Oh Dear, Prof Rona Moss-Morris calls PACE trial robust and its null effect impressive

OCTOBER 28, 2015
expert reaction to long-term follow-up study from the PACE trial on rehabilitative treatments for CFS/ME, and accompanying comment piece

A paper published in The Lancet Psychiatry reports results of a long-term follow-up study to the PACE trial for CFS/ME. The study has assessed the original trial participants’ health in the long-term, and asks whether their current state of health, two and a half years after entering the trial, has been affected by which treatment they received in the trial. These comments accompanied a briefing.



Prof. Rona Moss-Morris, Professor of Psychology as Applied to Medicine, King’s College London, said:

“I think this is a robust study with some limitations that the authors have been clear about. The original PACE trial published in 2011 showed that at one year people with CFS/ME who received either graded exercise therapy (GET) or cognitive behavioural therapy (CBT) in addition to standard medical care were significantly less fatigued than those who received standard care alone or those who received adapted pacing therapy. The authors concluded GET and CBT were moderately effective treatments for CFS. Now, moderately effective may not sound all that impressive until you consider that many of our commonly used pharmaceuticals for medical conditions have similar moderate treatment effects. When using pharmaceuticals as treatment, maintaining these effects may mean taking ongoing medicines. This study shows that even two years or more after treatment has completed, patients receiving GET and CBT sustain their clinical benefits. A small percentage of these patients accessed some further treatment, but even so, these sustained effects are impressive.

“Despite these impressive results, this isn’t time for complacency. Some patients do not benefit from the treatment. We need to do more to understand why. We also need to develop and tailor existing treatment to get larger effects. It is also important to note that the CBT and GET protocols used in PACE were developed specifically for CFS. They are not the same as CBT for depression and anxiety or the exercise training you may receive at a local gym. The therapies are based on a biopsychosocial understanding of CFS and the health care professionals in PACE received specific training and supervision in these approaches. This is an important note for commissioners as not all CBT and exercise therapies are equal. Specialist knowledge and competence in these therapies is needed to obtain these sustained treatment effects.”



‘Rehabilitative treatments for chronic fatigue syndrome: long-term follow-up from the PACE trial’ by Michael Sharpe et al. published in the Lancet Psychiatry on Wednesday 28 October 2015.

‘Chronic fatigue syndrome: what is it and how to treat?’ by Steven Moylan et al. published in the Lancet Psychiatry on Wednesday 28 October 2015.


Declared interests

Prof. Rona Moss-Morris: “Two authors of this study, Trudie Chalder and Kimberley Goldsmith, are colleagues of mine at King’s College London. I work with Trudie on other CFS work and with Kimberley on different work.  I published a small study on GET in 2005. I am a National Advisor for NHS England for improving access to psychological therapies for long-term conditions and medically unexplained symptoms. Peter White (another author of the present study) is Chair of trial steering committee for an HTA NIHR-funded RCT I am working on with people with irritable bowel syndrome.”

FROM: http://www.sciencemediacentre.org/expert-reaction-to-long-term-follow-up-study-from-the-pace-trial-on-rehabilitative-treatments-for-cfsme-and-accompanying-comment-piece/

Doctors who continue to promote or use GET for ME/CFS should be struck off + emprisoned for life for torturing patients

Doctors who continue to promote or use GET for ME/CFS should be struck off + emprisoned for life for torturing patients #MEcfs @gmcuk @rcpsych

Prof Gelman: More on the PACE (chronic fatigue syndrome study) scandal

Posted by Prof Gelman on 25 December 2015:

Last week we reported on the push to get the data released from that controversial PACE study on chronic fatigue syndrome.

Julie Rehmeyer points to a news article with background on the story:

Patients rapidly discovered serious scientific problems with the 2011 Lancet paper. Despite these errors, the study, known as the PACE trial, went on to inform recommendations from such influential bodies as the Centers for Disease Control and Prevention, the Mayo Clinic, and the British National Health Service. . . .

But just days before the new study was released, on Oct. 21, the San Francisco journalist David Tuller published a major investigation exposing deep methodological flaws in the entire PACE trial that put its validity in serious doubt.

And this time, the new study has been met with intense criticism from outside the world of patients and advocates. On Friday, six researchers, including prominent scientists such as virologist Vincent Racaniello of Columbia University and geneticist Ronald Davis of Stanford University, released an open letter to the Lancet demanding an independent review of the PACE trial.

“The whole study is unbelievably amateur,” says Jonathan Edwards, a biomedical researcher at University College London who signed the letter. “The trial is useless.”

Rehmeyer reports on a lag between the scientific community and medical practice:

The PACE trial has exerted a strong influence on American physicians: If you ask your doctor about CFS, odds are good you’ll hear that cognitive behavioral therapy (the flavor of psychotherapy used in the trial) and exercise are the only proven treatments for CFS.

The American scientific research community, on the other hand, has rejected the psychiatric model that PACE epitomizes and is instead looking for physiological explanations for the disease.

MORE @ andrewgelman.com

PS: Andrew Gelman is a professor of statistics and political science and director of the Applied Statistics Center at Columbia University.

The PACE trial song by Roger Waters

The PACE trial song by Roger Waters:

"I used to think the world was flat" "But oh, oh, oh, the tide is turning The tide is turning"

Just when you think it can't get worse, more shocking PACE trial revelations‏

From Margaret Williams : further details about PACE Trial data security. Permission to repost.

"Two points merit further consideration: (i) the matter of guaranteed confidential storage of PACE trial data and (ii) the Principal Investigators’ undeclared conflict of interest until after the consent forms were signed by participants.

The PACE trial Protocol published in BMC Neurology on 8 March 2007 was an abridged version
but, as noted by Alem Matthees, the Full Protocol (226 pages) states on page 110:
“Your GP and any other doctors you are consulting will be told you are joining our study. And occasionally, other researchers will need to see your notes so they can audit the quality of our work. An audit might be run by one of the universities helping with our study or hospital regulatory authorities, or by one of the organisations funding our study” http://www.meactionuk.org.uk/FULL-Protocol-SEARCHABLE-version.pdf

What Matthees did not mention was the fact that one of the organisations funding the study was the UK Department for Work and Pensions (DWP). How many participants looked at the funding bodies before signing the consent forms and realising to what they were giving their consent?
Quite how “confidentiality” could be guaranteed if the DWP had access to the data has never been explained, especially as ME/CFS is known to be a targeted disorder for the withdrawal of state benefits, with patients being harassed by the DWP who required a 60-page form to be completed because the DWP menacingly informed such patients: “We have reason to believe that you are capable of work”.
If the PACE trial therapists and Investigators deemed a participant “recovered” enough to resume work, then might that participant quickly discover that the DWP stopped paying benefit? The PACE Trial has been described as a “Trojan horse” for the DWP.
Regarding the secure storage of data, the Full Protocol is unambiguous:
“Will you keep my details confidential?”
“Yes. All your details and all recordings will be kept strictly confidential and held in a locked filing cabinet or on a secure computer. People on our research team will only see your records if they need to for the research”.
The DWP was not involved in research but still had participants’ signed permission to access their records/data.

From the outset, recordings were not kept in a locked filing cabinet: some were stolen and thus lost to review (see previous post on 19th December 2015: https://jcoynester.wordpress.com/2015/12/18/kings-college-london-stalls-some-more-reiterating-refusal-to-release-the-pace-trial-data/#comment-1375
 ).

The Consent Form 1 for baseline assessment which participants were required to sign was clear:

“3. I understand that any of my medical notes may be looked at by responsible individuals from either the trial or regulatory authorities where it is relevant to my taking part in research.

4. I give permission for these individuals to have access to my records.
…

14. I understand that information collected about me for the trial, including my personal details, a copy of this consent form and all of the questionnaires I complete for the trial, will be held securely by the local trial staff and at the PACE trial centre at Queen Mary, University of London. I give permission for this to happen”.
The PACE PIs obtained participants’ consent on the promise of keeping trial data secure, yet they had made no provision to do any such thing.
When the PACE Trial had been running for two years, the Participants’ newsletter (Issue 1, June 2006) reaffirmed that the trial data was safe: “The information is being entered onto a large and secure database, designed and maintained by an independent clinical trial unit at King’s College, London”. This was provided for participants even though the PIs knew that trial data had already been stolen (see previous post #‎comment
-1375).

In relation to the PIs’ undeclared conflict of interest, one of the pre-trial assessments was at Baseline Visit 1; this set out to collect personal data that seems to have little bearing on a clinical trial but could be of value to the DWP and the permanent health insurance industry because the collected data included not only the customary demographic details, date of birth, age, sex, ethnicity, marital or partner status, years of education, occupation (the latter would obviously afford information about a participant’s earnings) but also very detailed questions about participants’ permanent health insurance payments, for example, questions on page 172 ff of the Full Protocol included the following:
“Do you currently receive income protection benefit (income protection or total and permanent disability)?”
“ If yes, how much annually do you receive? £”
“If the participant chooses not to give an answer, please use the prompt card to show income brackets, and record the letter [an alphabetical letter designating an income bracket] that corresponds to the participant's income”.

“Do you currently receive a private medical / retirement pension?”
“If yes, how much weekly do you receive? £
OR
If yes, how much monthly do you receive? £
OR
If yes, how much annually do you receive? £”

“If the participant chooses not to give an answer, please use the prompt card to show income brackets, and record the (alphabetical) letter that corresponds to the participant's income”.

“In the past six months, have you received any one-off payments from income protection or insurance schemes as a result of your health?”

Such specific questions have no clinical relevance but would be of interest to the Chief PI of the PACE trial in his dual role as the re-insurer Swiss Re’s Chief Medical Officer.
As detailed by David Tuller, participants could not give fully informed consent because the PIs’ Iong-standing involvement with the permanent health insurance industry was never disclosed to them. Indeed, it appears that this significant conflict of interest was not initially disclosed even to the Trial Steering Committee: at the meeting on 22nd April 2004, all members present were asked to declare any conflict of interest. It was minuted that no financial conflicts of interest were declared and it was agreed that no-one present had any other substantial or material conflict relevant to their work on the PACE Trial. Amongst those present were Professors Peter White, Michael Sharpe and Trudie Chalder, all of whom worked for the permanent insurance industry. There was a brief mention of paid consultancy work done by the PIs in the BMC Neurology version of the Protocol, which was long after signed consent forms had been obtained."

Principal investigators of PACE and FINE trial were involved in writing Cochrane review protocol to review their own trials ...

King's College wrote to professor James Coyne that they did release PACE trial data for the Cochrane review (by Larun et al.).

What they forgot to mention is that the three principal investigators of the PACE trial, just like the principal investigator of the FINE trial, it's sister trial, were involved in writing the protocol for the Cochrane review of their own trials ...
(http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD011040/full)

And the principal investigator of the FINE trial, was also part of the PACE trial group
Trial Steering Committee ...

 That in essence is Cochrane's impartiality ...

Secret picture of the peer review process of the PACE trial ...

Vexatiousness, a Multisymptom Affective Disorder, aka M.A.D.

Abstract
Vexatiousness, a Multisymptom Affective Disorder, also known as M.A.D., is a disabling disorder of unknown cause, highly prevalent in a subgroup of British Psychiatrists. It's symptoms do not remit with rest, are made worse by requests for unreleased data from the PACE trial and there are a number of ways to define the condition. A few examples of the different triggering factors and manifestations of the disorder are mentioned below but it's important to realize that they can all be part of the same disorder.



The most common triggering factors of vexatiousness are:
Any request to release data, because according to research policies, data is supposed to be kept and stored safely for 10 years. Kept is from the verb to keep, which means you keep it yourself and you do not release it. Furthermore it's not in the public interest to find out that patients are right and psychiatrists are wrong for the umpteenth time in medical history

Assuming that the PACE trial is a mediating factor to please insurance companies some of the principal investigators work for

Not understanding that being ill or disabled is a form of recovery

Being interested in the full data of the subjective and objective outcomes of the PACE trial

Assuming that the CBT psychiatrists suffer from a severe case of evidence phobia driven by secondary gains

Trying to use a deconditioner, developed in Oxford to rigorous specifications, to recover from your exercise phobia and when it doesn't work ask for release of data from the PACE trial

Several meta-analyses of CBT and GET indicate moderate benefits for the affected psychiatrist from these treatments. Recovery from Vexatiousness without treatment is reported to be uncommon as a systematic review found that only 7% recovered over time but measurement of recovery could involve many domains and within the trial context these include reading requests for data release and measuring how the psychiatrists respond to it.

In this context it is important to note that many psychiatrists who are suffering from this disorder experience a request for release of data as a death threat.

Common symptoms of Vexatiousness include being afraid of patients who are bedridden and dependent on others, hysterical responses to normal questions, peer-review allergy, medically unexplained ignoring of evidence, and panic attacks when release of PACE trial data is mentioned.

Specialist doctors and therapists worked with affected psychiatrists to help monitor activity and symptoms, aiming to improve quality of life and create the best conditions for remission.

All requests for release of data were medically assessed by the affected psychiatrists who used the structured clinical denial form in accordance with the intent of the Oxford criteria to make sure that every request could be classed as vexatious.

The Dr Speedy Multicentre Research Ethics Committee ( DSMREC 93.3 ) approved the study. As with any trial conducted by Dr Speedy, thanks to his hypersensitivity to light he is already masked which is very practical in a randomized controlled trial even though psychiatrists might class this as a form of secondary gains.

All requesters were given an answer to deny their request consistent with vested interest psychiatry, as presently recommended by the principal authors of the PACE trial and Queen Mary from London. This is an important addition because other Queen Mary's who value transparency of research and science might well have another opinion on this matter.

The clinical global impression cumulative hierarchy of request denial was applied combined with the resulting odds ratios and 100% confidence intervals adjusted for the stratification variables to make sure that no request slipped through the net.

Both self-report and objective measures were used, and both were found to mediate the denial to release data, lending credence to the definitions of vexatiousness as mentioned above.

Telegraph UK: It’s time for doctors to apologise to their ME patients

It’s time for doctors to apologise to their ME patients, Telegraph.co.uk @ twitter:

Telegraph.co.uk, 07 Dec 2015:

Now we have the PACE trial – the largest and most recent assessment of CBT and GET, which has cost the taxpayer almost £5 million. At long term follow-up, and contrary to what was reported in the press, the PACE trial found no significant difference between CBT, GET, adaptive pacing and specialised medical care.

Public reaction to the spin that has been put on the PACE trial results for CBT and GET has resulted in over 10,000 people signing a petition calling for claims relating to so-called recovery to be retracted and six academic researchers calling for an independent review of the study.

XXXXXXXXXXXXX

The argument here is not with mental illness, which is just as real and horrible as physical illness. As with any long-term illness, some people will develop mental health problems where talking therapies can clearly be of help.

The argument is with a simplistic and seriously flawed model of causation that patients know is wrong and which has seriously delayed progress in understanding the underlying cause of ME and developing effective forms of treatment.

Opening the 2015 research collaborative section of neuropathology, Jose Montoya, professor of medicine at the University of Stanford, said: “I have a wish and a dream that medical and scientific societies will apologise to their ME patients."

I agree – the time has come for doctors and scientists to apologise for the very neglectful way in which ME has been researched and treated over the past 60 years. Doctors need to start listening to their patients and there must now be increased investment in biomedical research to gain a better understanding of the disease process and to develop treatments that these patients desperately need.