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.

Stanford researchers uncover patterns in how scientists lie about their data

When scientists falsify data, they try to cover it up by writing differently in their published works. A pair of Stanford researchers have devised a way of identifying these written clues.

BY BJORN CAREY

Even the best poker players have "tells" that give away when they're bluffing with a weak hand. Scientists who commit fraud have similar, but even more subtle, tells, and a pair of Stanford researchers have cracked the writing patterns of scientists who attempt to pass along falsified data.

The work, published in the Journal of Language and Social Psychology, could eventually help scientists identify falsified research before it is published.

There is a fair amount of research dedicated to understanding the ways liars lie. Studies have shown that liars generally tend to express more negative emotion terms and use fewer first-person pronouns. Fraudulent financial reports typically display higher levels of linguistic obfuscation – phrasing that is meant to distract from or conceal the fake data – than accurate reports.

To see if similar patterns exist in scientific academia, Jeff Hancock, a professor of communication at Stanford, and graduate student David Markowitz searched the archives of PubMed, a database of life sciences journals, from 1973 to 2013 for retracted papers. They identified 253, primarily from biomedical journals, that were retracted for documented fraud and compared the writing in these to unretracted papers from the same journals and publication years, and covering the same topics.

They then rated the level of fraud of each paper using a customized "obfuscation index," which rated the degree to which the authors attempted to mask their false results. This was achieved through a summary score of causal terms, abstract language, jargon, positive emotion terms and a standardized ease of reading score.

"We believe the underlying idea behind obfuscation is to muddle the truth," said Markowitz, the lead author on the paper. "Scientists faking data know that they are committing a misconduct and do not want to get caught. Therefore, one strategy to evade this may be to obscure parts of the paper. We suggest that language can be one of many variables to differentiate between fraudulent and genuine science."

The results showed that fraudulent retracted papers scored significantly higher on the obfuscation index than papers retracted for other reasons. For example, fraudulent papers contained approximately 1.5 percent more jargon than unretracted papers.

"Fradulent papers had about 60 more jargon-like words per paper compared to unretracted papers," Markowitz said. "This is a non-trivial amount."

The researchers say that scientists might commit data fraud for a variety of reasons. Previous research points to a "publish or perish" mentality that may motivate researchers to manipulate their findings or fake studies altogether. But the change the researchers found in the writing, however, is directly related to the author's goals of covering up lies through the manipulation of language. For instance, a fraudulent author may use fewer positive emotion terms to curb praise for the data, for fear of triggering inquiry.

In the future, a computerized system based on this work might be able to flag a submitted paper so that editors could give it a more critical review before publication, depending on the journal's threshold for obfuscated language. But the authors warn that this approach isn't currently feasible given the false-positive rate.

"Science fraud is of increasing concern in academia, and automatic tools for identifying fraud might be useful," Hancock said. "But much more research is needed before considering this kind of approach. Obviously, there is a very high error rate that would need to be improved, but also science is based on trust, and introducing a 'fraud detection' tool into the publication process might undermine that trust."

MEDIA CONTACT

Bjorn Carey, Stanford News Service: (650) 725-1944, bccarey@stanford.edu

At last, a powerful and reliable Honda for Fernando Alonso

Dr Le Fanu: The ‘psychiatric lobby’is seriously culpable in its resistance to the physical basis of CFS/ME causing such devastating symptoms

Dr James Online Clinic 13th November 2015:

"Thanks for being in touch.  The ‘psychiatric lobby’, as you describe it, is seriously culpable in its resistance to the proposition that there has to be a physical basis to CFS/ME to cause such devastating symptoms.  There has, as you will see, been a lot of correspondence on this matter."

Open letter to the editor of The Lancet, Dr. Richard Horton by 6 professors about the PACEtrial's fatal flaws

@ www.virology.ws:

Dr. Richard Horton
The Lancet125 London Wall
London, EC2Y 5AS, UK

Dear Dr. Horton:

In February, 2011, The Lancet published an article called “Comparison of adaptive pacing therapy, cognitive behaviour therapy, graded exercise therapy, and specialist medical care for chronic fatigue syndrome (PACE): a randomized trial.” The article reported that two “rehabilitative” approaches, cognitive behavior therapy and graded exercise therapy, were effective in treating chronic fatigue syndrome, also known as myalgic encephalomyelitis, ME/CFS and CFS/ME. The study received international attention and has had widespread influence on research, treatment options and public attitudes.

The PACE study was an unblinded clinical trial with subjective primary outcomes, a design that requires strict vigilance in order to prevent the possibility of bias. Yet the study suffered from major flaws that have raised serious concerns about the validity, reliability and integrity of the findings. The patient and advocacy communities have known this for years, but a recent in-depth report on this site, which included statements from five of us, has brought the extent of the problems to the attention of a broader public. The PACE investigators have replied to many of the criticisms, but their responses have not addressed or answered key concerns.

The major flaws documented at length in the recent report include, but are not limited to, the following:

*The Lancet paper included an analysis in which the outcome thresholds for being “within the normal range” on the two primary measures of fatigue and physical function demonstrated worse health than the criteria for entry, which already indicated serious disability. In fact, 13 percent of the study participants were already “within the normal range” on one or both outcome measures at baseline, but the investigators did not disclose this salient fact in the Lancet paper. In an accompanying Lancet commentary, colleagues of the PACE team defined participants who met these expansive “normal ranges” as having achieved a “strict criterion for recovery.” The PACE authors reviewed this commentary before publication.

*During the trial, the authors published a newsletter for participants that included positive testimonials from earlier participants about the benefits of the “therapy” and “treatment.” The same newsletter included an article that cited the two rehabilitative interventions pioneered by the researchers and being tested in the PACE trial as having been recommended by a U.K. clinical guidelines committee “based on the best available evidence.” The newsletter did not mention that a key PACE investigator also served on the clinical guidelines committee. At the time of the newsletter, two hundred or more participants—about a third of the total sample–were still undergoing assessments.

*Mid-trial, the PACE investigators changed their protocol methods of assessing their primary outcome measures of fatigue and physical function. This is of particular concern in an unblinded trial like PACE, in which outcome trends are often apparent long before outcome data are seen. The investigators provided no sensitivity analyses to assess the impact of the changes and have refused requests to provide the results per the methods outlined in their protocol.

*The PACE investigators based their claims of treatment success solely on their subjective outcomes. In the Lancet paper, the results of a six-minute walking test—described in the protocol as “an objective measure of physical capacity”–did not support such claims, notwithstanding the minimal gains in one arm. In subsequent comments in another journal, the investigators dismissed the walking-test results as irrelevant, non-objective and fraught with limitations. All the other objective measures in PACE, presented in other journals, also failed. The results of one objective measure, the fitness step-test, were provided in a 2015 paper in The Lancet Psychiatry, but only in the form of a tiny graph. A request for the step-test data used to create the graph was rejected as “vexatious.”

*The investigators violated their promise in the PACE protocol to adhere to the Declaration of Helsinki, which mandates that prospective participants be “adequately informed” about researchers’ “possible conflicts of interest.” The main investigators have had financial and consulting relationships with disability insurance companies, advising them that rehabilitative therapies like those tested in PACE could help ME/CFS claimants get off benefits and back to work. They disclosed these insurance industry links in The Lancet but did not inform trial participants, contrary to their protocol commitment. This serious ethical breach raises concerns about whether the consent obtained from the 641 trial participants is legitimate.

Such flaws have no place in published research. This is of particular concern in the case of the PACE trial because of its significant impact on government policy, public health practice, clinical care, and decisions about disability insurance and other social benefits. Under the circumstances, it is incumbent upon The Lancet to address this matter as soon as possible.

We therefore urge The Lancet to seek an independent re-analysis of the individual-level PACE trial data, with appropriate sensitivity analyses, from highly respected reviewers with extensive expertise in statistics and study design. The reviewers should be from outside the U.K. and outside the domains of psychiatry and psychological medicine. They should also be completely independent of, and have no conflicts of interests involving, the PACE investigators and the funders of the trial.

Thank you very much for your quick attention to this matter.

Sincerely,

Ronald W. Davis, PhD
Professor of Biochemistry and Genetics
Stanford University

Jonathan C.W. Edwards, MD
Emeritus Professor of Medicine
University College London

Leonard A. Jason, PhD
Professor of Psychology
DePaul University

Bruce Levin, PhD
Professor of Biostatistics
Columbia University

Vincent R. Racaniello, PhD
Professor of Microbiology and Immunology
Columbia University

Arthur L. Reingold, MD
Professor of Epidemiology
University of California, Berkeley

Shirley applying PACE trial logic to a broken ankle ...

It's not the broken ankle but the thoughts about the ankle
that make it painful to jog.



PS by Janet: recovery depends on not speaking to others with broken ankles ...

Professor Coyne: Why the scientific community needs the PACE trial data to be released

By James C. Coyne, PhD, Professor of Health Psychology at University Medical Center, Groningen, the Netherlands where he teaches scientific writing and critical thinking:

There are obvious parallels between the politics behind persistence of the claim in the US for psychotherapy increasing survival time for cancer patients and those in the UK about cognitive behavior therapy being sufficient treatment for schizophrenia in the absence of medication or producing recovery from the debilitating medical condition, Chronic Fatigue Syndrome/Myalgic Encephalomyelitis. There are also parallels to investigators making controversial claims based on multivariate analyses, but not allowing access to data to independently evaluate the analyses. In both cases, patient well-being suffers.

If the ICO upholds the release of data for the PACE trial in the UK, it will pressure the US NIH to stop hypocritically endorsing data sharing and rewarding investigators whose credibility depends on not sharing their data.

As seen in a PLOS One study, unwillingness to share data in response to formal requests is

associated with weaker evidence (against the null hypothesis of no effect) and a higher prevalence of apparent errors in the reporting of statistical results. The unwillingness to share data was particularly clear when reporting errors had a bearing on statistical significance.

Why the PACE investigators should not appeal

In the past, PACE investigators have been quite dismissive of criticism, appearing to have assumed that being afflicted with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis precludes a critic being taken seriously, even when the criticism is otherwise valid. However, with publication of the long-term follow-up data in Lancet Psychiatry, they are now contending with accomplished academics whose criticisms cannot be so easily brushed aside. Yes, the credibility of the investigators’ interpretations of their data are being challenged. And even if they do not believe they need to be responsive to patients, they need to be responsive to colleagues. Releasing the data is the only acceptable response and not doing so risks damage to their reputations.

QMUL, Professors White and Sharpe, let the People’s data go.

Prof Montoya: results of more in-depth immunological tests in ME/CFS were staggering

By Leela:

"Many physicians and researchers thought patients with CFS didn't show signs of active inflammation," says Montoya.

"But when we began to perform more in-depth tests, the results were staggering. A picture of patients with highly inflamed bodies emerged before our eyes and validated what they've been telling us for decades."

Why didn't we see the following simple explanation of the PACE trial's long-term follow-up data in the media ?

Text by Forbin:

Happy Birthday to Karina. This is her third birthday in captivity ...