A sudden reversal of fortune for the biopsychosocial model of illness

Actually, I think this has been coming for a long time, but it just might have happened this morning in the UK online newspaper, The Independent. The public conversation has shifted about the biopsychosocial model of myalgic encephalomyelitis (ME; formerly known as chronic fatigue syndrome) in ways that will not be readily reversed.

Time for unrest: why patients with ME are demanding justice.

A new film sheds light on a condition that is largely ignored. Nathalie Wright reports on the struggles patients based to be taken seriously by doctors.

The Independent article is a long read. I will only ask you to read the first three paragraphs. Unless I am mistaken, you probably read the rest. I encourage you to even count the short three sentence opening as one of those three paragraphs.

“I feel seen for the first time!” exalts one viewer. “I feel vindicated. I finally understand what’s wrong with me, I think I’ve had this all my life,” says another. A doctor admits, “I feel so ashamed.”

I have a brief anecdote about two sobbing, ashamed doctors that I encountered in Amsterdam, but I’ll leave that to the end. Now I only want to pick out a couple of paragraphs that I hope you will not miss if you take on this long read.

The patients’ dilemma

For patients, communicating the seriousness of their illness is often impossible. “I had this experience of trying to describe my symptoms in words to my doctors for 18 months as I was getting worse,” explains Brea. “I would talk about a burning in my brain or my spine or the fact that I would lose the ability to speak or sometimes I would collapse on the floor and I couldn’t lift my head.” When she later requested her medical records almost all of these serious symptoms were translated into “headache pain”.

The biopsychosocial model

Psychosomatic explanations of the disease were being further developed by a small, but influential, group of psychiatrists in the UK. They developed a theory of ME based on the biopsychosocial model of illness, a framework for illness that has also been adopted by the Department for Work and Pensions (DWP), first fully embraced by New Labour. The biopsychosocial model states that illnesses are part biological, part mental, part social. This idea seems common sense, but in practice it is often the psychological elements that are emphasised. Thus, the “biopsychosocial” model of ME is that a patient may have originally had a virus but after that, symptoms are not primarily the result of an ongoing disease process at all. Instead, patients simply have “dysfunctional” or “false” illness beliefs and thus adopt the “sick role”. Spending too much time in bed is the reason they have physical abnormalities, as they become deconditioned due to “exercise avoidance”, and it is assumed that symptoms are reversible by the patient’s own efforts.

My intrusive thought I probably should not share: I wonder if Sir Simon Wessely – if he read this far this morning – is feeling small.

The inseparable politics of the biopsychosocial model

The biopsychosocial model, and the assumption that if people who become disabled from conditions like ME adopted the correct attitudes and behaviours they could recover, seems to appeal to politicians looking to cut the costs of disability payments. “Benefits can often make [ME] patients worse” claimed psychiatrist Simon Wessely, one of the originators of the biopsychosocial model of ME, in 1993 in a meeting with a minister for the disabled. If giving disability benefits to patients, such as those with ME, may foster a culture of dependency, then cutting these benefits can be presented as a positive intervention. According to a document promoting the biopsychosocial framework circulated by Lord Freud, the former minister for welfare reform, it is important for those with health problems like ME to “recognise that the sick role is temporary, in the expectation of recovery” and that giving disability benefits to such patients, may foster a culture of dependency.

The dangerous militancy of patients has been “grossly exaggerated”

Throughout it all, patients were depicted as dangerous militants in the media for criticising the trial, even though they turned out to be vindicated. The tribunal which ordered the release of the trial’s data ruled that “assessment of activist behaviour was, in our view, grossly exaggerated”. The most severely ill (about a quarter of patients are bed or housebound) continued to receive no care at all, with 80 per cent of requests for home visits turned down by the NHS. Added to this, a dearth of social care and difficulty getting benefits meant many patients were left completely desperate and often without any support at all, with even family members often disbelieving their illness. The waste of human potential caused by ME was recently reckoned to cost the UK economy £3.3bn a year in a report by The Optimum Health Clinic Foundation.

Your conflict of interest is showing and should be disclosed

As critics are increasingly pointing out, the problems with PACE went beyond bad science. A 2006 report by the parliamentary Group on Scientific Research into Myalgic Encephalomyelitis had already pointed out that there is a “vested interest private medical insurance companies have in ensuring CFS/ME remains classified as a psychosocial illness”. The report also mentioned cases where advisers to the DWP had also had consultancy roles in such companies. These links were investigated further by the Centre for Welfare Reform who stated in 2016 that: “Emphasising the importance of psychosocial factors and classing ME as a mental health problem could bring immediate financial benefits to insurance companies when policies limit payouts for mental health problems.”

The Americans have moved on

Across the pond in the US, science is moving on. In 2013 the US government asked the Institute of Medicine to convene an expert committee to examine the evidence base for ME. Two years later, their report Redefining an Illness was published. The report stated ME is “an acquired, chronic multi-systemic disease biological in nature” symptoms of which include “immune, neurological and cognitive impairment”. After reviewing thousands of medical papers, the report “stresses that this is a medical – not a psychiatric or psychological – illness”.

Two sobbing, ashamed physicians

I spoke at a showing of Unrest at Amsterdam Medical Centre in October. You can find a copy of a video here.

After the showing, I was leaving to meet friends for dinner. I stopped when I encountered two stylish women still sitting in their seats in the emptying auditorium, sobbing as if one of them had just received a diagnosis of cancer. I said “Excuse me, can I help?” One woman started to talk, but the other had to finish for her.

“My sister and I are both physicians. We just learned tonight how much harm we had been doing to our patients. We were only trying to do what was best for them, but we refused to listen to them. We feel very badly.”

I said:

“I believe that you thought you would doing what was best. Now you feel differently. I’ll bet a lot of your colleagues aren’t there yet. Maybe you and your sister can feel a bit better about yourselves if you help your colleagues get there.”

I turned and walked anyway without seeing their responses.

 

Systematic review shows no improvement in quality of mindfulness research in 16 years

Should we still take claims about mental health benefits of mindfulness with a grain of  salt? A systematic review by one of mindfulness training’s key promoters suggests maybe so.

saltCritics have been identifying the same weaknesses in mindfulness research for almost two decades. This review suggests little improvement in 16 years the quality of randomized trials for mental health problems.

This study examined 171 articles reporting RCTs for:

(a) active control conditions, (b) larger sample sizes, (c) longer follow-up assessment, (d) treatment fidelity assessment, (e) reporting of instructor training, (f) reporting of ITT samples.

What was missed

Whether articles reporting RCTs had appropriate disclosure of financial or other conflicts of interest. COI pose significant risk of bias, especially when they are not reported.

This article discloses authors’ interests. One of the authors, Richard Davidson is a prominent promoter of mindfulness training.  A Web of Science search of Davidson RJ and mindfulness yielded 26 articles from 2002 to 2016. It would be interesting to check in see if these consistent weaknesses in mindfulness research are mentioned in these articles. To what extent do RCTs with Davidson as an author had these weaknesses, like being underpowered?

Critic: You say financial interests or other investments in a treatment are a risk of bias. Yet, this article is critical of mindfulness research. Wouldn’t you expect a more positive appraisal of the literature because of the authors having a confirmation bias?

Not necessarily. Conflicts of interest are a risk of bias, but don’t discredit an author, They only alert readers to be skeptical. Furthermore, the weaknesses in this literature are so pervasive, it would be difficult to put a positive spin on them.  Besides calling attention to specific weaknesses that need to be addressed in future research can become part of a pitch for more research.

The article

Goldberg SB, Tucker RP, Greene PA, Simpson TL, Kearney DJ, Davidson RJ. Is mindfulness research methodology improving over time? A systematic review. PLOS One. 2017 Oct 31;12(10):e0187298.

End of paper conclusion:

In conclusion, the 16 years of mindfulness research reviewed here provided modest evidence that the quality of research is improving over time. There may be various explanations for this (e.g., an increasing number of novel mindfulness-based interventions being first tested in less rigorous designs; the undue influence of early, high-quality studies). However, it is our hope that demonstrating this fact empirically will encourage future researchers to work towards the recommendations here and ultimately towards a clearer and scientifically-informed understanding of the potential and limitations of these treatments.

From the abstract

Objectives

The current systematic review examined the extent to which mindfulness research demonstrated increased rigor over the past 16 years regarding six methodological features that have been highlighted as areas for improvement. These feature included using active control conditions, larger sample sizes, longer follow-up assessment, treatment fidelity assessment, and reporting of instructor training and intent-to-treat (ITT) analyses.

Data sources

We searched PubMed, PsychInfo, Scopus, and Web of Science in addition to a publically available repository of mindfulness studies.

Study eligibility criteria

Randomized clinical trials of mindfulness-based interventions for samples with a clinical disorder or elevated symptoms of a clinical disorder listed on the American Psychological Association’s list of disorders with recognized evidence-based treatment.

Study appraisal and synthesis methods

Independent raters screened 9,067 titles and abstracts, with 303 full text reviews. Of these, 171 were included, representing 142 non-overlapping samples.

Results

Across the 142 studies published between 2000 and 2016, there was no evidence for increases in any study quality indicator, although changes were generally in the direction of improved quality. When restricting the sample to those conducted in Europe and North America (continents with the longest history of scientific research in this area), an increase in reporting of ITT analyses was found. When excluding an early, high-quality study, improvements were seen in sample size, treatment fidelity assessment, and reporting of ITT analyses.

Conclusions and implications of key findings

Taken together, the findings suggest modest adoption of the recommendations for methodological improvement voiced repeatedly in the literature. Possible explanations for this and implications for interpreting this body of research and conducting future studies are discussed.

Competing interests

RD is the founder, president, and serves on the board of directors for the non-profit organization, Healthy Minds Innovations, Inc. In addition, RD serves on the board of directors for the Mind and Life Institute. This does not alter our adherence to PLOS ONE policies on sharing data and materials

The variables examined in the systematic review

Six methodological features that have been recommended in criticisms of mindfulness research [10–12. 14]. These include: (a) active control conditions, (b) larger sample sizes, (c) longer follow-up assessment, (d) treatment fidelity assessment, (e) reporting of instructor training, (f) reporting of ITT samples.

…We graded the strength of the control condition on a five-tier system. We defined specific active control conditions as comparison groups that were intended to be therapeutic [17]. More rigorous control groups are important as they can provide a test of the unique or added benefit a mindfulness intervention may offer, beyond non-specific benefits associated with the placebo effect, researcher attention, or demand characteristics [11,14]. Larger sample sizes are important as they increase the reliability of reported effects and increase statistical power [11]. Longer follow-up is important for assessing the degree to which treatment effects are maintained beyond the completion of the intervention [10]. Treatment fidelity assessment allows an examination of the degree to which the given treatment was delivered as intended [12]. Treatment fidelity is commonly assessed through video or audio recordings of sessions that are coded and/or reviewed by treatment experts [18]. We coded all references to treatment fidelity assessment (e.g., sessions were recorded and reviewed, a checklist measuring adherence to specific treatment elements was completed). Relatedly, reporting of instructor training increases the likelihood that the treatment that was delivered by qualified individuals [12], which should, in theory, influence the quality of the treatment provided. Lastly, the reporting of ITT analyses involves including individuals who may have dropped out of the study and/or did not complete their assigned intervention [12]. Generally speaking, ITT analyses are viewed to be more conservative estimates of treatment effects [19,20], and are preferred for this reason.

 

No, seats on the US Institute of Medicine advisory committees are not for sale, despite what the Dutch Parliament was told

How the Executive Director of the Health and Medicine Division of the IoM responded to Professor Pim van Gool, the President of the Dutch Health Council disparaging the reputation of the IoM in testimony to the Dutch Parliament.

A likely reason for this unprofessional behavior is that van Gool was motivated to discredit the IoM’s stance on myalgic encephalomyelitis/chronic fatigue syndrome (MEcfs) because a recent document fron the IoM undermines the status quo concerning the illness in the Netherlands..

The incident speaks to the trustworthiness and commitment of the Dutch Health Council to best evidence in evaluating policies concerning MEcfs. Patients and their carers and advocates would do well to be vigilant for the next move from the Dutch Health Council.

The excerpt below is a translation of a transcript from a June 15, 2016 hearing before the Dutch Parliament. The President and Vice President of the Health Council of the Netherlands were appearing before Parliament to inform members about the installation of advisory committees concerning MEcfs.

Special thanks to Lou Corsius who provided the videotape, complete with English subtitles,  as well as the official response from the Institute of Medicine, which was a direct response to an inquiry from Lou.

The misrepresentation of the Institute of Medicine that occurred has immediate current relevance because of the likelihood that  Parliamentiary meetings will soon be held to reevaluate the official Dutch position on this illness.

Who’s who in the excerpt from the transcript

Pim van Gool: President of the Dutch Health Council

Henk Van Gerven: MP, Chairman of this meeting

Hans Severens: Vice President of the Dutch Health Council

Transcript [downloaded and edited from the subtitles provided by Lou Coursius

Starting at 6 minutes 54 seconds

Van Gool:  We received the request to advise in April 2015. At that time we had already been starting up because we knew this request would be submitted. We took explicitly notice of the IOM [Institute of Medicine] report in the US, dated February 2015.

Van Gerven: Can you explain IOM? Not everybody knows what that is.

Van Gool: Institute of Medicine. That is… we want to say that is a bit like the American Health Council. It is not exactly comparable. They  show a bit less scrutiny towards the interests of participants there. Amongst other things one can buy a chair to participate in the advisory process. That is an interesting business model but that is not the model we apply (Van Gool and Severens chuckle). Immediately in May & June one of our most experienced and respected scientific secretaries, dr De Neeling, has contacted 9 scientific associations, the general practitioners, the specialists in internal medicine, in physical rehabilitation, the neurologists, the association for behavioural therapy, the paediatricians, physicians in occupational medicine, etcetera, to actually ….as a hall stand (as a frame) we took that American report, more than 300 pages, very broad exploration, with also a very interesting new position that has been taken,  including a proposition to use another terminology for these issues (he does not use the word illness). We asked them to reflect on this IOM report as a start, actually.

Why did Pim van Gool misrepresent the Institute of Medicine?

 He and his fellow health council members were quite unhinged by the shift in the official American position concerning MEcfs in a report released by the IoM in February 2015. van Gool alludes to the report in the transcript excerpt suggests there is a mobilization of effort to undermine it.

Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness

The full IoM report  is freely available here

A 4-page official briefing on the IoM report is available here.

The primary message of the committee’s report is that ME/CFS is a serious, chronic, complex, systemic disease that often can profoundly affect the lives of can profoundly affect the lives of patients.

IOM diagnostic.PNGImportantly, the IOM report provided new diagnostic criteria that made post-exertional malaise (PEM) a requirement for a diagnosis. It is a defining symptom:  no PEM means no diagnosis of MEcfs is warranted.

PEM

Dutch treatment studies employed looser criteria that did not require PEM. The IOM diagnostic criteria have subsequently been used by the US Agency for Healthcare Quality Research (AHQR) to reject the relevance of any research, notably Dutch research, that did not include PEM in the entry criteria. Furthermore, patients who are characterized by PEM are likely to be harmed by cognitive behavioral therapy and graded exercise therapy, which are considered frontline treatment in current Dutch guidelines. The US Center for Disease Control would subsequently removed CBT and GET from the list of recommended treatments.

To preserve their status quo, the Dutch Health Council must discredit the IOM report.

Lou Corsius alerted the IOM to Pim van Gool and obtained this response:

The official response from the Institute of Medicine

Director IOM: Official statements President Dutch Health Council incorrect

Van: Behney, Clyde <CBehney@nas.edu>

Verzonden: zondag 19 juni 2016 22:40

Aan: Lou Corsius

CC: Frakes, Chelsea

Onderwerp: RE: Questions about scrutiny IOM, claims posed by president of Health Council of the Netherlands

Dear Mr. Corsius,

Thank you for bringing this matter to our attention.  The National Academies of Sciences, Engineering, and Medicine (the Academies) stand behind the Institute of Medicine (IOM) report, which was prepared by experts in the subject matter and was subjected to our rigorous peer review process before it was released, as we do for each of our studies.

I can assure you that the only way one can become a member of the National Academy of Medicine (NAM, formerly IOM) is by being elected by the members of the National Academy of Medicine based on distinguished professional achievement in a field related to medicine and health. One must first be nominated by two members of the NAM who are required to document how a nominee meets the criteria for membership and then be subsequently elected by the full membership of the NAM.

One cannot buy a membership in the NAM, nor can one buy a role as a member of one of the committees that conduct studies and produce our reports. Additionally, all members, including the chairs, of our study committees undergo a very strict review for conflicts of interest prior to their appointment, and we also notify the public about the proposed members for each of our committees twenty days before the first committee meeting so that the public can identify any potential conflicts of interest before the committee begins its work.

Thank you again for making us aware of the statements.

Very best regards,

Clyde

Clyde J. Behney

Executive Director

Health and Medicine Division

National Academies of Sciences,

Engineering, and Medicine

 

 

Parents should have been warned about unprofessional providers in Esther Crawley’s SMILE trial

The providers of Lightning Process in the SMILE trial were not credentialed health professionals and are not bound by ethical codes.

giphyEsther Crawley’s overdue publication of results from the SMILE trial  deserves close scrutiny for lots of reasons. But especially for what is said about the supervision and qualifications of Lightning Process practitioners who delivered the treatment.

Readers can easily gloss over a seemingly straightforward description of these practitioners in the paper. Yet, a little probing and checking of sources should cause some alarm among the parents who agreed to their children participating in the trial.

The details are alarming enough to cause worry about participating in any clinical trial involving Esther Crawley. She does not look after the safety and rights of children in her care.

This trial was approved by a number of committees at Bristol University. Assured by those well-publicized approvals, parents undoubtedly assumed that their children were protected from risks and needless exposure to quack treatments or providers not bound by enforceable ethical codes. The children did not have these protections, which should give pause to anyone contemplating allowing their children to participate in a trial regulated by Bristol University.

What was said in the published paper

LP practitioners have completed a diploma through the Phil Parker Training Institute in Neurolinguistic Programming, Life Coaching and Clinical Hypnotherapy. This diploma is examined through written and practical examinations and is accredited by the British Institute of Hypnotherapy and NLP. Following the diploma, LP practitioners undertake a further course to learn the tools and delivery required for the LP after which they must pass both a practical and written examination. Practitioners undertake supervision and continuous professional development in order to further develop their skills and knowledge. They are regulated by the register of LP practitioners, adhere to a code of conduct and there is a Professional Conduct Committee that oversees complaints and professional practice issues.

Let’s isolate and probe some of these statements.

LP practitioners have completed a diploma through the Phil Parker Training Institute in Neurolinguistic Programming, Life Coaching and Clinical Hypnotherapy.

advanced practitionerComment: This is does not represent anything approaching a degree from an accredited university or training institute. Phil Parker has been sanctioned by the UK Advertising Standards Authority for false claims about treating and even curing complex medical conditions. Yet the SMILE trial presented the Lighting Process as a treatment to the parents and children.

It would be fascinating to debrief the parents to discover what they assumed in consenting to their children’s participating in the trial. Did they think the children were being treated? Were they informed that the ASA forbade billing Lightning Process as a treatment? That the treatment providers were not chartered or qualified medical or mental health providers?

Neurolinguistic Programming has been widely discredited as quackery and is no longer is discussed in the scientific or clinical literatures.

Life Coaching is so vague a term as to be meaningless. There is no regulation or consistent specification of what is done or forbidden to be done in life coaching.

Clinical Hypnotherapy is not a restricted, independently recognized, nor chartered class of provider. Anyone can call themselves a clinical hypnotherapist. Phil Parker’s institute issues meaningless certificates that be hung on providers’ walls to confuse consumers.

This diploma is examined through written and practical examinations and is accredited by the British Institute of Hypnotherapy and NLP.

 Comment: Sounds impressive, huh? The ‘written and practical examinations’ involve showing adeptness in delivering a quack treatment that involves making false claims and offering pseudoscientific explanations to patients- messages defined by those who sell the training products.  Ability to meet these criteria involves taking trademarked training courses in quackery. Any deficiencies in knowledge or practice that examiners perceive are remedied by taking more courses. Essentially, this is a pyramid scheme from which Phil Parker benefits financially.

Reassured that providers are accredited by “British Institute of Hypnotherapy and NLP?” Go visit the website and you can readily see that it is an extension of Phil Parker’s marketing effort, not something independent or otherwise chartered or regulated. The site offers courses in referrals to people who have completed courses.

At the website a rotating variety of pseudoscientific explanations are provided with claims of dramatic effects of hypnosis that are at odds with the evidence. Visitors are led to believe that hypnotherapy is effective for reducing blood pressure and stopping smoking:

Hypnotherapy can help you kick the habit of smoking into touch for good.

Compare that to what is said by the Cochrane Collaboration:

Does hypnotherapy help people who are trying to stop smoking?

We have not shown that hypnotherapy has a greater effect on six-month quit rates than other interventions or no treatment. There is not enough evidence to show whether hypnotherapy could be as effective as counselling treatment. The effects of hypnotherapy on smoking cessation claimed by uncontrolled studies were not confirmed by analysis of randomized controlled trials.

The site also falsely claims that hypnotherapy can reduce blood pressure. The site is basically an advertisement for exaggerated claims about hypnosis backed by pseudoscientific explanations of how it works.

Hypnotherapists now understood neurology and physiology of using hypnosis and have the evidence of neurosciences support this understanding.

not psychologicalNonsense. This British Institute of Hypnotherapy and NLP is set up and run by a guy who claims neuroscience, osteopathy and neurolingustic programming explain the effects of the Lightning  Process, which are claimed to be physiological, not psychological. Who believes these additional claims about hypnosis are valid?

Consumer beware.

Practitioners undertake supervision and continuous professional development in order to further develop their skills and knowledge.

But the supervision is in use of a commercial product with a pseudoscientific explanation. So, apparently practitioners are supervised in their willingness and ability to adhere to the scripts they have received as part of products they have purchased. The “continuous professional development” is taking a steady stream of Phil Parker’s training courses. Because his materials are trademarked, no one who is not authorized by Parker to sell his merchandise.

They are regulated by the register of LP practitioners, adhere to a code of conduct and there is a Professional Conduct Committee that oversees complaints and professional practice issues.

There is a financial conflict of interest in Phil Parker offering courses and training and what the ASA has said cannot be described as treatment and then setting up a professional conduct committee is tied directly to his products.

What should parents be able to expect in bringing their children to a recognized, regulated healthcare site, like the NHS? The treatment providers should be professionals licensed by a governmental or independent body separate from any marketing of training. If not fully licensed or regulated professionals, they should be supervised by professionals, such as medical or mental health clinicians.

The class of providers should also be licensed or chartered so that sanctions with legal consequences can be applied for misconduct or unethical behavior. Providers working with children should be held to some ethical standards in terms of the safety and rights of both children and their parents.

None of these features are present in the treatment provided in the SMILE trial.

Christine Fenton, a retired Deputy Head of two high schools in the UK notes she was responsible for child protection in those roles. She expressed this concern about the basic conflict of Lightning Process and tenets of childhood protection:

LP participants are directed to not talk to others about it – keep secrets – to report positively regardless of their internal view is appalling to me. Child Protection has a key tenet ‘secrets are not ok’ – if an adult tells a youngster to keep a secret it is a form of control & creates an environment in which abuse can occur more easily.

Teachers, like other professionals coming in contact with children are required to take courses about child protective services and the duty to report abuse. They are held legally responsible for violation of the associated rules. However, legally, providers of the lightning process are only ordinary citizens, not professionals and are not held responsible in this manner.

In obtaining approval for the conduct of the SMILE trial from Bristol University, Pediatrician Esther Crawley claimed that sessions of the writing process were taped and that she had responsibility for reviewing the tapes. It strains credibility to claim that she actually listened to all the tapes from the study.

But what does it mean for a physician to supervise a quack treatment provided by quack providers who are not being allowed to call what they do treatment? How does Crawley react when physically ill, impaired children are instructed to deny their fatigue and pain to authority figures such as teachers and parents?

Truly mind-boggling to consider.

Conflict of interest in manuscript peer-review: Expert opinions

Discussion of a recent court case concerning a peer reviewer who failed to disclose a conflict of interest has broader application.

The Committee on Publication Ethics (COPE) has defined the need for authors to declare any potential conflicts of interest in review of the manuscript.

 Recently, Retraction Watch discussed a court case in which one issue was the failure of a reviewer to declare a conflict of interest. Retraction Watch interviewed that peer reviewer and obtained some expert opinions.

bruberg

Kjell Gundro Brurberg, the author accused of misconduct by the Editor of Journal of Health Psychlogy when he nominated reviewers with obvious conflicts of interest.

These opinions are directly relevant to a decision by the Editor of Journal of Health Psychology to reject an appeal of a previous negative decision about manuscript submitted to be part of the Special Issue on PACEgate. The author, Kjell Gundro Brurberg was given an unusual opportunity to nominate additional reviewers, but with the provision that the author ensure reviewers not have a conflict of interest. Nomination of three reviewers with blatant conflicts of interest led to the withdrawal of the opportunity for reconsideration and charges by the editor of authorial misconduct.

The issue of author conflict of interest is also relevant to the controversial Cochrane Review, which Brurberg  co-authored  with others associated with the PACE trial.

Committee on Publication Ethics: Basic Principles

The Retraction Watch article started with a link to the basic principles for reviewers of the Committee on Publication Ethics (COPE), which are clearly spelled out at COPE’s website.

cope basic principles

The legal case in whicn reviewer conflict of interest comes up.

Retraction Watch then summarized a case [A fascinating read, in itself]

Bryan Hardin testified that he was a peer reviewer on a 2016 paper in Critical Reviews in Toxicology, which found that asbestos does not increase the risk of cancer. In the deposition, Hardin—who works at the consulting firm Veritox—also said that he has testified in asbestos litigation on behalf of automakers, such as Ford, General Motors, and Chrysler, but said he had not disclosed these relationships to the journal.

Last year, the first author of the 2016 review withdrew a paper from another journal (by the same publisher) which concluded asbestos roofing products are safe, following several criticisms — including not disclosing the approving editor’s ties to the asbestos industry. In this latest case, the journal told us it believes the review process for the paper was up to snuff, but two outside experts we consulted said they believed Hardin’s relationships — and failure to disclose them — should give the journal pause.

After obtaining a transcript of the case, Retraction Watch interviewed the author and inquired whether he had disclosed a conflict of interest

“No. If — if that’s a new expectation, I’m not aware that as a peer reviewer you’re supposed to disclose that sort of thing, but I — I don’t recall that I did.”

The author further said:

“I have been a peer reviewer on more than one asbestos-related paper” and “I have been retained by ‘several’ companies involved in asbestos litigation.”

Expert opinon

In the article Retraction Watch raised the issue of whether the author’s  ties to the asbestos industry be considered a conflict of interest. An opinion was obtained from Elizabeth Wager, a member of the board of directors of The Center For Scientific Integrity, our parent non-profit organization:

“I’d definitely regard giving expert testimony as a conflict of interest that should be declared by a potential reviewer (or an author). This is also in line with the views of many journals, such as PLOS which specifically notes that “acting as an expert witness” constitutes a non-financial competing interest. In other words, it doesn’t matter whether or not you were paid for such services, just testifying suggests a strong allegiance or interest which editors deserve to know about.”

A further opinion was obtained by Retraction Watch from Trudo Lemmens, a professor of Law & Bioethics at the University of Toronto in Canada who was not involved in this case.

“In my opinion, a peer reviewer who has as an expert been working for a particular industry on a specific issue should at least disclose to the journal his ties to the industry whose interests can be affected by the publication of a paper on that topic.  And journal editors should exclude such peer reviewers from reviewing a paper on that or a related topic, or at least ensure that there are several other more independent reviews of the paper. If for one reason or another they think it is important to get a review by an expert with such a conflict of interest, they should assess that review much more critically. They should then also provide an opportunity to the authors to respond to the peer-review before making a publication decision.”

Lemmens added:

But the more cautious approach would be to exclude reviewers with such a clear COI.

Retraction Watch continued  the discussion with a further quote from Wager:

It’s up to the editor to decide whether a conflict of interest is so great as to disqualify the reviewer, but, whatever the editor decides, s/he obviously needs to be made aware of it by the invited reviewer…If a reviewer’s failure to disclose a relevant interest comes to light after publication the journal should look at the review comments again.

In the thread of comments on the Retraction Watch article

Commentor Richard David Feinman noted:

The problem assumes greater importance when it comes to competing theories in medicine and especially, my own area, medical nutrition. A editor is supposed to recognize a controversial subject and appoint reviewers from both sides of the controversy. Failure to do so constitutes de facto (or intentional) bias. The perfunctory, often inappropriate — take what you can get when you get people to work for you for nothing — guarantees that the party line will be heard and there will be little input from minority opinions.

And, if you do object, you are — if you are lucky — told to submit a letter to the editor. If they take it — no guarantee of publication — the original author has the last word and it is, in any case, like an objection in a court of law: even if sustained, the damage has been done.

Journal of Health Psychology Editor responds to misrepresentations by Cochrane author in Mental Elf blog

A Cochrane review author made a number of false claims in his Mental Elf blog post about why his manuscript about PACEgate was rejected by the Journal of Health Psychology.

Andre Tomlin, Editor of Mental Elf should accept responsibility for unfounded attack on integrity of editorial process at JHP.

Brurberg’s misrepresentations defending PACE suggest he is unfit to be a Cochrane reviewer and that he is a source of bias in Cochrane Reviews of graded exercise therapy for chronic fatigue syndrome

This incident lends weight to calls for release of data for independent reanalysis of Cochrane patient level meta analysis conducted by authors including Brurberg and the Principal Investigator of  the PACE trial.

Pacegate altBrurberg’s statements and the responses of David Marks, editor of Journal of Health Psychology

In his post at Mental Elf, Kjetil G. Brurberg claimed:

I was invited by the Journal of Health Psychology to comment on their ongoing PACE debate. Realizing that some people might view my role in a Cochrane review based on individual patient data as a potential conflict of interest (COI), I consulted the editor on these issues before accepting the invitation. Shortly thereafter, the editor confirmed that he did not see my potential COI a big problem.

david marksDavid Marks replies:

What I actually said was: ‘Almost everybody can be accused of ‘bias’ in one way or another. Any potential conflicts can be declared at the end of the article.” In his original submission, Brurberg declared his COIs as follows: “Kjetil G. Brurberg has co-authored a Cochrane Review about exercise for CFS/ME in which the PACE-trial is included. Brurberg is also a member of the steering committee for an Cochrane individual patient data review that is now submitted.”

Contrary to Brurberg’s statement, it is important to note that his declaration of a conflict of interest was not the reason for the rejection of his paper.  The paper was rejected because of several faults and flaws.  The reviewer’s report listed 14 issues with the paper and ended with the recommendation that “this commentary cannot be accepted without a response to cover the issues raised above.”

The rejection letter sent to the authors was in standard format and COI did not enter the equation. The rejection letter was as follows:

“01-Mar-2017

Dear Dr. Brurberg:

I write you in regards to manuscript # JHP-17-0133 entitled “A PACE-gate or an editorial without perspectives?” which you submitted to the Journal of Health Psychology.

In view of the criticisms of the reviewer found at the bottom of this letter, your manuscript has been denied publication in the Journal of Health Psychology. However I trust the reviewers’ comments will be helpful in the further development of your research for publication.

Thank you for considering the Journal of Health Psychology for the publication of your research.

With best wishes,

David F Marks PhD
Editor
Journal of Health Psychology

editorjhp@gmail.com

David Marks further states:

Brurberg is not telling the truth when he states: “The same COI, however, suddenly became a major issue when I submitted the commentary and my opinions were made known.”

brubergBrurberg also stated in the Mental_Elf  blog:

“all authors who have been supportive to the PACE-trials have been collectively refused.”

David Marks replies.

This statement is manifestly false. The paper by the PACE authors themselves (White, Chalder, Sharpe et al.) and the  paper supportive of PACE paper by Petrie and Weinman were both accepted for publication.  Three papers favorable to PACE were rejected following peer review, in two cases following appeal, because they were of poor  quality. In one case, that of Brurberg et al., the authors misrepresented the Conflict of Interest of the reviewers they had recommended. The attempt by Brurbergb  to deny the reviewers’ COI is futile. Their COI was unambiguously demonstrated and the evidence for it was provided to Brurberg.

Yet, in the thread of comments to his post at Mentsal Elf, Kjetil G. Brurberg compounded his misrepresentations.

The claim that I have nominated reviewers with known conflicts of interest is simply not true…

When asked to nominate reviewers to my own work, I find it important to suggest people who holds the needed distance to me and my work. As the distance increases, it becomes increasingly impossible to have a full overview of peoples’ social life during the last decade. I did not know that one of the suggested reviewers had been sitting next to one of the PACE-authors at a conference dinner, but I would not consider this as a serious conflict of interest.

 Editor Marks replies:

Brurberg fails to mention that the same person (prof x) who sat next to an author of the PACE trial paper at a dinner had also been supervised by another author of the PACE trial paper for 5 years!

When the reviewer recommended by Brurberg was asked to review Brurberg’s manuscript, he declined, stating,

“I might have a personal axe to grind, and having been supervised by Michael Sharpe (who may or may not have anything to do with this manuscript) between 5 and 10 years ago I would probably be regarded as irrevocably conflicted…”

Another reviewer nominated  by Brurberg, Professor Hans Knoop,  another nominated reviewer , wrote the laudatory editorial that accompanied  the original report of the PACE  trial in The Lancet.

The JHP Editor continued:

To bolster his crumbling position, Brurberg states:

“It should not be regarded as dishonest for authors or reviewers to have an opinion on disputed matters as the PACE trial.”

The JHP editor replies:

Nobody, and certainly not this editor, has ever stated that having an opinion is dishonest. What is dishonest is to falsely represent recommended reviewers as having no COI when their conflicts are manifestly strong and long-lasting.

Bruberg states in the blog post itself:

Despite being aware of my “conflicts of interest”, Journal of Health Psychology invited me to write a commentary on Geraghty’s editorial on the PACE trial. You did not declare however that JHP has intellectual conflicts of interests regarding the PACE trial, by only accepting reviewers representing the critics of the PACE trial, and rejecting papers from authors not sharing your views on the PACE trial.

If I had known, I would not have accepted the invitation.”

The Editor replies:

 I think I have already addressed this.

Part 2: What to look for in a Special Issue of Journal of Health Psychology concerning the PACE trial

Part 2: What to look for in the Special Issue of Journal of Health Psychology concerning the PACE trial

In a continuation of the last blog post, this one provides brief summaries and links to eight additional contributions to the special issue of Journal of Health Psychology. These articles include a reply to the PACE investigators’ response from Keith Geraghty, a defense of the trial from some friends and supporters (Petrie and Weinman) of the PACE investigators, and a commentary from Susanna Agardy on the conflicts of interest in this defense.

special issue spread

Apologies to the authors and readers for my not indicating yesterday that there were an additional eight summaries coming. Because of all the uncertainty about whether the special issue would be published on schedule or blocked, yesterday’s blog post was uploaded at the last minute and incomplete.

When the effort to block publication of the special issue failed, the PACE investigators got criticism posted at Science Media Centre. One commentary was attributed to anonymous sources at Oxford University and simply parroting things that the PACE investigators themselves have been saying all along. Another commentary was from Malcolm MacLeod, a former colleague of Michael Sharpe at University of Edinburgh, who also authored a paper with him. McLeod claims to have read the issue and found nothing of substance there. That was an amazing feat, because the Science Media Centre posted this critique only minutes before the special issue was available. We might conclude that McLeod is a speed reader. Judging from the superficiality of his comments, it could simply be a matter of his not having read the special issue

Who would’ve thought that a special issue of Journal of Health Psychology could garner such publicity?

McLeod also indiscreetly disclosed that he was a member of a committee advising PLOS One on whether to release to me the data from an article on the PACE trial. Availability of the data had been promised as a condition for publishing in PLOS One. Yet, over a year after my request, it has still not been provided. However the PLOS One article now prominently features an Expression of Concern, which often precedes a retraction. Regardless, McLeod’s disclosure cast doubt on the integrity of the decision-making process at PLOS One, given his obvious conflict of interest.

As a critic of the PACE trial from the United States, I noticed early on that I was dealing with a tight close-knit network, strongly interconnected with the British establishment, a real charmed circle. The opposition to the publication of the special issue of Journal of Health Psychology and the PACE investigators’ access to resources like Science Media Centre and placement of an article in The Times and who served as go-to sources put this network on public display.

However, the brouhaha and the foiled effort to block publication of the special issue and this extraordinary attentionin the media has  paradoxically generated considerable buzz about the special issue that would otherwise not have. We appreciate all the publicity we can get and we hope the PACE investigators will bring on some more. But for now, check out the brief summaries below and click on the links to the open access articles.

Special thanks to blogger John Peters for having put together these links and summaries.

 Eight articles from the Special Issue

Distress signals: Does cognitive behavioural therapy reduce or increase distress in chronic fatigue syndrome/myalgic encephalomyelitis?   Keith R Laws

Reducing the psychological distress associated with chronic fatigue syndrome/myalgic encephalomyelitis is seen as a key aim of cognitive behavioural therapy. Crucially, the claim by National Institute of Clinical Excellence that cognitive behavioural therapy reduces distress in chronic fatigue syndrome/myalgic encephalomyelitis is not only at odds with what patients repeatedly report in surveys, but with their own gold-standard randomised controlled trial and meta-analytic data.

Cognitive behaviour therapy and objective assessments in chronic fatigue syndrome Graham McPhee

Most evaluations of cognitive behavioural therapy to treat people with chronic fatigue syndrome/myalgic encephalomyelitis rely exclusively on subjective self-report outcomes to evaluate whether treatment is effective. A review of studies incorporating objective measures suggests that there is a lack of evidence that cognitive behavioural therapy produces any improvement in a patient’s physical capabilities or other objective measures such as return to work.

 PACE trial claims for recovery in myalgic encephalomyelitis/chronic fatigue syndrome – true or false? It’s time for an independent review of the methodology and results Charles Bernard Shepherd

Patient evidence has repeatedly found cognitive behaviour therapy is ineffective and graded exercise therapy can make the condition worse. The PACE trial methodology has been heavily criticised by clinicians, academics and patients. A re-analysis of the data has cast serious doubts on the recovery rates being claimed. The trust of patients has been lost. The medical profession must start listening to people with myalgic encephalomyelitis/chronic fatigue syndrome if trust is going to be restored.

The PACE trial: It’s time to broaden perceptions and move on Keith J Petrie, John Weinman

Differing beliefs about the causes of chronic fatigue syndrome still influence how scientific studies in this area are accepted and evaluated. Causal beliefs about chronic fatigue syndrome and a modern version of Cartesian dualism are important in understanding the reaction to the PACE trial. Science is incremental. An unfortunate outcome of the PACE controversy and intimidation of researchers may be less research in the area. It is time to move on from criticism and collect more data on effective treatments.

Defense of the PACE trial is based on argumentation fallacies Steven Lubet

In defense of the PACE trial, Petrie and Weinman employ a series of misleading or fallacious argumentation techniques, including circularity, blaming the victim, bait and switch, non-sequitur, setting up a straw person, guilt by association, red herring, and the parade of horribles. These are described and explained.

Chronic fatigue syndrome patients have no reason to accept the PACE trial results: Response to Keith J Petrie and John Weinman Susanna Agardy

Petrie and Weinman’s urging to accept the findings of the PACE trial is unreasonable in view of the failure of PACE to achieve evidence of recovery. The Institute of Medicine describes chronic fatigue syndrome not as psychological but as a serious, chronic, systemic disease, with post-exertional malaise as its main feature which inhibits exercise. Linking debate about PACE with intimidation of researchers is unjustifiable and damaging to patients.

Further commentary on the PACE trial: Biased methods and unreliable outcomes Keith J Geraghty

The PACE authors respond that ‘Dr Geraghty’s views are based on misunderstandings and misrepresentations of the PACE trial’. This article draws on expert commentaries to further detail the critical methodological failures and biases identified in the PACE trial, which undermine the reliability and credibility of the major findings to emerge from this trial.

PACE-GATE: An alternative view on a study with a poor trial protocol Bart Stouten

The controversies surrounding the effectiveness of cognitive behavioural therapy and graded exercise therapy for chronic fatigue syndrome are explained using Cohen’s d effect sizes rather than arbitrary thresholds for ‘success’. This article shows that the treatment effects vanish when switching to objective outcomes. The preference for subjective outcomes by the PACE trial team leads to false hope. This article provides a more realistic view, which will help patients and their doctors to evaluate the pros and cons.

What to look for in the Special Issue of Journal of Health Psychology concerning the PACE trial

special issue spread

 

A Special issue of Journal of Health Psychology concerns PACE, a trial of therapies for patients with myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS) that has attracted a great deal of controversy

Key points summarized from the David F. Marks’ introductory editorial

 Background

The idea for Special Issue started with Journal of Health Psychology receiving a manuscript from Keith Geraghty providing a critical review of the PACE Trial.

Following peer review and acceptance of a revision, the PACE investigators were offered an opportunity to respond to Keith Geraghty with an Open Peer Commentary paper.

The PACE investigators made a number of efforts to get Geraghty’s article outright retracted, either directly or through pressures on the editorial board.

When it was clear that the journal would not cave to such pressures, the  PACE investigators then demanded a partial retraction of the Geraghty  article and that the journal issue a correction reporting that the author had an undisclosed conflict of interest: he had failed to acknowledge that he was a patient suffering from myalgic encephalomyelitis.

The PACE investigators also demanded that their commentary manuscript will not be subject to peer review.

The PACE investigators received reviews of their manuscript. Editor Marks notes [Having been involved in editing this issue, I agree]:

After receiving critical reviews, the pro-PACE authors chose to make only cosmetic changesor not to revise their manuscripts in any way whatsoever. They appeared unwilling to enter into the spirit of scientific debate. They acted with a sense of entitlement not to have to respond to criticism.

The review and response from the PACE investigators was sent to more than 40 experts on both sides of the debate for commentaries.

After the online publication of several critical Commentaries, the PACE investigators were offered a further opportunity to respond to their critics in the round but they chose not to do so. There was little response, but a notable declining of further comment by the PACE investigastors:

As always, we would refer interested readers to our original publications and trial websitewhere most, if not all, the issues brought up by commentators are addressed

Conflict of interest.

[My comment: The PACE investigators and persons associated with them were quick to complain about the conflict of interest in the developing issie. As noted, this including a complaint about Geraghtybeing a patient and not disclosing it, mentioned above. But the investigators also threatened a formal complaint to the Committee on Publication Ethics concerning my having reviewed their manuscript. But there is an ironic backstory about the matter of conflict of interest. Some of which are discussed in contributions to the Special Issue:]

The PACE authors themselves appear to hold strong allegiances to cognitive behavioural therapy (CBT) and graded exercise therapy (GET) – treatments they developed for ME/CFS. Stark COI have been exposed by the commentaries including the PACE authors themselves who hold a double role as advisers to the UK Government.

 Department of Work and Pensions (DWP), a sponsor of PACE, while at the same time working as advisers to large insurance companies who have gone on record about thepotential financial losses from ME/CFS being deemed a long-term physical illness.In a further twist to the debate, undeclared COI of Petrie and Weinman (2017) werealleged by two of the commentators (Agardy, 2017; Lubet, 2017). Professors Weinman andPetrie adamantly deny that their work as advisers to Atlantis Healthcare represents a COI.

[My comment: In another instance, three pro-PACE authors attempted to subvert the journal’s policy on COI by recommending reviewers who were strongly conflicted, forcing rejection of their paper. I discussed this in another blog post.]

[My comment: Nonetheless, having gotten any commentary from the PACE investigators at all was an achievement. Even the limited responsiveness of the PACE investigators to Geraghty’s commentary, along with a supported commentary by their close colleagues Keith J Petrie and John Weinman, the special issue  represents one of most significant exchanges between defenders of the PACE trial and critics in a long while.]

ME/CFS research has been poorly served by the PACE Trial and a fresh new approach is needed by the PACE investigators to engage critics and skeptics.

Overall, the special issue provides, readers to make up their own minds about the scientific merits and demerits of the PACE Trial.  

Note that the entire Special Issue is available with free access.

journal of health psychologyThe individual papers

‘PACE-Gate’: When clinical trial evidence meets open data access. Keith J Geraghty

Published reports of the PACE trial overstated the effectiveness of cognitive behavioural therapy and graded exercise therapy, and did so  by lowering the thresholds they used to determine improvement. Reanalyzes conducted by professionals and patients revealed that the treatments tested had much lower efficacy after an information tribunal ordered the release of data from the PACE trial to a patient who had requested access using a freedom of information request.

Response to the editorial by Dr Geraghty. Peter D White, Trudie Chalder, Michael Sharpe, Brian J Angus, Hannah L Baber, Jessica Bavinton, Mary Burgess, Lucy V Clark, Diane L Cox, Julia C DeCesare, Kimberley A Goldsmith, Anthony L Johnson, Paul McCrone, Gabrielle Murphy, Maurice Murphy, Hazel O’Dowd, Laura Potts, Rebacca Walwyn and David Wilks

The trial found that adding cognitive behavior therapy or graded exercise therapy to specialist medical care was as safe as, and more effective than, adding adaptive pacing therapy or specialist medical care alone. Dr Geraghty has challenged these findings. We suggest that Dr Geraghty’s views are based on misunderstandings and misrepresentations of the PACE trial.

Once again, the PACE authors respond to concerns with empty answers. David Tuller

This commentary examines how the current response once again demonstrates the ways in which the investigators avoid acknowledging the obvious problems with PACE and offer non-answers instead—arguments that fall apart quickly under scrutiny.

Investigator bias and the PACE trial. Steven Lubet

Standards for determining researcher bias are considered and it is concluded that the PACE nvestigators’ impartiality might reasonably be questioned.

The problem of bias in behavioural intervention studies: Lessons from the PACE trial Carolyn Wilshire

In the PACE trial, cognitive behavioural therapy and graded exercise therapy had modest, time-limited effects trial on self-report measures, but little effect on more objective measures such as fitness and employment status.  In non-blinded trials, the issue of reporting biases deserves greater attention in future.

PACE trial authors continue to ignore their own null effect. Mark Vink

Protocols and outcomes for the PACE trial were changed after the start of the trial,  leading to exaggerated claims for the efficacy for both cognitive behavior therapy and graded exercise therapy. Findings of small, self-reported improvements in subjective measures cannot be used to say the interventions are effective, particularly in light of the absence of objective improvements with objective outcome measures.

The PACE trial missteps on pacing and patient selection. Leonard A Jason

The PACE trial investigators were not successful in designing and implementing a valid pacing intervention and patient selection ambiguity further compromised the study’s outcomes

Do graded activity therapies cause harm in chronic fatigue syndrome? Tom Kindlon

The trial’s poor results on objective measures of fitness suggest a lack of adherence to the activity component of these therapies. Therefore, the safety findings may not apply in other clinical contexts. Outside of clinical trials, many patients report deterioration with cognitive behavioural therapy and particularly graded exercise therapy. Also, exercise physiology studies reveal abnormalities in chronic fatigue syndrome patients’ responses to exertion. Given these considerations, one cannot conclude that these interventions are safe and risk-free.

PACE team response shows a disregard for the principles of science. Jonathan Edwards

The response by White et al. fails to address the key design flaw, of an unblinded study with subjective outcome measures, apparently demonstrating a lack of understanding of basic trial design requirements. The failure of the academic community to recognise the weakness of trials of this type suggests that a major overhaul of quality control is needed.

Bias, misleading information and lack of respect for alternative views have distorted perceptions of myalgic encephalomyelitis/chronic fatigue syndrome and its treatment. Ellen Goudsmit and Sandra Howes

These interventions delivered in the PACE trial are based on a model which assumes that symptoms are perpetuated by factors such as misguided beliefs and a lack of activity. Our analysis indicates that the researchers have shown significant bias in their accounts of the literature and may also have overstated the effectiveness of the above treatments. We submit that their approach to criticisms undermines the scientific process and is inconsistent with best practice.

PACE investigators’ response is misleading regarding patient survey results. Karen D Kirke

A review of survey data published between 2001 and 2015 reveals that for most patients, graded exercise therapy leads to worsening of symptoms, cognitive behavioural therapy leads to no change in symptoms, and pacing leads to improvement. The experience of people with ME/CFS as reflected in surveys is a rich source of information, made more compelling by the consistency of results. Consequently, patient survey evidence can be used to inform practice, research and guidelines. Misrepresentation of patient experience must be vigorously challenged, to ensure that patients and health professionals make decisions about therapies based on accurate information.

 

 

 

 

PACE-Gate: The Making of a Medical Scandal

An advance look at the press release for a forthcoming Editorial for a Journal of Health Psychology Special Issue on the PACE trial-A Medical Scandal.

Kudos to David Marks for the courage to put together this historic special issue.

Kudos to Keith Geraghty for his editorial around which the special issue of commentaries is organized.

‘PACE-Gate’: When clinical trial evidence meets open data access

The journal and its editorial board faced stiff resistance from the investigators from the PACE trial of cognitive behavioural therapy and graded exercise therapy for chronic fatigue syndrome.

The investigators first demanded a full retraction of Geraghty’s article. When their demand was rejected, they then demanded  a partial retraction, with a correction calling attention to Geraghty failure to disclose a conflict of interest- he suffers from chronic fatigue syndrome 

journal of health psychologyThe following press release provides an excellent background for the PACE trial and the controversy in which it has become embroiled. I hope it will whet your appetite for the freely available special issue.

THE PACE TRIAL: THE MAKING OF A MEDICAL SCANDAL

David F. Marks, JHP Editor

A Special Issue of the Journal of Health Psychology on the PACE Trial, is to be published and freely available online on Monday 31 July 2017. It marks a special contribution of the Journal of Health Psychology to the literature concerning interventions to manage chronic health problems. The PACE trial debate illustrates what can happen when researchers become entrenched in a particular point of view, and fail to engage in constructive exchange with critics and stakeholders. It reveals an unwillingness of the Co-Principal Investigators of the trial to engage in authentic discussion and debate. It leads one to question the wisdom of such a large investment from the public purse (£5million) on what is a textbook example of a poorly done trial.

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a controversial and poorly understood disease that blights the lives of over 250,000 people in the UK and at least 500,000 Americans. People with ME experience a dramatic decrease in their stamina for ordinary physical and cognitive activities, a characteristic dramatic increase in symptoms after minimal physical or cognitive exertion called post-exertional malaise, and a myriad of symptoms including sleep dysfunction, orthostatic intolerance and cognitive dysfunction as well as fatigue and pain. Normal activities like walking, showering, having a conversation or writing an email can leave people shattered for days or weeks or may simply be impossible. Most people with ME cannot work and 25% are confined to their homes or beds. The PACE Trial sought to test if two therapies, a talking therapy called ‘Cognitive Behavioural Therapy’ (CBT) and exercise in the form of ‘Graded Exercise Therapy’ (GET), might help.

The Trial attracted unprecedented criticism, not only because it cost taxpayers an extraordinary sum (almost £5 million) but the trial itself was deeply flawed. The results are, at best, unreliable, and, at worst, manipulated to produce a positive-looking result. Patient groups have cried foul because they believe they are being sold a lie that talk therapy and exercise can cure ME/CFS when in fact many experience actual harm.

The PACE Trial was led by Professor Peter White of Queen Mary University London (retired), Professor Michael Sharpe of Oxford University and Professor Trudie Chalder of Kings College London. They published their results in the Lancet in 2011 with the contentious claim that CBT and GET cured 22% of patients while over 60% improved. The patient community reacted with scepticism and after a long battle with the PACE authors, a patient from Australia, Mr Alem Matthees, won a Freedom of Information Tribunal case to gain access to a small sub-set of the PACE trial data.

It was discovered that the PACE authors had altered the way in which they measured improvement and recovery to increase the apparent benefit of the therapies.  Reanalysis by Wilshire and colleagues in 2016 in the Journal of Fatigue showed that the improvement rate fell from 60% to 21% and the recovery rate fell from 22% to just 7% when using the original study protocol. The genie was out of the bottle.

In 2016 the Journal of Health Psychology published an Editorial by Dr. Keith Geraghty of the University of Manchester entitled ‘PACE-GATE’.  Geraghty suggested that the PACE authors had altered their procedures to make CBT and GET look more beneficial. The PACE trial team reacted with anger and submitted a cursory reply. A host of experts on both sides of the debate were invited by JHP Editor Dr David F Marks to write Commentaries on the PACE Trial. All Commentaries were peer-reviewed. The majority agreed that the PACE Trial was flawed, that the PACE authors had altered their methods, breaking a fundamental principle of clinical trials, and that results from the trial were unreliable.

It also highlighted that the PACE Co-Principal Investigators had conflicts of interest by acting as consultants to large insurance companies and Professor White had also worked as an advisor to the Department of Work and Pensions, a main funder of the PACE trial, with a special interest in reducing social security benefits to disabled ME/CFS claimants.

Despite many serious concerns about the PACE Trial, the trial continues to be used by UK Governmental agencies, the NHS and the National Institute for Clinical Care Excellence  (NICE) as part of the evidence-base  to recommend CBT and GET to sufferers of ME/CFS. The current review by NICE of these treatments presents an opportunity to bring clinical practice properly in line with scientific evidence.

FOR FURTHER INFORMATION, PLEASE CONTACT:

UK & IRELAND:

Dr Keith Geraghty, JHP Editorial & Contributor: Department of Health Services Research and Population Health, University of Manchester; email: keith.geraghty@manchester.ac.uk; Twitter: @keithgeraghty 

Professor Keith R. Laws, JHP  Contributor: email k.laws@herts.ac.uk

Dr Ellen Goudsmit, JHP Editorial Board Member & Contributor: +44 (0) 20 8977 2386 (from 8am to 9 pm); ellengoudsmit@hotmail.com

Professor Jonathan Edwards, JHP Contributor: +44 (0)7340015831; jo.edwards@ucl.ac.uk

Dr Charles Shepherd, JHP Contributor & Medical Adviser at the MEA:  +44 (0) 1453 885462

Karen D Kirke, JHP Contributor: karen.d.kirke@gmail.com  – especially regarding patient experience of ME/CFS and patient feedback on GET and CBT.

United States:

Professor James Coyne, JHP Senior Associate Editor: jcoynester@gmail.com Twitter: @CoyneoftheRealm 

Professor Steven Lubet, JHP Contributor: Williams Memorial Professor,  Northwestern Pritzker School of Law, 357 E. Chicago Avenue, Chicago IL 60611: +1 312.503.6605 (tel); +1 312.503.8977 (fax); slubet@law.northwestern.edu

Professor Leonard A. Jason, JHP Contributor: Director, Center for Community Research, DePaul University, Chicago, Il. 60614: +1 773-325-2018; Website: https://leonardjason.wordpress.com/; LJASON@depaul.edu.

Europe:

Dr David F Marks, JHP  Editor:

FROM WHOM PRE-PUBLICATION COPIES OF THE SPECIAL ISSUE MAY BE OBTAINED.

Email: editorjhp@gmail.com; Twitter: @newhealthpsych

 

Misconduct in an author’s nomination of reviewers for his manuscript

An author, Kjell Gundro Brurberg  appealed the rejection of his manuscript. He was offered an opportunity to nominate additional reviewers, but to ensure they did not have conflicts of interest. What happened next…

kjetilKjell Gundro Brurberg happens to be an author on a controversial Cochrane review about which there are serious concerns about conflict of interest and coordinated outcome switching across trials.

He is also an author on a forthcoming Cochrane review for which Cochrane refuses to share data for independent reanalysis. This  whole incident adds the importance of Cochrane releasing the data from that review for independent reanalysis, which the organization is currently refusing to do.

Now Brurberg is misrepresenting what happened in a blog post at Mental Elf, a blog site that has consistently shown itself to not vet what is posted by bloggers.

I will document in this issue of Quick Thoughts what really transpired. But his blog post indicates that Brunberg just doesn’t get how he blew an opportunity to publish his manuscript with his bad behavior.

Giving authors the opportunity to nominate reviewers has benefits to both the authors and to editors, but it depends on trust and the option can be abused by authors.

The whole story is part of a larger narrative of how hard it is to obtain an independent critique of the PACE trial of cognitive behaviour therapy and graded exercise for chronic fatigue syndrome.

I know from experience as a Senior Consulting Editor at the Journal of Health Psychology. Under Editor-in-Chief David Marks, the journal accepted an editorial commentary critical of the PACE trial and invited responses from a variety of perspectives.  The journal has endured repeated assaults on its editorial independence and integrity since.

hypocrisyHere is my updated account of the PACE investigators’ pressures on Journal of Health Psychology to retract portions of the published commentary and to issue a correction acknowledging the author had an undeclared conflict of interest. Ah, the kettle calling the pot black.

But before we delve into the details of the current incident, let’s discuss the practice of allowing authors to nominate reviewers.

Background: Authors being allowed to nominate reviewers

Authors can be instructed not to nominate reviewers with obvious conflicts of interest or indications of being unlikely to provide an unbiased review. Even, better editors can ask authors to indicate explicitly that the reviewers they have nominated are free of conflict of interest. Authors declaring there is no conflict when there is an obvious conflict of interest can be seen as tantamount to scientific misconduct.

Until recently, authors were routinely asked to nominate reviewers for their manuscripts. What had been a common practice became controversial and was outright stopped at many journals when a major scandal in peer review occurred in 2013- 2015.

In what turned out to be only the first wave of continually uncovered problems with a number of journals, Springer and BMC (which Springer now owns) undertook an investigation and retracted 50+ papers for peer review manipulation and other issues. Commenting to Retraction Watch, one publisher said:

Alongside investigation into the identified papers, we have taken action to ensure that no further compromised papers can continue through to publication. BioMed Central has changed our policy on suggesting peer reviewers so that authors may do so in a cover letter with evidence of the peer reviewers’ authenticity.

Once the crisis went public, at least one journal continued to ask authors to recommend reviewers, but then made sure that that papers didn’t go out to any reviewers whom the authors had nominated. Ouch!

The crisis had seemed to ease, but a new record was recently set with a major publisher retracting more than 100 studies from a cancer journal over fake peer reviews. 

Not surprisingly, there is evidence that reviewers who are recommended by authors are more likely to give positive reviews.

Our results agree with those from other studies that editor-suggested reviewers rated manuscripts between 30% and 42% less favorably than author-suggested reviewers. Against this backdrop journal editors should consider either doing without the use of author-suggested reviewers or, if they are used, bringing in more than one editor-suggested reviewer for the review process (so that the review by author-suggested reviewers can be put in perspective).

Obviously, editors need to be diligent and skeptically probe author-nominated reviewers. But relying on some of these nominations can be helpful if an editor, particularly if nominations are screened and provide only a portion of the reviewers for a manuscript. Flagging that a particular reviewer was nominated by an author is also helpful in the editor’s interpreting discrepancies in a set of reviewer recommendations for publication.

Presumably reviewers recommended by authors will be familiar enough with the topic of a manuscript to accept a request to review and provide in a timely fashion.

Authors may actually be best qualified to identify reviewers for their particular areas of research, even if editors have to evaluate the potential for bias and conflict of interest.

Though I’m most comfortable handling manuscripts in my areas of research, I am serving as academic editor for a megajournal with a broad interdisciplinary focus. I can’t expect to be on top of every nook and cranny of every subfield.

I also may not be as familiar as authors are with the up and coming researchers in a particular area of research who do not yet have a large number of publications, but who have an impressive brand new or “early view” paper or two out.

Relying on some reviewers nominated by authors can also help the balance the Anglocentric –and in some fields –older male bias of editorial boards.

Sure, there are problems with relying too heavily on reviewers that authors suggest, but let’s not get too misty eyed nostalgic about peer review in the old days when editors tended to rely just on people that they only personally knew.

There was a lot of old boy cliques looking after each other that could be the formidable obstacles if you wanted to challenge dominant theories. Some specialized journals were dominated by senior investigators who kept out threats to their theories or particular findings.

That is certainly still a problem in particular areas of research, but with more democratization of peer review and transparency, it gets a bit easier to uncover and challenge old boy cliques.

But unless publishers provide user-friendly tools to evaluate suggestions or can hire private investigators, editors have to rely to considerable extent on simple searches of published papers and trusting the report of authors to evaluate whether reviewers are appropriate and that they have no conflict of interest. Instructing authors ahead of time that nominations have to be free of conflict of interest is important.

I once was suspicious of an author nomination in an appeal of a rejected manuscript in a highly contested area of research. Google Scholar revealed no shared publications, but a broader internet search quickly yielded wedding pictures with the reviewer as the author’s best man.

This brings us to a recent problem we faced at the Journal of Health Psychology. The Senior Editor, David Marks, rejected a manuscript based on a rather thorough negative review. The author appealed this decision and was offered the opportunity to nominate additional reviews. However, because the manuscript concerned the contentious issue of the PACE trial, the author was given the responsibility to pre-screen his nominations for reviewers and indicate in writing that there were no relevant conflicts of interest.

The letter to the author rejecting his nominations because he misrepresented the conflicts of interest of reviewers

Dear Dr. Brurberg:

I write you in regards to manuscript # JHP-17-0254 entitled “A PACE-gate or an editorial without perspectives” which you submitted to the Journal of Health Psychology within an appeal procedure. Your manuscript is rejected due to your misrepresentation of conflicts of interests.

I have sought advice from my Associate Editors and this email is therefore copied to two of them.

I was going to wait until the end of the month before letting you have a decision, but new information came to light about Dr. Y that makes further delay unnecessary. The three reviewers that you recommended were supposed to be neutral, independent experts with no known conflicts of interest.   Unfortunately, however, one declined the invitation to review (X) and the other two (Y and Z) have objectively proven conflicts of interest.

In light of your appeal, you were given the generous opportunity to have your manuscript re-reviewed by one or more impartial experts chosen by you. It is highly disappointing and curiously naive that you have attempted to subvert the appeal process by recommending people who are strongly conflicted, in one case (Dr. X) by his own admission is an associate of the PACE investigators. You stated that Prof X is: “Interested in medically unexplained diseases. Holds the needed distance to the ongoing PACE debate.” The latter could not be further from the truth. In his email on 26 April 2017 Prof X stated:

“Good evening.

Bit of a curve ball this one I suspect!

Having been trolled briefly by [ the author on whose paper a comment was submitted] a while ago I might have a personal axe to grind, and having been supervised by Michael Sharpe (who may or may not have anything to do with this manuscript) between 5 and 10 years ago I would probably be regarded as irrevocably conflicted by the anti-PACE-ists. Mind you, I’ve also sat next to Peter White at a couple of (enjoyable) conference dinners – even that probably renders me tainted to some eyes.

Anyway, I’m perfectly prepared to be grown-up, reflectively self-aware, and as neutral as possible, in carrying out a review for you. But if you do open peer review you will probably be trolled for asking me.

If you still wish me to review, then please just let me know. But I thought I would give you a more than usually full COI summary first!

-X

Hardly, a description of a reviewer who is likely to be independent and unconflicted.

In the second case, Dr. Y, has a clear COI by association with pro-PACE researchers through joint work and publication. You stated that Y has: “Expertise in exercise therapy and CBT. No COI with regard to commentary authors.” Yet I discovered on Google Scholar that Y was actually a visiting staff member of the School of Psychology at the University of Southampton. The working visit was made possible by a grant from the Dutch MS Research Foundation (Stichting MS Research). The original RCT was funded by a grant awarded to R. Moss-Morris by the New Zealand Neurological Foundation.” I am sure you don’t need me to tell you that Prof Moss-Morris is closely connected to the so-called ‘Biopsychosocial Model’/’Dysfunctional Beliefs Model’ of ME/CFS advocated by the PACE Trial team. This fact is evidenced by:

[A specific publication co-authored by someone central to the PACE controversy removed because it identifies the proposed reviewer.]

It is important to consider, in addition, your own conflicts of interest as a person who worked for the Cochrane Collaboration in the analysis of individual data on exercise therapy for CFS including data from the PACE Trial and from studies by Moss-Morris (2005) (already mentioned above). The relevant reference is:

Larun L, Brurberg KG, Odgaard-Jensen J, Price JR. Exercise therapy for chronic fatigue syndrome. Cochrane Database of Systematic Reviews 2015, Issue 2. Art. No.: CD003200. DOI: 10.1002/14651858.CD003200.pub3.

It is not often in my experience that an author misrepresents the facts about his/her recommended reviewers in such an audacious and palpable manner. If you lie these days, exposure is only a few clicks away. Norway is a small country, a country that I dearly love, not a place I normally associate with cheats and rogues. That impression just took a nose-dive. You have wasted a lot of my time and you won’t be given a 3rd or 4th chance. You have already blown it.

I recommend that you reflect on the ethics and professionalism of your actions and the potentially serious consequences for your professional career. Better luck next time! But please don’t try it on again with this journal.

Regards,

David F Marks PhD

Editor

Journal of Health Psychology

editorjhp@gmail.com

The authors’ response

On 26 June 2017 at 09:02, Brurberg, Kjetil Gundro <KjetilGundro.Brurberg@fhi.no> wrote:

Thank you,

You are right, this is completely my fault. It is obvious that I should have known that your ‘journal’ only accept reviewers who disregard the PACE-trial as well as the PACE-researchers. It would have helped me, though, if you had stated this policy when you first invited me to write this comment.

Best regards

Kjetil G. Brurberg

Postscript

 Some past posts relevant to complaints about the bias of the Cochrane review and my efforts to obtain the data from it for independent re-analysis. Unfortunately, despite advocating that others share data for independent reanalysis, Cochrane refuses to share.

 Why I am formally requesting the data set from a Cochrane review (April 13, 2017)

Conflicts of interest in Cochrane reports on psychological interventions January 15, 2017

 

Probing an untrustworthy Cochrane review of exercise for “chronic fatigue syndrome” April 23, 2016

 My response to an invitation to improve the Cochrane Collaboration by challenging its policies April 21, 2016

An open letter to the Cochrane Collaboration: Bill Silverman lies a-moldering in his grave March 6, 2016