MD, PhD, FMedSci, FSB, FRCP, FRCPEd

clinical trial

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Chronic pain is a common and serious problem for many patients. Treatment often includes non-pharmacological approaches despite the mostly flimsy evidence to support them. The objective of this study was to measure the feasibility and efficacy of hypnosis (including self-hypnosis) in the management of chronic pain in older hospitalized patients.

A single center randomized controlled trial using a two arm parallel group design (hypnosis versus massage). Inclusion criteria were chronic pain for more than 3 months with impact on daily life activities, intensity of > 4; adapted analgesic treatment; no cognitive impairment. Fifty-three patients were included. Pain intensity decreased significantly in both groups after each session. Average pain measured by the brief pain index sustained a greater decrease in the hypnosis group compared to the massage group during the hospitalization. This was confirmed by the measure of intensity of the pain before each session that decreased only in the hypnosis group over time. Depression scores improved significantly over the time only in the hypnosis group. There was no effect in either group 3 months post hospitals discharge.

The authors concluded that hypnosis represents a safe and valuable tool in chronic pain management of hospitalized older patients. In hospital interventions did not provide long-term post discharge relief.

So, hypnotherapy is better than massage therapy when administered as an adjunct to conventional pain management. As it is difficult to control for placebo effects, which might be substantial in this case, we cannot be sure whether hypnotherapy per se was effective or not.

Who cares? The main thing is to make life easier for these poor patients!

There are situations where I tend to agree with this slightly unscientific but compassionate point of view. Yes, the evidence is flimsy, but we need to help these patients. Hypnotherapy has very few risks, is relatively inexpensive and might help badly suffering individuals. In this case, does it really matter whether the benefit was mediated by a specific or a non-specific mechanism?

In 2009, we published a systematic review of studies testing acupuncture as a treatment of menopausal hot flushes. We searched the literature using 17 databases from inception to October 10, 2008, without language restrictions. We only included randomized clinical trials (RCTs) of acupuncture versus sham acupuncture. Their methodological quality was assessed using the modified Jadad score. In total, six RCTs could be included. Four RCTs compared the effects of acupuncture with penetrating sham acupuncture on non-acupuncture points. All of these trials failed to show specific effects on menopausal hot flush frequency, severity or index. One RCT found no effects of acupuncture on hot flush frequency and severity compared with penetrating sham acupuncture on acupuncture points that are not relevant for the treatment of hot flushes. The remaining RCT tested acupuncture against non-penetrating acupuncture on non-acupuncture points. Its results suggested favourable effects of acupuncture on menopausal hot flush severity. However, this study was too small to generate reliable findings. At the time, we concluded that sham-controlled RCTs fail to show specific effects of acupuncture for control of menopausal hot flushes. We also argued that more rigorous research is warranted.

It seems that such research has just become available.

The aim of a brand-new study – a stratified, blind (participants, outcome assessors, and investigators, but not treating acupuncturists were blinded to treatment allocation), parallel, randomized, sham-controlled trial with equal allocation – was to assess the efficacy of Chinese medicine acupuncture against sham acupuncture for menopausal hot flushes (HFs). It was funded by the Australian National Health and Medical Research Council.

Women older than 40 years were recruited; they had to be in the late menopausal transition or postmenopause with at least 7 moderate HFs daily, meeting criteria for Chinese medicine diagnosis of kidney yin deficiency. These patients received 10 treatments over 8 weeks of either standardized Chinese medicine needle acupuncture designed to treat ‘kidney yin deficiency’ or they got the same amount of non-insertive sham acupuncture. The primary outcome was HF score at the end of treatment. Secondary outcomes included quality of life, anxiety, depression, and adverse events. Participants were assessed at 4 weeks, the end of treatment, and then 3 and 6 months after the end of treatment. Intention-to-treat analysis was conducted with linear mixed-effects models.

In total, 327 women were randomly assigned to acupuncture (n = 163) or sham acupuncture (n = 164). At the end of treatment, 16% of participants in the acupuncture group and 13% in the sham group were lost to follow-up. Mean HF scores at the end of treatment period were 15.36 in the acupuncture group and 15.04 in the sham group. No serious adverse events were reported.

The authors concluded that Chinese medicine acupuncture was not superior to non-insertive sham acupuncture for women with moderately severe menopausal HFs.

The trial has several strengths: it includes a large sample size and the patients were adequately blinded to eliminate the effects of expectations. It was published in a top journal, and we can therefore assume that it was properly peer-reviewed. Combined with the evidence from our previous systematic review, this indicates that acupuncture has no effect beyond placebo.

In other words: ACUPUNCTURE IS NOTHING BUT A THEATRICAL PLACEBO.

One does not need to be a clairvoyant to predict that acupuncturists will now find what they perceive as a flaw in the new study and claim that its results were false-negative. Subsequently they will probably conduct their own trial which, because it is wide open to bias, will generate the finding they were hoping for.

This sequence of poor quality positive and high quality negative studies could go on ad infinitum.

This begs the question: how can such wasteful pseudo-research be stopped?

In theory, applications to ethics committees for research that is not aimed at answering open and important questions should get rejected. In practice, however, this is unlikely to happen. In my experience, the main reason preventing such actions is that, when it comes to alternative medicine, ethics committees tend to be too lenient (attempting to be ‘politically correct’), too uninterested (thinking that alternative medicine is not really a serious area of research) and too uninformed (failing to insist on a rigorous assessment of the already available evidence).

Cancer-related fatigue (CRF) is one of the most common symptoms reported by cancer patients, and it is a symptom that is often difficult to treat. As always in such a situation, there are lots of alternative therapies on offer. Yet the evidence for most is flimsy, to put it mildly.

But perhaps there is hope? The very first RCT with a 2016 date to be reviewed on this blog investigated the efficacy of the amino acid jelly Inner Power(®) (IP), a semi-solid, orally administrable dietary supplement containing coenzyme Q10 and L-carnitine, in controlling CRF in breast cancer patients in Japan.

Breast cancer patients with CRF undergoing chemotherapy were randomly assigned to receive IP once daily or regular care for 21 days. The primary endpoint was the change in the worst level of fatigue during the past 24 h (Brief Fatigue Inventory [BFI] item 3 score) from day 1 (baseline) to day 22. Secondary endpoints were change in global fatigue score (GFS; the average of all BFI items), anxiety and depression assessed by the Hospital Anxiety and Depression Scale (HADS), quality of life assessed by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) and EORTC Breast Cancer-Specific QLQ (EORTC QLQ-BR23), and adverse events.

Fifty-nine patients were enrolled in the study, of whom 57 were included in the efficacy analysis. Changes in the worst level of fatigue, GFS, and current feeling of fatigue were significantly different between the intervention and control groups, whereas the change in the average feeling of fatigue was not significantly different between groups. HADS, EORTC QLQ-C30, and EORTC QLQ-BR23 scores were not significantly different between the two groups. No severe adverse events were observed.

The authors concluded that ‘IP may control moderate-severe CRF in breast cancer patients.’

The website of the manufacturer provides the following information on IP:

Inner Power is a functional food that provides various nutrients, such as zinc and copper. Zinc is a nutrient that your body needs to maintain your sense of taste. Zinc is also vital in keeping the skin and mucous membranes healthy and in regulating metabolism of proteins and nucleic acids. Copper helps the body form red blood cells and bones and regulates many enzymes that are found in the body. One pouch of Inner Power each day is the recommended daily serving.

  • Consuming a large amount of the product will not cure any underlying disease or improve your health condition.
  • Do not consume too much of the product because excessive zinc intake may inhibit the absorption of copper.
  • Observe the recommended daily serving of the product. This product should not be given to infants or children.

The recommended daily serving of the product (1 pouch/day) contains 43% of the reference daily intake of zinc and 50% of the reference daily intake of copper. Inner Power is neither categorized as a food for special dietary use nor approved individually by the Ministry of Health, Labour, and Welfare. You should eat well-balanced meals consisting of staple foods, including a main dish and side dishes.

I cannot say that this inspires me with confidence.

What about the trial itself?

To be honest, I am not impressed. The most obvious flaw is, I think, that there was not the slightest attempt to control for placebo effects. As I pointed out so many times before: with the ‘A+B versus B’ design, one can make any old placebo appear to be effective.

The randomized, placebo-controlled, double-blind trial is usually the methodology to test the efficacy of a therapy that carries the least risk of bias. This fact is an obvious annoyance to some alt med enthusiasts, because such trials far too often fail to produce the results they were hoping for.

But there is no need to despair. Here I provide a few simple tips on how to mislead the public with seemingly rigorous trials.

1 FRAUD

The most brutal method for misleading people is simply to cheat. The Germans have a saying, ‘Papier ist geduldig’ (paper is patient), implying that anyone can put anything on paper. Fortunately we currently have plenty of alt med journals which publish any rubbish anyone might dream up. The process of ‘peer-review’ is one of several mechanisms supposed to minimise the risk of scientific fraud. Yet alt med journals are more clever than that! They tend to have a peer-review that rarely involves independent and critical scientists, more often than not you can even ask that you best friend is invited to do the peer-review, and the alt med journal will follow your wish. Consequently the door is wide open to cheating. Once your fraudulent paper has been published, it is almost impossible to tell that something is fundamentally wrong.

But cheating is not confined to original research. You can also apply the method to other types of research, of course. For instance, the authors of the infamous ‘Swiss report’ on homeopathy generated a false positive picture using published systematic reviews of mine by simply changing their conclusions from negative to positive. Simple!

2 PRETTIFICATION

Obviously, outright cheating is not always as simple as that. Even in alt med, you cannot easily claim to have conducted a clinical trial without a complex infrastructure which invariably involves other people. And they are likely to want to have some control over what is happening. This means that complete fabrication of an entire data set may not always be possible. What might still be feasible, however, is the ‘prettification’ of the results. By just ‘re-adjusting’ a few data points that failed to live up to your expectations, you might be able to turn a negative into a positive trial. Proper governance is aimed at preventing his type of ‘mini-fraud’ but fortunately you work in alt med where such mechanisms are rarely adequately implemented.

3 OMISSION

Another very handy method is the omission of aspects of your trial which regrettably turned out to be in disagreement with the desired overall result. In most studies, one has a myriad of endpoints. Once the statistics of your trial have been calculated, it is likely that some of them yield the wanted positive results, while others do not. By simply omitting any mention of the embarrassingly negative results, you can easily turn a largely negative study into a seemingly positive one. Normally, researchers have to rely on a pre-specified protocol which defines a primary outcome measure. Thankfully, in the absence of proper governance, it usually is possible to publish a report which obscures such detail and thus mislead the public (I even think there has been an example of such an omission on this very blog).

4 STATISTICS

Yes – lies, dam lies, and statistics! A gifted statistician can easily find ways to ‘torture the data until they confess’. One only has to run statistical test after statistical test, and BINGO one will eventually yield something that can be marketed as the longed-for positive result. Normally, researchers must have a protocol that pre-specifies all the methodologies used in a trial, including the statistical analyses. But, in alt med, we certainly do not want things to function normally, do we?

5 TRIAL DESIGNS THAT CANNOT GENERATE A NEGATIVE RESULT

All the above tricks are a bit fraudulent, of course. Unfortunately, fraud is not well-seen by everyone. Therefore, a more legitimate means of misleading the public would be highly desirable for those aspiring alt med researchers who do not want to tarnish their record to their disadvantage. No worries guys, help is on the way!

The fool-proof trial design is obviously the often-mentioned ‘A+B versus B’ design. In such a study, patients are randomized to receive an alt med treatment (A) together with usual care (B) or usual care (B) alone. This looks rigorous, can be sold as a ‘pragmatic’ trial addressing a real-fife problem, and has the enormous advantage of never failing to produce a positive result: A+B is always more than B alone, even if A is a pure placebo. Such trials are akin to going into a hamburger joint for measuring the calories of a Big Mac without chips and comparing them to the calories of a Big Mac with chips. We know the result before the research has started; in alt med, that’s how it should be!

I have been banging on about the ‘A+B versus B’ design often enough, but recently I came across a new study design used in alt med which is just as elegantly misleading. The trial in question has a promising title: Quality-of-life outcomes in patients with gynecologic cancer referred to integrative oncology treatment during chemotherapy. Here is the unabbreviated abstract:

OBJECTIVE:

Integrative oncology incorporates complementary medicine (CM) therapies in patients with cancer. We explored the impact of an integrative oncology therapeutic regimen on quality-of-life (QOL) outcomes in women with gynecological cancer undergoing chemotherapy.

PATIENTS AND METHODS:

A prospective preference study examined patients referred by oncology health care practitioners (HCPs) to an integrative physician (IP) consultation and CM treatments. QOL and chemotherapy-related toxicities were evaluated using the Edmonton Symptom Assessment Scale (ESAS) and Measure Yourself Concerns and Wellbeing (MYCAW) questionnaire, at baseline and at a 6-12-week follow-up assessment. Adherence to the integrative care (AIC) program was defined as ≥4 CM treatments, with ≤30 days between each session.

RESULTS:

Of 128 patients referred by their HCP, 102 underwent IP consultation and subsequent CM treatments. The main concerns expressed by patients were fatigue (79.8 %), gastrointestinal symptoms (64.6 %), pain and neuropathy (54.5 %), and emotional distress (45.5 %). Patients in both AIC (n = 68) and non-AIC (n = 28) groups shared similar demographic, treatment, and cancer-related characteristics. ESAS fatigue scores improved by a mean of 1.97 points in the AIC group on a scale of 0-10 and worsened by a mean of 0.27 points in the non-AIC group (p = 0.033). In the AIC group, MYCAW scores improved significantly (p < 0.0001) for each of the leading concerns as well as for well-being, a finding which was not apparent in the non-AIC group.

CONCLUSIONS:

An IP-guided CM treatment regimen provided to patients with gynecological cancer during chemotherapy may reduce cancer-related fatigue and improve other QOL outcomes.

A ‘prospective preference study’ – this is the design the world of alt med has been yearning for! Its principle is beautiful in its simplicity. One merely administers a treatment or treatment package to a group of patients; inevitably some patients take it, while others don’t. The reasons for not taking it could range from lack of perceived effectiveness to experience of side-effects. But never mind, the fact that some do not want your treatment provides you with two groups of patients: those who comply and those who do not comply. With a bit of skill, you can now make the non-compliers appear like a proper control group. Now you only need to compare the outcomes and BOB IS YOUR UNCLE!

Brilliant! Absolutely brilliant!

I cannot think of a more deceptive trial-design than this one; it will make any treatment look good, even one that is a mere placebo. Alright, it is not randomized, and it does not even have a proper control group. But it sure looks rigorous and meaningful, this ‘prospective preference study’!

The two dietary supplements chondroitin and glucosamine have been around for some time. They are being promoted mostly for osteoarthritis; some claim that they reduce pain, others even believe that they restore the damaged cartilage and thus reverse the disease process. But neither for a symptomatic nor causal therapy has the evidence so far been truly convincing. A new trial might change this situation.

This study compared the efficacy and safety of chondroitin sulfate plus glucosamine hydrochloride (CS+GH) versus celecoxib in patients with knee osteoarthritis and severe pain.

 TheDouble-blind Multicentre Osteoarthritis interVEntion trial with SYSADOA’ (MOVES) was conducted in France, Germany, Poland and Spain and evaluated treatment with CS+GH versus celecoxib in 606 patients with Kellgren and Lawrence grades 2–3 knee osteoarthritis and moderate-to-severe pain (Western Ontario and McMaster osteoarthritis index (WOMAC) score ≥301; 0–500 scale). Patients were randomised to receive 400 mg CS plus 500 mg GH three times a day or 200 mg celecoxib every day for 6 months. The primary outcome was the mean decrease in WOMAC pain from baseline to 6 months. Secondary outcomes included WOMAC function and stiffness, visual analogue scale for pain, presence of joint swelling/effusion, rescue medication consumption, Outcome Measures in Rheumatology Clinical Trials and Osteoarthritis Research Society International (OMERACT-OARSI) criteria and EuroQoL-5D.

The results show that the adjusted mean change (95% CI) in WOMAC pain was −185.7 (−200.3 to −171.1) (50.1% decrease) with CS+GH and −186.8 (−201.7 to −171.9) (50.2% decrease) with celecoxib, meeting the non-inferiority margin of −40: −1.11 (−22.0 to 19.8; p=0.92). All sensitivity analyses were consistent with that result. At 6 months, 79.7% of patients in the combination group and 79.2% in the celecoxib group fulfilled OMERACT-OARSI criteria. Both groups elicited a reduction >50% in the presence of joint swelling; a similar reduction was seen for effusion. No differences were observed for the other secondary outcomes. Adverse events were rare and similarly distributed between groups.

The authors concluded that CS+GH has comparable efficacy to celecoxib in reducing pain, stiffness, functional limitation and joint swelling/effusion after 6 months in patients with painful knee osteoarthritis, with a good safety profile.

This is a rigorous trial, and I do trust its findings. However, I am not entirely sure what they actually mean: is CS+GH as effective or as ineffective as the COX-2-inhibitor celecoxib? The most recent meta-analysis on the subject found that diclofenac (150 mg/day) was likely to be more effective in alleviating pain than celecoxib (200 mg/day). But that does, of course, not necessarily imply that celecoxib is ineffective.

The other big issue here is safety. COX-2-inhibitors had a bad press because of the risk of cardiovascular side-effects. In comparison, the CS+GH supplement is an almost risk-free alternative. Bearing in mind that we are dealing with long-term treatments here, I think the results of this study might persuade me, had I to choose between these two treatments, to opt for the dietary supplement.

The authors of a recent paper inform us that Reiki is a Japanese system of energy healing that has been used for over 2 500 years. It involves the transfer of energy from the practitioner to the receiver, which promotes healing, and can be done by either contact or non-contact methods. Both the receiver and the practitioner may feel the energy in various forms (warmth, cold, tingling, vibration, pulsations and/or floating sensations). Reiki can also be self-administered if one is a Reiki practitioner. Reiki is mainly used to address stress, anxiety, and pain reduction while also promoting a sense of well-being and improving quality of life.

Such statements should make us weary: what is presented here as fact is nothing more than conjecture – and very, very implausible conjecture too. Anyone who writes stuff like this in the introduction of a scientific paper is, in my view, unlikely to be objective and could be well on the way to present some nasty piece of pseudo-science.

But I am, of course, pre-judging the issue; let’s have a quick look at the article itself.

The purpose of this study was to determine the effects of a 20-week structured self-Reiki program on stress reduction and relaxation in college students. Students were recruited from Stockton University and sessions were conducted in the privacy of their residence. Twenty students completed the entire study consisting of 20 weeks of self-Reiki done twice weekly. Each participant completed a Reiki Baseline Credibility Scale, a Reiki Expectancy Scale, and a Perceived Stress Scale (PSS) after acceptance into the study. The PSS was completed every four weeks once the interventions were initiated. A global assessment questionnaire was completed at the end of the study. Logs summarizing the outcome of each session were submitted at the end of the study.

With the exception of three participants, participants believed that Reiki is a credible technique for reducing stress levels. Except for two participants, participants agreed that Reiki would be effective in reducing stress levels. All participants experienced stress within the month prior to completing the initial PSS. There was a significant reduction in stress levels from pre-study to post-study. There was a correlation between self-rating of improvement and final PSS scores. With one exception, stress levels at 20 weeks did not return to pre-study stress levels.

The authors concluded that this study supports the hypothesis that the calming effect of Reiki may be achieved through the use of self-Reiki.

QED – my suspicions were fully confirmed. This study shows precisely nothing, and it certainly does not support any hypothesis regarding Reiki.

If we recruited 20 volunteers who were sufficiently gullible to believe that watching an ice-cube slowly melting in the kitchen sink, or anything else that we can think of, has profound effects on their vital energy, or chi, or karma, or anything else, we would almost certaily generate similar results.

My conclusion is therefore very different from those of the original authors: THIS STUDY SUPPORTS THE HYPOTHESIS THAT GULLIBLE PEOPLE CAN BE EASILY MISLEAD ABOUT BOGUS THERAPIES WITH PSEUDO-SCIENTIFIC STUDIES BY IRRESPONSIBLE WOULD-BE SCIENTISTS.

No, I kid you not!

This abstract was actually published in the leading chiro-journal. The authors include three professors from the Canadian Memorial Chiropractic College, Research, Toronto, Canada. Its title is impressive but made my alarm bells ring a bit:

A Randomized Pragmatic Clinical Trial of Chiropractic Care for Headaches With and Without a Self-Acupressure Pillow.

And the actual texts does not disappoint those looking for of pure pseudo-science:

The purpose of this study was to determine if the addition of a self-acupressure pillow (SAP) to typical chiropractic treatment results in significantly greater improvement in tension-type and cervicogenic headache sufferers.

METHODS:

A pragmatic randomized clinical trial was conducted in a chiropractic college teaching clinic. Thirty-four subjects, including tension-type and cervicogenic headache sufferers, 21 to 60 years of age, male or female, completed the study. Group A (n = 15) received typical chiropractic care only (manual therapy and exercises), and group B (n = 19) received typical chiropractic care with daily home use of the SAP. The intervention period was 4 weeks. The main outcome measure was headache frequency. Satisfaction and relief scores were obtained from subjects in the SAP group. Analysis of variance was used to analyze the intergroup comparisons.

RESULTS:

Owing to failure of randomization to produce group equivalence on weekly headache frequency, analysis of covariance was performed showing a trend (P = .07) favoring the chiropractic-only group; however, this was not statistically significant. Group A obtained a 46% reduction of weekly headache frequency (t = 3.1, P = .002; d = 1.22). The number of subjects in group A achieving a reduction in headaches greater than 40% was 71%, while for group B, this was 28%. The mean benefit score (0-3) in group B of the use of the SAP was 1.2 (.86). The mean satisfaction rating of users of the SAP was 10.4 (2.7) out of 15 (63%).

CONCLUSION:

This study suggests that chiropractic care may reduce frequency of headaches in patients with chronic tension-type and cervicogenic headache. The use of a self-acupressure pillow (Dr Zaxx device) may help those with headache and headache pain relief as well as producing moderately high satisfaction with use.

Where to begin?

Perhaps it is best, if I simply concentrated on the bizarre research question: is chiropractic care plus the largely uncontrolled use of an ‘acupressure cushion’ better than chiropractic care alone? To savour the lunacy of it, we need to consider that:

  • chiropractic is not plausible;
  • chiropractic care is not proven to be effective for headaches;
  • acupressure is not plausible;
  • acupressure is not proven to be effective;
  • a self-administered acupressure cushion is also unproven and even less plausible;

This, I fear, renders the study one of the most nonsensical trials I have seen for a very long time. To make the bonanza in pseudo-science complete, the article is supplemented with a most bizarre conclusion about the effectiveness of chiropractic (which, of cause, cannot be examined in a trial of chiro vs chiro).

All this leads me to fear that:

  • the best journal of chiropractic is rubbish;
  • a professorship in a chiro school may not mean that the professor has the slightest idea about research methodology;
  • chiropractors will try to squeeze a conclusion that is favourable for their trade even out of a dead horse.

The aim of this study was to evaluate clinical effectiveness of Alexander Technique lessons or acupuncture versus usual care for persons with chronic, nonspecific neck pain.

Patients with neck pain lasting at least 3 months, a score of at least 28% on the Northwick Park Questionnaire (NPQ) for neck pain and associated disability, and no serious underlying pathology were randomised to receive 12 acupuncture sessions or 20 one-to-one Alexander lessons (both 600 minutes total) plus usual care versus usual care alone. The NPQ score at 0, 3, 6, and 12 months (primary end point) and Chronic Pain Self-Efficacy Scale score, quality of life, and adverse events (secondary outcomes) served as outcome measures. 517 patients were recruited. Their median duration of neck pain was 6 years. Mean attendance was 10 acupuncture sessions and 14 Alexander lessons. Between-group reductions in NPQ score at 12 months versus usual care were 3.92 percentage points for acupuncture (95% CI, 0.97 to 6.87 percentage points) (P = 0.009) and 3.79 percentage points for Alexander lessons (CI, 0.91 to 6.66 percentage points) (P = 0.010). The 12-month reductions in NPQ score from baseline were 32% for acupuncture and 31% for Alexander lessons. Participant self-efficacy improved for both interventions versus usual care at 6 months (P < 0.001) and was significantly associated (P < 0.001) with 12-month NPQ score reductions (acupuncture, 3.34 percentage points [CI, 2.31 to 4.38 percentage points]; Alexander lessons, 3.33 percentage points [CI, 2.22 to 4.44 percentage points]). No reported serious adverse events were considered probably or definitely related to either intervention.

The authors drew the following conclusions: acupuncture sessions and Alexander Technique lessons both led to significant reductions in neck pain and associated disability compared with usual care at 12 months. Enhanced self-efficacy may partially explain why longer-term benefits were sustained.

Where to begin? There is much to be criticised about this study!

For starters, the conclusions are factually wrong. They should read “acupuncture sessions plus usual care and Alexander Technique lessons plus usual care both led to significant reductions in neck pain and associated disability compared with usual care at 12 months. Enhanced self-efficacy may partially explain why longer-term benefits were sustained.

On this blog, we have repeatedly discussed the ‘A+B versus B’ study design and the fact that it cannot provide information about cause and effect because it fails to control for placebo effects and the extra attention, time and empathy (for instance here and here). I suspect that this is the reason why it is so very popular in alternative medicine. It can make ineffective therapies appear to be effective.

Another point is a more clinical concern. Neck pain is not a disease, it is a symptom. In medicine we should, whenever possible, try to treat the cause of the underlying condition and not the symptom. Acupuncture is at best a symptomatic treatment. Usual care is often not very effective because we normally fail to see the cause of neck pain. In my view, alternative treatments should either be tested against placebo or sham interventions or against optimal care.

What is optimal care for nonspecific neck pain? As its causes are often unclear and usually multifactorial, the optimal treatment needs to be multifactorial (one could also call it holistic) as well. The causes often range from poor ergometric conditions at work to muscular tension, stress, psychological problems etc. Thus optimal care would be a team work tailor-made for each patient possibly including physiotherapists, pain specialists, clinical psychologists, orthopaedic surgeons etc.

My points here are:

  • neither acupuncture nor Alexander technique take account of this complexity,
  • they claim to be holistic but, in fact, this turns out to be merely a good sales-slogan,
  • usual care is usually no good,
  • if pragmatic trials using the ‘A+B versus B’ design make any sense at all, they should employ not usual care but optimal care for the control group.

In the end, we are left with a study that looks fairly rigorous at first sight, but that really tells us next to nothing (except that dedicating 600 minutes to patients in pain is not without effect). I am truly surprised that a top journal like the Annals of Internal Medicine decided to publish it.

Alternative medicine encompasses many bizarre treatments, but one of the weirdest must be craniosacral therapy (CST). The assumptions underlying CTS are:

  1. light manual touch of the head moves the joints of the cranium;
  2. this movement stimulates the flow of the cerebrospinal fluid;
  3. the enhanced flow has profound and positive effects on human health.

None of these assumptions are supported by evidence. In fact, they are as implausible as assumptions in alternative medicine get.

CST was developed by the osteopath John Upledger, D.O. in the 1970s, as an offshoot osteopathy in the cranial field, or cranial osteopathy, which was developed in the 1930s by William Garner Sutherland. Apart from this confusing terminology, we are also confronted with a confusing array of therapeutic claims; CST seems to be recommended for most conditions.

And the evidence? As good as none!

This is why any new trial is worth a mention. A recent study tested CST in comparison to sham treatment in chronic non-specific neck pain patients. 54 blinded patients were randomized to either 8 weekly units of CST or light touch sham treatment. Outcomes were assessed before and after treatment (week 8) and a further 3 months later (week 20). The primary outcome was pain intensity on a visual analogue scale; secondary outcomes included pain on movement, pressure pain sensitivity, functional disability, health-related quality of life, well-being, anxiety, depression, stress perception, pain acceptance, body awareness, patients’ global impression of improvement and safety.

In comparison to sham, CST patients reported significant and clinically relevant effects on pain intensity at week 8 as well as at week 20. Minimal clinically important differences in pain intensity at week 20 were reported by 78% of the CST patients, while 48% even had substantial clinical benefit. Significant differences at week 8 and 20 were also found for pain on movement, functional disability, physical quality of life and patients’ global improvement. Pressure pain sensitivity and body awareness were significantly improved only at week 8; anxiety only at week 20. No serious adverse events were reported.

The authors from the Department of Internal and Integrative Medicine, University of Duisburg-Essen and the Institute of Integrative Medicine, University of Witten/Herdecke, Germany, concluded that CST was both specifically effective and safe in reducing neck pain intensity and may improve functional disability and quality of life up to 3 months post intervention.

Oddly, this is not even close to the conclusion I am going to draw: inadequate control for placebo and other non-specific effects generated a false-positive result.

Who is correct?

I suggest we wait for an independent replication to decide.

Bach flower remedies (BFR) are amazingly popular. They have been the subject of posts on this blog before (see here and here, for instance). They are as dilute as most homeopathic remedies and just as implausible. All the rigorous trials that have tested BFR have so far been squarely negative. Here is a truly surprising new study where BFR was administered externally which would seem to make an effect not more but less likely.

A randomized, placebo-controlled clinical trial was conducted with the aim of evaluating the effectiveness of a cream based on BFR for symptoms of carpal tunnel syndrome. Forty-three patients with mild to moderate carpal tunnel syndrome during their “waiting” time for surgical option were randomized into 3 parallel groups: Placebo (n = 14), blinded BFR (n = 16), and non-blinded BFR (n = 13). These groups were treated during 21 days with topical placebo or a cream based on BFR.

Significant improvements were observed on self-reported symptom severity and pain intensity favorable to BFR groups with large effect sizes. In addition, all signs observed during the clinical exam showed significant improvements among the groups as well as symptoms of pain, night pain, and tingling, also with large effect sizes (φ > 0.5). Finally, there were significant differences between the blinded and non-blinded BFR groups for signs and pain registered in clinical exam but not in self-reports.

The Cuban authors of this study concluded that the proposed BFR cream could be an effective intervention in the management of mild and moderate carpal tunnel syndrome, reducing the severity symptoms and providing pain relief.

This is truly amazing, not least because there is not much that we can offer such patients except for surgery which usually is very successful. The current Cochrane review of non-surgical interventions for carpal tunnel syndrome shows significant short-term benefit from oral steroids, splinting, ultrasound, yoga and carpal bone mobilisation. Other non-surgical treatments do not produce significant benefit. More trials are needed to compare treatments and ascertain the duration of benefit.

What then should we make of the new study?

I have to admit, I am not sure. It was published in one of the worst journals I know which has attracted our attention on this blog before. It was published by authors from Cuba who I know nothing about. More importantly, its findings sound far too good to be true.

If I had been the editor in charge, I would have asked for the original data and had them re-analysed by an independent statistician. As we cannot do that, our only option is to apply common sense and wait for an independent replication before conceding that BFR are effective.

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