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.

 

Patients writing about their health condition were abused by a peer reviewer and silenced by The BMJ

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giphyRecently I blogged about authors who were informed by The BMJ that they must keep a review confidential despite having submitted a manuscript under the journal’s laudable policy of open peer review. I did not actually post the review in its entirety because doing so might to make it more difficult for the editors of The BMJ to provide timely, appropriate amends, including an apology to the authors.

I contacted a number of The BMJ editorial staff, starting with the action editor who handled the manuscript. I either got no response or I was told the silencing of the authors concerning their mistreatment was not their doing or anything with which they were willing to intervene.

I am now providing the review, which is patently unprofessional, despite coming from a psychiatrist.

being bmjThe reviewer challenges whether the authors relied on self-diagnosis of chronic fatigue syndrome, perhaps bolstered by doctor shopping until they found agreement.

There were two reviews of this manuscript sent to the authors. Reviewer 1  was succinct and positive:

This is a very well-written and incisive analysis. I would however like to invite authors to comment whether the selection of patients by Oxford criteria might have also partially exaggerated the benefit of trial interventions with graded exercises and CBT.

Should patients submitting manuscripts concerning health conditions provide proof of their diagnoses, such as medical records or letters from their physicians?

Should The BMJ apologize to these patients and their academic collaborator co-authors, given that no such apology has been forthcoming from the Action Editor?

The Editor, Navjoyt Ladher, was trained at Kings College, London where Simon Wessely and Trudie Chalders are faculty.

The reviewer trained at Kings College as well.  He  collaborated  with Simon Wessely on articles concerning chronic fatigue syndrome. I am not revealing his name, but in his review, he indicates that he is a psychiatrist who has mostly practiced in the west of Scotland.

I start by calling attention to some noteworthy points in this 2700 word review. The numbers refer to 13 of the highlighted passages in the review that follows.

  1. The reviewer recommends the manuscript be published without the authors being given the opportunity of revision. The intent of this is that it would draw Rapid Responses protesting what patients with chronic fatigue syndrome have to put up with, including from patients who, like the authors, have the condition.
  2. The reviewer dislikes this paper and yet still wants it to be published.
  3. The reviewer claims the manuscript insults and demeans other patients.
  4. If the paper is published and the PACE investigators don’t respond as the reviewer hopes, the reviewer will post a comment to the authors “Shame on you.”
  5. The authors should just move on and be done with the PACE trial.
  6. The reviewer notes that the paper is billed as a collaboration between patients and scientists, but questions whether any of the authors qualify as “clinicians” or “scientists.”
  7. The reviewer expresses doubts that the patients meet criteria for chronic fatigue syndrome.
  8. The reviewer reiterates the doubt the patients meet criteria for chronic fatigue syndrome and suggests that they were erroneously self-diagnosed.
  9. The reviewer suggests that the authors were erroneously self-diagnosed and went doctor-shopping until they found agreement.
  10. After earlier mentioning that he had not obtained the author’s published review, he questions whether it is a major review.
  11. The reviewer asserts that the PACE investigators can defend the recovery rates they claimed in the PACE trial.
  12. The reviewer questions whether the authors are merely writing about themselves rather than persons with diagnosed chronic fatigue syndrome.
  13. The reviewer claims the authors insult patients with genuine chronic fatigue syndrome when they challenge Wessely’s model emphasizing “fearful cognitions.”

patients should be seenReviewer 2

One of the nice things about providing a referee’s report (and it is even nicer when I am the recipient) is when a fresh look at a manuscript provides simple suggestions that lead to clear improvements in the eventual published paper.  For the 1st time in the three decades that I have been refereeing scientific papers  [1]I am going to recommend publication of a manuscript but only on the condition that no changes are made based on any of my comments or questions or criticisms or praise.  This is because the tone of this paper and certain of its content provide a fascinating illustration of some of the problems that surround the management of people with severe and prolonged fatigue states.  As well as making some quite interesting points these authors provide examples of what people with severe and prolonged fatigue have to put up with – even from other people who themselves have severe and prolonged fatigue.  If this manuscript is published in the BMJ this will give the chance for correspondents in the Rapid Responses section to point out some of its flaws and hopefully a valuable debate will follow that will contribute to a more thoughtful approach to this whole difficult field. 

There has been and continues to be a great deal of scientific controversy surrounding the PACE trial of the treatment of chronic fatigue syndrome(s) using graded exercise therapy vs cognitive behavioural therapy vs adaptive pacing therapy all in addition to standardised care delivered by doctors with specialist experience of chronic fatigue syndrome(s).  The back and forth scientific controversy makes fascinating reading as does this manuscript by …

In my opinion, the differing scientific interpretations of this trial have little or nothing to do with the participants’ scientific training and expertise.  Rather, scientific stances are dependent on people’s personal background and/or their clinical training and/or their clinical experience of assessing and treating patients with severe fatigue states and/or their own personal experience of ill health and/or the illness experience of family members and/or their personal experience of clinical care especially the care they have received from doctors. I will try – briefly and I hope not too boringly – to weave into this referee’s report some of my own background which will perhaps give some understanding of why, overall, [2] I dislike this paper and yet still want it to be published in a widely-read journal.

Whether to publish this paper will not be a straightforward decision for the editors.  It is certainly not an original contribution to the scientific literature.  A paper with similar content by some of the same authors appeared only a couple of months ago in the journal “Fatigue, Biomedicine Health & Behaviour”.  However, if it is published in the BMJ then this would provide a readily accessible update on some of the continuing controversies surrounding the diagnosis, prognosis and treatment of people with severe and prolonged fatigue.  Because of the Rapid Responses/Correspondence section of the BMJ it will give the investigators in the PACE trial the opportunity to put their different scientific interpretations to a wider audience.  They have already published these different interpretations in “Fatigue, Biomedicine, Health & Behaviour”.  I am still waiting for that paper from my librarian but I am certain that these scientists are more than able to defend their trial.  An up to date defence of the PACE trial with balanced consideration of its strengths and weaknesses will be very helpful for clinicians and policy makers if it is published in the readily accessible BMJ.com.  This will, in turn, make it easier when clinicians and health service managers try to improve services for the wide range of patients with severe and prolonged fatigue.

The main reason I would like this paper to be accepted is because of some careless use of language by the authors.  This can happen to anybody and I am sure these authors do not really mean what they say.  [3]They have however insulted and demeaned a subgroup of people with severe and prolonged fatigue (see below).  This is in spite of the fact that [the authors] are themselves in poor health due to severely fatiguing illnesses.  [4] I am sure this will be picked up by the PACE investigators and other readers of the BMJ and highlighted in the Rapid Responses.  If not, then I will write in and tell the authors that they should know better and I think I would end with a “Shame on you”.   

If this manuscript is published in the BMJ and the authors receive the appropriate criticism (and credit) for some the things they have said I hope they will then get on with applying their skills and intelligence and insights to some proper work that will have a chance of genuinely benefiting patients with chronic fatigue syndromes and other overlapping disorders.  [5]It is about time that they moved on from their obsessive (in the non-psychiatric use of the term) poring over the results of a good (albeit imperfect) randomised controlled trial (…and name me one perfect trial that exists in any clinical field).

Here are some comments on the manuscript that may be helpful to the editors in deciding whether or not to publish this non-original paper in a major general journal.  I am hoping that these comments will help draw out how interesting this paper will be to many readers of the BMJ.

1)            These authors make no attempt whatsoever to acknowledge the heterogeneity of patients who are labelled with a diagnosis of chronic fatigue syndrome (and, in my experience, the even greater heterogeneity of the smaller number of patients who are labelled using the diagnostic concept of myalgic encephalomyelitis).

2)           [6] These authors make a big deal of the fact that their paper is the result of collaboration between patients and scientists.  I am still unsure whether that should be clinical scientists.  [authors]– do you have any clinical training and experience?

3)            From what I can gather from this paper and their other writings [authors]  seem to believe that the best definition of chronic fatigue syndrome is whatever condition it is that has led to ill health in [the authors].

4)           [7]  I am sorry to hear of these authors’ ill health.  I hope they will not be upset when I say that I do not accept their diagnosis of chronic fatigue syndrome.  I do not accept at face value anybody’s declared diagnosis of chronic fatigue syndrome until I have done my own history and examination.  The reasons for this are as follows.  When I was a junior registrar in neurology in 1981/1982 our team investigated referrals – including self referrals – of patients with severe fatigue.  They received a battery of investigations from brain scans through lumbar puncture through visual evoked responses to muscle biopsy.  Every test would be normal.  We never took a social history and never carried out a mental state examination.  Come to think of it we never even took a proper past medical history.  The patients would then be told that they had a condition called myalgic encephalomyelitis and would be sent home to rest with the prognosis that they would not improve but that there may be a cure in the future with advances in neurovirology.  As I have written before .. and I have thought to myself on many occasions since – may God forgive me for the part I played in destroying the lives of some of these vulnerable patients. 

I later did clinical work with referrals with severe fatigue in three different clinical and geographical settings between 1988 and 2011.  I found then that a substantial minority (for a period it was the majority) of patients with a diagnosis of chronic fatigue syndrome and myalgic encephalomyelitis had readily diagnosable conditions using basic knowledge of general medicine and general psychiatry.  Sometimes my rediagnosis/reformulation would lead on to effective treatment.  However, some patients would reject these alternative explanations.  Some, sadly, would be angry towards me and state that I was not taking their illness seriously.  It was very disconcerting and it raised major worries about the inadequacies of my clinical communication skills when I would tell a patient with a diagnosis of chronic fatigue syndrome or, more usually, myalgic encephalomyelitis that their profound fatigue and other serious symptoms were better explained by, for example, their recurrent diabetic ketoacidosis; or the systemic effects of their known severe rheumatoid arthritis and its treatment; or their severe psychotic illness and its treatment; or profound depressive illness; or crippling panic disorder; or Reiter’s disease; or obsessive compulsive disorder with co-morbid depression; or malnutrition due to anorexia nervosa; or the temporary aftermath of newly diagnosed and treated severe thyroid disease…….I could go on and on – and then be told by the patient that I was not taking their ill health seriously.

I accept that my experience must have been unrepresentative since I was working from psychiatric outpatient clinics and for most of this time I was based in the West of Scotland that was the epicentre of myalgic encephalomyelitis movement.  However, I cannot believe that I am the only doctor who encountered this phenomenon.  How can I be sure that [the authors]  do not have ill health that could be much better categorised using any one of a range of much more straightforward diagnoses?

5)            [8] Who diagnosed [the authors’] condition?  I do not expect an answer since their medical history is and should remain confidential.  However I have to raise the possibility that they are self diagnosed.  For a while at my clinic a clear majority of diagnoses of chronic fatigue syndrome or myalgic encephalomyelitis had been made by the patient themselves or by a relative or friend or neighbour and not by any doctor or other clinician.  Many (but not all) of these patients had other obvious reasons for their fatigue after taking a full history and doing a physical examination and mental state examination.  I accept that such high frequency of self diagnosis/lay diagnosis may not be found in other clinics but, once again, I cannot believe that I am the only clinician who has encountered this phenomenon.

6)           [9]If they have been diagnosed with chronic fatigue syndrome by a doctor was this by their own doctor?  There certainly used to be a phenomenon whereby patients with a self diagnosis of chronic fatigue syndrome and (even more so) myalgic encephalomyelitis used to go doctor shopping until they found a doctor who agreed with their own diagnosis.  In my experience many (but not all) of these patients had readily diagnosable and fairly straightforward alternative diagnoses. 

7)            I notice in the manuscript that [one of the authors]  says she has “recently co-authored a major critical review of the concept of psychological causation in medicine…”.[10] [Author], I mean no disrespect, but is it for you to say that your review is a major one?  I hope you will not mind my saying that I found it to be very unbalanced and highly selective in its use of the medical literature.  Once again, I want this manuscript as it stands to appear in a widely-read journal so that interested readers will be able to get a clearer view of [this author’s]  thinking and I hope it will be criticised appropriately.

8)            I think [the authors]  are right to question the number of subjects in whom there has been “recovery”.  They may not be aware that the word “recovery” has been hijacked throughout mental health services by the very influential and international Recovery Movement.  This is a positive example of a powerful and creative collaboration between service users and clinicians.  [The authors]  should look it up.  The Recovery Movement has contributed to improved care for many patients especially those with chronic psychotic illnesses.  I think I was the last person involved in mental health services in Scotland – patient or clinician – to argue against some uncritical approaches of the Recovery Movement but I ended up giving in.  I find myself talking to certain patients about recovery – who have no chance of recovery in the dictionary sense of the word.  [11]The PACE investigators will easily be able to defend themselves in regard to recovery in their trial since they have operationally defined what they meant by their use of this word and they have been very clear about changes they made in their definitions.  Nevertheless, [An author] and colleagues do have a point about how reported “recovery rates” could be misleading.     

9)    [The authors] are right that the PACE trial is not definitive.  I have only seen the PACE investigators say this on one occasion and in one paper although I may have missed some other instances.  I think this was just some careless use of language.  Give them a break.

10)   There is something unpleasant in the tone of this article (although I am also being influenced here by outpourings on the Internet).  I cannot help but get the impression that the authors were punching the air when they thought they had come up with support for their views that certain treatment methods for certain people with serious ill health were not as helpful as others (both patients and clinicians) had hoped.  [12] Are [the patient authors]  absolutely sure that they are writing about syndromes of chronic fatigue?  Are they sure they are not simply writing about themselves?

11)         [13] This brings me to the insulting language about certain patients with severe and prolonged fatigue states.  [The patient authors]  are absolutely certain that their condition is not influenced by psychological troubles or social stressors.  This does not give them and their co-authors any right to belittle other patients and understate the severity of illness in those with a diagnosis of chronic fatigue syndrome where such factors are playing a major part in their ill health.  These authors write “…the CBT programme considers patients’ concerns about exercise to be merely ‘fearful cognitions’ that need addressing”.  Earlier in the article they state “This model proposes that there is no major ongoing disease process in CFS – merely deconditioning due to recent inactivity, and its various consequences”.  Merely?  Have they never met anybody with near 100% disability due to mere fearful cognitions?  I have.  Have they never spoken with patients who are at risk of dying due to mere fearful cognitions and their consequences?  I have.  XWilshire and her colleagues should be ashamed of themselves and I think their shameful language should be published and then condemned.  They should then be given the opportunity to write what they really mean and apologise to those patients about whom they have been so offensive.  This is the main reason why I want this article to appear in a widely read general journal that has an active Correspondence/Rapid Responses section. 

I hope these comments are helpful to the editors.  There is such widespread and heated debate around this subject that I think it would be helpful for some of it to appear in a widely-read journal.  I hope the editors will agree with me and publish this article – then stand back and see how the debate unfolds in the Rapid Responses/Correspondence.  I think this will lead in the end to more people with severe and chronic fatigue getting better care packages – which will include for some cognitive behavioural therapy and for others graded exertion therapy and for yet others perhaps even adaptive pacing therapy and for others none of the above but with high quality informed medical care for everybody.  Hopefully it will also contribute to efforts to raise funding for more research projects that will join the PACE trial in giving us guidance about how to treat and how not to treat individual patients with severe fatigue be it explained or unexplained or simple or complicated.

 

 

Simon Wessely: Why PACE investigators aren’t keen on handing over the PLOS One data to Coyne

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In what has become his characteristic style, Simon Wessely smears me with innuendo, suggesting I might try to alter the PLOS One PACE data and use the altered data to damage the careers of the investigators. He further argues that any release of the data could hurt the careers of the investigators and he understands their resistance. I say “Nonsense! I should be provided with the data as the investigators promised in publishing in PLOS One.”

 

Simon Wessely discreetly stays in the shadows, but he’s been very much involved in the struggle over the PACE trial, including whether the data will be released to me. I first learned from Wessely, not PLOS One, that my asking for data promised as a condition for publishing in the journal had somehow been turned into a Freedom of Information Act request.

But before that, Simon and I were in regular contact by direct messages on Twitter. I gave a talk at King’s College on biomarkers in June 2015. Simon and I later discussed getting a drink together because he was not able to be there. Simon established that he’s a wine guy, not one for scotch or beer.

When I first started tweeting about the PACE study months later, Simon contacted me, asking me not to comment on this study until I had spent months familiarizing myself with it. When that strategy didn’t work, he asked me to tone down my criticism of the PACE study. He even suggested that the PACE investigators would meet me in a public debate that Andre Tomlin of Mental Elf was trying to set up. But Andre later confirmed that the PACE investigators had already indicated there was no way that they would debate me.

Simon has continued to work behind the scenes, conveying vague threats to early investigators who criticize PACE in print. Simon’s nudges have been followed up by further threats from the PACE investigators to the universities of these early investigators.

Journalists have also been contacted by Simon who discouraged them in emails marked confidential from commenting on PACE. Tacky and manipulative because Simon’s emails  came out of the blue, and Simon was suggesting that the journalists  should not tell anyone about them.

Journal editors have been contacted by PACE investigators with efforts to suppress publication of criticism.

Critics have asked Psychological Medicine to publish a letter to the editor reporting the switched scoring of PACE outcomes that had substantially inflated the recovery rates reported in that journal in 2013. The editor, Robin Murray – a close colleague of Simon’s at King’s College, London – rejected the possibility of any letter based only on re-analyses. Rather, any correction would have to be based on an independent replication of the £5 million study in another sample.

Something is rotten in the UK, not just the State of Denmark.

anna-sheridan-wood-2When one highly professional and mild-mannered early career researcher requested a small amount of data from the PACE trial, the PACE investigators did a background check on her and attacked her character. Her request was labeled “vexatious” and refused.

Nonetheless, a group of patients teamed up with an early career investigator.  Relying on normative data and reanalysis of the outcomes originally specified  in the PACE protocol, they concluded: 

None of the changes made to PACE recovery criteria were adequately justified. Further, the final definition was so lax that on some criteria, it was possible to score below the level required for trial entry, yet still be counted as ‘recovered’. When recovery was defined according to the original protocol, recovery rates in the GET and CBT groups were low and not significantly higher than in the control group (4%, 7% and 3%, respectively).

Critics need to be protected from bullying and their efforts to secure the data need to be supported. As I have noted before, the success of attempts to correct the untrustworthiness of the scientific literature depend on critics getting access to data, especially when replications are not feasible. That’s why the situation with the withholding of the PACE data should concern everybody, not just those focused on chronic fatigue syndrome.

It’s been over a year since I requested the PLOS One data. It wasn’t through a Freedom of Information Act request. I’m determined that early in the new year either I will get the data released or the PLOS One paper will be retracted. Stay tuned.

But for now, here is a communication from Simon to a patient who had tweeted about the PACE data back in March 2016. Some of the excuses made for not sharing the data with me were tried out at the UK Lower Tribunal and soundly rejected. Nonetheless, the excuses continue to be made by the PACE investigators to the press through the Science Media Centre London, which orchestrated the team’s unsuccessful effort to get Parliament to exclude university research from Freedom of Information Act requests.

There is international consensus that the usefulness of data sharing will be seriously compromised if those of us who request data are screened for whether the original authors think we have been naughty or nice. We are not asking the original authors to play Santa.

The many things that the PACE investigators have done with their data require forensic exploratory analyses of what the data may be hiding. This is especially important because of the policy implications that they are claiming and the financial benefits they are gaining from ties to the insurance and re-insurance industries.*

 The email:

 …I doubt anyone would actually be surprised to learn that they are not keen on handing anything over to someone who says they are “at war” with the PIs, that they are “coming to get your pathetic little trial”  and so on and so forth.  Hardly disinterested academic inquiry.   But I can tell you they do want to release the data, because they have absolutely nothing at all to hide, but it does come down to trust.  I have been suggesting that the sooner they get a robust system set up, which excludes them, the easier life will be for everyone.  And I am sorry, but there have to be safeguards.  For  a start, there are legal obligations on data sharing on any doctor.   And these are not easy to fulfil.  And there is the issue of consent…you simply cannot just ride over it.  And I am afraid some of the tweets do show a total lack of understanding what you can do with data, should you be so inclined.  And if you do that, then that becomes a serious charge against whoever gave you that data.  And in the weird, paranoid, sulphurous world of ME… I am afraid that fanciful notions of someone trying to do that, just to make life difficult and indeed possibly professionally terminal, for the PIs, is something that they don’t dismiss, and neither would I.   so it takes time to get it right.  and lawyers are going to be involved – because it’s a very complex area of the law.  I have actually written on data confidentiality for the academy of medical sciences, so I know of what I speak.  No one is going to hand over any data set these days without a data sharing agreement – I think you do really believe that you get a request, and say  “OK, now, where the CD, ah yes, let me put in the post for you”.   No academic would ever do that, they would be insane, and would probably also be unemployed fairly quickly

In fact the more intemperate some people become over the this, that just makes it worse, and also makes it easier for the PIs to perfectly legitimately use the current legal framework not to share data, because they are worried about all this, and so would I be, if it was.   They are worried about active malice – there are people out there who have downloaded my powerpoints, changed them (guess how) and then circulated false versions to make me look like an ogre – which is why for many years now I never ever allow my powerpoints to be placed in any public place, as usually happens with conferences  remember there are people also, and you know as well as I do who they are, who make up quotes claiming they are from me or peter and co – so its not paranoid to worry about what such people might do with a data set.

The other problem is that speaking frankly, I would say that nearly everyone who can analyse large clinical trial datasets, doesn’t have the slightest interest in doing so.  They don’t care.  PACE looks pretty good to the professionals.  I know you don’t believe that, but it does.

Anyway, I have been suggesting quietly that the sooner they rid of the issue – get the Wellcome, MRC or the US centres that provide a data sharing service  (there are several by the way)  to take this – then they can deal with the data sharing agreements, they can decide if Jim Coyne should get It and give reasons if not, they can police the system, they can check the pre specifcied analytic strategy  (which for sure will be required, trust me – no one is going to be permitted just to do random fishing exercises, because we all know that will create utterly spurious results which will do fantastic harm) –  but guess what,  some of these august bodies are not too keen .  I wonder why……

So I think it will happen. Its not been made easier by someone develop an illness I am afraid, which is certainly stress related  (when KCL said that they were concerned about the health of their eployees they were spot on).  But it will take time.  And here I do agree with you – the sooner it taken away from the PACE team the better for everyone.

Because there isn’t a smoking gun.  Sorry,…but there isn’t.  its just a well conducted huge trial with a rather modest but still useful result that adds to the evidence for the safety and efficacy of CBT and GET, which will remain the treatment of choice until something better comes along.  Because there isn’t anything else at the moment.

Simon

*Here is the declaration of conflict of interest that accompanied the 2011 article in The Lancet:

 PDW has done voluntary and paid consultancy work for the UK Departments of Health and Work and Pensions and Swiss Re (a reinsurance company). DLC has received royalties from Wiley. JB was on the guideline development group of the National Institute for Healthand Clinical Excellence guidelines for chronic fatigue syndrome and myalgic encephalomyelitis and has undertaken paid work for the insurance industry. GM has received royalties from Karnac. TC has done consultancy work for insurance companies and has received royalties from Sheldon Press and Constable and Robinson. MB has received royalties from Constable and Robinson. MS has done voluntary and paid consultancy work for government and for legal and insurance companies, and has received royalties from Oxford University Press. ALJ, BA, HLB, LVC, JCD, KAG, LP, MM, PM, HO, RW, and DW declare that they have no conflicts of interests.

ebook_mindfulness_345x550I will soon be offering scientific writing courses on the web as I have been doing face-to-face for almost a decade. Sign up at my new website to get notified about these courses, as well as upcoming blog posts at this and other blog sites.  Get advance notice of forthcoming e-books and web courses. Lots to see at CoyneoftheRealm.com

What should be done about the MEGA (ME/CFS Epidemiology and Genetics Alliance) project? Concerns and response

Update October 21, 2016: Professor Jonathan Edwards is now urging signing the petition opposing MEGA. Find the petition here.

7976304-special-edition-stampEarly this morning some thoughtful comments were approved at my PLOS Mind the Brain blog concerning the MEGA (ME/CFS Epidemiology and Genetics Alliance) project. After careful consideration, I felt these comments should not be left simply buried there, but put into a larger conversation. Below I have posted them, along with a directly relevant statement from Dr. Charles Shepherd.

I am not a ME/CFS patient or parent of a patient, I’m not even a resident of the UK. But I have been drawn into a long and complex struggle, starting with a comment that I made on Twitter, a rejection of Simon Wessely’s direct message to me that I should not get involved in the controversy over the PACE trial, and my making of a request for data that the PACE investigators had promised would be available as a condition of publishing in PLOS One. The PACE investigators publicly labeled my legitimate request as “vexatious” and almost a year later have not turned the data over.

mega-image-481x230At the outset, I should note that Professor George Davey Smith has key responsibility for the genomics section of this complex project. I have the greatest respect for his intellect and intellectual integrity. I have learned immensely from him.

However, I have serious concerns about other personnel involved in this project in terms of their recent conduct as physicians and scientists. Among other issues, the nature of their role in the project needs to be clarified. Conditions need to be in place that they will not use their role to inflict further abuse and bad science on the patient and scientific communities. Other personnel must step in and demonstrate that patients have an appropriate role in the design, implementation, and interpretation of the data published in peer-reviewed journals in a timely fashion. Patients should be heard, welcomed to  high-level participation in research, and not just used.

Concerns, criticisms and questions about the MEGA study are being expressed by the ME/CFS [   Myalgic encephalomyelitis)/Chronic Fatigue Syndrome] patient community on internet discussion forums.

Some clear inaccuracies are circulating, but there are some big issues yet to be settled.

If we are going to make progress in trying to sort out the different clinical and pathological sub-groups/phenotypes that currently come under the very messy umbrella of ME/CFS, as well as those with unexplained chronic fatigue, AND in the process develop diagnostic biomarkers that could then be used as objective diagnostic tests to identify specific sub-groups of patients that come under this ME/CFS umbrella, ALONG WITH helping to identify specific forms of treatment that are aimed at these specific sub-groups, we are going to have to look at the whole spectrum of patients who are currently being diagnosed with ME, CFS or ME/CFS, and possibly unexplained chronic fatigue as well. –Dr Charles Shepherd

And

“I think the project must be welcome but I am surprised by this sort of canvassing for support. So far no details are available of who would do what. Surely patients are entitled to judge a project on the basis of a written application, just as scientists do” – Professor Jonathan Edwards

A comment left at the PLOS Mind the Brain

There are now also concerns about Esther Crawley’s involvement in the MEGA project, which is presented as an omics and big data approach to stratifying ME/CFS patients.

Esther Crawley and Peter White are involved in this project as ME/CFS experts, despite significant patient opposition. That these are even involved calls into question the integrity of the rest of the team. White has engaged in fraud in the PACE trial. Crawley’s unethical behaviour is well described in this blog’s article.

That aside, the concern is that they (or other BPS model proponents) will introduce flawed definitions of the illness and its symptoms into the project. Crawley and White certainly have a history of downplaying, ignoring, or psychologizing physical symptoms of this illness, or simply conflating this life destroying illness with the not uncommon and often transient symptom of tiredness. On the project’s petition page, the important symptom “post-exertional malaise”, which is an objectively measurable, typically delayed, decline in function with an increase in symptom severity, is referred to as “post-exertional stress”. Redefining words and concepts in a misleading manner is something the PACE authors have done repeatedly, so one wonders if we’re already seeing the redefinition of an important physical symptom to make it fit into a narrative preferred by PACE authors and their colleagues. A vague term such as “post-exertional stress” certainly fits well into a “health anxiety” narrative of patients supposedly worrying excessively about ordinary muscle soreness after exercise, and mistaking this for symptoms of an illness.

Such a narrative would be particularly easy to construct if permissive case definitions were used. The project plans to recruit patients from NHS referral centers, which are operating according to the BPS / PACE paradigm, with NICE criteria which are permissive. NICE instructs doctors to only refer patients to these centers when they are mildly or moderately affect and believe that CBT and GEt are appropriate. For this, and other reasons, it is likely that this recruitment strategy will exclude or underrepresent the more severely ill.

In a large and important project, a solid foundation of knowledge and methodology is more important than ever.

There are also concerns about the patient advisory groups. Patient involvement is important according to MEGA study authors, and two patient advisory groups will be created. No details have been given on how patient representatives will be chosen. It would be problematic if the authors chose patient representatives that are not considered trustworthy by the larger patient community.

We suspect they will be drawn from the AFME and AYME charities. Many patients don’t trust these organizations. Crawley is medical officer of AYME, and AFME has a history of collaborating with PACE authors and generally being lenient and ignoring problems with the BPS approach and the PACE trial. AFME approved of the removal of actometers from the PACE trial with dubious justifications. It was repeatedly mentioned that patient advisors in the MEGA project will be able to prevent certain data from being collected and certain tests being performed. Will we see important questions not being asked, important data not being collected, important tests not being done because these undemocratic patient advisor groups with ties to the PACE authors believe that doing so is in the best interest of patients?

In general it is a problem that communications go through the untrusted intermediary AFME.

ME/CFS Research in the UK needs to divorce completely from the failing BPS model of the illness. Patients hate it, it’s scientifically flawed, and has produced no results when reasonably standards of evidence are applied. Consider that over 12000 patients signed a petition to the Lancet against the PACE trial, while the MEGA study has collected only 2130 signatures (with number of signatures essentially having stopped). The distrust of the BPS model is so great that any project touched by its influence becomes tainted. The MEGA study team should reconsider its current approach and whom it collaborates with.

Give this MEGA project a chance to fly – don’t try to strangle it at birth, says Dr Charles Shepherd | 3 October 2016

The MEGA (ME/CFS Epidemiology and Genetics Alliance) ‘big data’ research study – some comments from Dr Charles Shepherd following last week’s third annual scientific meeting of the UK CFS/ME Research Collaborative.

I can understand all the concerns, criticisms and questions about the MEGA study that are being expressed by the ME/CFS patient community on internet discussion forums.

I can also assure people that they will be transferred back to those at the CMRC (CFS/ME Research Collaborative) who are involved in preparing what is probably going to be the largest ever research grant application relating to ME/CFS here in the UK.

There are clearly a number of key decisions still to be made. And .if anyone followed the proceedings at the CMRC conference in Newcastle last week. they will know that I raised the crucial issue of patient selection criteria (narrow or broad) with Professor George Davey Smith and Dr Esther Crawley during the discussion section.

The key point I want to make at this stage is that the MEGA study is an important and complex new item of ME/CFS research that is going to make use of a wide range of relatively new and exciting technologies – metabolomics, proteomics, genomics, epigenetics etc.

The MEGA study will also involve some very high profile BIOMEDICAL scientists of international repute – several of whom are completely new to ME/CFS.

Researchers who will be involved include:

* Genomics – Prof George Davey-Smith (Bristol), Prof Chris Ponting (Edinburgh), Prof Colin Smith (Brighton)
* Epigenetics – Prof Caroline Relton (Bristol)
* Proteomics – Mr Tony Bartlett (Somalogic)
* Metabolomics – Dr Rick Dunn (Birmingham)
* Routinely collected data – Prof Andrew Morris (Edinburgh) and Prof David Ford (Swansea)
* Infection – Prof Paul Moss (Birmingham)
* Sleep – Prof Jim Horne (Loughborough)
* Pain – Prof Maria Fitzgerald (UCL)
* Prof Julia Newton (Newcastle)

The MEGA study has also attracted the very positive attention of the Wellcome Trust _ the largest provider of non governmental funding for biomedical research here in the UK and the largest research funding charity in the world

Wellcome Trust: >https://wellcome.ac.uk

And the numbers of patients involved is going to be huge – around 10,000 adults and 2,000 children.

However, when it comes to the aims and objectives of the research, there are some serious misunderstandings and inaccuracies being circulated on the internet as to how this ‘big data’ is going to be collected, analysed and used. This is NOT a treatment trial in any sense of the word and it has nothing to do with PACE, CBT or GET.

If we are going to make progress in trying to sort out the different clinical and pathological sub-groups/phenotypes that currently come under the very messy umbrella of ME/CFS, as well as those with unexplained chronic fatigue, AND in the process develop diagnostic biomarkers that could then be used as objective diagnostic tests to identify specific sub-groups of patients that come under this ME/CFS umbrella, ALONG WITH helping to identify specific forms of treatment that are aimed at these specific sub-groups, we are going to have to look at the whole spectrum of patients who are currently being diagnosed with ME, CFS or ME/CFS, and possibly unexplained chronic fatigue as well.

So the numbers need to be huge and a study of this nature may also need to include people with chronic fatigue states whom we will then want to exclude for both our benefit and for their benefit.

In my opinion, getting this right will clearly be dependent on having very detailed clinical information accompanying the biological samples – as is the case with the ME/CFS Biobank where we can check what diagnostic criteria (and symptoms) accompanies each individual blood sample that has been collected and stored.

I am not yet clear as to how this will be done in this study, which Is why I asked the question on patient selection at the conference. The nearest information we have was the reply from Dr Esther Crawley in which she stated that patients will meet NHS diagnostic criteria for ME/CFS and will be recruited from the NHS hospital-based referral centres for people with ME/CFS

So I would ask the ME/CFS patient community to see how the protocol develops and what information and inclusion criteria are going to be used.

If you are happy with the final research proposal, then there will obviously be ways of expressing public support.

If not, there will be ways of saying so as well!

As Professor Jonathan Edwards has said on the Phoenix Rising forum:

“I think the project must be welcome but I am surprised by this sort of canvassing for support. So far no details are available of who would do what. Surely patients are entitled to judge a project on the basis of a written application, just as scientists do”

So I hope that those people who are wanting to simply strangle this proposal before it has even been properly finalised will think very carefully about what they are doing – especially if this is mainly because they disagree with the inclusion of certain specific researchers.

It is difficult enough getting new and distinguished scientists and researchers, and major research funders such as the Wellcome Trust, interested in this subject without trying to scare them off almost as soon as they express a serious desire to get stuck into in a huge multidisciplinary project such as this, and the protocol is still being developed.

If people want to express concerns, criticisms, or have questions to ask, then I suggest that this should be done in the form of an open letter to the Board of the CMRC, which could be signed by anyone expresing such concerns, rather than a petition.

Dr Charles Shepherd
Hon Medical Adviser
The ME Association

So far, Dr. Shepherd’s statement has attracted numerous comments, which you can see by going to the website. However, I would like to, reproduce one comment by a noted patient citizen scientist.

Simon McGrath October 3, 2016 at 5:35 pm

Thanks, Charles.

I agree this study has huge potential and it’s great to see new biomedical talent come into the mecfs field.

“the reply from Dr Esther Crawley in which she stated that patients will meet NHS diagnostic criteria for ME/CFS and will be recruited from the NHS hospital-based referral centres for people with ME/CFS” I didn’t hear that (looking forward to the conference videos being posted) but it reassures me too.

Equally, I don’t think MEGA have made a great job of communicating the study to patients, and I understand why many feel aggrieved at being asked to back a study. I like the idea of an open letter.

Simon Wessely’s muddled views of the good psychotherapy trial: I. Misunderstanding control groups

A large clinical trial might be said to resemble an ocean liner…Very occasionally there is a shipwreck – Simon Wessely

Sir Simon Wessely is apparently still hawking cruises on a wrecked ship that can’t be salvaged. I urge refunds.

 After a long career, Wessely is in the twilight of his influence and relevance. His tired defense of the design of the PACE trial suggests that he is out of touch with contemporary thinking about psychotherapy trials and risks to their validity. But he still chastises those who disagree with his assessment of the PACE trial.

 I invite readers to read and decide….

If you haven’t read Julie Rehmeyer’s excellent article in STAT Bad science misled millions with chronic fatigue syndrome. Here’s how we fought back, you should at least bookmark it for reading later. A mathematics and science writer who happens to be a patient, Julie Rehmeyer’s piece has proven to be the right article at the right time to bring the controversy into the public eye over chronic fatigue syndrome (hereafter CFS/ME)* and what is widely seen as the demolished credibility of the 5 million pound PACE clinical trial of cognitive behavioral therapy (CBT) and graded  exercise therapy (GET) for chronic fatigue syndrome. The article has been rightfully republished and is receiving wide commentary in conventional and social media.

Rehmeyer’s article’s uniformly warm reception was marred only by a chilly comment from Sir Simon Wessely that began:

Sorry to spoil the party but some cold facts are necessaey [sic]

This blog post is the first in a series. I will respond to some of Wessely’s odd pronouncements about evaluating clinical trials and his dismissive defense of the PACE trial.

Wessely starts by lecturing his readers that they should check the PACE trial against the CONSORT checklist, which you can find here.

The PACE trial remains an excellent trial and a model of how to deliver a complex intervention RCT. Read the 2012 Lancet paper again. Check it against the CONSORT statement. You will see it is 100% compliant.

consortThis is a puzzling suggestion. The CONSORT checklist evaluates whether particular aspects of a clinical trial are reported in an article, not whether those aspects were competently implemented in the trial. For instance, an author could say that “Data for patients who did not respond to treatment as we hoped were discarded.” That would meet the criteria for disclosing whether or not analyses were conducted on an intention-to-treat  basis, but it would be a gross violation of best research practices. As we’ll see, simply relying on CONSORT to decide whether the PACE trial was properly done, would miss some egregious questionable research practices.

Wessely’s comment echoes a similarly condescending comment in his earlier Mental Elf blog, to which he provided a link in his comment on Julie’s article:

I am struck that some of the critics are not familiar with the fundamental strengths of the randomised control trial, and why medicine continues to value it so highly. Likewise, some show unfamiliarity with the core methodological components that contribute to the integrity of a clinical trial, and whose violation calls into question the findings, as compared to what one might call secondary less important features. In other words, what distinguishes a good trial whose results are likely to be sound from one in which there is a definite risk of bias.

Wessely simply doesn’t get it. The PACE trial is now being scrutinized by a large international audience who won’t tolerate being patronized.

Chris Chambers  recently remarked:

 What’s happened instead is that technology has empowered the new generation to speak freely and publicly on scientific issues, to critique poor quality science and practices, to bust fraud, and to break the bounds of peer review. Twitter in particular has shaken the traditional academic hierarchy to its core. On Twitter a PhD student with thousands of followers suddenly has a greater voice than an Ivy League professor who might have no social media presence at all.

Here are a few of the aspects of the PACE trial comparison of the active treatments – (CBT) and (GET)– to a control condition that Wessely encourages us to ignore.

  1. Inadequacy of the control group. All four of the conditions in the trial involved providing patients with “standardized specialty medical care” (SSMC). One condition provided only SSMC and served as the control/comparison for evaluating the CBT and GET.

The condition is grossly inadequate as a control group because it is deficient at the basic level of contact time – patients assigned to SSMC received only 3 medical sessions of 30 minute duration. In contrast, patients assigned to CBT or GET have access to these three medical sessions of SSMC plus 15 sessions of either CBT or GET.

The Lancet article describes SSMC:

 Standardised Specialist Medical Care SSMC will be given to all participants. This will include visits to the clinic doctor with general, but not specific advice, regarding activity and rest management, such as advice to avoid the extremes of exercise and rest, as well as pharmacotherapy for specific symptoms and comorbid conditions. SSMC is standardised in the SSMC Doctor’s Manual. As well as this, SSMC participants, like all other participants, will already have received the Patient Clinic Leaflet (PCL). The PCL is a generic leaflet explaining what CFS/ME is, its likely causes, and available treatments. There will be no additional therapist involvement.

 So, the patients assigned to SSMC got a pamphlet. In general, clinical and health psychologists researchers are convinced that getting a pamphlet is an inert intervention. So much so, that pamphlets are routinely provided as control inventions where researchers are intent on making their active intervention appear effective. And routinely criticized as an inadequate control condition.

In contrast to SSMC, the active treatments were delivered with a strong induction of positive expectations. Alem Matthees, the patient who obtained release of the PACE data with a FOI remarked in an email to me:

The CBT manuals for PACE assert with confidence that the therapy was safe and powerful (etc), and aimed the therapies at changing patients’ perceptions about their symptoms. Similarly, the GET manuals stated exercise reverses the pathophysiology responsible for symptoms and that most patients feel “much better” after therapy. No such equivalent in the other manuals. So it is difficult to separate any genuine benefit from methodological artefacts arising from placebo response and other reporting bias. If we assume subjective measures are important (which they are) and there is some genuine benefit (which there probably is), we must still consider the use of objective measures.

  1. The study was not blinded. Patients assigned to either CBT or GET knew they were getting more treatment. In contrast, patients assigned to the control group received only the SSMC.  They could see that they have gone to the bother of signing up for clinical research with the expectation that they would get more than SSMC, but now they are being left in that treatment with the added burden of all the research assessments.

The lack of blinding potentiates the problems of a control condition lacking the frequency and intensity of contact provided with the active treatment.

  1. Bolstering of positive expectations with a newsletter. A newsletter sent to patients while enrollment in the trial was still ongoing strengthened positive expectations and increased a sense of obligation from patients assigned to the control group. This effort was not specified in the original protocol. If this were a drug trial being scrutinized by the FDA, this would be a blatant protocol violation.

I noted in an earlier blog:

Before the intervention phase of the trial was even completed, even before accrual of patients was complete, the investigators published a newsletter in December 2008 directed at trial participants. An article appropriately reminds participants of the upcoming two and one half year follow-up. But then it acknowledges difficulty accruing patients, but that additional funding has been received from the MRC to extend recruiting. And then glowing testimonials appear on p. 3 of the newsletter about the effects of their intervention.

“Being included in this trial has helped me tremendously. (The treatment) is now a way of life for me, I can’t imagine functioning fully without it. I have nothing but praise and thanks for everyone involved in this trial.”

“I really enjoyed being a part of the PACE Trial. It helped me to learn more about myself, especially (treatment), and control factors in my life that were damaging. It is difficult for me to gauge just how effective the treatment was because 2007 was a particularly strained, strange and difficult year for me but I feel I survived and that the trial armed me with the necessary aids to get me through. It was also hugely beneficial being part of something where people understand the symptoms and illness and I really enjoyed this aspect.”

Taken together with the acknowledgment of the difficulty accruing patients, the testimonials solicit expression of gratitude and apply pressure on participants to endorse the trial by providing a positive evaluation of their outcome in the self-report measures they were provided. Some minimal effort is made to disguise the conditions from which the testimonials come. However, references to a therapist and, in the final quote above, to “control factors in my life that were damaging” leave no doubt that the CBT and GET favored by the investigators is having positive results.

Adequacy of control groups is of crucial importance. The US Agency for Healthcare Research and Quality (AHRQ) undertook a comprehensive systematic review and meta-analysis of meditation programs for psychological stress and well-being. I covered the agency’s report and the JAMA: Internal Medicine article in a recent blog post, Mindfulness research’s huge problem with uninformative control groups. The AHRQ report and JAMA article concluded that the widespread impression that meditation is an effective way of reducing stress and improving well-being largely comes from trials with inadequately matched control groups. When meditation, including mindfulness, iscompared to suitable active treatments, there is insufficient evidence of any superiority.

The same could be said for the PACE trial, but I’m just getting started. In my next blog post, I will take a critical look in a second comment on Julie’s article at Simon Wessely’s endorsement of outcomes switching as an admirable feature of the interpretation of clinical trials. What he says:

In essence though they decided they were using a overly harsh set of criteria that didn’t match what most people would consider recovery and were incongruent with previous work so they changed their minds – before a single piece of data had been looked at of course. Nothing at all wrong in that- happens in vast numbers of trials. The problem arises, as studies have shown, when these chnaged [sic] are not properly reported. PACE reported them properly. And indeed I happen to think the changes were right – the criteria they settled on gave results much more congruent with previous studies and indeed routine outcome measure studies of which there are many.

first-wessely-knight

Albrecht Dürer’s Knight, Death and the Devil

In a subsequent blog post, I’ll be arguing that Simon’s justification is factually incorrect and inconsistent with best research practices. Until my next post, for a condemnation of outcomes switching in pharmaceutical trials, see my recent blog post, Study protocol violations, outcomes switching, adverse events misreporting: A peek under the hood. I report on criticism by prominent senior psychiatrists of bad research practices in trials of antidepressants. After writing that blog post, I signed a letter with the senior psychiatrists demanding retraction of one of these papers the blog discussed. The paper reported data from a ghost written trial of antidepressants characterized by protocol violations, outcomes switching and adverse events misreporting. I’ve heard no evidence that the PACE trial was ghostwritten, but I think there is ample evidence of its sharing these other sins.

**I am using this term with some reservation, because it’s familiar to readers and because that is how a set of diverse conditions is named in the bulk of the scientific and in the media.  But for an excellent critique of the term, see another excellent article in STAT,  Why we shouldn’t call it ‘chronic fatigue syndrome’ . I expect we will see a retirement of the term “chronic fatigue syndrome.”

 

 

No, irritable bowel syndrome is not all in your head.

Updated May 22, 2016. I have added an opening summary, as well as a few links for readers who may want to learn more about IBS as a physical health problem about which we are learning a lot, not a mental health issue.

Irritable bowel syndrome (IBS) has symptoms in common with other physical conditions. IBS ranges in severity from mild and infrequent episodes to more frequent,severe, longer, and more debilitating episodes. It is thus a  recurrent, episodic condition. For many patients in many healthcare contexts, IBS remains an undiagnosed pattern of recurrent, but different symptoms that are presented without much relief.

Often IBS is effectively managed in primary care with lifestyle management and monitoring and identifying of triggers. However, when IBS is not effectively dealt with in primary care, a patient may need a referral to a specialist. This article argues that first specialist who  is considered should be a gastroenterologist, not a mental health professional.

Evidence is accumulating that IBS is often a disturbance in the gut-brain relationship. In that sense, it has a psychological component. But it is important to recognize that it is a matter of the gut influencing the brain by way of well-documented pathways.

IBS is increasingly seen as a  disturbance in the microbiota or microbiome (I explain what that means below) of the gut. President Obama has directed the NIH to study the human microbiota or microbiome as part of a larger initiative studying these phenomena in other ecological systems, including soil. There is a lot of enthusiasm for this broad initiative, but also some caution that the enthusiasm should not get too far ahead of the data. I have added some links about this.

Anxiety and depression often accompany IBS. The symptoms may reflect the uncertainty and discomfort of trying to managing an ill-defined condition. But this distress also may be a direct effect of the gut on the brain, again through increasingly known pathways.

Patients with undiagnosed IBS challenge and ultimately frustrate physicians. When physicians cannot resolve their complaints, patients sometimes get mistreated and blamed for their condition.

Previous explanations for IBS focused on it being an expression of unconscious conflicts. Psychoanalytically oriented explanations suggest anal conflicts in which the patient struggles with hostility that she cannot express directly. IBS can been seen as a conflict between retaining in expelling fecal contents. Diarrhea or loose bowel movements can be seen as symbolically crapping on somebody in a situation where anger cannot be directly expressed. Such explanations are creative and  even literary, but they are  testable hypotheses about an individual patient. Such ideas just do not hold up in research studies, often because the hypotheses cannot be coherently expressed with key variables  assessed with validated measures.

I’m not a physician and I’m not a position to offer advice to individual sufferers from IBS. But if I or a family member developed what looked like IBS, and it could not be brought under control in primary care. I would not recommend referral not to a mental health professional as the next step.

In the UK, IBS is considered a medically unexplained symptom (MUS). IBS patients are likely to be referred to psychological interventions for which there is only weak evidence. Patients with IBS may have to get educated on their own about the condition and fend for themselves in a medical system that is unresponsive to them.

Finally, some readers have attempted to leave comments on this blog post discussing benefits they sincerely believe they have received from treatments, including dietary supplements for which there is not scientific evidence. I have not accepted those comments for posting. I’m very skeptical of alternative and complementary medicine which is basically  unproven medicine. I also see suffers from IBS vulnerable to exploitation by all sorts of deliberate or innocent quackery.

A segment of CBS This Morning Saturday News showed the view of Irritable Bowel Syndrome (IBS) as  “all in your head” is outmoded. Placing the source of IBS as “all in the head” is unlikely to lead to improvement in a chronic, intermittent condition affecting millions of people, and disproportionately women.

Jonathan LaPookThe Host Was CBS News Chief Medical Correspondent, Jonathan LaPook.

 

 

 

 

 

 

Mark Pimental

Mark Pimentel MD (@MarkPimentelMD) on Twitter

He was interviewing Mark Pimental, MD, Associate Professor of Medicine, and Director of the G.I. Motility Program of Cedars-Sinai in Los Angeles.

 

 

 

 

 

 

 

At one point, Dr. LaPook poked fun at the obsolete approach to IBS in which physicians patted women on the head and told them that their condition was result of anxiety and depression.

pat on the head.PNGDr. Pimentel offered a view of IBS coming out of his research and specialty practice:

Irritable Bowel Syndrome (IBS) is one of the most common chronic medical conditions, affecting 10%-15% of the population in the United States and worldwide. Work on two distinct fronts has suggested that the pathophysiology of IBS may have microbial origins. First, a series of studies and meta-analyses over the last decade suggests that IBS can develop after a single episode of acute bacterial gastroenteritis (referred to as post-infectious IBS (PI-IBS). While these subjects exhibit characteristic gut immunologic changes (in the mucosa and myenteric ganglia), the mechanisms underlying the transition to an IBS phenotype remain unknown. Second, subjects with IBS have been shown to have specific changes in luminal bacterial contents, the most common of which is small intestinal bacterial overgrowth (SIBO), a condition whereby coliform bacterial counts in the small bowel become excessive. The presence of SIBO in IBS subjects has recently been confirmed by both small bowel culture and by quantitative PCR (qPCR) of duodenal contents.

Dr. LaPook advised sufferers of IBS to work with their primary care physicians to determine whether lifestyle changes could avoid episodes of IBS or at least make them less frequent and severe. If these efforts were not successful, Dr. LaPook recommended that they consult a specialist – a gastroenterologist, not a mental health professional!

More resources about contemporary views of IBS

Here’s a link to a US National Institute of Health webpage about Symptoms and Causes of Irritable Bowel Syndrome:

What causes IBS?

Doctors aren’t sure what causes IBS. Experts think that a combination of problems can lead to IBS.

Physical Problems

Brain-Gut Signal Problems

Signals between your brain and the nerves of your gut, or small and large intestines, control how your gut works. Problems with brain-gut signals may cause IBS symptoms.

GI Motility Problems

If you have IBS, you may not have normal motility in your colon. Slow motility can lead to constipation and fast motility can lead to diarrhea. Spasms can cause abdominal pain. If you have IBS, you may also experience hyperreactivity—a dramatic increase in bowel contractions when you feel stress or after you eat.

Pain Sensitivity

If you have IBS, the nerves in your gut may be extra sensitive, causing you to feel more pain or discomfort than normal when gas or stool is in your gut. Your brain may process pain signals from your bowel differently if you have IBS.

Infections

A bacterial infection in the GI tract may cause some people to develop IBS. Researchers don’t know why infections in the GI tract lead to IBS in some people and not others, although abnormalities of the GI tract lining and mental health problems may play a role.

Small Intestinal Bacterial Overgrowth

Normally, few bacteria live in your small intestine. Small intestinal bacterial overgrowth is an increase in the number or a change in the type of bacteria in your small intestine. These bacteria can produce extra gas and may also cause diarrhea and weight loss. Some experts think small intestinal bacterial overgrowth may lead to IBS. Research continues to explore a possible link between the two conditions.

Neurotransmitters (Body Chemicals)

People with IBS have altered levels of neurotransmitters—chemicals in the body that transmit nerve signals—and GI hormones. The role these chemicals play in IBS is unclear.

Younger women with IBS often have more symptoms during their menstrual periods. Post-menopausal women have fewer symptoms compared with women who are still menstruating. These findings suggest that reproductive hormones can worsen IBS problems.

Only at the bottom of the page is any reference to the traditional view that IBS somehow expresses psychological conflicts.

The dominant theme of the fact sheet is that IBS is often a disorder of the brain-gut signaling. However, the signaling problem originates in the gut which influences the brain.

Here is a link to a freely available  article in JAMA, the Journal of the American Medical Association, Small Intestinal Bacterial Overgrowth: A Framework for Understanding Irritable Bowel Syndrome.

IBS as a disorder of the microbiota or microbiome.

A microbiota is “the ecological community of commensal, symbiotic and pathogenic microorganisms that literally share our body space”.[1][2] Joshua Lederberg coined the term, emphasising the importance of microorganisms inhabiting the human body in health and disease. Many scientific articles distinguish microbiome and microbiota to describe either the collective genomes of the microorganisms that reside in an environmental niche or the microorganisms themselves, respectively.[3][4][5] However, by the original definitions these terms are largely synonymous There are trillions of microbes in the human microbiome, although the entire microbiome only accounts for about for 1-3% total body mass,[6] with some weight-estimates ranging as high as 3 pounds (approximately 48 ounces or 1,400 grams).[n 1] Research into the role that microbiota in the gut might play in the human immune system started in the late 1990s.[9] The microbiome of the gut has been characterised as a “forgotten organ”,[10] and the possibility has been raised that “the mammalian immune system, which seems to be designed to control microorganisms, is in fact controlled by microorganisms”.[11] The human microbiome may have a role in auto-immune diseases like diabetes, rheumatoid arthritis, muscular dystrophy, multiple sclerosis, fibromyalgia, and perhaps some cancers.[12] A poor mix of microbes in the gut may also aggravate common obesity.[13][14][15] Since some of the microbes in the human body can modify the regulation of some neurotransmitters, it may be possible to use certain microorganisms to supplement treatments for depression, bipolar disorder and other stress-related psychiatric disorders.[16]

BMC Medicine is assembling a new article collection “The Microbiome and Man,” guest edited by Dr Omry Koren.

But I warn you it is heavy going and highly technical.

Here’s a more accessible link describing President Barack Obama’s National Microbiome Initiative:

Microbiomes are the communities of microorganisms that live on or in people, plants, soil, oceans, and the atmosphere. Microbiomes maintain healthy function of these diverse ecosystems, influencing human health, climate change, food security, and other factors. Dysfunctional microbiomes are associated with issues including human chronic diseases such as obesity, diabetes, and asthma; local ecological disruptions such as the hypoxic zone in the Gulf of Mexico; and reductions in agricultural productivity.

Here is an interesting link to an account of a participant in a citizen scientist effort to map the human microbiota, Some of My Best Friends Are Germs:

 Microbiomes are the communities of microorganisms that live on or in people, plants, soil, oceans, and the atmosphere. Microbiomes maintain healthy function of these diverse ecosystems, influencing human health, climate change, food security, and other factors. Dysfunctional microbiomes are associated with issues including human chronic diseases such as obesity, diabetes, and asthma; local ecological disruptions such as the hypoxic zone in the Gulf of Mexico; and reductions in agricultural productivity.

This article from USA Today is reasonably well-informed:There’s 10 trillion microbes on you; the White House wants to figure them out.

This freely available article from Nature expresses enthusiasm about the US initiative, but indicates that there are some challenges ahead that require an international effort. It’s balanced: Microbiology: Create a global microbiome effort.

The outmoded view of IBS is dominant in the UK

Suzanne O’Sullivan’s  “It’s All in Your Head “is a collection of obsolete and simply wrong ideas about “psychosomatic conditions” in itself an outmoded term, but still in circulation in the UK. She specifically mentions IBS in an editorial based on the book in The Lancet:

 Some 20% of people in the UK have irritable bowel syndrome. This is one of the most common reasons for people to present to a gastroenterology clinic. It is also a condition that is affected by psychological distress and where no organic bowel disease is evident. And yet, to convince patients that psychosomatic disorders are an everyday problem that could affect any sort of person is very difficult. To tell somebody that their medical complaint might have an emotional cause is often met with anger. It is hard to believe that we can lose control of our bodies so completely and without our knowledge. And if our subconscious has chosen to mask our psychological distress and express it in a way more palatable to us then it follows that to remove the mask will be painful.

Suzanne O’Sullivan suggests the role of the physician in the UK is to convince the patient that IBS is all in her head. The notion that “our subconscious is choosing to mask psychological distress” is at the root of the problem would be considered rubbish by informed American professionals. It’s one of many neo-crypto-psychoanalytic ideas that of have crept into CBT in the UK, despite lacking empirical evidence and being untestable with the individual patient.

O’Sullivan doesn’t tell us, but she’s referring to the old psychoanalytic literature that considers IBS as expressing unresolved anal issues acquired in potty training. Then she expresses confusion why some patients are offended by this.

Stay tuned for a blog post in Mind the Brain that traces this idea to the fraudulent data of Hans Eysenck.

Simon Wessely has praised Suzanne O’Sullivan’s book.  It was picked for Wellcome book award as a ‘thoughtful, humane and heartfelt’ study” by Baroness Joan Bakewall. The  Baroness  closed her Twitter account and fled social media after making uninformed comments blaming sufferers of anorexia for their condition:

Bakewell, 82, said: “I am alarmed by anorexia among young people, which arises presumably because they are preoccupied with being beautiful and healthy and thin.

“No one has anorexia in societies where there is not enough food. They do not have anorexia in the camps in Syria. I think it’s possible anorexia could be about narcissism.”

She added: “To be unhappy because you are the wrong weight is a sign of the overindulgence of our society, over-introspection, narcissism, really.”

It’s all in your head”is also the view of IBS promoted by Trudie Chalder and her co-investigator Simon Wessely in a King’s College, London slide presentation aimed at getting primary-care physicians to refer patients to their PRINCE Project. PRINCE is an clumsy acronym for Persistent physical symptoms Reduction INtervention:  a system Change & Evaluation in Primary and Secondary Care.

first slide MUS presentation 2015-2-page-0

second slide MUS presentation 2015-2-page-0

third slide MUS presentation 2015-2-page-0

As can be seen, the brain-gut connection is portrayed as running from the controlling brain  down to the gut.

An article about CBT for medically unexplained symptoms is recommended for the GP’s self-study.

fourth slide MUS presentation 2015-2-page-0.jpg

The preferred treatment for IBS is CBT.

fifth slide-page-0.jpg

As an American, I can’t make a positive identification of this, but I strongly suspect a British attempt at humor. However, I find it quite revealing of how psychoanalysis intrudes into what passes for CBT in the UK. This is associated with lots of patient-blaming notions about somatic conditions expressing hidden conflicts about sex and aggression and dependency.

Participation in clinical trials should be based on patients being fully informed about alternatives. I don’t know if modern treatment of IBS is available in the UK. But if I had a friend who was approached by their GP in the UK about participating in PRINCE, I would recommend that the friend become acquainted with the contemporary view of IBS in the rest of the world, and if necessary, educate their GP.

When Simon Wessely shoved a Hans Eysenck scandal under the rug

Updated May 7, 2016

I have also now responded to Sir Simon Wessely ‘s comment on Twitter about this post. I invite a further reply from him.

  • Soon there may be a renewed call for an investigation of misconduct by famous UK psychologist Hans Eysenck.
  •  What happened the last time reflects on the ability of UK academia to self-correct atrociously bad science and bad publication practices.
  •  As we are currently seeing in other scandals, UK academia looks after its own, no matter what.

swept-rug-BruceKrasting-flickr-370x242The centenary of the birth of UK psychologist Hans Eysenck in March has already been marked by release of a special collection of articles from  about Eysenck from the archives of the British Psychological Association’s The Psychologist.

The centenary  will be also be celebrated with a special commemorative issue of Personality and Individual Differences, one of the journals that he started and edited. I assume many of the articles will praise Eysenck’s accomplishments as the founder of British clinical psychology, his key contribution to establishing cognitive behavior therapy in the UK, and his overall status as one of the most cited psychologists of all time.

If that’s the case, one contribution by UK psychiatrist Anthony Pelosi will stand out like a tuba joining a string ensemble, if it is anything like his past writings. Stay tuned.

Hans Eysenck oneIf he is consistent with his past writings, Tony may reignite earlier charges that Hans Eysenck was a fraudster, abused editorial privilege, and had huge, corrupting undisclosed conflicts of interest – payments not only from American tobacco companies but from their lawyers desperately trying to muster evidence that smoking did not cause cancer. Evidence that Hans Eysenck cooked up for them.

Then editor of The BMJ Richard Smith had backed Pelosi decades ago, as seen in Smith’s slides about editorial misconduct.

slide1 R Smith Eysenckslide 2 r smith should editors

Pelosi and fellow psychiatrist Louis Appleby had made their case earlier in two articles in The BMJ:

Pelosi AJ, Appleby L. Psychological influences on cancer and ischaemic heart disease. BMJ: British Medical Journal. 1992 May 16;304(6837):1295.

Pelosi AJ, Appleby L. Personality and fatal diseases. BMJ: British Medical Journal. 1993 Jun 19;306(6893):1666.

It was an extraordinary move for The BMJ to publish these articles. Lawyers had to clear them before they could be published. Note that Pelosi and Appleby’s scathing criticism of Eysenck’s work did not concern anything that The BMJ had published. Rather, they focused on articles that Eysenck had published in journals that he had founded and over which he still had editorial control. Try to find another example of The BMJ becoming a forum for this kind of thing, before or since.

Eysenck responded with a characteristically evasive and dismissive reply:

Eysenck HJ. Psychosocial factors, cancer, and ischaemic heart disease. BMJ: British Medical Journal. 1992 Aug 22;305(6851):457.

Pelosi made a formal complaint to the British Psychological Society.

According to Rodrick Buchanan’s biography of Eysenck, Playing with Fire:

The BPS investigatory committee deemed it “inappropriate” to set up an investigatory panel to look into the material Pelosi had sent them, and henceforth considered the matter closed. Pelosi disagreed, of course, but was left with little recourse.

Pelosi also made a complaint to the Committee on Publication Ethics (COPE):

Pelosi AJ. The responsibility of academic institutions and professional organisations after accusations of scientific misconduct. The COPE report 1998. London, BMJ Publishing 1998.

One might have thought that the fuss would grab attention in the British media. The only mention was an article by Simon Wessely in The Times. Wessely put out the fire.

Simon on Eysenck

 The normally calm pages of the British Medical Journal have carried a series of critical articles questioning the basis of what must be the most extraordinary claims ever made for the origin of cancer. At the heart of the dispute lies the ever controversial figure of Hans Eysenck, until recently professor of psychology at the Institute of Psychiatry, and his  Croat collaborator, Ronald Grossarth-Maticek.

Wessely identified Eysenck’s critics as members of the fold.

 … In a penetrating article, Tony Pelosi and Louis Appleby subjected Eysenck and Grossarth-Maticek’s series of papers to a critical analysis, which they have followed up with a second piece this week. According to the two psychiatrist, who both trained at the Institute of Psychiatry, the claims were too good to be true.

First, those with the cancer-prone personality died at an extraordinary rate – 121 times faster than the controls.

But there was praise for Hans Eysenck as well.

 Of course, Professor Eysenck, the most influential psychologists of our time, has faced many assaults before (including, unforgettably, physical ones). It would take more than a couple of psychiatrists to ruffle him.

And so it proved. His replies made no concessions to his critics. In essence, his reply was “either you believe these findings, or you don’t”. He was certainly correct on one point. If his results are true, the doctors have been scandalously negligent in ignoring what is the most dramatic breakthrough in the treatment of cancer for many years.

Wessely knew damn well these claims were not just too good to be true. Independent investigation by numerous scientists had revealed them to be fraudulent. Wessely missed his chance to join in calling for an investigation of Hans Eysenck. He passed on it and called for calm.

Of greater concern is that this affair has drawn attention away from the real progress has been made in the psychological management of cancer. In a series of careful studies spread over many years, British psychiatrists and psychologists have described the psychological impact of both the diagnosis of cancer and  the painful treatments that frequently follow. They’ve shown the effect of coping strategies on the prognosis of breast cancer – those who show either “fighting spirit”, or those who deny that there is any danger, seem to do better.

Simon was referring to a single, small, methodologically poor study making claims that having a fighting spirit prolonged life of cancer patients. As I have described elsewhere, a subsequent better designed study by the same authors could not replicate these findings. The authors expressed relief that their negative results provided some correction to the impression there earlier study had created. Namely, if having a fighting spirit does not matter for survival, patients who are dying from cancer cannot blame themselves or be blamed for not fighting harder.

As far as I can tell, there was no further comment in the British media.

Somehow, I don’t think Simon Wessely will be calling for an investigation of Hans Eysenck’s nefarious doings. As Yogi Berra would’ve said, it will be déjà vu all over again.theres-nothing-to-see-here

 Updated May 7, 2016.

Sir Simon Wessely has responded to my blog post on Twitter. I have invited him to respond further with a comment posted at this blog site. Meanwhile, I will reply to his tweet.

Simon tweet

My reply: Dr. Wessely, you conceded that for Pelosi’s articles to appear in The BMJ was truly extraordinary. There was pressure on the Institute of Psychiatry to investigate. There as also a formal complaint to the British Psychological Society. But instead of joining in a call for an investigation, you identified the “greater concern” that the “affair” has “drawn attention away from the real progress has been made in the psychological management of cancer.” What “real progress”?

Psychologist Maggie Watson would later express relief that a larger, better designed study did not replicate her very preliminary findings that adopting a “fighting spirit” allowed cancer patients to live longer. She was relieved because not replicating these findings meant cancer patients would not be blamed for succumbing to a dreadful disease. In retrospect, it was an improbable idea that could potentially hurt patients. And it was wrong.

In an 800 word editorial in The Times, you basically dismissed the serous issues that Pelosi and Appleby raised as a mere distraction. There was no further mention in the UK Press, no further investigation of Eysenck’s well documented fraud and scientific misconduct.

Do you think that was a good outcome? Does this “affair” have relevance to contemporary difficulties in UK academia correcting bad science and bad publication practices?

I welcome your reply. Thanks for having publicized my blog on Twitter.

 

 

 

UK government: Risk of reputational damage to investigators not an excuse for withholding data

The title is my interpretation of the implications of some announcements now appearing in British media. There are more forthcoming, but here is a place to start:

hands off FOIPress Gazette: Success for hands-off FoI campaign as government promises to leave the act alone

BBC News: Freedom of Information charges ruled out after review

BBC News: FOI commission: why has it surprised observers?

Background: I did not bother to make a FOI request for the PACE chronic fatigue  syndrome trial data because that wasn’t necessary. The PACE investigators had been foolish enough to publish a paper in PLOS One which involved a promise to make their data available upon request.

Nonetheless, the PACE investigators strategically decided to treat my request as having been made under FOI for two reasons. It would encumber our dispute with bureaucratic rules that would take months and lawyers to resolve. More importantly, the PACE investigators hoped they could take advantage of today’s much anticipated ruling that might restrict requests for data including mine. Pace Principal Investigator Peter White had written to Parliament and Simon Wessely’s Science Media Centre had organized a campaign to get other universities to use his letter as a template for their own 

King’s College London  announced the turning of my request into a FOI request and gave the following reasons for refusing me:

The university considers that there is a lack of value or serious purpose to your request. The university also considers that there is improper motive behind the request. The university considers that this request has caused and could further cause harassment and distress to staff.

… The university considers that the motive and purpose behind this request is polemical. The university notes the view of the Information Commissioner in decision FS50558352 that the request in that case was ‘more focussed on attacking and attempting to discredit the trial than in obtaining useful information on the topic.

… In conclusion, the university considers that when applying a holistic approach, this request can properly be considered to be vexatious.

Here are some key quotes from respectable media concerning the decision:

Press Gazette: Success for hands-off…

There will be no legal changes to the Freedom of Information (FOI) Act after a review of the legislation found it was “working well”, the Government has announced.

[The decision] It followed widespread fears that the Government Independent Commission on Freedom of Information would recommend new charges on the Act and new restrictions making it easier for public authorities to turn down requests. The Commission was partly prompted by concerns that the ministerial veto on FoI disclosures had been rendered impotent after it was overturned by The Guardian in the Supreme Court in the Prince Charles letters case.

Cabinet Office Minister Matt Hancock said: “After 10 years, we took the decision to review the Freedom of Information Act and we have found it is working well.

“We will not make any legal changes to FoI. We will spread transparency throughout public services, making sure all public bodies routinely publish details of senior pay and perks. After all, taxpayers should know if their money is funding a company car or a big pay off.”

On the public sector side: the Russell Group universities, Local Government Association and NHS authorities were among those arguing that the act was causing them an unnecessary “burden” and putting them at risk of “reputational damage”.

Bob Satchwell, executive director of the Society of Editors, said: “We have welcomed what appears to be a partial victory. Ministers have quite rightly backed away from restrictions to the Freedom of Information Act and have pledged to spread transparency throughout public services.

“A powerful case was made during the Review for extending the Act and cultural change is certainly required but that is difficult to achieve. We must maintain the campaign to change the default switch from tell them nothing unless forced to one where public bodies release information which the public is entitled to have unless there is an exceptional  reason for withholding it.”

BBC: Freedom of Information charges ruled out after review

How does FoI work?

  • Anyone can use the FoI Act to request information held by public bodies, such as the government, councils, schools, hospitals and the police
  • This can be done by letter, email or fax
  • Organisations must respond within 20 working days, although time extensions are allowed in certain circumstances
  • Information is usually provided for free, although there may be small charges for postage and photocopying
  • FoI requests may be rejected for various reasons, such as protecting national security or if dealing with the request would cost too much or take too much staff time

 

BBC: FOI commission: why has it surprised observers?

It is not yet clear how the government will respond to all the Commission’s recommendations. The Cabinet Office minister Matt Hancock says: “We will not make any legal changes to FOI”, so that would appear to rule out any legislation.

This would mean that many of the Commission’s ideas – both some promoting secrecy and others promoting openness – would not be implemented. Any change would then be limited to government guidance.

In which case the Freedom of Information Act would be left, as the Commission puts it, pretty much in its current state of “working well”.

Mr Blair has described himself as a “naive, foolish, irresponsible nincompoop” for introducing the law, saying: “There is really no description of stupidity, no matter how vivid, that is adequate. I quake at the imbecility of it.”

See also my blog posts:

Further insights into war against data sharing: Science Media Centre’s letter writing campaign to UK Parliament

King’s College London stalls some more, reiterating refusal to release the PACE trial data

 

 

 

As major medical journals balk, BMJ moves forward with routine data sharing.

  • Repeated signals that The BMJ is moving forward while editors of other key medical journals try to undermine data sharing.
  • Institutions are stiffening their resistance to release of the promised PACE trial data from the PLOS One article. This threatens to splinter the movement for routine data sharing.
  • But The BMJ continues to support for data sharing and persists in calls for release of PACE data to scientists and patients.

To_deposit_or_not_to_deposit,_that_is_the_question_-_journal.pbio.1001779.g001As I have recently noted, activists for routine sharing of data from clinical trials should curb their enthusiasm about 14 medical journals publishing the International Committee of Medical Journal Editors (ICMJE) statement.

No editors wanted to be seen refusing to publish it, particularly when there was ample reassurance that it is only a proposal, merely aspirational, and far from being implemented. But there is distancing and undermining by editors going on.

I swear crossed fingersNew England Journal of Medicine editors Dan Longo and Jeffrey Drazen quickly drew ridicule in the social media with their attempts to distance themselves from the ICMJE statement and their raising of the specter of “research parasites.”

”…people who had nothing to do with the design and execution of the study but use another group’s data for their own ends, possibly stealing from the research productivity planned by the data gatherers, or even use the data to try to disprove what the original investigators had posited. There is concern among some front-line researchers that the system will be taken over by what some researchers have characterized as ‘research parasites’.”

Old guard Richard Horton, who is committed to “a permanent attack on the present,” exercised his prerogative as editor to cleverly preempt implications of The Lancet publishing the statement. He published a stirring account  of a conference on the reproducibility and reliability of biomedical research but notably failed to mention one of the key solutions being considered at the conference was publicly accessible data.

On a more positive note, a recent twitter exchange called renewed attention to a contrasting 2015 The BMJ editorial:

Loder E, Groves T. The BMJ requires data sharing on request for all trials. BMJ. 2015 May 7;350:h2373.

The movement to make data from clinical trials widely accessible has achieved enormous success, and it is now time for medical journals to play their part. From 1 July The BMJ will extend its requirements for data sharing to apply to all submitted clinical trials, not just those that test drugs or devices.The data transparency revolution is gathering pace. Last month, the World Health Organization (WHO) and the Nordic Trial Alliance released important declarations about clinical trial transparency.

The editorial ends on a strong note:

Hoarding data and limiting access to them is inimical to the data sharing society envisioned in the IOM report. Making anonymised patient level data from clinical trials available for independent scrutiny allows other researchers to replicate key analyses, reduces the possibility that studies will be unnecessarily duplicated, and maximises use of the information from trials—an important moral obligation to trial participants. An initial investment of time and money is needed to prepare trial data for sharing, but after the first use there are few additional costs; in essence, the value of the data increases with each use.

What was said on Twitter

You can see the actual exchange and more by following Trish Groves on Twitter. . She indicates that the tweets are her own, but that she is Deputy editor, The BMJ and editor in chief, BMJ Open (qualifications MBBS, MRCPsych).

trish1

trish2

 

I was still caught up in the 2013 statement and Trish Groves clarified it had been expanded to all trials.

trish3

She gave an example:

trish5

trish insert

trish7

 

Richard Smith, former editor of The BMJ calls for release of the PACE data

Many members of the British establishment ran for cover in the face of Peter White and the PACE investigators’ refusal to release the data to me. Yet, Richard Smith, the former editor of The BMJ responded with a blog post, the title of which says it all:

Richard Smith: QMUL and King’s college should release data from the PACE trial [

His concluding statement:

I fear that QMUL and King’s are defending the indefensible and like King Canute failing to stop a tide that is coming in fast.

That was followed up by Richard Lehman, a British primary care physician, academic and author of the regular blog, Richard Lehman’s Journal Review, taking aim at the NEJM editors in Share data or be damned:

Having signed the remarkably radical ICMJE proposal, Jeff Drazen, editor of NEJM, co-authors an editorial simply titled “Data Sharing.” It begins by mocking a delusive biscuit-tin landscape of everybody happily sharing data, moves on to grave warnings about “research parasites” feeding off other people’s hard work, and ends up advocating “research symbiosis,” by which the original researchers collaborate with others in moving beyond the data already gathered. I think they are trying to be witty, and I don’t want to discourage that, but they make it clear that they regard re-analysis and meta-analysis as little better than what a tapeworm gets up to in the bowel, as illustrated on p.234.

Personally, I think we need all the data parasites we can get, as well as symbionts and all sorts of other creatures which this ill-chosen metaphor can’t encompass. What this piece really shows, in my opinion, is how far the authors are from understanding and supporting the true opportunities of clinical data sharing.

The BMJ’s call for greater patient involvement in interpreting research vs the spoiled identity of patients with chronic fatigue syndrome/myalgic encephalomyelitis (ME) or ME/CFS

colonial_submissionPeter White and the PACE investigators’ crude, personal, and unprofessional response to my request for data was reflexive. They are accustomed to receiving those requests from patients in a culture where patients should be seen and not heard. They were responding as if I was somehow below them in the hierarchy in which their views should be uncritically accepted with all the deference that colonialists are due. How vexatious of me to challenge the interpretations of their data that they were putting forth…

Once I was cast among the patients, I was subject to the usual smearing and collective punishment for real and imaginary hostile actions of a few patients in a familiar narrative crafted by Simon Wessley’s Science Media Centre . Although I have a stronger publication record  than any of the PACE investigators, concerns were raised about releasing data to those who are incapable of analyzing it.

Over time, I’ve gotten to know some of the individuals who have previously requested data, although I have never met them. They impress me as amply qualified to analyze data, and they often analyze data that I report in my blogs, with them asking for no credit. Many of them have been academics or have had other professional achievements. Others were progressing well along in their educational pathways before they were struck by their illness. Still others become citizen-scientists with the capacity to publish peer reviewed letters to the editor as a result of struggling to deal with their misunderstood medical condition.

There is something ugly, pernicious going on here, more fundamental than the question of data sharing. Being a patient with chronic fatigue syndrome/ myalgic encephalomyelitis is what sociologists like Erving Goffman would call a spoiled identity . Being a patient means being stripped of all other significant social identities and being reduced to a common denominator, stigmatized role.

Long after the current crisis about data sharing is resolved, issues about respect for patients that have been uncovered in the UK will remain. These issues are shocking to outsiders. In the United States, they would variously framed as discrimination and even human rights issues. I wouldn’t be surprised if there is not some movement in the UK to identify these issues in the same terms.

But there is also an affront to any conception of patient empowerment. After all, the PACE investigators are making claims that have profound implications for the treatment and well-being of patients.

A recent blog post of mine, What patients should require before consenting to participate in research…  argued that patients should refuse to consent to research unless their role is more clearly specified than as mere passive providers of data. I drew heavily on an editorial from The BMJ’s editor-in-chief calling for more explicitly defined patient involvement in the design, implementation and interpretation of research.

Godlee, F. Call for greater involvement of patients. BMJ 2015; 351 doi: http://dx.doi.org/10.1136/bmj.h6525 (Published 03 December 2015)

It stated

More than three million NHS patients took part in research over the past five years. Bravo. Now let’s make sure that patients are properly involved, not just as participants but in trial conception, design, and conduct and the analysis, reporting, and dissemination of results. You may have noticed the new “patient involvement” box in The BMJ’s research articles. Sadly, all too often the text reads something like, “No patients were involved in setting the research question or the outcome measures; nor were they involved in the design and implementation of the study. There are no plans to involve patients in the dissemination of results.” We hope that the shock of such statements will stimulate change.

This is clearly aspirational, and may still be well beyond reach. As an article cited in the editorial stated:

Thornton S. Beyond rhetoric: we need a strategy for patient involvement in the health service. BMJ. 2014 Jun 23;348:g4072. [http://www.bmj.com/content/348/bmj.g4072.short]

UK government is heavy on the hyperbole of empowering patients but lacks a robust strategy.

Respect for a patient’s individual autonomy is an accepted principle in modern medicine. In the past half century, the concept of autonomy has usurped medical paternalism in almost all of its forms and has aspired to promote patients from passive recipients of care to partners in planning their own treatment.1 Now the concept has extended beyond individual autonomy to an expectation of empowerment at the population level.

But the editorial clearly puts the issue on the table in a way that is in sharp contradiction to the way patients are being treated by Peter White and the PACE investigators.

 Update: Simon Wessely continues to fight release PACE data

For someone who adamantly proclaims he has no dog in the fight, Simon Wessely is quite active behind the scenes. He sends regular emails and direct messages to players in the struggle for the PACE data, including myself and numerous patients.

Recently he emailed blogger Leonid Schneider signaling that maneuvering to prevent release of the PACE data is set to challenge the legitimacy of having to share data at all.

What is clear is that the general atmosphere around data sharing, especially of sensitive data such as medical information, is in a state of flux. Indeed several reviews are ongoing in this country which are likely to make data linkage and sharing more onerous, and eventually there will be new legal rulings, which again are unlikely to produce a more liberal approach to data sharing/linkage.

Sooner or later I anticipate there will be a collision between the open data movement and the legal framework around data protection, at least in the UK.

As an epidemiologically trained researcher I am anxious about the consequences of this, since I doubt very much it will make data sharing and linkage easier, rather the reverse. I hope I am wrong, but the fallout from care.data has been so toxic that I suspect the direction of travel will be in one direction only. At least in England.

The battle lines are getting more clearly drawn and the stakes are being raised. We need everybody supporting data sharing to unite.

The BMJ and patients with chronic fatigue syndrome/ myalgic encephalomyelitis have an unfortunate history with perceived injustices and wounds on both sides. I see a clear indication The BMJ editorial staff is willing to put that aside. I hope the patients can do similarly.

 

 

Further insights into war against data sharing: Science Media Centre’s letter writing campaign to UK Parliament

plos oneMy requesting the PACE trial data is much simpler than it is being portrayed. The PACE investigators promised the data would be available upon request as a condition for publishing in PLOS One. No one forced Peter White and colleagues to publish in an open access journal committed to data sharing, but by doing so they incurred an obligation. So, they should simply turn over the data.

Of course, providing me with the data would involve the risk of my analyses exposing what they have been hiding or falsely claiming.

The PACE investigators have thus far refused to turn over the data. They have treated my request as falling under a Freedom of Information request, which it does not. But with my request conceptualized in this way, they denied it because they deemed my motives in seeking the data “vexatious,” a strategy that they have used with other requests.

The PACE investigators are playing hardball.

Stephan Lewandowsky

Stephan Lewandowsky

Peter White previously enlisted Stephan Lewandowsky to disseminate a misrepresentation of the PACE investigators’ commitment to transparency:

 

Some requests were complied with, so long as they did not compromise medical confidentiality, future publications, or academic safe space to deliberate…Our deliberate policy, to help allay concerns about the trial, was to be as transparent as possible regarding what we did, while also protecting medical confidentiality and our staff and patient [p 17].

We know of course this isn’t true. The collusion of Lewandowsky in this caper undercuts his claim that he and Dorothy Bishop are not ‘intimately familiar with the details’ of the PACE Trial. (See comments on their Nature article, Research integrity: Don’t let transparency damage science) Lewandowsky’s claim was made in reaction to the two of them being criticized for lumping those who seek the PACE data, like me, with science deniers who must be resisted:

Orchestrated and well-funded harassment campaigns against researchers working in climate change and tobacco control are well documented. Some hard-line opponents to other research, such as that on nuclear fallout, vaccination, chronic fatigue syndrome or genetically modified organisms, although less resourced, have employed identical strategies.

Is there a remarkable coincidence in Lewandowsky and Bishop attempting to make data sharing so complicated, just when the PACE investigators are urgently seeking reasons not to share their data? Here is some evidence that it is not a coincidence.

Dorothy Bishop is an adviser to the Science Media Centre  founded by Simon Wessely. The SMC is coordinating a letter writing campaign to Parliament instigated by Peter White attempting to get an exclusion from the Freedom of Information Act for request for data.

What was revealed by a response to a request made under the Freedom of Information Act

A FOIA request produced an email from Fiona Fox of the Science Media Centre dated October 30, 2013:

Those of you, like the SMC, a worried about the malicious use of FOIA against researchers may like to see this and use it in your own efforts. I’ve just been briefed about [redacted] FOIing a number of universities about the primate research [redacted] is a convicted animal rights extremists!!! Surely this was never the intent of FOI!!!

Cheers

Fiona

The email is attached to a further thread of emails. The source for the October 28, 2013 email is redacted but the CC to Fiona Fox is revealed along with the subject letter:

Dear all.

As you can read, QMUL are lobbying MPs to get a good FOIA exemption passed into law that properly defends research. Please use this as a basis for asking your own Universities and other likely lobbyists to get in touch with their own or your own friendly MPs.

Best wishes,

Peter

I think when you read the letter template, you can see that there is no doubt that the source is Queen Mary University of London’s Peter White.

The template letter that is attached for sending to Parliament attempts specifically to get an exemption for the PACE trial:

Dear XXX,

The Intellectual Property bill currently going through Parliament includes a proposed exemption for current research from disclosure under the Freedom of Information Act requests and would prevent the premature release of data in academic research.

We very much welcome this necessary exemption as we believe that it will do much to avoid the significant risks to academic freedom presented under the current pre-publication exemption of the Act. We also believe that it will help ensure the ability and willingness of researchers to engage in free inquiry into important areas of research.

We are writing to you because we are concerned that the bill as it stands may not fully clarify when the exemption from requests applies. In many cases, a research project proceeds via a series of publications, rather than one alone, progressively investigating and reporting outcomes. This, for example, is the case with the P/VCE Trial, an important study into the safety and efficacy of various treatments for Chronic Fatigue Syndrome in which QMUL researchers have participated for the last 10 years. Here there have been separate papers, published according to a defined research and publication strategy, that have addressed, or will address in sequence the main results of the effectiveness and safety of the treatments, their cost-effectiveness, long-term follow-up and the mediators of the treatments to explain how they work. [Emphasis added]

It is not immediately clear from the bill as it stands whether information from such a continuing series of publications within a given research project would fall within the exemption beyond the first publication, since it may be argued that a “report of the research” has already been published under the present wording of proposed Section 20.

We would therefore suggest the following slight change to clarify “the programme” and “publication… of a report”:

“the programme is continuing with a view to the publication, by a public authority or any other person, of a report of the research that either includes the requested data or the analysed results thereof.” [Emphasis in the original]

We hope that you will raise this issue in Parliament so that the bill may be ensured to have its intended and necessary effect.

With best regards

XXX

My previous blog post, Glimpses into the assault on data sharing discussed how the UK Independent Commission on Freedom of Information issued a call for evidence. Peter White, submitted testimony to the UK Independent Commission on Freedom of Information some time between October 9 and December 7, 2015:

“Section 22a of the Act is insufficient protection for science into controversial subjects, and requires that the research is on-going, so is irrelevant to completed research. We need science in the UK to be protected or it will continue to be damaged as this trial has been (other examples include climate change science, and research into the health effects of tobacco). Exempting Universities from the FOIA would achieve that. Exempting scientific research data produced by Universities and other higher educational institutes might be a workable alternative.”

Another blog post, King’s College London stalls some more, reiterating refusal to release the PACE trial data discusses a press release dated December 18, 2015 in which Kings College, London reiterated its refusal to release the PACE trial data.

King’s College, London had not communicated with me directly, but I learned of the press release from a tweet by Simon Wessely. I recommend following Simon on Twitter @WesselyS to get the latest updates on the maneuvering by the PACE investigators to resist sharing their data.

The press release indicated:

We are…concerned for the rights and welfare of trial participants. Participants did not give consent to the public release of their data when they entered the trial. In particular we are concerned to ensure that there is no risk of misuse of the data such as through inadvertent personal identification. The scientists who have already received data have all signed a formal confidentiality agreement, approved by the independent PACE Trial Steering Committee, which required that they respect the confidential nature of the data, and keep them secure, as agreed with trial participants when they consented to take part. We stand by our decisions to decline two recent applications for trial data as we believe that they did not meet these requirements.

We are currently seeking further ethical and scientific advice, as well as the advice of patients, on how best to provide independent decisions about appropriate access to relevant data in a way that balances the rights of trial participants, and future progress of the trial analysis and follow up, with the public interest in releasing trial data.”

The Nature comment by Stephan Lewandowsky and Dorothy Bishop expands on these concerns. Of course, that’s only a coincidence.

In future blog posts, I will be discussing more about the Science Media Centre’s well-orchestrated campaign to protect the claims of the PACE investigators’ interpretation of their data, including by attacking the motives and character of those who criticize it and request the data for independent reanalysis.

The motive is simple. If the claims of the PACE investigators are as credible, then disabled people who are getting payments from the government can be required to get cognitive behaviour therapy as a condition for continuing their payments. Of course, it has been gradually unfolding that CBT or Graded Exercise Therapy (GET) can not get chronic fatigue/myalgic encephamyelitis patients back to work. And a course of GET makes many of them more disabled. But who cares when requirement that these patients be in such treatment can be used to deny social welfare payments to them?

smc media campaign

Science Media Centre organized media campaign inaccurately portraying benefits of CBT

A future blog post will also reveal the government and corporate funding sources  for the Science Media Centre, including energy company BP, Proctor & Gamble, Rolls-Royce and pharmaceutical company Astra Zeneca. Another blog post will discuss the origins of the smearing of critics of the PACE trial as science deniers. I’ll explain why we are being lumped with animal rights activists and climate change deniers, but not opponents of fracking.

I’m sure that many readers were as confused as I was by Dorothy Bishop’s apparent about-face from a November blog, Who’s afraid of Open Data to the recent Nature commentary with Stephan Lewandowsky. In November Bishop was saying

“Fears about misuse of data can be well-justified when researchers are working on controversial areas where they are subject to concerted attacks by groups with vested interests or ideological objections to their work. There are some instructive examples here and here. Nevertheless, my view is that such threats are best dealt with by making the data totally open. If this is done, any attempt to cherrypick or distort the results will be evident to any reputable scientist who scrutinises the data. This can take time and energy, but ultimately an unscientific attempt to discredit a scientist by alternative analysis will rebound on those who make it.  In that regard, science really is self-correcting. If the data are available, then different analyses may give different results, but a consensus of the competent should emerge in the long run, leaving the valid conclusions stronger than before.”

I think this seeming contradiction could be resolved if Dorothy Bishop publicly clarified her relationship to the Science Media Centre, including where she stands, as an adviser, on its campaign against data sharing.