MD, PhD, FMedSci, FRSB, FRCP, FRCPEd.

research

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The aims of this bibliometric analysis are to describe the characteristics of articles published on the efficacy of osteopathic interventions and to provide an overall portrait of their impacts in the scientific literature. A bibliometric analysis approach was used. Articles were identified with searches using a combination of relevant MeSH terms and indexing keywords about osteopathy and research designs in MEDLINE and CINAHL databases. The following indicators were extracted: country of the primary author, year of publication, journals, impact factor of the journal, number of citations, research design, participants’ age group, system/body part addressed, primary outcome, indexing keywords and types of techniques.

A total of 389 articles met the inclusion criteria. The number of empirical studies doubled every 5 years, with the United States, Italy, Spain, and the United Kingdom being the most productive countries. Twenty-three articles were cited over 100 times. Articles were published in 103 different indexed journals, but more than half (53.7%) of articles were published in one of three osteopathy-focused readership journals. Randomized control trials (n = 145; 37.3%) and case reports (n = 142; 36.5%) were the most common research designs. A total of 187 (48.1%) studies examined the effects of osteopathic interventions using a combination of techniques that belonged to two or all of the classic fields of osteopathic interventions (musculoskeletal, cranial, and visceral).

The authors concluded that this bibliometric analysis shows that publications about efficacy of osteopathy are relatively recent and have increased at a rapid pace over the last three decades. More than half of these publications are published in three osteopathic journals targeting a limited, disciplinary-focused readership. Our results highlight important needs for large efficacy and effectiveness trials, as well as study designs to further understanding of the mechanisms of action of the techniques being investigated. Finally, this bibliometric analysis can assist to identify osteopathy techniques and populations where further clinical research is required.

What the authors fail to state is that their analysis discloses osteopathy to be an area of utter unimportance. Less than 400 studies in 52 years is a dismal result. The fact that they were mostly published in journals of no impact makes it even worse. Twenty-three articles were cited more than 100 times; this is dismal! To put it in perspective, I have ~250 articles that were cited more than 100 times. Does that suggest that my work has made about 10 times more impact than the entire field of osteopathy?

Recently, I received this comment from a reader:

Edzard-‘I see you do not understand much of trial design’ is true BUT I wager that you are in the same boat when it comes to a design of a trial for LBP treatment: not only you but many other therapists. There are too many variables in the treatment relationship that would allow genuine , valid criticism of any design. If I have to pick one book of the several listed elsewhere I choose Gregory Grieve’s ‘Common Vertebral Joint Problems’. Get it, read it, think about it and with sufficient luck you may come to realize that your warranted prejudices against many unconventional ‘medical’ treatments should not be of the same strength when it comes to judging the physical therapy of some spinal problems as described in the book.

And a chiro added:

EE: I see that you do not understand much of trial design

Perhaps it’s Ernst who doesnt understand how to research back pain.

“The identification of patient subgroups that respond best to specific interventions has been set as a key priority in LBP research for the past 2 decades.2,7 In parallel, surveys of clinicians managing LBP show that there are strong views against generic treatment and an expectation that treatment should be individualized to the patient.6,22.”

Journal of Orthopaedic & Sports Physical Therapy
Published Online:January 31, 2017Volume47Issue2Pages44-48

Do I need to explain why the Grieve book (yes, I have it and yes, I read it) is not a substitute for evidence that an intervention or technique is effective? No, I didn’t think so. This needs to come from a decent clinical trial.

And how would one design a trial of LBP (low back pain) that would be a meaningful first step and account for the “many variables in the treatment relationship”?

How about proceeding as follows (the steps are not necessarily in that order):

  • Study the previously published literature.
  • Talk to other experts.
  • Recruit a research team that covers all the expertise you need (and don’t have yourself).
  • Formulate your research question. Mine would be IS THERAPY XY MORE EFFECTIVE THAN USUAL CARE FOR CHRONIC LBP? I know LBP is but a vague symptom. This does, however, not necessarily matter (see below).
  • Define primary and secondary outcome measures, e.g. pain, QoL, function, as well as the validated methods with which they will be quantified.
  • Clarify the method you employ for monitoring adverse effects.
  • Do a small pilot study.
  • Involve a statistician.
  • Calculate the required sample size of your study.
  • Consider going multi-center with your trial if you are short of patients.
  • Define chronic LBP as closely as you can. If there is evidence that a certain type of patient responds better to the therapy xy than others, that might be considered in the definition of the type of LBP.
  • List all inclusion and exclusion criteria.
  • Make sure you include randomization in the design.
  • Randomization should be to groups A and B. Group A receives treatment xy, while group B receives usual care.
  • Write down what A and B should and should not entail.
  • Make sure you include blinding of the outcome assessors and data evaluators.
  • Define how frequently the treatments should be administered and for how long.
  • Make sure all therapists employed in the study are of a high standard and define the criteria of this standard.
  • Train all therapists of both groups such that they provide treatments that are as uniform as possible.
  • Work out a reasonable statistical plan for evaluating the results.
  • Write all this down in a protocol.

Such a trial design does not need patient or therapist blinding nor does it require a placebo. The information it would provide is, of course, limited in several ways. Yet it would be a rigorous test of the research question.

If the results of the study are positive, one might consider thinking of an adequate sham treatment to match therapy xy and of other ways of firming up the evidence.

As LBP is not a disease but a symptom, the study does not aim to include patients that all are equal in all aspects of their condition. If some patients turn out to respond better than others, one can later check whether they have identifiable characteristics. Subsequently, one would need to do a trial to test whether the assumption is true.

Therapy xy is complex and needs to be tailored to the characteristics of each patient? That is not necessarily an unsolvable problem. Within limits, it is possible to allow each therapist the freedom to chose the approach he/she thinks is optimal. If the freedom needed is considerable, this might change the research question to something like ‘IS THAT TYPE OF THERAPIST MORE EFFECTIVE THAN THOSE EMPLOYING USUAL CARE FOR CHRONIC LBP?’

My trial would obviously not answer all the open questions. Yet it would be a reasonable start for evaluating a therapy that has not yet been submitted to clinical trials. Subsequent trials could build on its results.

I am sure that I have forgotten lots of details. If they come up in discussion, I can try to incorporate them into the study design.

 

 

Regular readers of this blog will know the US homeopath, Dana Ullman. He has been the star of several of my posts (for instance here, here, and here). Dana is prolific in his writing but he has published not published much in proper journals. Now he has almost doubled this list by publishing TWO (!) proper papers in real journals within just one month.

Congratulations, Dana!

The first is in CUREUS, a very unusual journal with a most unusual peer-review process. Allow me to show you the abstract of Dana’s article:

Homeopathic medicine is a controversial system of medicine that has been used worldwide for over 200 years. Recently, several governments, in part, owing to government-funded reviews of research on homeopathic medicine, have stopped reimbursements for homeopathic medicines and have discouraged their use by medical professionals. This review critically evaluates four government-funded reviews of clinical research on homeopathic medicine. An analysis of government-sponsored reviews of clinical research on homeopathic medicine was conducted, including two studies from Switzerland, one from England, and one from Australia. Three of the four government-funded reviews were critical of homeopathy, claiming that there was no reliable evidence that homeopathic medicines were effective. Three of these reviews had significant flaws, with potential ethical concerns raised in one of the reviews. The most comprehensive review of homeopathic research, including analysis of clinical and basic science concerns, found the most positive results for homeopathy.

The second paper was published in a journal called DOSE RESPONSE. The editor in chief of this journal is Prof E J Calabrese who has published numerous articles about homeopathy/hormesis. Here is the abstract of Dana’s 2nd article:

Serially diluted succussed solutions of a suitable drug/toxic substance can exhibit physicochemical and biological properties even far beyond Avogadro’s limit defying conventional wisdom. They can show hormesis, and homeopathy uses them as medicines. Many studies confirm that they can have an impact on gene expression different than controls. Water in the exclusion zone phase can have memory but for a short period. However, the nanoparticle as the physical substrate can hold information. Nanoparticle and exclusion zone duo as nanoparticle-exclusion zone shell can provide a prolonged memory. The Nanoparticle-Exclusion Zone Shell Model may be an important step toward explaining the nature and bioactivity of serially diluted succussed solutions used as homeopathic medicines. This model may also provide insight into the workings of hormesis. Hormesis is the primary phenomenon through which homeopathic phenomenon may have evolved exhibiting the principle of similars. Hahnemann exploited it to establish homeopathy. The nanoparticle-exclusion zone shells present in the remedy, selected on the principle of similars, can be patient-specific nanoparticles in a symptom syndrome-specific manner. They can carry the drug-specific information for safer clinical applications in an amplified form for high yielding. It suggests homeopathy is a type of nanopharmacology.

So, are Dana’s two articles significant? Both are reviews. The 1st tries to persuade us that homeopathy has clinical effects beyond placebo and that reports that say otherwise are full of errors and fraud and thus not reliable. The second tells us that these clinical effects of homeopathy can be explained by nano-pharmacology.

Is he right?

Please tell me what you think.

This study assessed the effects of being born under the zodiac sign Pisces on mortality. For that purpose, a retrospective observational study was conducted of the data from 26 Scandinavian intensive care units between 2009 and 2011. Patients aged 18 years or older with severe sepsis and in need of fluid resuscitation were included from the Scandinavian Starch for Severe Sepsis/ Septic Shock (6S) trial. The main outcome measure was the 90-day mortality.

The researchers included all 798 patients in the study; 70 (9%) of them were born under the sign of Pisces. The primary outcome (death within 90 days) occurred in 25 patients (35.7%) in the Pisces group, compared with 348 patients (48%) in the non-Pisces group (relative risk, 0.75; 95% CI, 0.54-1.03; one-sided P = 0.03).

The authors concluded that in a multicentre randomised clinical trial of IV fluids, being born under the sign of Pisces was associated with a decreased risk of death. Our study shows that with convenient use of statistics and an enticing explanatory hypothesis, it is possible to achieve significant findings in post-hoc analyses of data from large trials.

This is an excellent paper! It showcases the sort of nonsense one can do with datasets, statistics, and post hoc hypotheses. The authors entitled their article “Gone fishing in a fluid trial”, and this title should ensure that there are not some astrology nutters who mistake correlation for causation

… I hope

… but, of course, I am an optimist.

While working on yesterday’s post, I discovered another recent and remarkable article co-authored by Prof Harald Walach. It would surely be unforgivable not to show you the abstract:

The aim of this study is to explore experiences and perceived effects of the Rosary on issues around health and well-being, as well as on spirituality and religiosity. A qualitative study was conducted interviewing ten Roman Catholic German adults who regularly practiced the Rosary prayer. As a result of using a tangible prayer cord and from the rhythmic repetition of prayers, the participants described experiencing stability, peace and a contemplative connection with the Divine, with Mary as a guide and mediator before God. Praying the Rosary was described as helpful in coping with critical life events and in fostering an attitude of acceptance, humbleness and devotion.

The article impressed me so much that it prompted me to design a virtual study for which I borrowed Walach’s abstract. Here it is:

The aim of this study is to explore experiences and perceived effects of train-spotting on issues around health and well-being, as well as on spirituality. A qualitative study was conducted interviewing ten British adults who regularly practiced the art of train-spotting. As a result of using a tangible train-spotter diary and from the rhythmic repetition of the passing trains, the participants described experiencing stability, peace, and a contemplative connection with the Divine, with Mary as a guide and mediator before the almighty train-spotter in the sky. Train-spotting was described as helpful in coping with critical life events and in fostering an attitude of acceptance, humbleness, and devotion.

These virtual results are encouraging and encourage me to propose the hypothesis that Rosary use and train-spotting might be combined to create a new wellness program generating a maximum holistic effect. We are grateful to Walach et al for the inspiration and are currently applying for research funds to test our hypothesis in a controlled clinical trial.

 

Prince Charles has claimed that people struggling to return to full health after having the coronavirus should practice yoga. This is what the GUARDIAN reported about it on Friday:

In a video statement on Friday to the virtual yoga and healthcare symposium Wellness After Covid, the heir apparent said doctors should work together with “complementary healthcare specialists” to “build a roadmap to hope and healing” after Covid. “This pandemic has emphasised the importance of preparedness, resilience and the need for an approach which addresses the health and welfare of the whole person as part of society, and which does not merely focus on the symptoms alone,” Charles said. “As part of that approach, therapeutic, evidenced-informed yoga can contribute to health and healing. By its very nature, yoga is an accessible practice which provides practitioners with ways to manage stress, build resilience and promote healing…”

… Charles, who has previously espoused the benefits of yoga, is not the only fan in the royal family. His wife, the Duchess of Cornwall, has said “it makes you less stiff” and “more supple”, while Prince William has also been pictured doing yogic poses. In 2019, the Prince of Wales said yoga had “proven beneficial effects on both body and mind”, and delivered “tremendous social benefits” that help build “discipline, self-reliance and self-care”.

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END OF QUOTE

Yoga is a complex subject because it entails a host of different techniques, attitudes, and life-styles. There have been numerous clinical trials of various yoga techniques. They tend to suffer from poor study design as well as incomplete reporting and are thus no always reliable. Several systematic reviews have summarised the findings of these studies. A 2010 overview included 21 systematic reviews relating to a wide range of conditions. Nine systematic reviews arrived at positive conclusions, but many were associated with a high risk of bias. Unanimously positive evidence emerged only for depression and cardiovascular risk reduction.[1] There is no evidence that yoga speeds the recovery after COVID-19 or any other severe infectious disease, as Charles suggested.

Yoga is generally considered to be safe. However, a large-scale survey found that approximately 30% of yoga class attendees had experienced some type of adverse event. Although the majority had mild symptoms, the survey results indicated that patients with chronic diseases were more likely to experience adverse events.[2]  It, therefore, seems unlikely that yoga is suited for many patients recovering from a COVID-19 infection.

The warning by the Vatican’s chief exorcist that yoga leads to ‘demonic possession’[3] might not be taken seriously by rational thinkers. Yet, experts have long warned that many yoga teachers try to recruit their clients into the more cult-like aspects of yoga.[4]

Perhaps the most remarkable expression in Charles’ quotes is the term ‘EVIDENCE-INFORMED‘. It crops up regularly when Charles (or his advisor Dr. Michael Dixon) speaks or writes about so-called alternative medicine (SCAM). It is a clever term that sounds almost like ‘evidence-based’ but means something entirely different. If a SCAM is not evidence-based, it can still be legitimately put under the umbrella of ‘evidence-informed’: we know the evidence is not positive, we were well-informed of this fact, we nevertheless conclude that yoga (or any other SCAM) might be a good idea!

In my view, the regular use of the term ‘evidence-informed’ in the realm of SCAM discloses a lack of clarity that suits all snake-oil salesmen very well.

 

[1] Ernst E, Lee MS: Focus on Alternative and Complementary Therapies Volume 15(4) December 2010 274–27

[2] Matsushita T, Oka T. A large-scale survey of adverse events experienced in yoga classes. Biopsychosoc Med. 2015 Mar 18;9:9. doi: 10.1186/s13030-015-0037-1. PMID: 25844090; PMCID: PMC4384376.

[3] https://www.social-consciousness.com/2017/06/vaticans-chief-exorcist-warns-that-yoga-causes-demonic-possession.html

[4] https://www.theguardian.com/lifeandstyle/2020/jun/26/experience-my-yoga-class-turned-out-to-be-a-cult

 

Mind-body interventions (MBIs) are one of the top ten so-called alternative medicine (SCAM) approaches utilized in pediatrics, but there is limited knowledge on associated adverse events (AE). The objective of this review was to systematically review AEs reported in association with MBIs in children.

Electronic databases MEDLINE, Embase, CINAHL, CDSR, and CCRCT were searched from inception to August 2018. The authors included primary studies on participants ≤ 21 years of age that used an MBI. Experimental studies were assessed for whether AEs were reported on or not, and all other study designs were included only if they reported an AE.

A total of 441 were included as primary pediatric MBI studies. Of these, 377 (85.5%) did not explicitly report the presence/absence of AEs or a safety assessment. In total, there were 64 included studies: 43 experimental studies reported that no AE occurred, and 21 studies reported AEs. A total of 37 AEs were found, of which the most serious were grade 3. Most of the studies reporting AEs did not report on severity (81.0%) or duration of AEs (52.4%).

The authors concluded that MBIs are popularly used in children; however associated harms are often not reported and lack important information for meaningful assessment.

SCAM is far too often considered to be risk-free. This phenomenon is particularly stark if the SCAM in question does not involve physical or pharmacological treatments. Thus MBIs are seen and often waved through as especially safe. Consequently, many researchers do not even bother to monitor AEs in their clinical trials. This might be understandable, but it is nevertheless a violation of research ethics.

This new review is important in that it highlights these issues. It is high time that we stop giving researchers in SCAM the benefit of the doubt. They may or may not make honest mistakes when not reporting AEs. In any case, it is clear that they are not properly trained and supervised. All too often, we still see clinical trials run by amateurs who have little idea of methodology and even less of ethics. The harm this phenomenon does is difficult to quantify, but I fear it is huge.

In the world of homeopathy, Prof Michael Frass is a famous man. He is the First Chairman of the Scientific Society for Homeopathy (WissHom), the president of the Umbrella organization of Austrian Doctors for Holistic Medicine, and the Vicepresident of the Doctors Association for Classical Homeopathy. Frass has featured on this blog before, not least because he has published numerous studies of homeopathy, none of which has ever failed to produce a positive result

This is not just remarkable, in my view, it defies logic and the laws of nature. Even if homeopathy were a supremely effective therapy – a very broad consensus holds that it is not! – one would occasionally expect some negative results. No treatment works under all circumstances

… that is no treatment except homeopathy, according to Frass.

Recently Frass amazed even the world of oncology by publishing a study suggesting that homeopathy can prolong the survival of lung cancer patients. Every oncologist I know was flabbergasted.

Can this be true? This is the question, many people have been asking for some time in relation to Frass’s research.

In my quest to shine more light on it, I was recently alerted to an article by the formidable Austrian investigative journalist, Alwin Schönberger. In 2015, he came across a press release announcing that “HOMEOPATHY HAD BEEN PROVEN TO WORK AFTER ALL” (strikingly similar to one issued in 2018). It came from Austria’s leading manufacturer who was giving an award to an apparently outstanding thesis supervised by Frass. Even today, this piece of research has not been published in the peer-reviewed literature.

Yet, after some difficulties, Schönberger managed to obtain a copy. What he found was surprising, and he thus published his findings in the respected Austrian journal ‘Profil’ (2. Mai 2015 • profil 22).

Frass’s student had been given the task to systematically review all the homeopathy trials published between 2008 and 2012. Contrary to the hype of the press release, the meta-analysis merely suggested a very small effect. When digging deeper, Schönberger found several inconsistencies and mistakes in the analysis. They all were such that they produced a false-positive picture for homeopathy. Upon their correction, homeopathy turned out to be no longer significantly superior to placebo. Frass was then interviewed about it and claimed that the inconsistencies were only ‘errors’ but insisted that homeopathy is not a placebo therapy.

Yes, of course, errors happen in research. But if they all go in one direction and if that direction coincides with the interests of the researchers, we have the right, perhaps even the duty, to be suspicious. The questions that arise from this story are, I think, as follows:

  • Have the errors been corrected?
  • Are there perhaps other errors in Frass’s research?
  • Can we trust anything that Frass says?
  • Is it time to consider an official investigation into Frass’s studies of homeopathy?

 

 

Guest post by Alan Henness

When I discovered a homeopath admitting on camera that she believed she and her fellow homeopaths had managed to unblind a triple-blinded homeopathy trial they were taking part in, I submitted a complaint to the journal that published the paper on the trial, the university of the researcher who had conducted the trial and the current university of the homeopath who had subsequently moved into research.

The paper concerned is the 2004 paper by Weatherley-Jones et al. A randomised, controlled, triple-blind trial of the efficacy of homeopathic treatment for chronic fatigue syndrome. This was published in the Journal of Psychosomatic Research.

The homeopath was Clare Relton, currently Senior Lecturer in Clinical Trials at the Centre for Primary Care and Public Health at Queen Mary University of London and Honorary Senior Research Fellow, School of Health and Related Research at the University of Sheffield.

She gave a presentation at the 2019 conference of the Homeopathy Research Institute. Billed as an International Homeopathy Research Conference, it was subtitled, Cutting edge research in homeopathy. The videos of the conference were sponsored by homeopathy manufacturing giant, Boiron.

My complaint email (see below) explains what I discovered and sets the context. As a result of the investigation by the journal, the current editor along with two former editors have just published a peer-reviewed paper on my complaint and their investigation:

When is lack of scientific integrity a reason for retracting a paper? A case study

Misconduct and unethical behaviour

It’s worth noting how serious the Journal of Psychosomatic Research considered the misconduct they identified by Relton and others. From the Results section of the paper:

We found the presentation by Dr. Relton disturbing on multiple grounds. This admission of unethical behavior calls her scientific integrity into question. The premise for her actions rests on an errant assumption widespread among clinicians, based on anecdotal experience, that one possesses an ultimate knowledge of what works and doesn’t work without the need for rigorous study. The history of medicine, unfortunately, has been littered by countless treatments that practitioners believed in and dispensed, only to be later found not beneficial or even harmful [4]. This underscores the importance of rigorous study for treatments where equipoise exists in the scientific community, as it arguably did for the use of homeopathy for chronic fatigue syndrome. Dr. Relton likely did not hold that equipoise herself, but if she had ethical concerns about the study, the appropriate action would have been to not participate in it. Instead, she purports to have enlisted colleagues to deliberately and systematically undermine the study.

In watching the presentation, the purpose of this admission seemed to be to discount the results of a rigorous but essentially negative study in the context of promoting her own ideas related to trial design. While we cannot know for certain that her motivation was to discount the results of this study, what she said clearly seeks to undermine the credibility of a trial whose results challenged her firmly held but untested beliefs about the benefit of a treatment that she had high allegiance to. Regardless of her intent or what actually happened during the trial, Dr. Relton’s presentation is ipso facto evidence of either an admitted prior ethical breach or is itself an ethical breach for the following reasons. Either she indeed undermined an ambitious effort to study of the efficacy of homeopathy for chronic fatigue syndrome, negating the work of all other investigators, study staff, and participants involved in the study as well as the investment of the public, or she is conducting a late and inappropriate attack on the study’s credibility. Her presentation certainly warrants formal censure from the scientific community, and this paper may contribute to that. Despite this clear indictment, after discussing and considering the complaint of Mr. Henness for several months, we ultimately decided not to retract the paper.

They decided not to retract the paper but instead use it for ethical reflection. However, they concluded I had highlighted “undisputable evidence of scientific misconduct” by the homeopaths concerned:

When is lack of scientific integrity a reason for retracting a paper? A case study

Objective: The journal received a request to retract a paper reporting the results of a triple-blind randomized placebo-controlled trial. The present and immediate past editors expand on the journal’s decision not to retract this paper in spite of undisputable evidence of scientific misconduct on behalf of one of the investigators.

Methods: The editors present an ethical reflection on the request to retract this randomized clinical trial with consideration of relevant guidelines from the committee on Publication Ethics (COPE) and the International Committee of Medical Journal Editors (ICMJE) applied to the unique contextual issues of this case.

Results: In this case, scientific misconduct by a blinded provider of a homeopathy intervention attempted to undermine the study blind. As part of the study, the integrity of the study blind was assessed. Neither participants nor homeopaths were able to identify whether the participant was assigned to homeopathic medicine or placebo. Central to the decision not to retract the paper was the fact that the rigorous scientific design provided evidence that the outcome of the study was not affected by the misconduct. The misconduct itself was thought to be insufficient reason to retract the paper.

Conclusion: Retracting a paper of which the outcome is still valid was in itself considered unethical, as it takes away the opportunity to benefit from its results, rendering the whole study useless. In such cases, scientific misconduct is better handled through other professional channels.

Ethical misconduct

The authors had additional ethical concerns:

Apart from the intention of ‘circumventing the blind’, there is another unethical aspect to the behavior of Dr. Relton, namely the fact that patients were systematically subject to an intervention (carcinosin administration) that was not part of the original research protocol and to which they did not consent as part of the study. Although the systematic administration of carcinosin was not part of the study protocol, it was administered only to patients taking part in the study, and because they took part in the study. Presumably, these patients were not properly informed, or maybe even misinformed, about the rationale of a double-blind trial design and/or the true reason for administrating carcinosin. Apparently, ‘deep listening and deep understanding’ does not necessarily need to be accompanied by an honest and open attitude towards patients that participate in research. Dr. Relton stated in her lecture ‘I’m not trained to be deceiving people’, but that is exactly what she did. Not only did she deceive patients, but also the researchers and study leaders that she is supposed to collaborate with as a colleague. [emphasis in original]

Sanctions

The authors said:

The authors are of the opinion that in case the misconduct was not conducted by or on behalf of the principal investigator – as is the case here -, the initiative for further action should lie with them. Not only is the principal investigator the one that was deceived, but they are in a better position to report the misconduct to the institution and funding body. If the principal investigator is responsible for the misconduct, the editor is probably the only one that can initiate further action, in which case the researcher’s institution should be informed and requested to take appropriate action.

It will be interesting to see what further action, if any, is taken by Weatherley-Jones as is suggested.

I had already brought my concerns to the attention of both the University of Sheffield and Queen Mary University of London. The former concluded:

This is to confirm that the University of Sheffield has now completed its assessment of this matter, and it has been agreed that it would not be appropriate for the University of Sheffield to undertake a research misconduct investigation of the allegation against Clare Relton, since she is not a current member of University staff, nor was she a member of staff at the time of the clinical trial in question.

In relation to the potential concerns about the reliability of the published research findings, the University is satisfied that the Journal of Psychosomatic Research is consulting with the authors and taking steps to address the concerns as appropriate. The University will therefore be taking no further action.

I received no response from Queen Mary University of London, despite their Principal being copied in on all the relevant correspondence.

I will be writing again to both and Weatherley-Jones now the paper has been published.

Acknowledgements

My thanks to Jess G. Fiedorowicz, Editor, Journal of Psychosomatic, for his thorough investigation of my complaint.


My complaint

Hi

The results of a trial were published in the Journal of Psychosomatic Research in 2004 (see attached copy):

A randomised, controlled, triple-blind trial of the efficacy of homeopathic treatment for chronic fatigue syndrome

doi:10.1016/S0022-3999(03)00377-5

Elaine Weatherley-Jones a,*, Jon P Nicholl a, Kate J Thomas a, Gareth J Parry a, Michael W McKendrickb, Stephen T Green b, Philip J Stanley c, Sean PJ Lynch d

a Medical Care Research Unit, School of Health and Related Research, University of Sheffield, Regent Court, 30 Regent Street, Sheffield, S1 4DA, UK
b Communicable Diseases Directorate, Royal Hallamshire Hospital, Sheffield, UK
c Seacroft Hospital, Leeds Teaching Hospitals NHS Trust, Leeds, UK
d St. James’s University Hospital, University of Leeds, Beckett Street, Leeds, UK

* Corresponding author. Tel.: +44-114-222-0744; fax: +44-114-222-0749.
E-mail address: e.weatherley-jones@sheffield.ac.uk (E. Weatherley-Jones)

The paper is indexed in PubMed here.

Elaine Weatherley-Jones is listed as the Corresponding author at the Medical Care Research Unit, School of Health and Related Research, University of Sheffield as are others.

One of the homeopaths involved in providing treatment was Clare Relton, currently Senior Lecturer in Clinical Trials at the Centre for Primary Care and Public Health at Queen Mary University of London.

The full list of those involved in providing treatment during the trial is given as:

The Homeopathic Trials Group: Homeopaths— Gill de Boer, MBChB, MFHom, Maryjoan Foster, RSHom, Susanne Hartley, RSHom, Jane Howarth, BRCPHom, Pat Mayborne RSHom, Georgina Ramsayer RSHom, Clare Relton, RSHom, Pat Strong, MBBS, MFHom, Angela Zajac, BSc, RSHom, BRCPHom.

Dr Relton gave a talk at the Conference in London of the Homeopathy Research Institute held 14 to 16 June 2019. The video of her talk has recently been published: https://www.hrilondon2019.org/films/#clip=eitxmhl1ilss. I have a copy of this video.

I invite you to watch all 30 minutes of it.

At about five minutes in, she begins to discuss the above trial, having just said she was a non-medical homeopath at the Wellforce Clinic in Sheffield. She is currently listed as Chair of Directors.

She then goes on to describe how she took part as one of the homeopaths in the trial and relates how she came up with “a cunning way of circumventing the blinding”.

I offer the following transcript of the segment of her talk where she discusses this (all transcription errors are mine):

Timestamp 05:12

So while I was still a homeopath in the Wellforce clinic, a researcher from the University of Sheffield which was actually only five minutes away from my clinic which was really handy came along and said, “I’ve got some money from Lord Sainsbury to do a trial of chronic fatigue syndrome of homoeopathy” and she described the design and I remember thinking, “not sure what that’s going to show”.

But anyway there were ten homeopaths recruited in Sheffield and Leeds and we saw patients with chronic fatigue syndrome.

A lot of us were getting patients with chronic fatigue syndrome anyway and particularly if they were never been well since glandular fever couple of doses of carcinosin 30 or 200 and they seem to make a really good recovery.

So we’re pretty confident about taking part in this trial.

So there were 130 or 140 patients recruited to the trial and then allocated to the homeopaths: there were five at our clinic and I was one of them.

Patients would arrive; you would do the normal thing, have the consultation with them. They seemed a bit standoffish, they were quite distant – I couldn’t work out why.

And then at the end of the consultation I had to say to them “well there’s a 50% chance that whatever I prescribe you is going to be a placebo”, which sort of sort of lowered the temperature in the in the in the Consulting room because you know they came because they have chronic fatigue; they came… didn’t come because they wanted to take part in an experimental game.

So we would ring the pharmacy up and tell them our prescription. Helios Pharmacy would then send out either placebo or the real remedy according to the allocation of the patient.

The patient would come back four weeks later and if they were better, great and if they weren’t it was really, really difficult. So, had I got the wrong prescription or were they on placebo?

So after about six months of this we started working out there was a cunning way of circumventing the blinding and we worked out, well if we give them all a dose of carcinosin they’re going to have some reaction: there’s going to be a dream there’s going to be some change and if when they come back at the second appointment they haven’t changed then we know they’re on placebo. So don’t bother doing all that trying to find the right remedy; just use all your other amazing skills you have as a homeopath: the deep listening we have the deep understanding of what we know about what’s toxic in our systems, about diet and counselling.

So that’s what we did. Because we’re homeopaths. We’re trained to treat people I’m not trained to be deceiving people. That’s what I do, that’s what I did then; that’s what all my colleagues did.

So ok, so the trial ended and at the end the results came out I’m sure quite a few of us are familiar with it.

There were two groups, so there was a group… everybody in the patient… everybody in the trial received treatment… a course of treatment by a homeopath and 50% of them received a placebo remedy 50% the real remedy, the verum.

And the results… both groups got better and the group that received the real remedy improved better than the group that received the placebo but was the difference clinically significant? Not quite. How many trials do we have that? So this trial was so much realisation, so many questions came out of my experience being inside, inside a double-blind placebo randomised controlled trial. What is seen as the… you know the… summit of evidence-based medicine in terms of rigorousness, I  just thought “what is this doing?” I don’t know what… I don’t know what this has shown.

This is what’s called an explanatory trial and I thought well it’s explaining nothing to me, apart from the fact that the system for designing and conducting randomised controlled trials at the moment isn’t working.

So lots of questions.

Timestamp 09:02

The paper states:

Patients were successfully blinded to their group allocation, and therefore we have assumed that whatever the reasons for nonresponse, they are the same for the treatment arm and the placebo arm and that the data are comparable. Therefore, intention to treat analyses was done on actual data plus imputed missing item data, but all unit missing data were excluded from analyses.

and:

Checking of double blinding showed that prediction of treatment group was made by neither homeopaths (j =. 07, P c.60) nor patients (j = 0.11, P c.48).

The trial was of a triple-blind design but there is no mention of the deliberate attempts to circumvent the blinding in the paper. The effects on participants by the actions – inadvertent or otherwise – of Relton and her colleagues are not considered and not known.

I believe the actions of Relton, the other four homeopaths at her clinic whom she clearly implicates in this circumvention of blinding, and possibly the remaining four homeopaths if they were all known to each other and in contact with each other since they were all in the same area of Leeds/Sheffield, compromised the trial design, rendered the results unreliable and seriously undermined the integrity of the paper and its conclusions. I do not believe it matters whether or not they were in fact able to circumvent the blinding, but it does matter that Relton and others believed they had because she admits it led to different behaviour on their part resulting in contamination of the results.

I believe the actions amount to misconduct.

I note additional criticism of this paper by Prof Edzard Ernst (see attached).

I ask that Sheffield University investigate this matter and that along with Queen Mary University of London and the Editor-in-chief of the Journal of Psychosomatic Research, Jess Fiedorowicz, MD, PhD, decide what actions to take. I ask that consideration is given to retracting this unsound paper.

Please consider this email as a formal complaint against Dr Clare Relton and others.

Please acknowledge receipt by return and keep me informed of your progress in investigating this matter and of your conclusions and outcome.

If you require any further information, please do not hesitate to contact me.

Best regards.
Alan Henness

On Twitter, the hype had begun even before its text was available. Priti Gandhi, for instance, tweeted:

Yet another feather in India’s cap!! 1st evidence-based, CoPP-WHO GMP certified medicine for Covid-19 released today. Congratulations to @yogrishiramdev ji, @Ach_Balkrishna ji & the team of scientists at Patanjali Research Institute. Your efforts have been successful!! #Ayurveda

So, what is it all about? This study included 100 patients and was designed to evaluate the impact of traditional Indian Ayurvedic treatment on asymptomatic patients with COVID-19 infection. It is a placebo-controlled randomized double-blind pilot clinical trial that was conducted at the Department of Medicine in the National Institute of Medical Sciences and Research, Jaipur, India.

The verum treatment consisted of:
  • 1 g of Giloy Ghanvati (Tinospora cordifolia)
  • 2 g of Swasari Ras (traditional herbo-mineral formulation)
  • 0.5 g of Ashwagandha (Withania somnifera)
  • 0.5 g of Tulsi Ghanvati (Ocimum sanctum)

The treatment was given orally to the patients in the treatment group twice per day for 7 days. Medicines were given in the form of tablets and each tablet weighed 500 mg. While Swasari Ras was administered in powdered form, 30 min before breakfasts and dinners, rest were scheduled for 30 min post-meals. Patients in the treatment group also received 4 drops of Anu taila (traditional nasal drop) in each nostril every day 1 h before breakfast. Patients in the placebo group received identical-looking tablets and drops, post-randomization, and double-blinded assortments. The RT-qPCR test was used for the detection of viral load in the nasopharyngeal and oropharyngeal swab samples of study participants during the study. Chemiluminescent immunometric assay was used to quantify serum levels of interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), and high sensitivity C-reactive protein (hs-CRP) on day 1 and day 7 of the study. Patient testing negative for SARS-CoV-2 in the RT-PCR analysis was the primary outcome of this study.

By day three, 71.1 % and 50.0 % of patients recovered in the treatment and placebo groups, respectively. The treatment group witnessed 100 % recovery by day 7, while it was 60.0 % in the placebo group. Average fold changes in serum levels of hs-CRP, IL-6, and TNF-α in the treatment group were respectively, 12.4, 2.5 and 20 times lesser than those in the placebo group at day 7. There was a 40 % absolute reduction in the risk of delayed recovery from infection in the treatment group.

The authors concluded that Ayurvedic treatment can expedite virological clearance, help in faster recovery and concomitantly reduce the risk of viral dissemination. Reduced inflammation markers suggested less severity of SARS-CoV-2 infection in the treatment group. Moreover, there was no adverse effect observed to be associated with this treatment.

I have the following concerns or questions about this trial:

  • Why do the authors call it a pilot study? A pilot study is merely for testing the feasibility of a trial design and is not meant to yield definitive efficacy results.
  • The authors state that the patients were asymptomatic yet in the discussion they claim they were asymptomatic or mildly symptomatic.
  • Some of the effect sizes reported here are extraordinary and seem almost too good to be true.
  • The claim of no adverse effect is implausible; even placebos would cause perceived adverse effects in a percentage of patients.
  • If the study is solid and withstands the scrutiny of the raw data, it is of huge relevance for public health. So, why did the authors publish it in PHYTOMEDICINE, a relatively minor and little-known journal?

An article in The Economic Times’ reported this:

Patanjali Ayurved released what it called the first “evidence-based” medicine for Covid-19 on Friday. It claimed it has been “recognised by the WHO (World Health Organization) as an ayurvedic medicine for corona”.

Patanjali promoter, yoga guru Baba Ramdev, released a scientific research paper in this regard at the launch, presided over by Union health minister Harsh Vardhan and transport minister Nitin Gadkari.

The Ayurveda products maker said it has received a certification from the Ayush ministry. “Coronil has received the Certificate of Pharmaceutical Product (CoPP) from the Ayush section of Central Drugs Standard Control Organisation (CDSCO) as per the WHO certification scheme,” it said in a statement.

Under the CoPP, Coronil can be exported to 158 countries, the company said, adding that based on the presented data, the ministry has recognised Coronil as medicine for “supporting measure in Covid-19”.

Am I the only one who fears that something is not entirely kosher about the study? (This is an honest question, and I would be pleased to receive answers from my readers)

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