The PACE Study: Open Access and Conflicts of Interest [UPDATED with a note to commenters]

The ME/CFS advocates who pursue this PACE debacle on the basis of how psychs deliberately skewed data make no sense to me.
Considering the original Holmes CFS excluded psychiatric disease and the British psychs created an alternate "Oxford CFS" in the UK to be somatization disorder, nailing them how mishandling the PACE trial without pointing this out is like prosecuting for reckless driving while ignoring the fact the thieves were driving that way because it was a stolen car.

I am sorry to interject politics, but that's the only thing I think about these days…. Perhaps this is one reason why HRC lost some key votes in battleground States? That's what my Trump supporter buddies tell me…

One other legal principle is objectivity and obtaining the full facts of the dispute before rushing to judgement and I am afraid you haven't done that. It might have been an idea to see the authors' previous responses to the claims made, the refutations on alleged non disclosures, outcome measures etc etc , all of which have been reproduced in journals and the trial website (see the website on the QMUL web). The issue around refusals to share data is also nothing like as simple as you describe and actually raises key ethical issues that might interest you rather than a blanket 'gosh how could they be so blind/wicked' line. It's an old trial with consent forms from 2003 – read them first before you rush to judgement and also see the previous legal rulings about this before the last different but still contested one. Have a read of my blog on this for a different picture as well. I think you will find it is , as they say, a bit more complicated than you think and perhaps actually more interesting bit less. http://www.nationalelfservice.net/other-health-conditions/chronic-fatigue-syndrome/the-pace-trial-for-chronic-fatigue-syndrome-choppy-seas-but-a-prosperous-voyage/

Sorry about the delay in publishing the above comment by Simon Wessely. It was initially caught in the spam filter because it includes a hyperlink.

Is that the same Professor Simon Wessely who, according to a journalist speaking at a lunchtime session during a 2012 Conference at Stanford, had an audience of insurance representatives rolling in the aisles with his mimicry of ME/CFS patients?

Is the FOI tribunal ruling regarding PACE contested? QMUL fought long and hard to the tune of £250,000 to prevent release of a small data set from the PACE trial but as QMUL chose not to appeal the final ruling, it does seem unreasonable of Professor Wessely to state the contrary.
An interesting point noted in the tribunal findings was relating to the claims of harassment and threats made by PACE researchers thoughout the PACE trial and subsequent publications by the researchers which have received much publicity in newspapers and beyond. It was noted that the evidence provided by the researchers amounted to one incident of heckling during a conference.

Among other things, the PACE trial authors published in PLOS ONE. The very first sentence of PLOS's Data Availability Policy reads, "PLOS journals require authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception." The PACE trial authors did not abide by that agreement and resisted all attempts, by both researchers and patients, to make data of their publicly funded trial available.

Simon Wessely continues to defend the actions of the PACE trial's authors, as well as the trial's supposed findings, when the raw data simply does not support those assertions. The fact that he has steadfastly refused to accept this and continues to defend a fatally flawed study is incredibly disappointing.

As always, Dr. Wessely is repeating past claims but saying nothing of substance. It is simply not true that the PACE authors have responded to the legitimate concerns raised by patients and by me, in my investigation of the PACE trial on Virology Blog. They have never explained what it means to be "recovered" or "within normal range" of the two primary outcome measures at baseline, and why this was not reported in The Lancet or Psychological Medicine. Their own reanalysis shows that by using the definition of "improvement" they themselves outlined in the protocol, they got "improvement" rates one third of the "improvement" rates they reported in The Lancet, once they changed the way they defined "improvement." The Virology Blog reanalysis of the "recovery" data showed that they had null results for "recovery," per their original methods. In terms of refuting charges of conflicts of interest, they have never explained why they violated their own protocol promise to obtain informed consent by informing prospective participants of "any possible conflicts of interest." Since they did not, they have no legitimate informed cosent for ANY of their 641 participants. End of story. They should never have been allowed to publish any data in the first place. Face it, Simon. PACE is collapsing, and you can't save it, no matter how much you try to spin.

"Have a read of my blog on this for a different picture as well. I think you will find it is , as they say, a bit more complicated than you think and perhaps actually more interesting bit less.

http://www.nationalelfservice.net/other-health-conditions/chronic-fatigue-syndrome/the-pace-trial-for-chronic-fatigue-syndrome-choppy-seas-but-a-prosperous-voyage/ "

I highly recommend this blog, and especially the readers' comments below it exposing Prof Wessely's self-serving tripe for what it is.

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"Simon Wessely continues to defend the actions of the PACE trial's authors, as well as the trial's supposed findings, when the raw data simply does not support those assertions. The fact that he has steadfastly refused to accept this and continues to defend a fatally flawed study is incredibly disappointing."

I wonder if that refusal is because Wessely has a massive vested interest in defending PACE and the CBT-GET model upon which it was based, seeing as he was one of the originators of that model (lead author on the formal paper, if I remember correctly), and has relentlessly and ruthlessly promoted it and dined out well on it ever since, long before it had been adequately tested, and even after it had been (by PACE) and found seriously wanting.

Problem for Wessely is that if PACE goes down – and it is going down – then so does his precious psycho-ideology, along with his reputation and career. They are all inextricably locked together in a death spiral.

As he knows all too well. Hence his increasingly desperate and ludicrous defense of the utterly indefensible. Because he does not have the basic courage and decency to admit he was seriously wrong, and inflicted great distress and suffering on large numbers of already very sick and burdened people, for no good reason at all.

Time for PACE-gate supporters to have their academic credentials reviewed. Why are Oxford University, Queen Mary of London, Kings College, Bristol University- not taking action to look into this matter?

Ron: Let's ease up on the accusations. The PACE trial was deeply flawed and its continuing supporters are in denial, but it was not fraudulent.

Charges of misconduct will only make it harder to get study retracted by The Lancet or at least rejected by the rest of the profession.

Simon Wessley – the problems with PACE are the misleading use of raw data to substantiate unfounded and false claims of the use of CBT and GET as being effective "treatments" for people with the neurological disease ME/CFS.
The PACE authors were asked to reanalysis their raw data as per the trial protocol published in the BMJ in 2007. QMUL refused, saying that they didn't have a statistician and that it would cost more than 450 pounds to analysis the data as per the original (pre view of the data) protocol.
The raw data was requested so that independent scientists could do what QMUL wouldn't.
As the first tribunal judge pointed out QMUL released the raw data, that it said it couldn't release to its friendly colleagues.
As you are well aware the Wessley School of thought and biopsychosocial model for CFS are fatally flawed, have never been substantiated by science and rely on a host of contrived artifacts to make them look at all possible e.g. redefining recovered patients to include those still severely disabled and calling this a strict criteria for recovery.
Show/quote the science that supports your views????

Some of the PACE authors failed to declare their involvement with medical insurers whom they advised, and these, as well as the DWP, save money as long as the disease is categorised as a mental illness. Professor Wessely has been paid by medical insurers for his advice to this effect. I think that commentators from the US underestimate the breadth and depth of his involvement with government agencies and the British establishment. He has been honoured, and knighted, and via the Science Media Centre, has influence with the UK media. For example, the Invest in ME conference, which has been held in London for eleven years, is never mentioned in the mainstream media in the UK. Health reporters for The Guardian and the Independent support Wessely, the BBC Health reporter is a major figure in the Science Media Centre, and the Science Media Centre reported Crawley's statements without comment, criticism, or presenting any other points of view or information about ME/CFS. Following their record back, all you find are reports of the harrassment of ME researxhers, nothing about research developments. This is a situation worthy of very in-depth investigative reporting, as well as a sociological study of the currents in society which support the treatment of ME/CFS patients.. ideas about women as 'complaining', the idea that exercise is a cure-all, the pressure on people to take palliative medicines and keep on working, the shift from attention to the patient and the patient's narrative to attention to questionnaires and technology…if the computer tells us something, it must be right, there can't possibly be anything wrong with the questionnaire, the statistical analysis, or the machine itself. Finally, people with ME are the most helpless of the helpless, and helplessness can attract both the best and the worst of human responses.

Simon Wessley, its time to stop defending the indefensible. The PACE trial ignores fundamental scientific principles. Patient testimony was that they were harmed by the trial and that the health "professionals" did not allow them to report adverse effects. Recruitment was slow and drop out huge, harm during the trial unreported.
NO objective measures of health recorded- the Canadian Consenus Criteria and the International Consensus Criteria detail many easily measurable physiological abnormalities- none measured.
The USA has rejected your broadly defined Oxford definition and your broadly defined NICE definition is another attempt to hide the reality of the disease ME/CFS.
It is totally feasible to sub group categories of patients within a trial and given the clear physiologically different sub groups described in the CCC and the ICC – I put it to you that it is negligent not to do so.
The CCC was published in 2003, long before the PACE-gate saga began..
To fail to identify the PACE participants who have the physiological abnormalities is a grave oversight and one that is at odds with a genuine effort by researchers to understand a disease.

Let's not forget how many were sectioned for resisting the flawed CBT/GET model, how many (more than 50%-possibly 74%) had their health destroyed by being forced to over-exert to meet the requirements pushed on them in CBT/GET. Nor should we forget the children stolen from their families and taken into care, where they were sometimes horribly abused, all in the name of CBT/GET. Neither forget the unfortunate Danish woman who was incarcerated for three years and tortured according to the methods of CBT/GET, so that her brain and body are now severely damaged. And never forget all those who died and are dying because CBT/GET supplanted biomedical investigation, causing fantasies of non-existent psychological explications for a disease that features aspects of polio, MS, and HIV-AIDS causing millions to be kept from therapies, cures, care and even humane treatment.

The PACE saga has been yet another horrible episode in the history of humankind's horrible mass-scale mistreatments of fellow humans, and it continues even as I write. It is loud evidence of how Labour threw the NHS under the bus, and its remedy must be part of Labour's commitments for the future. Indeed, all parties must be made to pledge on this, but none more than Labour; it was under Blair's prime ministership that the gospel of CBT/GET was indulged, took root, and became a monopoly of treatment in the NHS. What good is a Labour party that cares nothing for the health of its citizens, but instead prescribes their maltreatment?

In seeking to defend the PACE trial investigators, Prof. Wessely wants to complicate the discussion. However, more than 2 months after the release of the patient data, one of the "complications" he might be less keen to discuss is the complete absence of any identification of PACE trial participants from that data – a fear (like several others) which was hyped to a ridiculous extent by QMUL and their expert witness during the data release tribunal.

I suspect that Prof. Wessely knows that the "erroneous illness belief" paradigm of ME/cfs (which he was instrumental in contriving) is now well into its death throws, but his hubris prevents him from acknowledging that reality. His ongoing efforts to rewrite his involvement in the history of this disease don't fool seasoned observers of this master of manipulation.

Perhaps if his much professed concern for patient's well-being was genuine, he would break the habit of a lifetime and take cognisance of the latest biological evidence, particularly that which points to this illness being some kind of hypo-metabolic state – which makes the idea of exercising your way out of it seem quite ridiculous.

I thought Wessely's comment had some strange logic. Firstly he says we need to look at all the information to make an assessment. Then he argues as to why we should be denied some of the information.

Much of what patients have asked for is for the data to be open so that they can make their own assessment of the outcome of the trial. The protocol changes twisted the concept of recovery to make it non-recovery. Yet Wessely argues that we should trust the figures and changes that were made by this group and hides behind patient confidentiality even though not PII has been released. The PACE group themselves had released individual patient data in the SAE data within the appendix of the Lancet paper.

Wessely points to his blog where he says as long as a committee has approved changes then patients should accept this. Yet we have been denied access to the decisions and reasoning of the committee so they are unaccountable. To many their decisions seem to lack rigorous analysis especially in allowing massive changes to the primary outcomes and recovery secondary outcome with no well argued coherent reasons (and sometimes incorrect reasons being given in the papers). Perhaps they just approved the statistical analysis plan which does not talk of the protocol changes and failed to go back and check. But we are not allowed to know that information. Perhaps Wessely's argument that we should look at all the information is actually one of we should look and believe his opinions.

My problem with CBT and GET is that most of the CFS patiënts get much worse after this treatment. Wessely, White and Chalder never reported these complaints. That is unethical. Also their behavior in the Pace Trial saga is unprofessional. They are a shame for science and the community. Maybe they can get some CBT to learn about their unethical and ridiculous behavior. Maybe they have some hidden trauma from their childhood.

FWIW there is a profile of Simon Wessely on MEpedia. It gives a bit more detail on his career.

http://me-pedia.org/wiki/Simon_Wessely

Ten years ago the UK Parliament Group on Scientific Research into ME (The Gibson Inquiry) [1] called for a thorough investigation of conflicts of interest surrounding the Wessely School:

"CFS/ME is defined as a psychosocial illness by the Department for Work and Pensions (DWP) and medical insurance companies. Therefore claimants are not entitled to the higher level of benefit payments. We recognise that if CFS/ME remains as one illness and/or both remain defined as psychosocial then it would be in the financial interest of both the DWP and the medical insurance companies."

"[There are] numerous cases where advisors to the DWP have also had consultancy roles in medical insurance companies. Particularly the Company UNUMProvident. Given the vested interest private medical insurance companies have in ensuring CFS/ME remain classified as a psychosocial illness there is blatant conflict of interest here." [2]

Patients and advocates are still waiting for the investigation.

[1] http://erythos.com/gibsonenquiry/Report.html
[2] https://en.wikipedia.org/wiki/Controversies_related_to_chronic_fatigue_syndrome#Political

I am a sociologist and research methodologist who is also a carer to a disabled family member. I was one of the first major critics of the PACE trial, identifying methodological flaws even before the trial started, and wrote a formal complaint to the Lancet when the PACE trial was published, although to date I have been ignored by them. My work has, sadly, been largely left out of the narrative of the PACE controversy. I actually believe all published PACE papers should be retracted because their 'findings' are unsafe: a consequence of the many methodological flaws of the trial. By 'unsafe' I mean both scientifically unsound and, actually more importantly, dangerous to patients. My critique can be summarised thus:

1. Serious risks to clinical patient safety caused by unsound claims made about the efficacy of CBT and GET following the PACE trial;

2. Gross discrepancies between research and clinical cohorts, and how clinical patients (and the physiological dysfunction associated with them) appear to have been actively excluded from PACE and other research by the research group involved in PACE, which has, ironically, caused serious resulting risks to clinical patient safety in the UK in particular;

3. Related to the above, gross discrepancies in how various sets of patient criteria were used (and/or rejected), including but not limited to a changing of the London criteria by PACE authors from its original state, a set of criteria which was already controversial and problematic to start with for a number of reasons;

4. Failure of the PACE trial authors to acknowledge the range and depth of scientific literature documenting serious physiological dysfunction in patients given diagnoses of ME or CFS, and how CBT and GET approaches may endanger patients in this context;

5. The inclusion of major mental illnesses in the research cohort;

6. The distortion by PACE trial researchers of 'pacing' from an autonomous flexible management strategy for patients into a therapist led Graded Activity approach;

7. The post hoc dismissal of adverse outcomes as irrelevant to the trial, in direct contradiction to what is scientifically known about the physiological dysfunctions of people given diagnoses of Myalgic Encephalomyelitis or Chronic Fatigue Syndrome;

8. The instability of 'specialist medical care' as a treatment category, and the lack of any sound category of 'control' group.

ANNOTATED BIBLIOGRAPHY

1. Regarding my concerns about PACE's (and other projects') studied ignoring of the Canadian Guidelines:

http://bmj.bmjjournals.com/cgi/eletters/bmj.38301.587106.63v1

Also my response "Problems in the PACE Trial" (13 November 2007)
to the White et al paper "Protocol for the PACE trial":

https://bmcneurol.biomedcentral.com/articles/10.1186/1471-2377-7-6/comments

See also my complaint to the Lancet: http://pacedocuments.blogspot.co.uk/2011/04/complaint-to-editor-of-lancet-regarding.html

See also my book "Authors of our own Misfortune? The Problems with Psychogenic Explanations for Physical Illnesses" (2012) Market Rasen: The Village Digital Press, especially chapters 2, 4, and 6.

2. Regarding the problems of the London Criteria in particular:

Online exchange with Ellen Goudsmit following my response "Problems in the PACE Trial" (13 November 2007)
to the White et al paper "Protocol for the PACE trial":

https://bmcneurol.biomedcentral.com/articles/10.1186/1471-2377-7-6/comments

See also an online discussion on Phoenix Rising:

http://forums.phoenixrising.me/index.php?threads/pace-trial-and-the-criteria-for-m-e-used.10766/

See also my complaint to the Lancet: http://pacedocuments.blogspot.co.uk/2011/04/complaint-to-editor-of-lancet-regarding.html

3. Regarding the problems around criteria used generally:

http://bmj.bmjjournals.com/cgi/eletters/bmj.38301.587106.63v1

https://bmcneurol.biomedcentral.com/articles/10.1186/1471-2377-7-6/comments

http://forums.phoenixrising.me/index.php?threads/pace-trial-and-the-criteria-for-m-e-used.10766/

http://forums.phoenixrising.me/index.php?threads/pace-study-and-oxford-criteria.8880/

See also my complaint to the Lancet: http://pacedocuments.blogspot.co.uk/2011/04/complaint-to-editor-of-lancet-regarding.html

See also my book "Authors of our own Misfortune? The Problems with Psychogenic Explanations for Physical Illnesses" (2012) Market Rasen: The Village Digital Press, especially chapters 2, 4, and 6.

4. Regarding PACE and/or other research excluding ME patients (a neurological disease according to WHO ICD-10) with neurological dysfunction (and signs of physical illness) from research:

http://forums.phoenixrising.me/index.php?threads/pace-trial-and-the-criteria-for-m-e-used.10766/

http://forums.phoenixrising.me/index.php?threads/pace-study-and-oxford-criteria.8880/

http://forums.phoenixrising.me/index.php?threads%2Fpoll-swollen-lymph-nodes-did-you-have-these-before-getting-me-cfs-or-did-they-only-appear-after.9250%2F

See also: "RE: Authors Response" (Angela Kennedy replied to Anthony_Cleare on 13 Jan 2010 at 23:18 GMT)

http://www.plosone.org/annotation/listThread.action?root=1669

See also: Questions about 'CFS' and 'ICF' selection criteria of cohort' Response to Byrnes et al ('Expression in
Peripheral Blood Leukocytes in Monozygotic Twins Discordant for Chronic Fatigue: No Evidence of a
Biomarker' PLoS ONE 4(6): e5805 2009) 3 January 2011.
http://www.plosone.org/annotation/listThread.action?root=3801

See also: "'Cost-effectiveness' is irrelevant when safety has not even been addressed in the PACE trial 02 Aug 2012 at 11:35 GMT in response to McCrone et al "Adaptive Pacing, Cognitive Behaviour Therapy, Graded Exercise, and Specialist Medical Care for Chronic Fatigue Syndrome: A Cost-Effectiveness Analysis"

http://www.plosone.org/annotation/listThread.action?root=52481

See also my complaint to the Lancet: http://pacedocuments.blogspot.co.uk/2011/04/complaint-to-editor-of-lancet-regarding.html

See also my book "Authors of our own Misfortune? The Problems with Psychogenic Explanations for Physical Illnesses" (2012) Market Rasen: The Village Digital Press, especially chapters 2, 4, and 6.

5. Regarding claims to safety and efficacy:

http://www.plosone.org/annotation/listThread.action?root=52481

http://bmj.bmjjournals.com/cgi/eletters/bmj.38301.587106.63v1

See also my complaint to the Lancet: http://pacedocuments.blogspot.co.uk/2011/04/complaint-to-editor-of-lancet-regarding.html

See also my book "Authors of our own Misfortune? The Problems with Psychogenic Explanations for Physical Illnesses" (2012) Market Rasen: The Village Digital Press, especially chapters 2, 4, and 6.

6. Regarding the failure to address the biomedical evidence available detailing serious organic physiological dysfunction in patients who receive a 'CFS' or 'ME' diagnosis:

https://bmcneurol.biomedcentral.com/articles/10.1186/1471-2377-7-6/comments

See also my complaint to the Lancet: http://pacedocuments.blogspot.co.uk/2011/04/complaint-to-editor-of-lancet-

7. Other points:

https://bmcneurol.biomedcentral.com/articles/10.1186/1471-2377-7-6/comments

See also my complaint to the Lancet: http://pacedocuments.blogspot.co.uk/2011/04/complaint-to-editor-of-lancet-

See also my book "Authors of our own Misfortune? The Problems with Psychogenic Explanations for Physical Illnesses" (2012) Market Rasen: The Village Digital Press, especially chapters 2, 4, and 6.

Dear Prof Lubet

Thanks for drawing attention to Dr Keith Geraghty's article, which is indeed excellent. I wrote a comment to the journal where it appeared, with more details of PACE conflicts of interest, but the editor has replied that they don't publish correspondence. Since then, you've posted another blog directly addressed to Prof Wessely, which makes some of the same points. I hope you don't mind my using your blog to post my letter, for the record, with apologies for any repetition.

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Keith Geraghty’s clear account of some of the many controversies surrounding the PACE trial for ME/CFS published in the Lancet in 2011 is most welcome (White, Goldsmith et al. 2011; Geraghty 2016). Geraghty notes the strong published opinions of the PACE investigators, some of whom had devised and promoted the Graded Exercise Therapy and the version of CBT used in the trial. On the general problem of scientists testing treatments which they favour, he sensibly calls for greater scrutiny of such ties before trials receive official approval.

The PACE protocol says that it complied with the Declaration of Helsinki on Ethical Principles for Medical Research Involving Human Subjects (White, Sharpe et al. 2007). We should be reassured, then, that patients with ME/CFS were made aware of the investigators’ conflicts of interest, even if the commissioning bodies and ethical committees that approved PACE were not. The Declaration states that each participant must be "adequately informed of the aims, methods, sources of funding, any possible conflicts of interest, institutional affiliations of the researcher, the anticipated benefits and potential risks of the study and the discomfort it may entail. … After ensuring that the potential subject has understood the information, the physician or another appropriately qualified individual must then seek the potential subject’s freely-given informed consent, preferably in writing.”

The assumption that patients entered the trial with full knowledge that it was designed and run by proponents of the BPS model of ME/CFS can be tested by consulting the information leaflet for potential recruits (PACE Trial 2006). Doing so reveals that, although the trial appears to be Helsinki-compliant regarding disclosure of funding sources, affiliations, risks and so on, conflicts of interest are not mentioned.

This is disturbing because, as well as their strong prior beliefs noted by Geraghty, several of the authors subsequently declared in the Lancet in 2011 that they did advisory and consultancy work for the disability insurance industry as well as the DWP (which part-funded the trial). Two of the authors, PD White and T Chalder, set up a company in 2002, specifically “in order to promote a system of healthcare based on the biopsychosocial model of ill-health … using evidence and influence” (One Health 2002). The authors did not declare this ambitious programme for NHS change in the Lancet, perhaps thinking it unnecessary given that their company was wound up in 2010.

It appears therefore that patients were not adequately informed of the investigators’ clear and substantive conflicts of interest before they were recruited, despite the PACE protocol’s assurance that they were. Simon Wessely thinks it is unreasonable to expect current open data aspirations to be met by an "old trial with consent forms from 2003" (Lubet 2016). But gaining informed patient consent to conflicts of interest is not a new ethical requirement. The Declaration of Helsinki dates from 1964, 40 years before PACE began.

Geraghty, K. J. (2016). "‘PACE-Gate’: When clinical trial evidence meets open data access." Journal of Health Psychology(Nov): 1-7.

Lubet, S. (2016). "The PACE Study: Open Access and Conflicts of Interest " The Faculty Lounge Retrieved 14 Nov, 2016, from http://www.thefacultylounge.org/2016/11/the-pace-study-open-access-and-conflicts-of-interest.html.

One Health. (2002). "Memorandum and Articles of Association." Companies House Retrieved 14 Nov, 2016, from https://beta.companieshouse.gov.uk/company/04364122/filing-history.

PACE Trial. (2006). "invitation to join the PACE trial." Retrieved 14 Nov, 2016, from http://www.wolfson.qmul.ac.uk/images/pdfs/trialinfo.pdf.

White, P. D., K. A. Goldsmith, et al. (2011). "Comparison of adaptive pacing therapy, cognitive behaviour therapy, graded exercise therapy, and specialist medical care for chronic fatigue syndrome (PACE): a randomised trial." Lancet 377(9768): 823-36.

White, P. D., M. C. Sharpe, et al. (2007). "Protocol for the PACE trial: a randomised controlled trial of adaptive pacing, cognitive behaviour therapy, and graded exercise, as supplements to standardised specialist medical care versus standardised specialist medical care alone for patients with the chronic fatigue syndrome/myalgic encephalomyelitis or encephalopathy." BMC Neurol 7: 6.

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