it not for this, most of the ‘significant’ P values are marginal (only slightly less than 0.05). It is now well known that the type 1 error rate gives an optimistic view. What matters is the false positive rate – the chance that a ‘significant’ result is a false positive. A p-value close to 0.05 implies that there is at least a 30% chance that they are false positives. If one thought, a priori, that the chance of colic being cured by sticking needles into a baby was less than 50%, the false positive rate could easily be greater than 80%2. It is now recognised that this misinterpretation of p-values is a major contributor to the crisis of reproducibility.
“Other problems concern the power calculation. A priori calculations of power are well-known to be overoptimistic, because small trials usually overestimate the effect size. In this case the initial estimated sample size was not attained, and a rather mysterious recalculation of power was used.
“Another small problem: the discussion points out that ‘the majority of infants in this cohort did not have colic’.
“The nature of the control group is not very clear. An appropriate control might have been to cuddle the baby – this was used in a study in which another implausible treatment, chiropractic, was shown not to work. This appears not to have been done.
“Lastly, p-values are reported in the text without mention of effect sizes. This is contrary to all statistical advice.
“In conclusion, the design of the trial is reasonable (apart from the control group) but the statistical analysis is appalling. It’s very likely that there aren’t any real effects of acupuncture at all. This paper serves more to muddy the waters than to add useful information. It’s a model for the sort of mistakes that have led to the crisis in reproducibility. The BMJ should not be publishing this sort of stuff, and the referees seem to have no understanding of statistics.”
END OF QUOTE
Despite these rather obvious – some would say fatal – flaws, the editor of ACUPUNCTURE IN MEDICINE (AIM) thought this trial to be so impressively rigorous that he issued a press-release about it. This, I think, is particularly telling, perhaps even humorous: it shows what kind of a journal AIM is, and also provides an insight into the state of acupuncture research in general.
The long and short of it is that conclusions about specific therapeutic effects of acupuncture are not permissible. We know that colicky babies respond even to minimal attention, and this trial confirms that even a little additional TLC in the form of acupuncture will generate an effect. The observed outcome is most likely unrelated to acupuncture.