MD, PhD, FMedSci, FSB, FRCP, FRCPEd

clinical trial

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Cranio-sacral therapy has been a subject on this blog before, for instance here, here and here. The authors of this single-blind, randomized trial explain in the introduction of their paper that “cranio-sacral therapy is an alternative and complementary therapy based on the theory that restricted movement at the cranial sutures of the skull negatively affect rhythmic impulses conveyed through the cerebral spinal fluid from the cranium to the sacrum. Restriction within the cranio-sacral system can affect its components: the brain, spinal cord, and protective membranes. The brain is said to produce involuntary, rhythmic movements within the skull. This movement involves dilation and contraction of the ventricles of the brain,  which produce the circulation of the cerebral spinal fluid. The theory states that this fluctuation mechanism causes reciprocal tension within the membranes, transmitting motion to the cranial bones and the sacrum. Cranio-sacral therapy and cranial osteopathic manual therapy originate from the observations made by William G. Sutherland, who said that the bones of the human skeleton have mobility. These techniques are based mainly on the study of anatomic and physiologic mechanisms in the skull and their relation to the body as a whole, which includes a system of diagnostic and therapeutic techniques aimed at treatment and prevention of diseases. These techniques are  based on the so-called primary respiratory movement, which is manifested in the mobility of the cranial bones, sacrum,  dura, central nervous system, and cerebrospinal fluid. The main difference between the two therapies is that cranial osteopathy, in addition to a phase that works in the direction of the lesion (called the functional phase), also uses a phase that worsens the injury, which is called structural phase.”

With this study, the researchers wanted to evaluate the effects of cranio-sacral therapy on disability, pain intensity, quality of life, and mobility in patients with low back pain. Sixty-four patients with chronic non-specific low back pain were assigned to an experimental group receiving 10 sessions of craniosacral therapy, or to the control group receiving 10 sessions of classic massage. Craniosacral therapy took 50 minutes and was conducted as follows: With pelvic diaphragm release, palms are placed in transverse position on the superior aspect of the pubic bone, under  the L5–S1 sacrum, and finger pads are placed on spinal processes.  With respiratory diaphragm release, palms are placed transverse under T12/L1 so that the spine lies along the start of fingers and the border of palm, and the anterior hand is placed on the breastbone. For thoracic inlet release, the thumb and index finger are placed on the opposite sides of the clavicle, with the posterior hand/palm of the hand cupping C7/T1. For the hyoid release, the thumb and index finger are placed on the hyoid, with the index finger on the occiput and the cupping finger pads on the cervical vertebrae. With the sacral technique for stabilizing L5/sacrum, the fingers contact the sulcus and the palm of the hand is in contact with the distal part of the sacral bone. The non-dominant hand of the therapist rested over the pelvis, with one hand on one iliac crest and the elbow/forearm of the other side over the other iliac crest. For CV-4 still point induction, thenar pads are placed under the occipital protuberance, avoiding mastoid sutures.  Classic massage protocol was compounded by the following sequence techniques of soft tissue massage on the  low back: effleurage, petrissage, friction, and kneading. The maneuvers are performed with surface pressure, followed by deep pressure and ending with surface pressure again. The techniques took 30 minutes.

Disability (Roland Morris Disability Questionnaire RMQ, and Oswestry Disability Index) was the primary endpoint. Other outcome measures included the pain intensity (10-point numeric pain rating scale), kinesiophobia (Tampa Scale of Kinesiophobia), isometric endurance of trunk flexor muscles (McQuade test), lumbar mobility in flexion, hemoglobin oxygen saturation, systolic blood pressure, diastolic blood pressure, hemodynamic measures (cardiac index), and biochemical analyses of interstitial fluid. All outcomes were measured at baseline, after treatment, and one-month follow-up.

No statistically significant differences were seen between groups for the main outcome of the study, the RMQ. However, patients receiving craniosacral therapy experienced greater improvement in pain intensity (p ≤ 0.008), hemoglobin oxygen saturation (p ≤ 0.028), and systolic blood pressure (p ≤ 0.029) at immediate- and medium-term and serum potassium (p = 0.023) level and magnesium (p = 0.012) at short-term than those receiving classic massage.

The authors concluded that 10 sessions of cranio-sacral therapy resulted in a statistically greater improvement in pain intensity, hemoglobin oxygen saturation, systolic blood pressure, serum potassium, and magnesium level than did 10 sessions of classic massage in patients with low back pain.

Given the results of this study, the conclusion is surprising. The primary outcome measure failed to show an inter-group difference; in other words, the results of this RCT were essentially negative. To use secondary endpoints – most of which are irrelevant for the study’s aim – in order to draw a positive conclusion seems odd, if not misleading. These positive findings are most likely due to the lack of patient-blinding or to the 200 min longer attention received by the verum patients. They are thus next to meaningless.

In my view, this publication is yet another example of an attempt to turn a negative into a positive result. This phenomenon seems embarrassingly frequent in alternative medicine. It goes without saying that it is not just misleading but also dishonest and unethical.

A new Cochrane review evaluated the effectiveness and safety of Chinese herbal medicines (CHM) in the treatment of menopausal symptoms. Its authors conducted a thorough search for randomised controlled trials (RCTs) comparing the effectiveness of CHM with placebo, hormone therapy (HT), pharmaceutical drugs, acupuncture, or another CHM formula in women suffering from menopausal symptoms.

Two review authors independently assessed 864 studies for eligibility. Data extractions were performed by them with disagreements resolved through group discussion and clarification of data or direct contact with the study authors. Data analyses were performed in accordance with Cochrane Collaboration guidelines.

In total, 22 RCTs (2902 women) could be included. When CHM was compared with placebo (8 RCTs), there was little or no evidence of a difference between the groups for the following outcomes: hot flushes per day (MD 0.00, 95% CI -0.88 to 0.89; 2 trials, 199 women; moderate quality evidence); hot flushes per day assessed by an overall hot flush score in which a difference of one point equates to one mild hot flush per day (MD -0.81 points, 95% CI -2.08 to 0.45; 3 RCTs, 263 women; low quality evidence); and overall vasomotor symptoms per month measured by the Menopause-Specific Quality of Life questionnaire (MENQOL, scale 0 to 6) (MD -0.42 points; 95% CI -1.52 to 0.68; 3 RCTs, 256 women; low quality evidence). In addition, results from individual studies suggested there was no evidence of a difference between the groups for daily hot flushes assessed by severity (MD -0.70 points, 95% CI -1.00, -0.40; 1 RCT, 108 women; moderate quality evidence); or overall monthly hot flushes scores (MD -2.80 points, 95% CI -8.93 to 3.33; 1 RCT, 84 women; very low quality evidence); or overall daily night sweats scores (MD 0.07 points, 95% CI -0.19 to 0.33, 1 RCT, 64 women; low quality evidence); or overall monthly night sweats scores (MD 1.30 points, 95% CI -1.76 to 4.36, 1 RCT, 84 women; very low quality evidence). However, one study reported that overall monthly vasomotor symptom scores were lower in the CHM group (MD -4.79 points, 95% CI -5.52 to -4.06; 1 RCT, 69 women; low quality evidence).

When CHM was compared with HT (10 RCTs), only two RCTs reported monthly vasomotor symptoms using MENQOL. It was uncertain whether CHM reduces vasomotor symptoms (MD 0.47 points, 95% CI -0.50 to 1.44; 2 RCTs, 127 women; very low quality evidence).

Adverse effects were not fully reported in the included studies. Adverse events reported by women taking CHM included mild diarrhoea, breast tenderness, gastric discomfort and an unpleasant taste. Effects were inconclusive because of imprecise estimates of effects: CHM versus placebo (RR 1.51; 95% CI 0.69 to 3.33; 7 trials, 705 women; I² = 40%); CHM versus HT (RR 0.96; 95% CI 0.66 to 1.39; 2 RCTs, 864 women; I² = 0%); and CHM versus specific conventional medications (such as Fluoxetine and Estazolam) (RR 0.20; 95% CI 0.03 to 1.17; 2 RCTs, 139 women; I² = 61%).

The authors concluded: We found insufficient evidence that Chinese herbal medicines were any more or less effective than placebo or HT for the relief of vasomotor symptoms. Effects on safety were inconclusive. The quality of the evidence ranged from very low to moderate; there is a need for well-designed randomised controlled studies.

This review seems well done and reports clear findings. The fact that there was insufficient evidence for CHM is probably no surprise to most readers of this blog. However, I would like to draw your attention to a finding that could easily be missed: most of the primary studies failed to mention adverse effects; to be perfectly clear: they did not state “there were no adverse effects”, but they simply did not mention the subject of adverse effects at all.

In my view, this is a breach of research ethics. I have been banging on about this phenomenon for some time now, because I think it is important. Many if not most clinical trials in this area neglect reporting adverse effects. This means that we get an entirely misleading impression about the safety of the treatments in question. Reviewers of such studies are bound to conclude that they seem to be safe, while, in fact, researchers have only been withholding crucial information from us.

The solution to this fast-growing problem would be simple: trialists must be forced to fully report adverse effects. This is less complicated that it might seem: journal editors must insist that all authors fully report adverse effects of alternative treatments. Even if there were none at all – a very unlikely proposition if you think about it – they must disclose this fact.

No, I don’t want to put you off your breakfast… but you probably have seen so many pictures of attractive athletes with cupping marks and read articles about the virtues of this ancient therapy, that I feel I have to put this into perspective:

Cupping burnsI am sure you agree that this is slightly less attractive. But, undeniably, these are also cupping marks. So, if you read somewhere that this treatment is entirely harmless, take it with a pinch of salt.

Cupping has existed for centuries in most cultures, and there are several variations of the theme. We differentiate between wet and dry cupping. The above picture is of wet cupping gone wrong. What the US Olympic athletes currently seem to be so fond of is dry cupping.

The principles of both forms are similar. In dry cupping, a vacuum cup is placed over the skin which provides enough suction to create a circular bruise. Eventually the vacuum diminishes, and the cup falls off; what is left is the mark. In wet cupping, the procedure is much the same, except that the skin is injured before the cup is placed. The suction then pulls out a small amount of blood. Obviously the superficial injury can get infected, and that is what we see on the above picture.

In the homeopathic hospital where I worked ~40 years ago, we did a lot of both types of cupping. We used it mostly for musculoskeletal pain. Our patients responded well.

But why? How does cupping work?

The answer is probably more complex than you expect. It clearly has a significant placebo effect. Athletes are obviously very focussed on their body, and they are therefore the ideal placebo-responders. Evidently, my patients 40 years ago also responded to all types of placebos, even to the homeopathic placebos which they received ‘en masse’.

But there might be other mechanisms as well. A TCM practitioner will probably tell you that cupping unblocks the energy flow in our body. This might sound very attractive to athletes or consumers, and therefore could even enhance the placebo response, but it is nevertheless nonsense.

The most plausible mode of action is ‘counter-irritation’: if you have a pain somewhere, a second pain elsewhere in your body can erase the original pain. You might have a headache, for instance, and if you accidentally hit your thumb with a hammer, the headache is gone, at least for a while. Cupping too would cause mild to moderate pain, and this is a distraction from the muscular pain the athletes aim to alleviate.

When I employed cupping 40 years ago, there was no scientific evidence testing its effects. Since a few years, however, clinical trials have started appearing. Many are from China, and I should mention that TCM studies from China almost never report a negative result. According to the Chinese, TCM (including cupping) works for everything. More recently,also some trials from other parts of the world have emerged. They have in common with the Chinese studies that they tend to report positive findings and that they are of very poor quality. (One such trial has been discussed previously on this blog.) In essence, this means that we should not rely on their conclusions.

A further problem with clinical trails of cupping is that it is difficult, if not impossible, to control for the significant placebo effects that this treatment undoubtedly generates. There is no placebo that could mimic all the features of real cupping in clinical trials; and there is no easy way to blind either the patient or the therapist.

So, we are left with an ancient treatment backed by a host of recent but flimsy studies and a growing craze for cupping fuelled by the Olympic games. What can one conclude in such a situation?

Personally, I would, whenever possible, recommend treatments that work beyond a placebo effect, because the placebo response tends to be unreliable and is usually of short duration – and I am not at all sure that cupping belongs into this category. I would also avoid wet cupping, because it can cause substantial harm. Finally, I would try to keep healthcare costs down; cupping itself is cheap but the therapist’s time might be expensive.

In a nutshell: would I recommend cupping? No, not any more than using a hammer for counter irritation! Will the Olympic athletes care a hoot about my recommendations? No, probably not!

 

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!

Yesterday, a press-release reached me announcing that a Chinese herbal medicine, ‘Phynova Joint and Muscle Relief Tablets’, containing the active ingredient Sigesbeckia, is now on sale in the UK for the first time in Boots The Chemist: 

Sigesbeckia is the first traditional Chinese treatment granted a traditional herbal registration (THR) under the traditional herbal medicines product directive in the UK, by drug safety watchdog the Medicines and Healthcare Products Regulatory Agency (MHRA).  Oxford based Phynova which manufactures the product was granted the UK licence last year. 

Containing 500mg of the active ingredient, Phynova Joint and Muscle Relief Tablets are specially formulated for the relief of backache, arthritis, minor sports injuries, rheumatic or muscular pains and general aches and pains in muscles or joints.  Two tablets are taken each day, one in the morning and one in the evening. They have no known side effects and are non-addictive. .. 

The product, which retails at £19.99 for one month’s supply of 60 tablets, is available in 950 UK Boots outlets and online via Click and Collect from all stores.  It will be sold both Over the Counter (OTC) by pharmacist staff and off the shelf as part of Boots’ pain relief fixture… 

END OF QUOTE

What on earth is a ‘joint and muscle relief’? Personally I do not want to be relieved of my joints and muscles!!!

Yes, I know, they probably mean ‘joint and muscle pain relief’ but were not allowed to say so because this is a medical indication.

And what about the claim of ‘no side-effects’; is it possible that a pharmacological treatment has positive effects without any risks at all? This is not what they told me during my pharmacology course, if I remember correctly. And anyway, even placebos have side-effects!

I admit, I was puzzled.

The covering letter of the press-release provided more amazement: it informed me that “Phynova joint and muscle relief contains the active ingredient Sigesbeckia which has been through clinical trials and has been used for pain relief in China for hundreds of years…” It was the remark about clinical trials (PLURAL!!!) that caught my interest most.

So, I looked up ‘Sigesbeckia’ on Medline and found as good as nothing. This is mainly because the plant is spelled correctly ‘Siegesbeckia’ in honour of the famous botanist Siegesbeck.

Looking up ‘Siegesbeckia’, I found many pre-clinical studies but no clinical trials.

Next I searched for a comment from the MHRA and discovered that their account makes it very clear that a licence has been granted to this product “exclusively upon long standing use… and not upon data from clinical trials.”

So, who is right?

Are there clinical trials of this product or not? And, if there are any, where are they?

Perhaps someone from Phynova can enlighten us?

 

Turmeric (Curcuma longa) is a truly fascinating plant with plenty of therapeutic potential. It belongs to the ginger family, Zingiberaceae and is native to southern Asia. Its main active ingredients are curcumin (diferuloylmethane) and the related compounds, demethoxycurcumin and bis-demethoxycurcumin (curcuminoids) which are secondary metabolites. Turmeric  has been used extensively in Ayurvedic medicine and has a variety of pharmacologic properties including antioxidant, analgesic, anti-inflammatory, and antiseptic activities.

In the often weird world of alternative medicine, turmeric is currently being heavily hyped as the new panacea. Take this website, for instance; it promotes turmeric for just about any ailment known to mankind. Here is a short excerpt to give you a flavour (pun intended, turmeric is, of course, a main ingredient in many curries):

It comes at a surprise to a lot of people that herbs can be highly effective, if not more effective, than conventional medications …

To date, turmeric is one of the top researched plants. It was involved in more than 5,600 peer-reviewed and published biomedical studies. In one research project that extended over a five year period, it was found that turmeric could potentially be used in preventive and therapeutic applications. It was also noted that it has 175 beneficial effects for psychological health…

The 14 Medications it Mimics

Or should we say the 14 medications that mimic turmeric, since turmeric has been around much longer than any chemical prescription drug. Here’s a quick look at some of them:

  • Lipitor: This is a cholesterol drug that is used to reduce inflammation and oxidative stress inside of patients suffering from type 2 diabetes. When the curcuminoid component inside of turmeric is properly prepared, it can offer the same effects (according to a study published in 2008).
  • Prozac: This is an antidepressant that has been overused throughout the past decade. In a study published back in 2011, turmeric was shown to offer beneficial effects that helped to reduce depressive behaviors (using animal models).
  • Aspirin: This is a blood thinner and pain relief drug. In a study done in 1986, it was found that turmeric has similar affects, which makes it a candidate for patients that are susceptible to vascular thrombosis and arthritis.
  • Metformin: This is a drug that treats diabetes. It is used to activate AMPK (to increase uptake of glucose) and helps to suppress the liver’s production of glucose. In a study published in 2009, it was found that curcumin was 500 to 100,000 times more effective at activating AMPK ad ACC.
  • Anti-Inflammatory Drugs: This includes medications like ibuprofen, aspirin and dexamethasone, which are designed to reduce inflammation. Again, in 2004, it was proven that curcumin was an effective alternative option to these chemical drugs.
  • Oxaliplatin: This is a chemotherapy drug. A study done in 2007 showed that curcumin is very similar to the drug, acting as an antiproliferative agent in colorectal cell lines.
  • Corticosteroids: This is a steroid medication, which is used to treat inflammatory eye diseases. In 1999, it was found that curcumin was effective at managing this chronic condition. Then in 2008, curcumin was used in an animal model that proved it could also aid in therapy used to protect patients from lung transplantation-associated injuries by “deactivating” inflammatory genes.

Turmeric Fights Drug-Resistant Cancers… it’s been shown that curcumin can battle against cancers that are resistant to chemotherapy and radiation…

END OF QUOTE

As I said, turmeric is fascinating and promising, but such hype is clearly counter-productive and dangerous. As so often, the reality is much more sobering than the fantasy of uncritical quacks. Research is currently very active and has produced a host of interesting findings. Here are the conclusions (+links) of a few, recent reviews:

Overall, there is early evidence that turmeric/curcumin products and supplements, both oral and topical, may provide therapeutic benefits for skin health. However, currently published studies are limited and further studies will be essential to better evaluate efficacy and the mechanisms involved.

This meta-analysis of RCTs suggested a significant effect of curcumin in lowering circulating TNF-α concentration.

While statistical significant differences in outcomes were reported in a majority of studies, the small magnitude of effect and presence of major study limitations hinder application of these results.

Overall, scientific literature shows that curcumin possesses anti-diabetic effects and mitigates diabetes complications.

The highlighted studies in the review provide evidence of the ability of curcumin to reduce the body’s natural response to cutaneous wounds such as inflammation and oxidation. The recent literature on the wound healing properties of curcumin also provides evidence for its ability to enhance granulation tissue formation, collagen deposition, tissue remodeling and wound contraction. It has become evident that optimizing the topical application of curcumin through altering its formulation is essential to ensure the maximum therapeutical effects of curcumin on skin wounds.

What emerges from a critical reading of the evidence is that turmeric has potential in several different areas. Generally speaking, clinical trials are still thin on the ground, not of sufficient rigor and therefore not conclusive. In other words, it is far too early to state or imply that we all should rush to the next health food store and buy the supplements.

On the contrary, at this stage, I would even warn people not to be seduced by the unprofessional hype and wait until we know more – much more. There might be risks associated with ingesting turmeric at high doses over long periods of time. And there are fundamental open questions about oral intake. One recent review cautioned: …its extremely low oral bioavailability hampers its application as therapeutic agent.

WATCH THIS SPACE!

Seasonal allergic rhinitis (hay fever) is a common condition which can considerably reduce the quality of life of sufferers. Homeopathy is often advocated – but does it work?

A new study was meant to be an “assessment of the clinical effectiveness of homeopathic remedies in the alleviation of hay fever symptoms in a typical clinical setting.”

The investigator performed a ‘clinical observational study’ of eight patients from his private practice using Measure Yourself Medical Outcome Profile (MYMOP) self-evaluation questionnaires at baseline and again after two weeks and 4 weeks of individualized homeopathic treatment which was given as an add-on to conventional treatments.

The average MYMOP scores for the eyes, nose, activity and wellbeing had improved significantly after two and 4 weeks of homeopathic treatment. The overall average MYMOP profile score at baseline was 3.83 (standard deviation, SD, 0.78). After 14 and 28 days of treatment the average score had fallen to 1.14 (SD, 0.36; P<0.001) and 1.06 (SD, 0.25; P<0.001) respectively.

The author concluded as follows: Individualized homeopathic treatment was associated with significant alleviation of hay fever symptoms, enabling the reduction in use of conventional treatment. The results presented in this study can be considered as a step towards a pilot pragmatic study that would use more robust outcome measures and include a larger number of patients prescribed a single or a multiple homeopathic prescription on an individualized basis.

It is hard to name the things that are most offensively wrong here; the choice is too large. Let me just list three points:

  • The study design is not matched to the research question.
  • The implication that homeopathy had anything to do with the observed outcome is unwarranted.
  • The conclusion that the results might lend themselves to develop a pilot study is meaningless.

The question whether homeopathy is an effective therapy for hay fever has been tested before, even in RCTs. It seems therefore mysterious why one needs to revert to tiny observational studies in order to plan a pilot, and even less for an assessment of effectiveness.

There are few conditions which are more time-dependent than hay fever. Any attempt of testing the effectiveness of medical interventions without a control group seems therefore not just questionable but wasteful. Clinical studies absorb resources; even if the author was happy to waste his time, he should not assume that he can freely waste the time, effort and availability of his patients.

Two final points, if I may:

  • An observational study of homeopathy for hay-fever without a control group might be utterly useless but it is still an investigation that requires certain things. As far as I can see, this study did not even have ethics approval nor is there a mention of informed consent. Strictly speaking, this makes it an unethical study.
  • If we allow research of this nature to take place and be published, we give clinical research a bad name and undermine the confidence of the public in science.

I am puzzled how such a paper could pass peer review and how an Elsevier journal could even consider publishing it.

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.

Acupuncture, like most other alternative therapies, is particular popular for indications that are

  1. chronic,
  2. associated with a high burden of suffering,
  3. not easily treatable with conventional therapies,
  4. are frequently resolved without any intervention.

Infertility or subfertility tick most of these boxes. It is therefore not surprising that acupuncturists the world over claim that acupuncture can cure infertility. But is this claim based on evidence or on wishful thinking?

The objective of this new study was to find out. Specifically, the authors wanted to provide preliminary data to explore whether women with subfertility undergoing a course of acupuncture and lifestyle modification compared with an active control of lifestyle modification alone would demonstrate improved reproductive outcomes, improved menstrual cycles, and increased fertility awareness.

In a pragmatic randomised controlled trial, with the A+B versus B design, sub/infertile women were offered an intervention of acupuncture and lifestyle modification or lifestyle modification only. There was a statistically significant increase in fertility awareness in the acupuncture group (86.4%) compared to 40% of the lifestyle only participants. Changes in menstrual regularity were not statistically significant. There was no statistical difference in the pregnancy rate with seven women achieving pregnancy during the course of the study intervention. Those receiving the acupuncture conceived within an average of 5.5 weeks compared to 10.67 weeks for the lifestyle only group.

The authors concluded that the acupuncture protocol tested influenced women who received it compared to women who used lifestyle modification alone: their fertility awareness and wellbeing increased, and those who conceived did so in half the time.

The first sentences of the authors’ discussion are, I think, revealing: The main findings were that this acupuncture intervention, compared to lifestyle only, resulted in significant increases in fertility awareness and quality of life measures in relation to wellbeing; it increased the ability of the recipients to engage in desired activities, such as exercise or rest, and it shortened the time to conception by half. The findings provide preliminary evidence that the acupuncture intervention is acceptable and is not inert and that acupuncture dose may have a significant influence on outcomes. 

In my view, the main findings of this study are entirely different. Let me propose alternatives:

  • In alternative medicine, if you did a lousy study, you can just call it a ‘pilot study’ and all is forgiven.
  • The infamous A+B vs B design continues to be popular for those who cannot bring themselves to publishing negative findings.
  • It works perfectly for subjective parameters but less convincingly for objective ones, such as pregnancy rates.
  • Doing such research on infertility is good for the cash flow of acupuncturists.
  • Making women aware of fertility increases (surprise, surprise!) fertility awareness.

No need to be so cynical!, some will think. After all, the results showed that women receiving the acupuncture conceived within an average of 5.5 weeks compared to 10.67 weeks for the lifestyle only group. True! But there was no statistically significant difference between these two figures. And that means, the difference was a chance finding (which has no place in an abstract) which probably has no relevance whatsoever.

Or perhaps I am wrong?

I am told to always keep an open mind!

So, let’s keep our minds open to some truly alternative explanations. How about this one: regular acupuncture increases the rate of adultery, which, in turn, decreases the time to conception.

Makes sense, doesn’t it? Has anyone a better idea?

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].

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