MD, PhD, FMedSci, FSB, FRCP, FRCPEd

false positive

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A new RCT of Reiki healing has been published by US authors from the following institutions: Union Institute & University, Psychology Program, Brattleboro, VT, Coyote Institute, Augusta and Bangor, ME, Eastern Maine Medical Center and Acadia Hospital, Bangor, ME, University of New England College of Osteopathic Medicine, Biddeford, ME, Coyote Institute, Orono, ME. The purpose of this study was to determine if 30 minutes of healing touch could reduce burnout in community mental health clinicians.

The authors utilized a crossover design to explore the efficacy of Reiki versus sham Reiki, a pseudo treatment performed by volunteers who had no experience with Reiki and pretended to be healers vis-à-vis the patients. This sham control intervention was designed to mimic true Reiki.

Subjects were randomized to whether they started with Reiki or sham. The Maslach Burnout Inventory-Human Services Survey (MBI-HSS) and the Measure Your Medical Outcome Profile Version 2 (MYMOP-2) were used as outcome measures. Multilevel modeling was used to represent the relations among variables.

The results showed that real Reiki was significantly better than sham Reiki in reducing burnout among community mental health clinicians. Reiki was significant in reducing depersonalization, but only among single people. Reiki reduced the primary symptom on the MYMOP also only among single people.

The authors concluded that the effects of Reiki were differentiated from sham Reiki. Reiki could be helpful in community mental health settings for the mental health of the practitioners.

My team has published on Reiki (see here and here, for instance), and on this blog I have repeatedly been expressed my doubts that Reiki is more than an elaborate placebo (see here and here, for instance). Do these new results mean that I need to eat my words and henceforth praise the wonders of Reiki? No, I don’t think so!

Having conducted studies on ‘energy healing’ myself, I know only too well of the many pitfalls and possibilities of generating false-positive findings with such research. This new study has many flaws, but we need not look far to find the reason for the surprising and implausible finding. Here is my explanation why this study suggests one placebo to be superior to another placebo.

The researchers had to recruit 16 Reiki healers and several non-Reiki volunteers to perform the interventions on the small group of patients. It goes without saying that the Reiki healers were highly motivated to demonstrate the value of their therapy. This means they (unintentionally?) used verbal and non-verbal communication to maximise the placebo effect of their treatment. The sham healers, of course, lacked such motivation. In my view, this seemingly trivial difference alone is capable of producing the false-positive result above.

There are, of course, ways of minimising the danger of such confounding. In our own study of ‘energy healing’ with sham healers as controls, for instance, we instructed both the healers and the sham healers to abstain from all communication with their patients, we filmed each session to make sure, and we asked each patient to guess which treatment they had received. None of these safeguards were incorporated in the present study – I wonder why!

The press officers of journals like to send out press-releases of articles which are deemed to be particularly good and important. Sadly, it is not often that articles on alternative medicine fulfil these criteria. I was therefore excited to receive this press-release which seemed encouraging, to say the least:

Medical evidence supports the potential for acupuncture to be significantly more effective in the treatment of dermatologic conditions such as dermatitis, pruritus, and urticaria than alternative treatment options, “placebo acupuncture,” or no treatment, according to a review of the medical literature published in The Journal of Alternative and Complementary Medicine, a peer-reviewed publication from Mary Ann Liebert, Inc., publishers

The abstract was equally promising:

Objectives: Acupuncture is a form of Traditional Chinese Medicine that has been used to treat a broad range of medical conditions, including dermatologic disorders. This systematic review aims to synthesize the evidence on the use of acupuncture as a primary treatment modality for dermatologic conditions.

Methods: A systematic search of MEDLINE, EMBASE, and the Cochrane Central Register was performed. Studies were limited to clinical trials, controlled studies, case reports, comparative studies, and systematic reviews published in the English language. Studies involving moxibustion, electroacupuncture, or blood-letting were excluded.

Results: Twenty-four studies met inclusion criteria. Among these, 16 were randomized controlled trials, 6 were prospective observational studies, and 2 were case reports. Acupuncture was used to treat atopic dermatitis, urticaria, pruritus, acne, chloasma, neurodermatitis, dermatitis herpetiformis, hyperhidrosis, human papillomavirus wart, breast inflammation, and facial elasticity. In 17 of 24 studies, acupuncture showed statistically significant improvements in outcome measurements compared with placebo acupuncture, alternative treatment options, and no intervention.

Conclusions: Acupuncture improves outcome measures in the treatment of dermatitis, chloasma, pruritus, urticaria, hyperhidrosis, and facial elasticity. Future studies should ideally be double-blinded and standardize the control intervention.

One has to read the actual full text article to understand that the evidence presented here is dodgy to the extreme. In fact, one has to go into the tedious details of the methods section to find the reasons why:  All searches were limited to clinical trials, controlled studies, case reports, comparative studies, and systematic reviews published in the English language.

There are many more weaknesses of this review, but the inclusion of uncontrolled studies and even anecdotes is, in my view, a virtual death sentence to its credibility. It means that no general conclusions about the effectiveness of acupuncture, such as the authors have decided to make, are possible.

Such overt exaggerations are sadly no rarities in the realm of alternative medicine.  I think, this begs a number of serious questions:

  1. Does this cross the line between flawed research and scientific misconduct?
  2. Why did the reviewers not pick up these flaws?
  3. Why did the editor pass this article for publication?
  4. How can the publisher tolerate such dubious behaviour?
  5. Should this journal (which I have commented on before here and which is one with the highest impact factor of all the alt med journals) be de-listed from Medline?

I don’t think that we will get answers from the people responsible for this disgrace, but I would like to learn my readers’ opinions.

Chiropractors are back pain specialists, they say. They do not pretend to treat non-spinal conditions, they claim.

If such notions were true, why are so many of them still misleading the public? Why do many chiropractors pretend to be primary care physicians who can take care of most illnesses regardless of any connection with the spine? Why do they continue to happily promote bogus treatments? Why do chiropractors, for instance, claim they can treat gastrointestinal diseases?

This recent narrative review of the literature, for example, was aimed at summarising studies describing the management of disorders of the gastrointestinal (GI) tract using ‘chiropractic therapy’ broadly defined here as spinal manipulation therapy, mobilizations, soft tissue therapy, modalities and stretches.

Twenty-one articles were found through searching the published literature to meet the authors’ inclusion criteria. The retrieved articles included case reports to clinical trials to review articles. The majority of articles chronicling patient experiences under chiropractic care reported that they experienced mild to moderate improvements in GI symptoms. No adverse effects were reported.

From this, the authors concluded that chiropractic care can be considered as an adjunctive therapy for patients with various GI conditions providing there are no co-morbidities.

I think, we would need to look for a long time to find an article with conclusions that are more ridiculous, false and unethical than these.

The old adage applies: rubbish in, rubbish out. If we include unreliable reports such as anecdotes, our finding will be unreliable as well. If we do not make this mistake and conduct a proper systematic review, we will arrive at very different conclusions. My own systematic review, for instance, of controlled clinical trials drew the following conclusion: There is no supportive evidence that chiropractic is an effective treatment for gastrointestinal disorders.

That probably says it all. I only want to add a short question: SHOULD THIS LATEST CHIROPRACTIC ATTEMPT TO MISLEAD THE PUBLIC BE CONSIDERED ‘SCIENTIFIC MISCONDUCT’ OR ‘FRAUD’?

The last time I had contact with Dr Fisher was when he fired me from the editorial board of his journal ‘Homeopathy’. He did that by sending me the following letter:

Dear Professor Ernst,

This is to inform you that you have been removed from the Editorial Board of Homeopathy.  The reason for this is the statement you published on your blog on Holocaust Memorial Day 2013 in which you smeared homeopathy and other forms of complementary medicine with a ‘guilt by association’ argument, associating them with the Nazis.

I should declare a personal interest….[Fisher goes on to tell a story which is personal and which I therefore omit]…  I mention this only because it highlights the absurdity of guilt by association arguments.

Sincerely

Peter Fisher Editor-in-Chief, Homeopathy

I did not expect to have any more dealings with him after this rather unpleasant encounter. But, as it turns out, I recently did have a further encounter.

When the BMJ invited me to write a debate article about the question whether homeopathy should continue to be available on the NHS, I accepted (with some reservations, I hasten to add). At the time, I did not know who would do the ‘other side’ of this debate. It turned out to be Peter Fisher, and our two articles have just been published.

As one would expect from a good journal, the articles were both peer reviewed. One of the peer-reviewers of my piece was most scathing of it essentially claiming that it was entirely worthless. Feeling that this was a bit harsh and very impolite, I was keen to see who this reviewer had been; it was none other than Andrew Vickers. This is remarkable because Vickers had not only published several homeopathic papers with Fisher, but also had been in the employment of the ‘Royal London Homeopathic Hospital’ under Fisher. To the best of my knowledge, his conflicts of interested had not been disclosed. I did point that out to the BMJ, but they seemed to think nothing of it.

Anyway, I was pleased to eventually (the whole procedure took many months) see the articles published, but at the same time somewhat irritated by Fisher’s piece. It contained plenty of misleading information that the peer-reviewers obviously had failed to correct. Here is a small sample from Fishers piece:

… recent overviews have had more favourable conclusions, including a health technology assessment commissioned by the Swiss federal government that concluded that homeopathy is “probably” effective for upper respiratory tract infections and allergies.

Readers interested in the clinical evidence can access the CORE-HOM database of clinical research in homeopathy free of charge (www.carstens-stiftung.de/core-hom). It includes 1117 clinical trials of homeopathy, of which about 300 are randomised controlled trials.

In the podcast that accompanies the articles Fisher insists that, on this database, there are well over 300 RCT, and I had to admit that this was new to me. Keen to learn more, I registered with the database and had a look. What I found startled me. True, the database does claim that almost 500 RCTs are available, but just a very superficial scrutiny of these studies reveals that

  • some are not truly randomised,
  • some are not even clinical trials,
  • the list includes dual publications, re-analyses of already published studies as well as aborted trials,
  • many have never been peer-reviewed,
  • many are not double-blind,
  • many are not placebo controlled,
  • the majority are of poor methodological quality.

As to the other thing mentioned in the above excerpt from Fisher’s article, the famous ‘health technology assessment commissioned by the Swiss federal government’, I can refer my readers to a blog post by J W Nienhuys which probably says it all, if not, there is plenty more criticism of this report available on the Internet.

My conclusion from all this?

THE QUEEN’S HOMEOPATH USES ARGUMENTS THAT SEEM JUST AS BOGUS AS HOMEOPATHY ITSELF.

A paper entitled ‘Real world research: a complementary method to establish the effectiveness of acupuncture’ caught my attention recently. I find it quite remarkable and think it might stimulate some discussion on this blog.  Here is its abstract:

Acupuncture has been widely used in the management of a variety of diseases for thousands of years, and many relevant randomized controlled trials have been published. In recent years, many randomized controlled trials have provided controversial or less-than-convincing evidence that supports the efficacy of acupuncture. The clinical effectiveness of acupuncture in Western countries remains controversial.

Acupuncture is a complex intervention involving needling components, specific non-needling components, and generic components. Common problems that have contributed to the equivocal findings in acupuncture randomized controlled trials were imperfections regarding acupuncture treatment and inappropriate placebo/sham controls. In addition, some inherent limitations were also present in the design and implementation of current acupuncture randomized controlled trials such as weak external validity. The current designs of randomized controlled trials of acupuncture need to be further developed. In contrast to examining efficacy and adverse reaction in a “sterilized” environment in a narrowly defined population, real world research assesses the effectiveness and safety of an intervention in a much wider population in real world practice. For this reason, real world research might be a feasible and meaningful method for acupuncture assessment. Randomized controlled trials are important in verifying the efficacy of acupuncture treatment, but the authors believe that real world research, if designed and conducted appropriately, can complement randomized controlled trials to establish the effectiveness of acupuncture. Furthermore, the integrative model that can incorporate randomized controlled trial and real world research which can complement each other and potentially provide more objective and persuasive evidence.

In the article itself, the authors list seven criteria for what they consider good research into acupuncture:

  1. Acupuncture should be regarded as complex and individualized treatment;
  2. The study aim (whether to assess the efficacy of acupuncture needling or the effectiveness of acupuncture treatment) should be clearly defined and differentiated;
  3. Pattern identification should be clearly specified, and non-needling components should also be considered;
  4. The treatment protocol should have some degree of flexibility to allow for individualization;
  5. The placebo or sham acupuncture should be appropriate: knowing “what to avoid” and “what to mimic” in placebos/shams;
  6. In addition to “hard evidence”, one should consider patient-reported outcomes, economic evaluations, patient preferences and the effect of expectancy;
  7. The use of qualitative research (e.g., interview) to explore some missing areas (e.g., experience of practitioners and patient-practitioner relationship) in acupuncture research.

Furthermore, the authors list the advantages of their RWR-concept:

  1. In RWR, interventions are tailored to the patients’ specific conditions, in contrast to standardized treatment. As a result, conclusions based on RWR consider all aspects of acupuncture that affect the effectiveness.
  2. At an operational level, patients’ choice of the treatment(s) decreases the difficulties in recruiting and retaining patients during the data collection period.
  3. The study sample in RWR is much more representative of the real world situation (similar to the section of the population that receives the treatment). The study, therefore, has higher external validity.
  4. RWR tends to have a larger sample size and longer follow-up period than RCT, and thus is more appropriate for assessing the safety of acupuncture.

The authors make much of their notion that acupuncture is a COMPLEX INTERVENTION; specifically they claim the following: Acupuncture treatment includes three aspects: needling, specific non-needling components drove by acupuncture theory, and generic components not unique to acupuncture treatment. In addition, acupuncture treatment should be performed on the basis of the patient condition and traditional Chinese medicine (TCM) theory.

There is so much BS here that it is hard to decide where to begin refuting. As the assumption of acupuncture or other alternative therapies being COMPLEX INTERVENTIONS (and therefore exempt from rigorous tests) is highly prevalent in this field, let me try to just briefly tackle this one.

The last time I saw a patient and prescribed a drug treatment I did all of the following:

  • I greeted her, asked her to sit down and tried to make her feel relaxed.
  • I first had a quick chat about something trivial.
  • I then asked why she had come to see me.
  • I started to take notes.
  • I inquired about the exact nature and the history of her problem.
  • I then asked her about her general medical history, family history and her life-style.
  • I also asked about any psychological problems that might relate to her symptoms.
  • I then conducted a physical examination.
  • Subsequently we discussed what her diagnosis might be.
  • I told her what my working diagnosis was.
  • I ordered a few tests to either confirm or refute it and explained them to her.
  • We decided that she should come back and see me in a few days when her tests had come back.
  • In order to ease her symptoms in the meanwhile, I gave her a prescription for a drug.
  • We discussed this treatment, how and when she should take it, adverse effects etc.
  • We also discussed other therapeutic options, in case the prescribed treatment was in any way unsatisfactory.
  • I reassured her by telling her that her condition did not seem to be serious and stressed that I was confident to be able to help her.
  • She left my office.

The point I am trying to make is: prescribing an entirely straight forward drug treatment is also a COMPLEX INTERVENTION. In fact, I know of no treatment that is NOT complex.

Does that mean that drugs and all other interventions are exempt from being tested in rigorous RCTs? Should we allow drug companies to adopt the RWR too? Any old placebo would pass that test and could be made to look effective using RWR. In the example above, my compassion, care and reassurance would alleviate my patient’s symptoms, even if the prescription I gave her was complete rubbish.

So why should acupuncture (or any other alternative therapy) not be tested in proper RCTs? I fear, the reason is that RCTs might show that it is not as effective as its proponents had hoped. The conclusion about the RWR is thus embarrassingly simple: proponents of alternative medicine want double standards because single standards would risk to disclose the truth.

One could define alternative medicine by the fact that it is used almost exclusively for conditions for which conventional medicine does not have an effective and reasonably safe cure. Once such a treatment has been found, few patients would look for an alternative.

Alzheimer’s disease (AD) is certainly one such condition. Despite intensive research, we are still far from being able to cure it. It is thus not really surprising that AD patients and their carers are bombarded with the promotion of all sorts of alternative treatments. They must feel bewildered by the choice and all too often they fall victim to irresponsible quacks.

Acupuncture is certainly an alternative therapy that is frequently claimed to help AD patients. One of the first websites that I came across, for instance, stated boldly: acupuncture improves memory and prevents degradation of brain tissue.

But is there good evidence to support such claims? To answer this question, we need a systematic review of the trial data. Fortunately, such a paper has just been published.

The objective of this review was to assess the effectiveness and safety of acupuncture for treating AD. Eight electronic databases were searched from their inception to June 2014. Randomized clinical trials (RCTs) with AD treated by acupuncture or by acupuncture combined with drugs were included. Two authors extracted data independently.

Ten RCTs with a total of 585 participants were included in a meta-analysis. The combined results of 6 trials showed that acupuncture was better than drugs at improving scores on the Mini Mental State Examination (MMSE) scale. Evidence from the pooled results of 3 trials showed that acupuncture plus donepezil was more effective than donepezil alone at improving the MMSE scale score. Only 2 trials reported the incidence of adverse reactions related to acupuncture. Seven patients had adverse reactions related to acupuncture during or after treatment; the reactions were described as tolerable and not severe.

The Chinese authors of this review concluded that acupuncture may be more effective than drugs and may enhance the effect of drugs for treating AD in terms of improving cognitive function. Acupuncture may also be more effective than drugs at improving AD patients’ ability to carry out their daily lives. Moreover, acupuncture is safe for treating people with AD.

Anyone reading this and having a friend or family member who is affected by AD will think that acupuncture is the solution and warmly recommend trying this highly promising option. I would, however, caution to remain realistic. Like so very many systematic reviews of acupuncture or other forms of TCM that are currently flooding the medical literature, this assessment of the evidence has to be taken with more than just a pinch of salt:

  • As far as I can see, there is no biological plausibility or mechanism for the assumption that acupuncture can do anything for AD patients.
  • The abstract fails to mention that the trials were of poor methodological quality and that such studies tend to generate false-positive findings.
  • The trials had small sample sizes.
  • They were mostly not blinded.
  • They were mostly conducted in China, and we know that almost 100% of all acupuncture studies from that country draw positive conclusions.
  • Only two trials reported about adverse effects which is, in my view, a sign of violation of research ethics.

As I already mentioned, we are currently being flooded with such dangerously misleading reviews of Chinese primary studies which are of such dubious quality that one could do probably nothing better than to ignore them completely.

Isn’t that a bit harsh? Perhaps, but I am seriously worried that such papers cause real harm:

  • They might motivate some to try acupuncture and give up conventional treatments which can be helpful symptomatically.
  • They might prompt some families to spend sizable amounts of money for no real benefit.
  • They might initiate further research into this area, thus drawing money away from research into much more promising avenues.

IT IS HIGH TIME THAT RESEARCHERS START THINKING CRITICALLY, PEER-REVIEWERS DO THEIR JOB PROPERLY, AND JOURNAL EDITORS STOP PUBLISHING SUCH MISLEADING ARTICLES.

You may feel that homeopaths are bizarre, irrational, perhaps even stupid – but you cannot deny their tenacity. Since 200 years, they are trying to convince us that their treatments are effective beyond placebo. And they seem to get more and more bold with their claims: while they used to suggest that homeopathy was effective for trivial conditions like a common cold, they now have their eyes on much more ambitious things. Two recent studies, for instance, claim that homeopathic remedies can help cancer patients.

The aim of the first study was to evaluate whether homeopathy influenced global health status and subjective wellbeing when used as an adjunct to conventional cancer therapy.

In this pragmatic randomized controlled trial, 410 patients, who were treated by standard anti-neoplastic therapy, were randomized to receive or not receive classical homeopathic adjunctive therapy in addition to standard therapy. The main outcome measures were global health status and subjective wellbeing as assessed by the patients. At each of three visits (one baseline, two follow-up visits), patients filled in two questionnaires for quantification of these endpoints.

The results show that 373 patients yielded at least one of three measurements. The improvement of global health status between visits 1 and 3 was significantly stronger in the homeopathy group by 7.7 (95% CI 2.3-13.0, p=0.005) when compared with the control group. A significant group difference was also observed with respect to subjective wellbeing by 14.7 (95% CI 8.5-21.0, p<0.001) in favor of the homeopathic as compared with the control group. Control patients showed a significant improvement only in subjective wellbeing between their first and third visits.

Our homeopaths concluded that the results suggest that the global health status and subjective wellbeing of cancer patients improve significantly when adjunct classical homeopathic treatment is administered in addition to conventional therapy.

The second study is a little more modest; it had the aim to explore the benefits of a three-month course of individualised homeopathy (IH) for survivors of cancer.

Fifteen survivors of any type of cancer were recruited by a walk-in cancer support centre. Conventional treatment had to have taken place within the last three years. Patients scored their total, physical and emotional wellbeing using the Functional Assessment of Chronic Illness Therapy for Cancer (FACIT-G) before and after receiving four IH sessions.

The results showed that 11 women had statistically positive results for emotional, physical and total wellbeing based on FACIT-G scores.

And the conclusion: Findings support previous research, suggesting CAM or individualised homeopathy could be beneficial for survivors of cancer.

As I said: one has to admire their tenacity, perhaps also their chutzpa – but not their understanding of science or their intelligence. If they were able to think critically, they could only arrive at one conclusion: STUDY DESIGNS THAT ARE WIDE OPEN TO BIAS ARE LIKELY TO DELIVER BIASED RESULTS.

The second study is a mere observation without a control group. The reported outcomes could be due to placebo, expectation, extra attention or social desirability. We obviously need an RCT! But the first study was an RCT!!! Its results are therefore more convincing, aren’t they?

No, not at all. I can repeat my sentence from above: The reported outcomes could be due to placebo, expectation, extra attention or social desirability. And if you don’t believe it, please read what I have posted about the infamous ‘A+B versus B’ trial design (here and here and here and here and here for instance).

My point is that such a study, while looking rigorous to the naïve reader (after all, it’s an RCT!!!), is just as inconclusive when it comes to establishing cause and effect as a simple case series which (almost) everyone knows by now to be utterly useless for that purpose. The fact that the A+B versus B design is nevertheless being used over and over again in alternative medicine for drawing causal conclusions amounts to deceit – and deceit is unethical, as we all know.

My overall conclusion about all this:

QUACKS LOVE THIS STUDY DESIGN BECAUSE IT NEVER FAILS TO PRODUCE FALSE POSITIVE RESULTS.

Nonspecific neck pain is extremely common, often disabling, and very costly for us all. If we believe those who earn their money with them, effective treatments for the condition abound. One of these therapies is osteopathy. But does osteopathic manipulation/mobilisation really work?

The objective of a recent review (the link I originally put in here does not work, I will supply a new one as soon as the article becomes available on Medline) was to find out. Specifically, the authors wanted to assess the effectiveness of osteopathic manipulative treatment (OMT) in the management of chronic nonspecific neck pain regarding pain, functional status, and adverse events.

Electronic literature searches unrestricted by language were performed in March 2014. A manual search of reference lists and personal communication with experts identified additional studies. Only randomized clinical trials (RCTs) were included, and studies of specific neck pain or single treatment techniques were excluded. Primary outcomes were pain and functional status, and secondary outcome was adverse events.

Studies were independently reviewed using a standardized data extraction form. Mean difference (MD) or standard mean difference (SMD) with 95% confidence intervals (CIs) and overall effect size were calculated for primary outcomes. GRADE was used to assess quality of the evidence.

Of 299 identified articles, 18 were evaluated and 15 excluded. The three included RCTs had low risk of bias. The results show that moderate-quality evidence suggested OMT had a significant and clinically relevant effect on pain relief (MD: -13.04, 95% CI: -20.64 to -5.44) in chronic nonspecific neck pain, and moderate-quality evidence suggested a non-significant difference in favour of OMT for functional status (SMD: -0.38, 95% CI: -0.88 to -0.11). No serious adverse events were reported.

The authors concluded that, based on the three included studies, the review suggested clinically relevant effects of OMT for reducing pain in patients with chronic nonspecific neck pain. Given the small sample sizes, different comparison groups, and lack of long-term measurements in the few available studies, larger, high-quality randomized controlled trials with robust comparison groups are recommended.

Yet again I am taken aback by several things simultaneously:

  • the extreme paucity of RCTs, particularly considering that neck pain is one of the main indication for osteopaths,
  • the rather uncritical text by the authors,
  • the nonsensical conclusions.

Let me offer my own conclusions which are, I hope, a little more realistic:

GIVEN THE PAUCITY OF THE RCTs AND THEIR SMALL SAMPLE SIZES, IT IS NOT POSSIBLE TO CLAIM THAT OMT FOR NONSPECIFIC NECK PAIN IS AN EVIDENCE-BASED APPROACH

This is a question which I have asked myself more often than I care to remember. The reason is probably that, in alternative medicine, I feel surrounded by so much dodgy research that I simply cannot avoid asking it.

In particular, the co-called ‘pragmatic’ trials which are so much ‘en vogue’ at present are, in my view, a reason for concern. Take a study of cancer patients, for instance, where one group is randomized to get the usual treatments and care, while the experimental group receives the same and several alternative treatments in addition. These treatments are carefully selected to be agreeable and pleasant; each patient can choose the ones he/she likes best, always had wanted to try, or has heard many good things about. The outcome measure of our fictitious study would, of course, be some subjective parameter such as quality of life.

In this set-up, the patients in our experimental group thus have high expectations, are delighted to get something extra, even more happy to get it for free, receive plenty of attention and lots of empathy, care, time, attention etc. By contrast, our poor patients in the control group would be a bit miffed to have drawn the ‘short straw’ and receive none of this.

What result do we expect?

Will the quality of life after all this be equal in both groups?

Will it be better in the miffed controls?

Or will it be higher in those lucky ones who got all this extra pampering?

I don’t think I need to answer these questions; the answers are too obvious and too trivial.

But the real and relevant question is the following, I think: IS SUCH A TRIAL JUST SILLY AND MEANINGLESS OR IS IT UNETHICAL?

I would argue the latter!

Why?

Because the results of the study are clearly known before the first patient had even been recruited. This means that the trial was not necessary; the money, time and effort has been wasted. Crucially, patients have been misled into thinking that they give their time, co-operation, patience etc. because there is a question of sufficient importance to be answered.

But, in truth, there is no question at all!

Perhaps you believe that nobody in their right mind would design, fund and conduct such a daft trial. If so, you assumed wrongly. Such studies are currently being published by the dozen. Here is the abstract of the most recent one I could find:

The aim of this study was to evaluate the effectiveness of an additional, individualized, multi-component complementary medicine treatment offered to breast cancer patients at the Merano Hospital (South Tyrol) on health-related quality of life compared to patients receiving usual care only. A randomized pragmatic trial with two parallel arms was performed. Women with confirmed diagnoses of breast cancer were randomized (stratified by usual care treatment) to receive individualized complementary medicine (CM group) or usual care alone (usual care group). Both groups were allowed to use conventional treatment for breast cancer. Primary endpoint was the breast cancer-related quality of life FACT-B score at 6 months. For statistical analysis, we used analysis of covariance (with factors treatment, stratum, and baseline FACT-B score) and imputed missing FACT-B scores at 6 months with regression-based multiple imputation. A total of 275 patients were randomized between April 2011 and March 2012 to the CM group (n = 136, 56.3 ± 10.9 years of age) or the usual care group (n = 139, 56.0 ± 11.0). After 6 months from randomization, adjusted means for health-related quality of life were higher in the CM group (FACT-B score 107.9; 95 % CI 104.1-111.7) compared to the usual care group (102.2; 98.5-105.9) with an adjusted FACT-B score difference between groups of 5.7 (2.6-8.7, p < 0.001). Thus, an additional individualized and complex complementary medicine intervention improved quality of life of breast cancer patients compared to usual care alone. Further studies evaluating specific effects of treatment components should follow to optimize the treatment of breast cancer patients. 

The key sentence in this abstract is, of course: complementary medicine intervention improved quality of life of breast cancer patients… It provides the explanation as to why these trials are so popular with alternative medicine researchers: they are not real research but they are quite simply promotion! The next step would be to put a few of those pseudo-scientific trials together and claim that there is solid proof that integrating alternative treatments into conventional health care produces better results. At that stage, few people will bother asking whether this is really due to the treatments in questioning or to the additional attention, pampering etc.

My question is ARE SUCH TRIALS ETHICAL?

I would very much appreciate your opinion.

A new study of homeopathic arnica suggests efficacy. How come?

Subjects scheduled for rhinoplasty surgery with nasal bone osteotomies by a single surgeon were prospectively randomized to receive either oral perioperative arnica or placebo in a double-blinded fashion. A commercially available preparation was used which contained 12 capsules: one 500 mg capsule with arnica 1M is given preoperatively on the morning of surgery and two more later that day after surgery. Thereafter, arnica was administered in the 12C potency three times daily for the next 3 days (“C” indicates a 100-fold serial dilution; and M, a 1000-fold dilution)

Ecchymosis was measured in digital “three-quarter”-view photographs at three postoperative time points. Each bruise was outlined with Adobe Photoshop and the extent was scaled to a standardized reference card. Cyan, magenta, yellow, black, and luminosity were analyzed in the bruised and control areas to calculate change in intensity.

Compared with 13 subjects receiving placebo, 9 taking arnica had 16.2%, 32.9%, and 20.4% less extent on postoperative days 2/3, 7, and 9/10, a statistically significant difference on day 7. Color change initially showed 13.1% increase in intensity with arnica, but 10.9% and 36.3% decreases on days 7 and 9/10, a statistically significant difference on day 9/10. One subject experienced mild itching and rash with the study drug that resolved during the study period.

The authors concluded that Arnica montana seems to accelerate postoperative healing, with quicker resolution of the extent and the intensity of ecchymosis after osteotomies in rhinoplasty surgery, which may dramatically affect patient satisfaction.

Why are the results positive? Pervious systematic reviews confirm that homeopathic arnica is a pure placebo. First, I thought the answer lies in the 1M potency. It could well still contain active molecules. But then I realised that the answer is much more simple: if we apply the conventional level of statistical significance, there are no statistically significant differences to placebo at all! I had not noticed the little sentence by the authors: a P value of 0.1 was set as a meaningful difference with statistical significance. In fact, none of the effects called significant by the authors pass the conventionally used probability level of 5%.

So, what so the results of this new study truly mean? In my view, they show what was known all along: HOMEOPATHIC REMEDIES ARE PLACEBOS.

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