CFS- a request for even less objective info from the PACE trial just the STEP test results at baseline and 52 weeks

Response to this request is long overdue. By law, under all circumstances, Queen Mary, University of London should have responded by now (details). You can complain by requesting an internal review.

Kathryn Dickenson

Dear Queen Mary, University of London,

I have narrowed my request further, I am only requesting the:
i/ Self-paced step. Test of fitness (BMC reference 43), including the
Borg test (scale of perceived exertion) and end heart rate.

This information is requested for two of the specified time periods:
- Baseline
- Final assessment – 52 week/39 week time point

The amount of data I have requested is tiny and is likely to be less than 200 Kb in size.

In support of this request refer to:

1/ My original request: (your reference number FOI 2017/F158) which was made on 5 May 2017 and refused on 8 June 2017, due a claim that it would cost more than 450 pounds to provide the information.

2/ My second request for small % of the information: (my reference FOI 2017/F158 (b)) made on 13 June 2017 and refused on 25 July 2017, due a claim that it would cost more than 450 pounds to provide the information.

3/ My third request: (my reference FOI 2017/F158 (c)), made on 27 July 2017, is largely the same as FOI 2017/F158 (b) however I excluded the 6 minute walk test results, as these results are in the public domain. I've not received a response to this request.

4/ This is my fourth request: (my reference FOI 2017/F158 (d). I have removed the request for the actometer data. This data is of limited use. QMUL only measured the physical activity of the trial participants at baseline and not, as is normal scientific practice, also at the end of the trial. From memory, the reason given by Peter White, Trudi Chaldler, Micheal Sharpe and Simon Wessley, for this omission is that it was too onerous, for the trial participants, to wear a 28g actometer for a week, post "treatment". This claim is at odds with the fact that the participants, were healthy enough to wear a 28g actometer for a week pre-"treatment". This claim is also at odds with the fact that surveyed patients have stated that GET (74%) and CBT (14%) made them sicker, some severely, yet none appear to have ever stated that the wearing of a 28g actometer, adversely affects their health.

The FAILURE by QMUL, to require PACE authors to stick to it's published trial protocol, and objectively measure the participants activity levels, at the end of the trial is at odds with quality scientific endeavors. It appears more likely this decision was made, because, after the PACE trial commenced other researchers published results showing that CBT/GET "treatments" do not increase the patients objectively measured activity levels (e.g. activity levels measured by actometer) despite subjective records of "improvement".

QMUL has claimed that it does not have a statistician for the PACE trial, as per its response to FOI 2017/F158 (b). This claim is at odds with my request and irrelevant. At no time, have I asked for the information held by QMUL, to be analysed. I am merely seeking the raw results.

The provision of the data requested will help patients who are using heart rate based monitoring to pace effectively, as touched on in the NICE Guidelines. Given the lack of guidance in UK literature many patients are relying on the work of USA exercise physiologists such as Prof. Mark Van Ness, Todd Davenport, Staci Stevens (Workwell Foundation and associated Universities) to manage their activity levels, and to ensure that they rest adequately. Many patients struggle with staying below 50% of their age predicted maximum heart rate, doing their activities of daily living e.g. rolling over in bed, walking to the toilet, dressing etc...but are improving by ensuring that they spend most of their day in the "resting heart rate zone".

For these patients the provision of the objective data will enable them to compare their progress from following USA protocols, with the treatment regimes carried out by the 4 arms of the PACE trial.

Yours faithfully,

Kathryn Dickenson

FOI 2017/F158
Links to previous requests, annotations and history:
https://www.whatdotheyknow.com/request/c...
https://www.whatdotheyknow.com/request/c...
https://www.whatdotheyknow.com/request/c...

Kathryn Dickenson left an annotation ()

Trial by Error: Retired PACE Investigator Peter White and Swiss Re
7 AUGUST 2017
By David Tuller, DrPH

On November 17, 2015, a few weeks after publication of my 15,000-word investigation of the PACE trial, I posted a blog about a talk Peter White gave to Swiss Re employees on the findings from his bogus study. Professor White, of course, was the lead PACE investigator and also served–and apparently still serves–as “chief medical officer” for the insurance company.

Swiss Re has released information about its 2017 “insurance medicine summit,” to be held this coming November. Not surprisingly, Professor White is on the schedule. Although he has retired from his academic position, he apparently continues his work promoting his egregious research to insurers. His talk is called “Burn out, vital exhaustion and chronic fatigue syndrome: Old wine in new bottles?” Presumably he will once more be discussing the false PACE trial results and perhaps the campaign of “harassment” that he claims angry patients have waged against him.

It cannot be repeated often enough that the tribunal decision from last summer, which ordered the release of the raw trial data, dismissed the claims of harassment as baseless. The tribunal found that the only credible evidence of such behavior was that Professor Trudie Chalder was once heckled during a lecture. However, the tribunal’s scathing decision hasn’t prevented these dishonest researchers from continuing their disinformation campaign against the patient community.

Given Professor White’s ongoing role with the Swiss Re, I decided to repost the 2015 blog below. Shortly after I initially posted the blog, the insurance company removed from its website the article touting Professor White’s presentation. Therefore, in this version, I am linking instead to a screen-shot of the “disappeared” page. (Thanks, Anil van der Zee!)

**********

Trial by Error, Continued: PACE Team’s Work for Insurance Companies Is “Not Related” to PACE. Really?

By David Tuller, DrPH

In my initial story on Virology Blog, I charged the PACE investigators with violating the Declaration of Helsinki, developed in the 1950s by the World Medical Association to protect human research subjects. The declaration mandates that scientists disclose “institutional affiliations” and “any possible conflicts of interest” to prospective trial participants as part of the process of obtaining informed consent.

The investigators promised in their protocol to adhere to this foundational human rights document, among other ethical codes. Despite this promise, they did not tell prospective participants about their financial and consulting links with insurance companies, including those in the disability sector. That ethical breach raises serious concerns about whether the “informed consent” they obtained from all 641 of their trial participants was truly “informed,” and therefore legitimate.

The PACE investigators do not agree that the lack of disclosure is an ethical breach. In their response to my Virology Blog story, they did not even mention the Declaration of Helsinki or explain why they violated it in seeking informed consent. Instead, they defended their actions by noting that they had disclosed their financial and consulting links in the published articles, and had informed participants about who funded the research–responses that did not address the central concern.

“I find their statement that they disclosed to The Lancet but not to potential subjects bemusing,” said Jon Merz, a professor of medical ethics at the University of Pennsylvania. “The issue is coming clean to all who would rely on their objectivity and fairness in conducting their science. Disclosure is the least we require of scientists, as it puts those who should be able to trust them on notice that they may be serving two masters.”

In their Virology Blog response, the PACE team also stated that no insurance companies were involved in the research, that only three of the 19 investigators “have done consultancy work at various times for insurance companies,” and that this work “was not related to the research.” The first statement was true, but direct involvement in a study is of course only one possible form of conflict of interest. The second statement was false. According to the PACE team’s conflict of interest disclosures in The Lancet, the actual number of researchers with insurance industry ties was four—along with the three principal investigators, physiotherapist Jessica Bavington acknowledged such links.

But here, I’ll focus on the third claim–that their consulting work “was not related to the research.” In particular, I’ll examine an online article posted by Swiss Re, a large reinsurance company. The article describes a “web-based discussion group” held with Peter White, the lead PACE investigator, and reveals some of the claims-assessing recommendations arising from that presentation. White included consulting work with Swiss Re in his Lancet disclosure.

The Lancet published the PACE results in February, 2011; the undated Swiss Re article was published sometime within the following year or so. The headline: “Managing claims for chronic fatigue the active way.” (Note that this headline uses “chronic fatigue” rather than “chronic fatigue syndrome,” although chronic fatigue is a symptom common to many illnesses and is quite distinct from the disease known as chronic fatigue syndrome. Understanding the difference between the two would likely be helpful in making decisions about insurance claims.)

The Swiss Re article noted that the illness “can be an emotive subject” and then focused on the implications of the PACE study for assessing insurance claims. It started with a summary account of the findings from the study, reporting that the “active rehabilitation” arms of cognitive behavioral therapy and graded exercise therapy “resulted in greater reduction of patients’ fatigue and larger improvement in physical functioning” than either adaptive pacing therapy or specialist medical care, the baseline condition. (The three intervention arms also received specialist medical care.)

The trial’s “key message,” declared the article, was that “pushing the limits in a therapeutic setting using well described treatment modalities is more effective in alleviating fatigue and dysfunction than staying within the limits imposed by the illness traditionally advocated by ‘pacing.’”

Added the article: “If a CFS patient does not gradually increase their activity, supported by an appropriate therapist, then their recovery will be slower. This seems a simple message but it is an important one as many believe that ‘pacing’ is the most beneficial treatment.”

This understanding of the PACE research—presumably based on information from Peter White’s web-based discussion—was wrong. Pacing is not and has never been a “treatment.” It is also not one of the “four most commonly used therapies,” as the newsletter article declared, since it has never been a “therapy” either. It is a self-help method practiced by many patients seeking the best way to manage their limited energy reserves.

The PACE investigators did not test pacing. Instead, the intervention they dubbed “adaptive pacing therapy” was an operationalized version of “pacing” developed specifically for the study. Many patients objected to the trial’s form of pacing as overly prescriptive, demanding and unlike the version they practiced on their own. Transforming an intuitive, self-directed approach into a “treatment” administered by a “therapist” was not a true test of whether the self-help approach is effective, they argued–with significant justification. Yet the Swiss Re article presented “adaptive pacing therapy” as if it were identical to “pacing.”

The Swiss Re article did not mention that the reported improvements from “active rehabilitation” were based on subjective outcomes and were not supported by the study’s objective data. Nor did it report any of the major flaws of the PACE study or offer any reasons to doubt the integrity of the findings.

The article next asked, “What can insurers and reinsurers do to assist the recovery and return to work of CFS claimants?” It then described the conclusions to be drawn from the discussion with White about the PACE trial—the “key takeaways for claims management.”

First, Swiss Re advised its employees, question the diagnosis, because “misdiagnosis is not uncommon.”

The second point was this: “It is likely that input will be required to change a claimant’s beliefs about his or her condition and the effectiveness of active rehabilitation…Funding for these CFS treatments is not expensive (in the UK, around £2,000) so insurers may well want to consider funding this for the right claimants.”

Translation: Patients who believe they have a medical disease are wrong, and they need to be persuaded that they are wrong and that they can get better with therapy. Insurers can avoid large payouts by covering the minimal costs of these treatments for patients vulnerable to such persuasion, given the right “input.”

Finally, the article warned that private therapists might not provide the kinds of “input” required to convince patients they were wrong. Instead of appropriately “active” approaches like cognitive behavior therapy and graded exercise therapy, these therapists might instead pursue treatments that could reinforce claimants’ misguided beliefs about being seriously ill, the article suggested.

“Check that private practitioners are delivering active rehabilitation therapies, such as those described in this article, as opposed to sick role adaptation,” the Swiss RE article advised. (The PACE investigators, drawing on the concept known as “the sick role” in medical sociology, have long expressed concern that advocacy groups enabled patients’ condition by bolstering their conviction that they suffered from a “medical disease,” as Michael Sharpe, another key PACE investigator, noted in a 2002 UNUMProvident report. This conviction encouraged patients to demand social benefits and health care resources rather than focus on improving through therapy, Sharpe wrote.)

Lastly, the Swiss Re article addressed “a final point specific to claims assessment.” A diagnosis of chronic fatigue syndrome, stated the article, provided an opportunity in some cases to apply a mental health exclusion, depending upon the wording of the policy. In contrast, a diagnosis of myalgic encephalomyelitis did not.

The World Health Organization’s International Classification for Diseases, or ICD, which clinicians and insurance companies use for coding purposes, categorizes myalgic encephalomyelitis as a neurological disorder that is synonymous with the terms “post-viral fatigue syndrome” and “chronic fatigue syndrome.” But the Swiss Re article stated that, according to the ICD, “chronic fatigue syndrome” can also “alternatively be defined as neurasthenia which is in the mental health chapter.”

The PACE investigators have repeatedly advanced this questionable idea. In the ICD’s mental health section, neurasthenia is defined as “a mental disorder characterized by chronic fatigue and concomitant physiologic symptoms,” but there is no mention of “chronic fatigue syndrome” as a discrete entity. The PACE investigators (and Swiss Re newsletter writers) believe that the neurasthenia entry encompasses the illness known as “chronic fatigue syndrome,” not just the common symptom of “chronic fatigue.”

This interpretation, however, appears to be at odds with an ICD rule that illnesses cannot be listed in two separate places—a rule confirmed in an e-mail from a WHO official to an advocate who had questioned the PACE investigators’ argument. “It is not permitted for the same condition to be classified to more than one rubric as this would mean that the individual categories and subcategories were no longer mutually exclusive,” wrote the official to Margaret Weston, the pseudonym for a longtime clinical manager in the U.K. National Health Service.

Presumably, after White disseminated the good news about the PACE results at the web-based discussion, Swiss Re’s claims managers felt better equipped to help ME/CFS claimants. And presumably that help included coverage for cognitive behavior therapy and graded exercise therapy so that claimants could receive the critical “input” they needed in order to recognize and accept that they didn’t have a medical disease after all.

In sum, contrary to the investigators’ argument in their response to Virology Blog, the PACE research and findings appear to be very much “related to” insurance industry consulting work. The claim that these relationships did not represent “possible conflicts of interest” and “institutional affiliations” requiring disclosure under the Declaration of Helsinki cannot be taken seriously.

Update 11/17/15 12:22 PM: I should have mentioned in the story that, in the PACE trial, participants in the cognitive behavior therapy and graded exercise therapy arms were no more likely to have increased their hours of employment than those in the other arms. In other words, there was no evidence for the claims presented in the Swiss Re article, based on Peter White’s presentation, that these treatments were any more effective in getting people back to work.

The PACE investigators published this employment data in a 2012 paper in PLoS One. It is unclear whether Peter White already knew these results at the time of his Swiss Re presentation on the PACE results.

Update 11/18/15 6:54 AM: I also forgot to mention in the story that the three principal PACE investigators did not respond to an e-mail seeking comment about their insurance industry work. Lancet editor Richard Horton also did not respond to an e-mail seeking comment.

Kathryn Dickenson left an annotation ()

Dr Naviaux, during Open Medicine Foundation ME/CFS symposium Q&A:
"We consider autism and MECFS as part of the same biologic and physiologic spectrum. The things that differ are the fact that in one case, autism, the triggers were encountered - and may in fact be genetic - early in life in critical neuro-development. Then in MECFS the triggers are encountered later in life and lead to this outcomes of this syndrome, Many of the same genetic predispositions, the genes that come up, predispose to autism and to MECFS. The other interesting thing is that it's a common observation in autism but not made enough of yet in patients with MECFS, but I find it to be true, is that the people who are affected are among our generations best and brightest. These are individuals who are born with unique gifts - the ability to sense the world in novel ways, that we "normal" human beings are not able to. To sense subtle differences in the social network and groups of people that children with autism as well as children and adults with MECFS can sense. The ability to actually see colour more vividly, to smell things more vividly, to taste more vividly. You know these are actually created by cellular differences that create unique vulnerabilities, and those vulnerabilities then lead to this sequence of pathogenesis that we now call ME/CFS. "

QM FOI Enquiries, Queen Mary, University of London

FOI 2017/F255
 
Dear Kathryn Dickenson
 
Thank you for your email of 7th August where you requested:
‘Self-paced step. Test of fitness (BMC reference 43), including the Borg
test (scale of perceived exertion) and end heart rate.
 
This information is requested for two of the specified time periods:
- Baseline
- Final assessment – 52 week/39 week time point’
 
As per the correspondence here:
[1]https://www.whatdotheyknow.com/request/c...,
for the sake of completeness this request is refused under s.14(2) of the
Freedom of Information Act 2000 as it is a repeat of part of the request
made on 27th July, found at the previous link.
 
Please accept this as a refusal notice.
 
If you are dissatisfied with this response, you may ask QMUL to conduct a
review of this decision.  To do this, please contact the College in
writing (including by fax, letter or email), describe the original
request, explain your grounds for dissatisfaction, and include an address
for correspondence.  You have 40 working days from receipt of this
communication to submit a review request.  When the review process has
been completed, if you are still dissatisfied, you may ask the Information
Commissioner to intervene. Please see [2]www.ico.org.uk for details.

Yours sincerely
 
Paul Smallcombe
Records & Information Compliance Manager
 

References

Visible links
1. https://www.whatdotheyknow.com/request/c...
2. http://www.ico.org.uk/

Kathryn Dickenson

Dear Queen Mary, University of London,

Please pass this on to the person who conducts Freedom of Information reviews.

I am writing to request an internal review of Queen Mary, University of London's handling of my FOI request 'CFS- a request for even less objective info from the PACE trial just the STEP test results at baseline and 52 weeks'.
I request a review of the decision, to refuse the release of the information request.
I agree that the request is a narrowing down of the information sought in the previous request.
QMUL refused to release the accelerometer and STEP test results, on the basis that the 2 pages of data sought were too onerous and would take more than 18 hours to find, locate and upload to this website.
I narrowed the request to just the STEP test results as any objective data would be better than none. To date the only objective data released by QMUL is the 6 minute walking data and 28% of the final test results are missing.
I put it to QMUL that given the misleading claims made by PACE authors, the flaws and faults in the trial that they have refused to address in any meaningful manner that it is negligent to continue to hide objective data, from the UK tax payer, independent researchers and patients.
A full history of my FOI request and all correspondence is available on the Internet at this address: https://www.whatdotheyknow.com/request/c...

I trust that QMUL will comply with its legal obligation to respond promptly and provide the 2 pages of data sought (estimated).

Yours faithfully,

Kathryn Dickenson

Kathryn Dickenson left an annotation ()

PACE update
http://www.virology.ws/2017/08/14/trial-...

Trial by Error: My E-Mail Exchange With NICE Chief Executive
14 AUGUST 2017
By David Tuller, DrPH

On Friday, I had an e-mail exchange with Sir Andrew Dillon, chief executive of the NICE Guidance Executive. The other seven Guidance Executive members are various directors within the NICE hierarchy, including the communications director. This group will make the final decision about whether to accept the provisional decision of a NICE surveillance review team to leave as is CG53, the guidance for CFS/ME released in 2007. (I have written about the NICE review process on CG53 here, here and here.)

That ten-year-old CFS/ME guidance recommends treatment with graded exercise therapy and cognitive behavior therapy. NICE reaffirmed the guidance after the 2011 publication of the first PACE results, which were taken as evidence that these treatments were effective. As part of the current review process, NICE provided stakeholders with a two-week window last month to submit comments about the provisional decision not to change CG53. Not surprisingly, this recommendation has alarmed many patients and advocates.

I didn’t expect to get answers to my questions from the Guidance Executive, but I felt an obligation to pose them anyway, given the importance of the issues. In fact, Sir Andrew responded to my e-mail within an hour. He explained that no comments would be forthcoming while the Guidance Executive was reviewing the situation. I have posted his response below my initial e-mail.

**********

Sir Andrew Dillon
Chief Executive
National Institute for Health and Care Excellence

Dear Sir Andrew:

I am a journalist and public health researcher at the University of California, Berkeley. I have reported on the current review of CG53, the NICE guidance for CFS/ME, for the science site Virology Blog, which is hosted by Professor Vincent Racaniello, a microbiologist at Columbia University. I have previously reported for Virology Blog on the PACE trial and other issues related to graded exercise therapy and cognitive behavior therapy. Earlier this year, I co-authored a commentary about the serious problems with PACE for the Sunday opinion section of The New York Times.

In my role as a journalist covering this issue, I have some questions for you and the other members of the NICE Guidance Executive about the decision-making process concerning the provisional recommendation to make no changes to CG53:

1) For many years, the U.S. Centers for Disease Control recommended GET and CBT as treatments, citing PACE. In late June or early July, the agency removed all references to these therapies from its main pages on the illness. Does the Guidance Executive plan to consult with American public health officials about what prompted this major “dis-endorsement” of these two therapies that NICE continues to promote?

2) In 2015, both the U.S. National Institutes of Health and the Institute of Medicine (now the National Academy of Medicine) released reports on the illness (they call it ME/CFS). These reports both concluded that it is a serious organic disease involving pathophysiological processes and not a psychological or psychiatric disorder—a determination that would have significant impact on treatment options. Does the Guidance Executive plan to consider these two reports and consult with any of the members of the panels that wrote them?

3) Other fields of medicine have abandoned the use of the trial design favored in this entire body of research, including PACE: open-label studies with subjective outcomes. That’s because other fields of medicine recognize that the combination of those two features in one study inherently produces bias. Does the Guidance Executive share these concerns about results from open-label studies with subjective outcomes, or does it believe that such studies can produce reliable and unbiased evidence suitable for clinical decision-making?

4) In PACE and other studies from this field, objective measures have largely failed to support the subjective results that have generated claims of “recovery” or significant clinical improvement. Does this pattern of sharp contradiction between objective and subjective results raise questions for the Guidance Executive about whether patients are objectively getting better?

5) In the 2011 Lancet paper, 13 % of the PACE participants had already met one of the study’s outcome thresholds at trial entry—that is, although assessed as “disabled” enough in physical function to qualify for the study, they were also found to be “within normal range” for physical function, before any treatment at all. In the 2013 Psychological Medicine paper, the same 13 % were already “recovered” for physical function at baseline, before any treatment at all—that is, they were simultaneously “disabled” for physical function and “recovered” for physical function. These facts were not included in the published papers but emerged later through a patient’s freedom-of-information request. Does the Guidance Executive have confidence in the reported results of a study in which a significant minority of participants have already met a key outcome threshold at baseline? If so, can the Guidance Executive point to other studies in the clinical trial literature in which a significant number of participants have already met a key outcome threshold at baseline? Does the Guidance Executive believe that the published PACE papers should have mentioned the fact that a signifiant minority of participants had already met a key outcome threshold at baseline?

6) In February 2016, forty-two leading scientists and clinicians signed an open letter to The Lancet in which they outlined the methodological lapses of the PACE trial, stated unequivocally that “such flaws have no place in published research,” and demanded an independent investigation. In March 2017, more than 100 experts signed an open letter to Psychological Medicine, asking the journal to retract immediately its core finding that GET and CBT helped patients “recover.” Does the Guidance Executive plan to review these open letters and consult with any of the signatories–from Columbia, University College London, Harvard, Stanford, Berkeley, etc.—about their reasons for publicly dismissing the PACE findings as invalid?

7) Both GET and CBT, as described in PACE and other studies from this field of research, involve telling participants that the treatments can reverse the illness and return them to a state of health. Is the Guidance Executive concerned that telling study participants repeatedly about the effectiveness of the treatments could bias their responses, augmenting any bias already inherent in open-label studies with subjective outcomes?

8) Some defenders of PACE note that CBT is also recommended for patients with cancer and other chronic diseases. But the approach advocated in PACE and related studies is not the kind of CBT focused on helping patients adapt to the reality of their illness. Rather, this form of CBT is specifically designed to alleviate patients of their purportedly “unhelpful” beliefs of having an ongoing medical disease that can be exacerbated by activity and exercise. Is the Guidance Executive aware of this critical distinction between CBT as normally administered in the case of other chronic illnesses and the adapted form of CBT investigated in PACE and other studies in this field?

9) The PACE trial used the Oxford criteria to identify participants. This case definition requires only six months of unexplained fatigue, so its use could result in the selection of participants with depression or other unidentified fatiguing illnesses. Some of these other illnesses might resolve spontaneously or respond to behavioral and psychological interventions like GET and CBT. In fact, the NIH report noted that using the broad Oxford case definition could “impair progress and cause harm,” and recommended that it be “retired.” Is the Guidance Executive concerned that populations derived using the Oxford criteria might contain many participants experiencing prolonged fatigue for a range of reasons unrelated to the illness being investigated? Is the Guidance Executive concerned that such heterogeneity in study samples could lead to erroneous findings about treatments?

10) The U.S. Agency for Healthcare Research and Quality found evidence to support GET and CBT for ME/CFS in its review of multiple studies. However, when the agency subsequently removed Oxford criteria studies from this analysis, it found no evidence that GET provided any benefits and almost no evidence that CBT provided benefits. Is the Guidance Executive considering this AHRQ re-analysis in its decision-making? Does the Guidance Executive plan to consult with officials at the agency to discuss why they conducted this re-analysis and how it subsequently led them to downgrade their assessments of the therapies?

11) The surveillance review team cites Cochrane reviews of GET and CBT to support the recommendation to leave the 2007 guidance as is. Many of the trials included in these Cochrane reviews rely on a broad case definition like the Oxford criteria. Is the Guidance Executive comfortable relying on Cochrane reviews for confirmation of controversial findings when the reviews themselves include the studies that feature the methodological problems being questioned? Will the Guidance Executive consider asking Cochrane to follow the lead of American public health officials and conduct a re-analysis of its GET and CBT reviews with Oxford criteria studies removed from the sample?

12) In the PACE trial protocol, the investigators promised to follow the Declaration of Helsinki, which requires researchers to tell prospective participants about “any possible conflicts of interest.” The three main PACE investigators have had longstanding relationships with insurance companies, advising them to offer GET and CBT to claimants diagnosed with the illness. Yet the investigators did not tell prospective PACE participants about these extensive consulting and financial links with insurance companies or include the information in consent forms. Is the Guidance Executive concerned that this clear violation of the investigators’ protocol promise to disclose “any possible conflicts of interest” to prospective participants means that they did not obtain properly “informed” consent? Does the Guidance Executive believe it should base clinical guidelines on studies that have not obtained properly “informed” consent?

13) More than 15,000 people signed the ME Association’s online petition outlining their concerns with the 2007 guidance and their objection to the provisional decision to leave it unchanged. Is it unusual for that many people to sign a petition protesting a NICE guidance?

14) Surveys of patients who have undergone GET have routinely found that more patients report harms from the intervention than benefits. In making its decision, does the Guidance Executive plan to consider these reports based on the clinical experiences of patients receiving GET in the real world?

15) The conduct and findings of the PACE trial have become a worldwide controversy. The study has been presented as a paragon of bad science at conferences of epidemiologists and statisticians and in graduate-level seminars. Leading scientists and clinicians have publicly denounced the trial’s perplexing irregularities. The CDC has removed references to PACE and has dropped the associated treatment recommendations. In making its decision about the 2007 guidance, does the Guidance Executive plan to consider that large segments of the scientific and public health worlds have already rejected the evidence base for GET and CBT as interventions for CFS/ME, ME/CFS, or whatever the disease entity is called? Given the public health stakes involved, will the Guidance Executive consider commissioning a more extensive, authoritative, independent and unbiased review of the evidence–and perhaps even a review in which the reviewers read the actual studies on which they are basing their recommendations, and not just the study abstracts?

I have other questions, but will leave it at that for now. I would be delighted should you and/or other members of the Guidance Executive choose to respond.

Kind regards–David

David Tuller, DrPH
Senior fellow in public health and journalism
Center for Global Public Health
School of Public Health
University of California, Berkeley

**********

Sir Andrew’s réponse to me:

Dear Dr Tuller,

Thank you for your enquiry.

It looks like you are aware that we have recently concluded a public consultation about our provisional decision on the review of this clinical guideline. We are in the process of reviewing the results of that consultation and will make our final decision in due course. We will make that decision public, together with any other statements we think will be helpful to contextualise it. Until then, we don’t intend to respond to enquiries about the provisional decision. It may be that our final decision, when placed in the public domain, will help you with some of your questions, but if not, we will endeavour to answer them as best we can at that time.

Yours sincerely,

Andrew Dillon
Chief Executive
National Institute for Health and Care Excellence
10 Spring Gardens | London | SW1A 2BU | United Kingdom

Kathryn Dickenson

Dear QM FOI Enquiries,

To aid you with understanding this request for information I have compiled the attached document, which demonstrates the repeated narrowing of my request of objective physical and physiological data collected by the PACE trial authors.

The annotations have not been provided to QMUL, and are available in full on the website, What do they know?

I remind QMUL that the FOI act requires a prompt response to requests.

On 5 June 2017 in its refusal response to the original request of 6 May 2017, QMUL acknowledged the fact that it holds the data requested. It is estimated that the volume of data in this drastically narrowed request, is contained within a 2 page, less than 100 kB table and it is at odds with the FOI Act to claim that it is onerous to provide a document of this tiny size.

I would appreciate a copy of the information by return.

Yours sincerely,

Kathryn Dickenson

FOI requests for PACE objective raw data.

Summary
Reference numbers and links to the website, What do they know?
FOI 2017/F158 - 6 May 2017-KD Submitted an FOI request via What do they know? QMUL gave it the reference number FOI 2017/F158.
Request entitled: CFS - PACE trial objective data enable comparison with patients own objective data. https://www.whatdotheyknow.com/request/c....
6 June 2017 KD narrowed the request and removed the information that QMUL stated that they did not hold most of the information and that given the time already taking ascertaining what they held it would be to onerous for QMUL to provide the information.
8 June 2017 KD narrowed the request yet again.
QMUL refused the request.
FOI 2017/F158 (b) 13 June 2017-KD Submitted a narrowed, FOI request via the website What do they know?
Request entitled: CFS - a small % of the objective physical and physiological data from PACE trial
Link to the request:
https://www.whatdotheyknow.com/request/c...
QMUL said that they were treating it as a continuation of the previous request. KD refers to it by the reference number FOI 2017/F248 (b). The request was refused currently with internal review
FOI 2017/F158 (c) 27 July 2017 KD submitted a narrowed, FOI request via What do they know?
Entitled: CFS - a small % of the objective physical and physiological data from PACE trial (6 minute walk test already in public domain).
Link to the request:
https://www.whatdotheyknow.com/request/c...
KD refers to this request as FOI 2017/F158 (c)
No response to this request was received from QMUL. The request was withdrawn on 19 August 2017, as it did not fufil its intended purpose of clarifying the FOI status.
FOI 2017/F158 (d) FOI 2017/F255 7 August 2017, KD submitted a narrowed FOI request via What do they know?
Entitled: CFS- a request for even less objective info from the PACE trial just the STEP test results at baseline and 52 weeks
Link to the request:
https://www.whatdotheyknow.com/request/c...
KD has used the reference number FOI 2017/F158(d) to refer to this request, however on 17 August 2017 QMUL gave the narrowed request a new reference number i.e. FOI 2017/F255. QMUL refused the request on the basis that the request is a narrowing of the request FOI 2017/F158(b), and hence overlaps with it. The refused request is with QMUL internal review
--------------------------------------------------------------------------------------------------------------
Timeline
FOI request lodged via the website, What do they know?
6 May 2017- FOI 2017/F158
CFS - PACE trial objective data enable comparison with patients own objective data. https://www.whatdotheyknow.com/request/c....
“Dear Queen Mary, University of London,
I am writing to request the release of the objective physiological and physical data, collected during the PACE trial, and at follow up. This data was collected according to the procedures detailed in the PACE trial manual and the trial protocol published in the BMC in 2007 and follow up papers.
It is appropriate to release this data since, the State, and taxpayers, ultimately fund clinical research for the benefit of patients, so it’s important patients are provided with accurate, reliable information on the effectiveness of any proclaimed treatments.
This is particularly imperative in cases such as the PACE trial, where the beliefs and claims made by the authors, their colleagues and the insurance industry appear to be at odds, with the patient experience of living with the disease, biomedical research findings, physiological findings and those of CFS clinicians based outside the mental health field.
There is no evidence that the disclosure of the trial’s objective raw data will prejudice to QMUL’s research programme, reputation, or funding streams. In the contrary, it could be claimed, that the non-release of the data, may look like an attempt to hide scientific findings from scrutinty and be harmful to the universities reputation.
I request this data so that myself and other independent researchers may determine the effect of PACE-style GET, CBT, APT and SMC on reducing physiological/physical dysfunction in patients with CFS.
I request, that the data is provided in a manner that enables me to distinguish between data from patients with CFS and those with mental health disorders, since these 3 patient cohorts were included in the PACE trial:
(i) Patients diagnosed with CFS and no mental health disorders
(ii) Patients diagnosed with psychiatric disorder
(iii) Patients diagnosed with depressive disorder
This separation of patient streams is necessary as the mixing of patients diagnosed with psychiatric and depressive disorders and “pure” CFS patients, may severely affect the results and compromise the conclusions. Other, authors have found that CFS and mental health disorders respond very differently and in opposite directions to exertion and exercise and in fact this difference may be used, in part, to distinguish between the disease CFS and mental health disorders [1]. In addition, the recent Centre for Disease Control multi-site clinical study, found severe physiological and biological abnormalities in patients with CF, yet these very ill patients had good mental and emotional health [2].
QMUL is aware that the objective raw data, may be anonymised to the extent that the risk of identification is remote. The release of some of the subjective PACE trial raw data and the raw data from PACE’s sister trial, the FINE trial has not led to the identification of any patient/s.
In contrast to the subjective observations favoured by the PACE authors, patients are documenting objective improvements in their health and the release of the objective data will enable them to compare their progress using other management techniques such as flexible pacing and pacing assisted by a heart rate monitor to the PACE trial findings.
Patients appear to be benefiting from findings of the Workwell Foundation [3], the International Consensus Criteria [4] and exercise physiological principles used for other categories of severely ill patients, such as those with congestive heart disease. These ideas are largely consistent with the ideas of the UK CFS doctors achieving positive outcomes such as Dr. Nigel Speight, Dr. Sarah Myhill, Dr. Peter Smith.
Ironically one of the PACE authors Peter White, published a paper on the successful use of a physiologically based exercise program in 1997 [5]. It is not clear why physiologically guided programs were dropped. Replacement of physiologically based programs, with uncontrolled programs where CFS patients are told to ignore their symptoms, and exercise despite worsening health appears to have been detrimental to CFS patients. Patients report worsening of health and unsustainable increases in activity that lead to a severe worsening of health, on these programs.
Many patients are now wearing continuous heart rate monitors and are identifying and quantifying severely abnormal heart rate drops and rises, in response to everyday activities. Many patients find that they need to REDUCE their activity levels, in the first instance to enable sustainable health improvements in the longer term.
The release of the objective data from the 5 million pound PACE trial will enable independent researchers and patients to compare their own findings and data with that measures during the trial.
In order to ease the burden of staff and not requiring them to do any calculations themselves once the relevant data is located and retrieved. I would like to request the data on the following selection of assessments, as detailed in the published protocol [6] and the PACE, GET manual version 7, MREC Version 2; 16/11/04 [7].
I seek the data for all 640 individual PACE Trial participants, for which the requested data exists, in a spreadsheet or equivalent file with separate columns for each variable/descriptor and the three clinical groups of patients as described above be provided separately.
MEASURE
Actometer results (BMC reference 18)
VO2 max (manual page 40)
TUAG (timed up and go. Chair-stand-walk 3 metres-turn- walk back -sit down (manual page 88)
Sit-stand test (count number in one minute – manual page 88))
2-minute walk (manual page 88)
6 minute walk objective measure of recovery (BMC reference 31)
Self-paced step. Test of fitness (BMC reference 43)
Exercise and activity scale (BMC reference 36)
For each physiological measure I require, The time, End heart rate and Borg measure. (Borg Scale of perceived physical exertion [BMC reference 44], is used to measure effort with exercise.)
I request, the information for each of the time periods, that the PACE authors specified they would collect, objective measurements of physical functioning, as follows:
Baseline (PACE manual)
After randomisation (BMC)
10 weeks
12 weeks (authors response to review)
Mid assessment (PACE manual)
24 weeks
Final assessment (PACE manual)
39 weeks
One year follow up
2.5 year follow up”
8 May 2017 - QMUL Acknowledge receipt of the request of 6 May.
(A number of PACE related annotations added to the What do they know site)
21 May 2017 annotation FOI 2017/F158
Cite this as: BMJ 2015;350:h227
Tom Kinlon

Tackling fears about exercise is important for ME treatment, analysis indicates. Objective measures found a lack of improvement for CBT & GET in the PACE Trial: subjective improvements may simply represent response biases or placebo effects in this non-blinded trial
21 May 2017 annotation FOI 2017/F158
http://journals.sagepub.com/doi/full/10....

PACE trial claims for recovery in myalgic encephalomyelitis/chronic fatigue syndrome – true or false?

It’s time for an independent review of the methodology and results
Charles Bernard Shepherd
First Published April 9, 2017

21 May 2017 annotation FOI 2017/F158
http://www.virology.ws/2017/03/13/an-ope...

An open letter to Psychological Medicine about “recovery” and the PACE trial
13 MARCH 2017
Sir Robin Murray and Dr. Kenneth Kendler
Psychological Medicine

21 May 2017 annotation FOI 2017/F158
http://www.thelancet.com/pdfs/journals/l...

Correspondence
www.thelancet.com/psychiatry Vol 3 February 2016

PACE: CBT and GET are not rehabilitative therapies
22 May 2017 annotation FOI 2017/F158

http://journals.sagepub.com/doi/pdf/10.1...

David Tuller on the PACE trial authors failure to address flaws in the trial.

https://doi.org/10.1177/1359105317703788
Journal of Health Psychology 1–5

24 May 2017 annotation FOI 2017/F158
The USA Centre for Disease Control

https://www.cdc.gov/features/cfsawarenes...

24 May 2017 annotation FOI 2017/F158

The Invest in ME Research 2017. IIMEC12 Pre-conference dinner. David Tuller will be our guest presenter.

David Tuller DrPh, is academic coordinator of University of California Berkeley's joint masters program in public health and journalism. He was a reporter and editor for 10 years at the San Francisco Chronicle, served as health editor at Salon.com and frequently writes about health for The New York Times.

David's presentation - #TearItUp - will include his work in exposing the flaws in the PACE Trial.
1 June 2017 annotation FOI 2017/F158
Key websites:
Press & research
Added in 2017

TED TALK: Jen Brea describes the obstacles she’s encountered in seeking treatment for her condition: What happens when you have a disease doctors can’t diagnose

2 June 2017 annotation FOI 2017/F158
http://journals.sagepub.com/doi/10.1177/...

Relevant article regarding PACE

Once again, the PACE authors respond to concerns with empty answers
David Tuller
Abstract
In their response to Geraghty, the PACE investigators state that they have “repeatedly addressed” the various methodological concerns raised about the trial.
While this is true, these responses have repeatedly failed to provide satisfactory explanations for the trial’s very serious flaws.
This commentary examines how the current response once again demonstrates the ways in which the investigators avoid acknowledging the obvious problems with PACE and offer non-answers instead—arguments that fall apart quickly under scrutiny.
2 June 2017 annotation FOI 2017/F158
David Tuller - podcast regarding the flaws and faults with PACE and the FOI release ordered by the First Tribunal and International and Worldwide concern about the trial.

No statistical recovery and subjective outcome only. No verifiable objective data released.

http://www.microbe.tv/twiv/twivs-tuller3/
3 June 2017 – KD sent a reminder. FOI 2017/F158
5 June 2017 - QMUL refused the request and issued a refusal notice under s.17.FOI 2017/F158
“Firstly, not all of the information you have requested is held. Many of
the measures specified seem to be based on being listed in the trial’s
manuals. However, this has no bearing on what was measured in the trial
and you should refer to the protocol. We do not hold data on VO2 max,
TUAG, sit-stand test, 2 minute walk. We hold the actometer measures, but
only at baseline, not at the other time points requested. The only measure
for which we hold Borg and end heart rate is the step test. There are no
data measured direct after randomisation, at 10 weeks, separately at mid
assessment (this is the 12 week data), separately at the final assessment
(this is the 52 week data) or 39 week time points. No exercise data were
measured at long term follow-up, so these data are not held.”
“With regards to the rest of the data that we do hold, we estimate - given
the time already expended ascertaining what is held as well - that to
provide all of the information would exceed the appropriate limit.”

Narrowed the request, 6 June 2017 FOI 2017/F158– KD narrowed the request and removed the information that QMUL stated that they did not hold.
“I note your advice that the protocols described in the PACE manual, have “no bearing on what was measured in the trial”.
“On the basis of your advice I have modified my information request to the information that QMUL states was measured, and make the following amendments, to my request for objective physiological/physical data :
1/ Actometer results (BMC reference 18) – QMUL advise that the actometer results were only measured at baseline. Request raw data actometer, baseline measurements.
2/ VO2 max (manual page 40) - QMUL advise this is not held.
3/ TUAG (timed up and go. Chair-stand-walk 3 metres-turn- walk back -sit down (manual page 88) - QMUL advise this is not held.
4/ Sit-stand test (count number in one minute – manual page 88)) - QMUL advise this is not held - QMUL advise this is not held.
5/ 2-minute walk (manual page 88)- QMUL advise this is not held.
6/ 6 minute walk objective measure of recovery (BMC reference 31) – Request raw data.
7/ Self-paced step. Test of fitness (BMC reference 43) - QMUL advise have Borg test (scale of perceived exertion) and end heart rate – Request raw data.
8/ Exercise and activity scale (BMC reference 36) – Request raw data.
9/ For each physiological measure I require, The time, End heart rate and Borg measure. (Borg Scale of perceived physical exertion [BMC reference 44], is used to measure effort with exercise.) QMUL advise that the “only measure for which we hold Borg and end heart rate is the step test” – Request raw data for the heart rate and Borg measure for the step test.
Time periods, that the PACE authors specified they would collect, objective measurements of physical functioning:
10/ Baseline (PACE manual) – request the raw data
After randomisation (BMC) – QMUL advise this measurement did not take place.
10 weeks - QMUL advise this measurement is the 12 week data.
11/ 12 weeks (authors response to review) – request the raw data
Mid assessment (PACE manual) - QMUL advise was not measured
12/ 24 weeks - request the raw data
13/ Final assessment (PACE manual) – request the raw data
14/ 39 weeks - QMUL advise data was not measured at this time point.
15/ 52 week data - QMUL advise this measurement time point is the same as the 39 week time point and the final assessment time point.
16/ One year follow up - request the raw data.
17/ 2.5 year follow up - QMUL advise that data was not obtained at long term follow up.
Hence my modified request is as follows:
i/ Actometer results (BMC reference 18) – raw data actometer, baseline measurements.
ii/ 6 minute walk objective measure of recovery (BMC reference 31).
iii/ Self-paced step. Test of fitness (BMC reference 43), including the Borg test (scale of perceived exertion) and end heart rate.
iv/ Exercise and activity scale (BMC reference 36).
At the specified time periods, that the PACE authors specified they would collect the data:
v/ Baseline
vi/ 12 weeks
vii/ 24 weeks
viii/ Final assessment – 52 week/39 week time point
ix/ One year follow up
I request, that the data is provided in a manner that enables me to distinguish between data from patients with CFS and those with mental health disorders:
(i) Patients diagnosed with CFS and no mental health disorders
(ii) Patients diagnosed with psychiatric disorder
(iii) Patients diagnosed with depressive disorder”

8 June 2017 FOI 2017/F158 – QMUL clarified that the refusal applied to the modified request
“Where we do hold data, this has been refused under s.12 of the Freedom of Information Act.”
8 June 2017 FOI 2017/F158– KD thanked QMUL for responding
KD narrowed the request, FOI 2017/F158– reducing the number of time points requested, and removing the separation of patients into mental health and non-mental health patients requested, the third version of the request
“I have reduced my information request to asking for even less information.
I have reduced the number of time points, removed the request for the exercise and activity scale data and removed, the request for a copy of the data in a format that separated the patients without depressive or psychiatric disorders from those with the mental health issues.”
My reduced information request is as follows:
i/ Actometer results (BMC reference 18) – raw data actometer, baseline measurements.
ii/ 6 minute walk objective measure of recovery (BMC reference 31).
iii/ Self-paced step. Test of fitness (BMC reference 43), including the Borg test (scale of perceived exertion) and end heart rate.
At the specified time periods, that the PACE authors specified they would collect the data:
iv/ Baseline
v/ Final assessment – 52 week/39 week time point
13 June 2017 FOI 2017/F158 – KD chased up an acknowledgement that QMUL had received the narrowed request
13 June 2017 FOI 2017/F158– QMUL
“We are proceeding with this request now that it has been narrowed. We will be in touch in due course.”
14 June 2017 – KD advises FOI 2017/F158
…“After I didn't receive a response to my reduced request for information. I submitted a fresh request. In part as it appears quite likely that this FOI could follow the footsteps of Alem Mattews one and end up before the Information Commissioner, in which case it might be clearer to have the request as a "fresh start".
Hence, I refer you to my request entitled:
"CFS - a small % of the objective physical and physiological data from PACE trial"

13 June 2017 lodged a new request via the website, What do they know? FOI 2017/F158(b)
Entitled: CFS - a small % of the objective physical and physiological data from PACE trial.
The link to the website is:
https://www.whatdotheyknow.com/request/c...
“I have amended my request in response to your claim that it would cost more than 450 pounds to provide the objective data requested in FOI 2017/F158, and hence refusal of the request.”…
…“My amended information request is as follows:
i/ Actometer results (BMC reference 18) – raw data actometer, baseline measurements.
ii/ 6 minute walk objective measure of recovery (BMC reference 31).
iii/ Self-paced step. Test of fitness (BMC reference 43), including the Borg test (scale of perceived exertion) and end heart rate.
This information is requested for two of the specified time periods:
iv/ Baseline
v/ Final assessment – 52 week/39 week time point”
15 June 2017 – KD advises FOI 2017/F158 (b)
...“To clarify this request is a narrowing of FOI 2017/F158, which QMUL refused on the basis that:
i) the PACE trial authors did not obtain the data from all the objective outcome measures specified in the PACE manual (version 7),
ii) it would cost more than 450 pound, to provide a copy of the raw data from the objective outcome measures, that PACE authors did collect.
I have marked FOI 2017/F158, as refused, as per QMUL's advice.”…
11 July 2017 – KD advises FOI 2017/F158 (b)
..”I am writing to remind QMUL that it has a legal obligation to respond promptly to a request and that a response to this request is due by 11 July 2017, at the latest.”…
12 July 2017 – KD advises FOI 2017/F158 (b)
..”I am writing to remind QMUL that by law, public authorities must respond promptly to requests for information, requested under the FOI Act and that legally you must respond within 20 working days.
Your response to this request is overdue.”…
13 July 2017 – KD request for internal review FOI 2017/F158 (b)
..”I am writing to request an internal review of Queen Mary, University of London's handling of my FOI request 'CFS - a small % of the objective physical and physiological data from PACE trial'.
QMUL has not responded to my request for this data that was collected by the PACE trial principal investigators Micheal Sharpe, Peter White and Trudi Chaldler, under the guidance of the principal adviser Simon Wessley. Nor has QMUL responded to my emails chasing up a response.”…
…“Note that this request for a small % of the objective data from the 5 million pound PACE trial, was drafted after my request for all of the objective trail data was refused on the basis of cost. ..

13 July 2017 – KD details the need for the objective data for a submission regarding the NICE Guidelines FOI 2017/F158 (b)
…”I am concerned that your failure to respond this request and to my original request for all the objective physical and physiological data, promptly and within 20 days, is putting the health of CFS patients at risk UK wide.
QMUL must be aware of the dichotomy between UK mental health "experts" proclaiming CFS to be a mental health disease and graded exercise therapy (GET) to be safe and the USA , patients and exercise physiologists who on the basis of objective research findings, patients and patient carers reports have found GET to be extremely harmful.
The USA Centre for Disease Control's is so concerned about the negative impact of GET on the health of patients with CFS (and its lack of effectiveness) that it has removed all reference to GET from its website.
The requested information is required urgently, as the time frame for stakeholders to make a submission substantiating why NICE should overturn its decision not to up date its guideline for CFS is only a few days.
I will bring the fact that QMUL's failure to comply with its legal obligations to respond to requests as required by law has serious health implications for patients and hence tax payers to the attention of the Information Commissioner and hold QMUL responsible for all legal costs associated with this matter.”…

16 July 2017 -annotation added)
Future studies of chronic fatigue syndrome/myalgic encephalomyelitis should include some objective assessments as primary outcomes. If this is to include activity monitors, we first need a sound baseline dataset.
Journal of Health Psychology 1-6
2017
DOI:10.1177/1359105317707215
Journals.sagepub.com/home/hpo
16 July 2017 -annotation added)
Graham McPhee requested the objective data from PACE via a FOI request, QMUL responded advising that his request was vexatious. QMUL's response to my original request for all the objective data was to say the provision of the data would cost more than 450 pounds.

20 July 2017 – KD advises FOI 2017/F158 (b)
…”I will lodge a complainant with the Information Commissioner in relation to the failure of QMUL to comply with its legal obligations under the FOI Act, i.e. the requirement to response promptly and within 20 days of the request.”..

20 July 2017 – QMUL advises FOI 2017/F158 (b)
“We are planning to respond to this request and apologise for the delay.”
20 July 2017 – KD advises FOI 2017/F158 (b)
..”I have previously detailed why delays in the provision of the objective raw data from the PACE trial, may adversely affect chronic fatigue syndrome (CFS) patients ie the data is required for a submission to NICE.”..
“The non-release of the objective raw data from the UK tax payer funded the 5 million pound study enables the PACE authors, to continue to peddle their false belief that GET and/or CBT result in improved health in patients with CFS throughout the UK.
QMUL appear to be complicit in perpetuating the PACE authors misleading claims.
Since your apology appears to be merely a delaying tactic, I need to proceed with lodging a complaint to the Information Commissioner.”…

21 July 2017 -annotation added)
Another ‘False Start’ in ME/CFS Clinical Trials: The GETSET Study by Todd Davenport, Associate Professor and Program Director, Department of Physical Therapy, University of the Pacific.

25 July 2017 – QMUL advises FOI 2017/F158 (b)
- 6 minute walking test results provided as QMUL has already put them in public domain.
“We have not treated this as a new request but
rather as a narrowing of your request received on 08/05/2017, which was
initially refused on 05/06/2017. I apologise for the slight delay in
responding.”..

…”your request remains impossible to fulfil without exceeding the appropriate limit as defined by the Freedom of
Information and Data Protection (Appropriate Limit) Regulations 2004. For
your information this is £450, calculated as the estimated cost of one
person spending 18 hours in determining whether the information is held,
then locating, retrieving and extracting the information. Section 12 of
the Freedom of Information Act 2000”
QMUL advised that
“ The extraction and analysis required
must be done by a statistician and QMUL does not employ one for PACE.
However, at no time have I requested any analysis to be carried out, I have merely sought raw data. In fact, my request specifically states that “in order to ease the burden of staff and not requiring them to do any calculations themselves once the relevant data is located and retrieved”

25 July 2017 – KD advises FOI 2017/F158 (b)
…”I contend that some of the 5 million pounds of tax payers money, spent on the PACE trial, would have included putting the actometer and the self paced STEP test results into a table.

As illustrated by the table of the 6 minute walking test data, (that QMUL provided as it was already in the public domain), the information requested is not onerous, and is merely the content of two small tables.

I contend that locating, retrieving and extracting the table of results, will not cost more than 450 pounds i.e. take more than 18 hours.

I contend that the claim QMUL by staff that they can not find these tables in less than 18 hours is preposterous.

I contend that a willing person, could find the data in minutes, if not seconds.
I suggest that a search entry such as "Peter White", "PACE trial", "actometer results" "STEP test results" in the QMUL database would quickly locate the data.
I request that QMUL, complies with its legal obligation to the UK tax payers, and promptly provides the following information”…

27 July 2017 annotation FOI 2017/F158 (b)
No confidence’: Charities reject NICE ‘no update’ proposal for ME/CFS guideline
Support for CBT and GET, the treatments in question, is largely due to the claimed results of the UK PACE Trial. However, 42 experts wrote an open letter accusing the researchers of that trial of bias and misrepresentation.
27 July 2017 annotation FOI 2017/F158 (b)
The NICE guideline for CFS/ME is not fit for purpose and needs a complete revision

“I think that the single most damaging misconception perpetrated on ME patients is
the idea that deconditioning is the problem and that exercise is the antidote.
“I have seen many people now, well-motivated, who have made themselves much
worse with exercise, often on the advice of their GPs who have been gullible enough to
swallow the deconditioning hypothesis.
“I think this needs to be properly emphasised with NICE, otherwise their advice
concerning graded exercise will always be assumed to be "exercise to fitness" which
is always destructive.
“Sadly, the people who get worse with exercise, because they exceed their anaerobic
threshold on multiple occasions with further reduction of the latter, are then assumed
to be imagining their disability and treated accordingly. It would be farcical if it wasn't
so serious.”

27 July 2017 – KD advises FOI 2017/F158 (b)
…To avoid future confusion if the case goes to the First Tribunal, I've been advised to mark this request refused as per the advice from QMUL and submit an amended request, without the request for the 6 minute walking test as that information is in the public domain.”..
30 July 2017 A Baldwin left an annotation FOI 2017/F158 (c)
In a response to Anna Wood's FoI concerning the mean 6mwt distances for people who they claimed were recovered QMUL claimed that it would take them over 18 hours to calculate.

After the release of data for Mr Matthees's FoI it tool me about an hour to calculate these values. Most of that time was taken working out how they had changed the Oxford definition within the recovery paper to include additional thresholds.
27 July 2017 Narrowed request lodged via the website, What do they know.
FOI 2017/F158 (c)
CFS - a small % of the objective physical and physiological data from PACE trial (6 minute walk test already in public domain) https://www.whatdotheyknow.com/request/c...
“I refer to:
1/ My original request: (your reference number FOI 2017/F158) which was made on 5 May 2017 and refused on 8 June 2017, due a claim that it would cost more than 450 pounds to provide the information.
2/ My second request for small % of the information: (my reference FOI 2017/F158 (b)) made on 13 June 2017 and refused on 25 July 2017, due a claim that it would cost more than 450 pounds to provide the information.
3/ This third request: (my reference FOI 2017/F158 (c)), it is largely the same as request 2/ however I am not requesting the 6 minute walk test results, as these results are in the public domain.
I request that QMUL, complies with its legal and moral obligation to UK tax payers and CFS patients, and promptly provides the following information from the PACE trial:

27 July 2017 annotation FOI 2017/F158 (c)

THE PACE TRIAL: THE MAKINGS OF A MEDICAL SCANDAL

Special issue on the PACE trial, Vol 22, No 9, Aug 2017.
Publication date 31 July 2017
http://journals.sagepub.com/toc/hpqa/cur...

28 July 2017 annotation FOI 2017/F158 (c)
PACE-gate Papers

http://journals.sagepub.com/action/doSea...
29 July 2017.. KD advises FOI 2017/F158 (c)
“I am writing to put on record the small size of the file/s containing the objective actometer and STEP test results from the PACE trial as detailed in requests FOI 2017/F158, FOI 2017/F158 (b) and FOI 2017/F158 (c).
Depending on how the data has been tabulated there may be 1-4 tables of data.
It is estimated that these files will be less than 20 Kb in size each and hence easily copied and transposed digitally.
The size of the data files is estimated, based on the fact that the table for the PACE trial 6 minute walking test data, is is 1.7 kB in size.
The information is likely to be stored, in files near the PACE trial 6 minute walking test data and easy to locate.
The claim made in response to FOI 2017/158 (b) that it would take more than 18 hours to locate and provide copies of this information is rejected.
For clarity I have resubmitted this request, with the request for the 6 minute walking test data deleted, since this data is in the public domain.
I refer this narrowed request as FOI 2017/158 (c).
It is nearly 3 months since my request for objective information from the 5 million pound, PACE trial, was first made.”
31 July 2017 annotation FOI 2017/F158 (c)
PACE-gate

Last ditch attempt to block publication of special issue of Journal of Health Psychology foiled

by James C Coyne July 30, 2017

Publication of the special issue of Journal of Health Psychology will go forward as planned on Monday July 31.
31 July 2017 annotation FOI 2017/F158 (c)
Journal of Health Psychology

David F Marks First Published July 31, 2017 Editorial

Download PDFPDF download for Special issue on the PACE Trial Article information

Abstract
We are proud that this issue marks a special contribution by the Journal of Health Psychology to the literature concerning interventions to manage adaptation to chronic health problems. The PACE Trial debate reveals deeply embedded differences between critics and investigators. It reveals an unwillingness of the co-principal investigators of the PACE trial to engage in authentic discussion and debate. It leads one to question the wisdom of such a large investment from the public purse (£5million) on what is a textbook example of a poorly done trial.
31 July 2017 annotation FOI 2017/F158 (c)
https://jcoynester.wordpress.com/2017/08...

QUICK THOUGHTS
One of James C. Coyne's Blogs

The unfolding story of removal of data from a PLOS One article
31 July 2017 - KD advises FOI 2017/F158 (c)
“Please advise if QMUL intends to respond to this request and if so by what date.
As per the previous FOI requests, I am adding comments on and publications relating to the PACE-gate trial, in the annotations section of my request.
When adding an annotation to this request, I noticed a typo...the size of the file containing the 6 minute walk test data is actually 17 kB.”
1 August 2017 FOI 2017/F158 (c)

Scientists trade insults over myalgic encephalomyelitis (ME) study

1 August 2017 – KD advises FOI 2017/F158 (b)
..”I am not sure which is the most appropriate way forward with this request and have submitted a narrowed request given that some of the 6 minute walking test data is in the public domain. I am also detailing the need for an internal review here.”…
..”The volume of information requested is less than one gigabyte and is most likely located in a file adjacent or near the 6 minute walking trial data.”..
My interest in the objective data, is because patients are using bio feed back such as continuous heart rate monitoring, and following the Workwell video's to improve their quality of life.
I want to see how the PACE trial objective outcomes compare to the scientific and physiologically based methods being used successfully by patients worldwide.”..
..“The PACE trial for all its flaws and faults did collect some objective data from 640 patients with CFS. This data does not appear to be being collected by NHS clinics hence is not able to be obtained elsewhere.”…
“The 6 minute walking test data showed that after a year of the PACE GET, the patients could walk on average an extra 30 metres, this result appears to be significantly less than the results being obtained by individualised, physiologically based programs.
It is not onerous for QMUL to produce the requested data , it might take a couple of minutes to locate the file and a couple more minutes to upload the data to this website.
It is in the tax payers and patients interests to facilitate open and honesty in scientific research and to cease protecting those whose agenda is at odds with scientific progress, regardless of the human cost of their false belief systems.”..
The Information Commisioner's office advises that it is reasonable to expect a response to a request for an internal review within 20 days of the request being made.
10 August 2017 – KD advises FOI 2017/F158 (b)
“It is now over 3 months since I first lodged a request for the release of objective data from the PACE trial with QMUL.
It is nearly 2 months since I lodged this narrowed request” FOI 2017/F158 (b) “with QMUL.”
Does QMUL intend to respond to this request for an internal review? If so when? If not why not?”
7 August 2017 KD submitted a further narrowing of the information request via the website What do they know?
FOI 2017/F158 (d)
Entitled: CFS- a request for even less objective info from the PACE trial just the STEP test results at baseline and 52 weeks
Link to the website: https://www.whatdotheyknow.com/request/c...
“In support of this request refer to:
1/ My original request: (your reference number FOI 2017/F158) which was made on 5 May 2017 and refused on 8 June 2017, due a claim that it would cost more than 450 pounds to provide the information.
2/ My second request for small % of the information: (my reference FOI 2017/F158 (b)) made on 13 June 2017 and refused on 25 July 2017, due a claim that it would cost more than 450 pounds to provide the information.
3/ My third request: (my reference FOI 2017/F158 (c)), made on 27 July 2017, is largely the same as FOI 2017/F158 (b) however I excluded the 6 minute walk test results, as these results are in the public domain. I've not received a response to this request.
4/ This is my fourth request: (my reference FOI 2017/F158 (d). I have removed the request for the actometer data. This data is of limited use. QMUL only measured the physical activity of the trial participants at baseline and not, as is normal scientific practice, also at the end of the trial. From memory, the reason given by Peter White, Trudi Chaldler, Micheal Sharpe and Simon Wessley, for this omission is that it was too onerous, for the trial participants, to wear a 28g actometer for a week, post "treatment". This claim is at odds with the fact that the participants, were healthy enough to wear a 28g actometer for a week pre-"treatment". This claim is also at odds with the fact that surveyed patients have stated that GET (74%) and CBT (14%) made them sicker, some severely, yet none appear to have ever stated that the wearing of a 28g actometer, adversely affects their health.”…
…”The provision of the data requested will help patients who are using heart rate based monitoring to pace effectively, as touched on in the NICE Guidelines. Given the lack of guidance in UK literature many patients are relying on the work of USA exercise physiologists such as Prof. Mark Van Ness, Todd Davenport, Staci Stevens (Workwell Foundation and associated Universities) to manage their activity levels, and to ensure that they rest adequately. Many patients struggle with staying below 50% of their age predicted maximum heart rate, doing their activities of daily living e.g. rolling over in bed, walking to the toilet, dressing etc...but are improving by ensuring that they spend most of their day in the "resting heart rate zone".
For these patients the provision of the objective data will enable them to compare their progress from following USA protocols, with the treatment regimes carried out by the 4 arms of the PACE trial.”
8 August 2017 annontation FOI 2017/F158 (d)
Trial by Error: Retired PACE Investigator Peter White and Swiss Re
7 AUGUST 2017
By David Tuller, DrPH

On November 17, 2015, a few weeks after publication of my 15,000-word investigation of the PACE trial, I posted a blog about a talk Peter White gave to Swiss Re employees on the findings from his bogus study. Professor White, of course, was the lead PACE investigator and also served–and apparently still serves–as “chief medical officer” for the insurance company.

11 August 2017 KD requests an internal review of the FOI 2017/F158 (b)
“ pass this on to the person who conducts Freedom of Information reviews.
I refer to my request an internal review of Queen Mary, University of London's handling of my FOI request 'CFS - a small % of the objective physical and physiological data from PACE trial' , submitted 13 June 2017.
I refer QMUL to the What do you know website:
"Internal reviews should be quick. If one takes longer than 20 working days then the authority should write and let you know, and it should never take longer than 40 working days (see this good practice guide). You will then either get the information that you originally requested, or you will be told that the review upholds the original decision."

11 August 2017 annotation FOI 2017/F158 (b)
PACE authors are not the only ones who drop objective measures of the trial participants physical functioning ( actometer /actigraph results). The PACE authors colleagues in the Netherlands did the same and this paper details how subjective results are over inflated and no borne out by the objective findings.

http://www.mdpi.com/2076-328X/7/3/52/htm
Open Access
Behavioral Sciences 2017, 7(3), 52; doi: 10.3390/bs7030052
Review

15 August 2017 – QMUL advises FOI 2017/F158 (b)
“Please clarify that you wish QMUL to carry out an internal review of this request despite the fact that you have subsequently submitted a new request, which narrows the original.
We have presumed that the latter request superseded this one, with the effect that this one has been withdrawn”

15 August 2017 – KD advises FOI 2017/F158 (b)
“I apologise for any confusion, I would like all the information requested.
The reason that, I narrowed the request was to obtain at least some of the information, within a reasonable time frame.
To date, I have not received any information.
We are talking about a few tiny tables of data of only a few hundred kilobytes.”

16 August 2017 – QMUL advises FOI 2017/F158 (b)
...” It is not altogether clear when overlapping requests are received before we have had an opportunity to respond.

Given your reply, please confirm that you wish to withdraw the request
made in your email of 7^th August at 1.30a.m. Or do you wish us to refuse
that under s.14(2) of the Freedom of Information Act 2000, since it
repeats in part what you have requested in the present request, in order
to close that one? We have received at least 16 emails from you since May
and in some cases you have requested internal reviews only to put in a
narrowed request, or before the time for compliance has been reached. We
currently have two open requests from you: this one due on 25^th August
and the one of 7^th of this month due on 5^th September.

Please clarify that by 'all the information requested' you are referring
to your email of 27^th July, which QMUL has assigned the reference above,
if you wish for us to deal with this one.”…

16 August 2017 – KD advises FOI 2017/F158 (b)
“I request all the information that I have asked for. I apologise for the confusion, I am profoundly ill with ME/CFS and have the physical and physiological abnormalities detailed, in the International Consensus Criteria 2011 and the Canadian Consensus Criteria 2003, this adversely impacts on my cognition, especially after exertion.
In my opinion instead of prevaricating and debating the semantics of my request, if QMUL was acting in good faith. you would take a few minutes, to upload the requested information, to this website.
It would be much appreciated if the broadest list of information was provided.”…
16 August 2017 – QMUL advises FOI 2017/F158 (d) [QMUL advises reference number FOI 2017/F255 is allocated to this request)
“FOI 2017/F255

Thank you for your email of 7th August where you requested:
‘Self-paced step. Test of fitness (BMC reference 43), including the Borg
test (scale of perceived exertion) and end heart rate.

This information is requested for two of the specified time periods:
- Baseline
- Final assessment – 52 week/39 week time point’

As per the correspondence here:
[1]https://www.whatdotheyknow.com/request/c...,
for the sake of completeness this request is refused under s.14(2) of the
Freedom of Information Act 2000 as it is a repeat of part of the request
made on 27th July, found at the previous link.

Please accept this as a refusal notice.”
18 August 2017- KD seeks an internal review of the decision to refuse FOI 2017/F158 (d)- FOI 2017/F255
“I am writing to request an internal review of Queen Mary, University of London's handling of my FOI request 'CFS- a request for even less objective info from the PACE trial just the STEP test results at baseline and 52 weeks'.
I request a review of the decision, to refuse the release of the information request.
I agree that the request is a narrowing down of the information sought in the previous request.
QMUL refused to release the accelerometer and STEP test results, on the basis that the 2 pages of data sought were too onerous and would take more than 18 hours to find, locate and upload to this website.
I narrowed the request to just the STEP test results as any objective data would be better than none. To date the only objective data released by QMUL is the 6 minute walking data and 28% of the final test results are missing.
I put it to QMUL that given the misleading claims made by PACE authors, the flaws and faults in the trial that they have refused to address in any meaningful manner that it is negligent to continue to hide objective data, from the UK tax payer, independent researchers and patients.
A full history of my FOI request and all correspondence is available on the Internet at this address: https://www.whatdotheyknow.com/request/c...
I trust that QMUL will comply with its legal obligation to respond promptly and provide the 2 pages of data sought (estimated).”

19 August 2017 – KD withdraws FOI 2017/F158 (c)
“I sent this request to QMUL with the intent of clarifying the status of my "narrowing" of requests for objective data from the PACE trial.
I now think it clearer to leave FOI 2017/F158 (b) and FOI 2017/F158 (c) standing.
Please withdraw this request.”
19 August 2017 KD Error correction
“Requests FOI 2017/F158 (b) and FOI 2017/F158 (d) are still standing.”
20 August 2017
Summary provided to QMUL.
FOI 2017/F255 (originally referred to as FOI 2017/F158 (d) by KD, prior to QMUL allocating it it’s own reference number) and FOI 2017/F158 (b)

Kathryn Dickenson left an annotation ()

http://journals.sagepub.com/doi/pdf/10.1...

Journal of Health Psychology
2017, Vol. 22(9) 1181–1186

A review of studies incorporating objective measures suggests that
there is a lack of evidence that cognitive behavioural therapy produces any improvement in a patient’s
physical capabilities or other objective measures such as return to work.

Kathryn Dickenson left an annotation ()

PACE and NICE are very light on how to exercise despite the fact that patients are having good results by following UK experts work. One only has to look to the experts revered by patients to find out how to effectively manage this disease.

Dr Sarah Myhill is one such doctor, Dr Nigel Speight another. In the USA Prof Mark Van Ness, Todd Davenport, Staci Stevens, Dr Nancy Klimas. In Canda Dr Alison Bested. In Australia Prof Sonya Marshall-Gradnisk, Prof Don Staines, Dr Don Lewis.

http://www.drmyhill.co.uk/wiki/Exercises...

Exercise - the right sort in Chronic Fatigue Syndrome
My view is that CFSs are on the same energy spectrum, but the opposite end, to elite athletes. The processes and principles for improving energy efficiency apply equally to both. See Exercise - the right sort.
In CFS the first step is to put in place all the necessary dietary, nutritional and detox mechanisms so that your mitochondria are working efficiently. At this point clinically you should be feeling absolutely fine doing absolutely nothing . Until this point is achieved one dare not exercise because this will just cause massive tissue damage! Indeed we already know this – CFS is characterised by running a high cell free DNA which is a measure of tissue damage.
Please see Pattern of recovery, where the stages of recovery are explained in more detail. Read this page in detail BEFORE attempting any of the exercise regimes mentioned here.
However once you feel absolutely fine doing very little, and your mitochondrial tests, cell free DNA and antioxidant status are all improved, ideally normalised, together with any other problems that you know about, then the principles should be as per Exercise - the right sort.
These exercises are about increasing the numbers of mitochondria. This is equivalent to upgrading your car from a 500cc Deux Cheveaux ( as here) to a Rolls Royce V8 ! ( see here!) So first you have to get your mitochondria working well, then you need to increase their numbers.

Queen Mary, University of London FOI, Queen Mary, University of London

Dear Kathryn Dickenson
We will not be carrying out an internal review of this request because, as already explained, it has been refused as repeated, since it consists of a smaller part of a wider request to which we intend to respond by 25th August 2017. Please await our response to that.

Yours sincerely
Queen Mary University of London
(F255)

Kathryn Dickenson

Dear Queen Mary, University of London FOI,

Thank you for your advice that QMUL will respond to my request for the actometer (only obtained at baseline) and STEP data (baseline and 52 weeks), that was submitted on 13 June 2017, by 25 August 2017, and has the reference number FOI 2017/F158 (b) .

In the event that QMUL refuses my request of 13 June 2017, I request that the internal review of this decision proceeds and I do not accept that the clock has stopped on this narrowed request i.e. FOI 2017/F158 (d) FOI 2017/F255

Yours sincerely,

Kathryn Dickenson

Kathryn Dickenson

Dear Queen Mary, University of London,

Please pass this on to the person who conducts Freedom of Information reviews.

I am writing to request an internal review of Queen Mary, University of London's handling of my FOI request 'CFS- a request for even less objective info from the PACE trial just the STEP test results at baseline and 52 weeks i.e. FOI2017/F255.

As QMUL is aware this request is a narrowing of the narrowing of request FOI 2017/F158 (b), as described in the FOI request submitted on 13 June 2017, on this website. Approximately 1/2 of the data, that was requested on that date is now requested.

I trust that QMUL will respond promptly, as per its legal obligation under the FOI Act.

A full history of my FOI request and all correspondence is available on the Internet at this address: https://www.whatdotheyknow.com/request/c...

Yours faithfully,

Kathryn Dickenson

Kathryn Dickenson left an annotation ()

Myalgic encephalomyelitis/chronic fatigue syndrome patients’ reports of symptom changes following cognitive behavioural therapy, graded exercise therapy and pacing treatments: Analysis of a primary survey compared with secondary surveys

Keith Geraghty, Mark Hann, Stoyan Kurtev First Published August 29, 2017 Research Article

Journal of Health Psychology

Abstract
Cognitive behavioural therapy and graded exercise therapy are promoted as evidence-based treatments for myalgic encephalomyelitis/chronic fatigue syndrome. This article explores patients’ symptom responses following these treatments versus pacing therapy, an approach favoured by many sufferers. We analyse data from a large cross-sectional patient survey (n = 1428) and compare our findings with those from comparable patient surveys (n = 16,665), using a mix of descriptive statistics and regression analysis modelling. Findings from analysis of primary and secondary surveys suggest that cognitive behavioural therapy is of benefit to a small percentage of patients (8%–35%), graded exercise therapy brings about large negative responses in patients (54%–74%), while pacing is the most favoured treatment with the lowest negative response rate and the highest reported benefit (44%–82%).

Keywords chronic fatigue syndrome, cognitive behavioural therapy, graded exercise therapy, patient satisfaction, treatment
Background
Epidemiological estimates suggest around 1 million people in the United States (Green et al., 2015) and around 250,000 in the United Kingdom (Department of Health, 2002) suffer from myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS). The World Health Organization (WHO) classifies ME, sometimes differentiated from CFS, as a neurological disease (WHO, 2007). The abbreviation ‘ME/CFS’ is often used in the literature to denote the illness, taking account of the controversies surrounding the aetiology and pathogenesis. Despite a relatively large number of sufferers, the disease remains poorly understood. Doctors and scientists have yet to agree on a cause; thus, various treatments have been applied experimentally without reference to a universally accepted model of disease pathogenesis. In 2015, the US Institute of Medicine conducted an extensive review of scientific evidence and suggested renaming ME/CFS ‘Systemic Exertion Intolerance Disease’ to better reflect the profound physical disabilities most sufferers endure, including prolonged relapses and symptom exacerbation after minimal exertion (Institute of Medicine, (IOM), 2015). The illness has a major negative impact on the quality of life, economic and social status (Drachler Mde et al., 2009; Jason et al., 2008).

A wide range of treatments have been tested on ME/CFS patients, ranging from drug therapies, mainly antidepressants and immunological agents, to non-pharmacological therapies, often psychobehavioural therapies (Smith et al., 2015). Over the last two decades, two treatments, cognitive behavioural therapy (CBT) and graded exercise therapy (GET), have gained prominence. CBT originated from the work of Beck (1976), an intervention for patients with depression. GET is an exercise therapy designed to increase the physical activity through gradual increasing of exercise tolerance levels. The role of CBT in ME/CFS is to challenge patients’ illness beliefs and unwanted cognitions (Knoop et al., 2010; Sharpe, 2010), while GET is used to address fear activity avoidance behaviours and to prevent or reverse physiological deconditioning (Moss-Morris et al., 2005). The aim of CBT and GET, often used in combination, is to alter the ‘perpetuating’ or ‘maintaining’ factors within a CBT model of ME/CFS (Deary et al., 2007). This CBT model of ME/CFS emerged in the late 1980s (Wessely et al., 1989) with empirical testing during the 1990s by Sharpe et al. (1991) and Surawy et al. (1995) and with later refinements by Moss-Morris et al. (2003) and Wiborg et al. (2010).

CBT and GET are often compared against usual care provided by health care practitioners (e.g. family doctors) or pacing, self-pacing used by sufferers to manage their physical activity or pacing therapy (PT) guided by a therapist. However, vigorous debate has emerged concerning the appropriateness and efficacy of these treatment approaches. The PACE trial is a randomised controlled trial (RCT) that compared CBT, GET and PT, against standard care (White et al., 2011) with a 59–61 per cent improvement rate and a 22 per cent recovery rate following CBT-GET (White et al., 2013). However, a 2-year follow-up study from PACE revealed that between-group differences fell away as the standard medical care and PT groups showed a similar level of improvement (Sharpe et al., 2015). Recent reanalyses of data from the PACE trial suggest that the actual improvement and recovery rates are much lower than first reported, improvement rates fell from 60 per cent to circa 20 per cent and recovery rates fell from 22 to 4 per cent for GET and 7 per cent for CBT, with 3 per cent for PT (Wilshire et al., 2016). A Cochrane Review of CBT for the treatment of ME/CFS found some benefit for a small portion of sufferers with mild-to-moderate severity, but lack of evidence of long-term benefit and inconsistent evidence that CBT has a positive impact on physical function in the disease (Price et al., 2008). The US Agency for Health Care Research and Quality (AHRQ) recently downgraded their rating of CBT and GET for ME/CFS following a review that showed that the effectiveness varied according to the diagnostic criteria used in RCTs (Smith et al., 2016). In the United Kingdom, the National Institute for Health and Care Excellence (NICE; 2007) recommends CBT and GET as evidence-based treatments for ME/CFS. In contrast, patient surveys suggest that these treatments lead to negative outcomes for a large percentage of patients. The ME Association (2015) in the United Kingdom, a leading UK ME/CFS charity, conducted a large patient survey to gauge sufferers’ experiences and views of the three main interventions, CBT, GET and PT. This article presents an independent analysis of this large patient data set and compares findings against similar previously published surveys (2000–2015).

Methods
A survey was opened for 4 months and nationally advertised for anyone with ME/CFS to participate in the study (not only members of the ME Association). Respondents were asked a series of 228 questions and subquestions regarding treatment, particularly CBT, GET or PT. The survey had 1428 respondents. Respondents were required to confirm an affirmative diagnosis of ME/CFS from a qualified medical professional. Respondents also had to confirm that they had taken part in either one-to-one or group course therapy (CBT, GET and PT). Respondents had to indicate the severity of their illness and symptoms before and after their treatment course. We used these data to explore the effect that delivered treatment courses (CBT, GET and PT) had on patients’ reported changes in symptoms and illness severity. Of the 1428 respondents, only 954 indicated that they had a confirmed medical diagnosis of ME/CFS, had participated in at least one of the three courses of treatment and completed questions on their symptoms and illness severity status, before and after treatment (our main analysis cohort). Using ordered logistic regression, we first model the direct effect of course approach on change in symptoms (post-course); second, we consider the effects of course composition after adjusting for demographic, condition-specific and course-specific variables. We also comment on the effect that these variables have on change in symptoms (see Appendix 1 for details of our methods). We compare our results against those of other comparable patient surveys.

Results
Respondent demographics
In our survey, 72 per cent of respondents reported having received a positive diagnosis of ME/CFS by a specialist, 22 per cent from a general practitioner (family doctor) and 4.5 per cent from other professionals; 17 per cent reported that their ME/CFS symptoms started prior to age 18 and the average age of ME/CFS onset fell around 35 years. This closely resembles the epidemiological evidence which suggests an average age at onset of 33 years, with ME/CFS age distribution ranging from less than 10 years to 70 years and older (IOM, 2015). Klonoff (1992) reported average illness duration to be 4.4 years. In our survey, the average illness duration was close to 6 years with 6 per cent of respondents having the illness for less than 2 years (12%, 3–4 years; 33%, 5–10 years; 31%, 11–20 years; 18%, 21+ years), suggesting a bias towards more long-term sufferers. Most respondents were women (79%). This finding is consistent with other studies that found female-to-male ratio of between 3:1 and 6:1 (Capelli et al., 2010; Faro et al., 2016). Prognostic data on recovery in ME/CFS suggest a recovery rate of between 5 and 31 per cent (Cairns, 2005). Recovered sufferers are unlikely to be captured by a survey of this kind. The demographics of our survey sample appear representative of the general ME/CFS population (Nacul et al., 2011).

Patients’ responses to treatment courses
Table 1 depicts ‘change in degree of severity of symptoms’ by ‘course composition’. A small number of respondents are unused here (n = 21 from 954) due to ambiguous answers to some questions regarding treatment overlap. A total of 302 patients (32%) reported worsening of their symptoms post-therapy, 455 (49%) reported that they stayed the same and in 176 (19%) the symptoms showed improvement. When considering the main course content (ignoring other elements), Pacing Therapy (PT) brought about a greater improvement rate in symptoms (44%), versus just 8% in CBT and 12%. GET recorded the largest negative response (74% of patients) versus 18 per cent in CBT and 14 per cent in PT.

Table
Table 1. Patients’ symptom changes post-treatment.

Table 1. Patients’ symptom changes post-treatment.

CBT: cognitive behavioural therapy; GET: graded exercise therapy.

View larger version
Irrespective of composition, on average 64 per cent of patients in CBT reported symptoms remaining the same (with those remaining the same or worse totally at 88%). Where CBT was the main content, 91 per cent of patients reported no positive change in symptoms (88% using any treatment combination). The only real deviation from this figure was when both elements of GET and PT were present alongside the main CBT content; approximately two-thirds reported no change (65.0%) and approximately equal numbers reported worse symptoms (19.1%) or an improvement (15.9%). Where GET was the main content or included in combination with any other treatment course (CBT or PT), patients tended to state that their symptoms worsened more frequently than improved. In contrast, the addition of elements of PT improved outcomes, relative to the corresponding courses in which it was not present. These observations were formally tested using ordered logistic regression. Table 2 depicts the distribution of the demographic, condition-specific and course-specific independent variables included in the model.

Table
Table 2. Patients’ symptom changes post-treatment by demographic, condition-specific and course-specific variables.

Table 2. Patients’ symptom changes post-treatment by demographic, condition-specific and course-specific variables.

ME: myalgic encephalomyelitis.

View larger version
Ordered logistic regression analysis of ‘patient response to treatment courses’ on ‘course content’ and ‘respondent demographics’
Without controlling for any covariates, our model shows (Table 3) that a greater percentage of CBT in the course has a non-significant negative effect on symptom change post-course (βCBT = –0.0049; 95% CI (–0.0795, 0.0697); p = 0.897). A greater percentage of GET has a significant negative effect on symptom change – patients report a worsening of symptoms post-therapy (βGET = –0.3226; 95% CI (–0.3932, –0.2519); p < 0.001), while a greater percentage of PT has a significant positive effect on symptom change – patients report an improvement in symptoms post-therapy (βPT = 0.2190; 95% CI (0.1503, 0.2877); p < 0.001). These conclusions were unchanged after controlling for the demographic, condition-related and course-related variables (Table 3), although the strength of association between symptom change and the percentage of GET or PT in the course substantially weakened (βGET = –0.2247; βPT = 0.1179), while the association between symptoms and percentage of CBT became positive (βCBT = 0.0591).

Table
Table 3. Parameter estimates from ordered logistic regression analyses.

Table 3. Parameter estimates from ordered logistic regression analyses.

CBT: cognitive behavioural therapy; GET: graded exercise therapy; ME: myalgic encephalomyelitis; PT: pacing therapy; CI: confidence interval.

View larger version
The strongest independent association with change in symptoms was with appropriateness of the course (χ2(2)=164.9χ(2)2=164.9; p < 0.001); patients who rated the course ‘not appropriate’ (or only partially so) reported a significant worsening of symptoms post-therapy than patients who thought the course wholly appropriate. Course attendance was also associated with symptom change (χ2(4)=17.9χ(4)2=17.9; p = 0.001); patients who did not attend the full course reported a significant worsening of symptoms compared with patients who attended the full course. This was particularly true if attending less than half the course. ‘Course Dynamic’ was not associated with change in symptoms (p = 0.711). Age at ME onset was marginally associated with change in symptoms (χ2(5)=11.6χ(5)2=11.6; p = 0.041); compared with 35–44 year olds, all other age groups reported some improvement in their symptoms post-therapy (apart from patients aged 12 years and under), with teenagers reporting the greatest improvement. Men reported a significantly better improvement in their symptoms post-therapy than women (p = 0.018). Both duration of ME (significantly: χ2(4)=13.7χ(4)2=13.7; p = 0.008) and therapist’s beliefs (weakly: χ2(3)=6.6χ(3)2=6.6; p = 0.086) were associated with reported changes in symptoms, but not the health professional who gave the diagnosis. In the former case, compared to patients who had had ME for less than 12 months, patients who had had ME for more than 12 months reported a significant worsening of symptoms post-therapy (especially patients who had had ME for >2 years). The belief that ME was psychological (vs physical) resulted in some reported worsening of symptoms post-therapy (but not for mixed beliefs).

Comparing results with previous patient surveys
We conducted a search of common scientific literature databases (PubMed and others) and patient organisation websites (grey literature) to identify similar published patient surveys to compare our primary results with previous ME/CFS patient surveys (2000–2015) that offered data on patients’ symptom profile following CBT, GET and PT. Our search revealed more than 15 relevant surveys. We excluded 5 surveys due to lack of clarity regarding treatment approach, leaving 10 included comparable surveys. Table 4 summarises results from crude analysis of these secondary surveys. We present aggregate scores concerning whether or not interventions improved symptoms, had no change or worsen/deteriorate symptoms. CBT brought about improvement in symptoms for approximately 35 per cent of respondents (65% unchanged/worse). In total, 25 per cent of GET reported improvement in symptoms (17% unchanged/54% worse), while 82 per cent reported benefit following PT with only 4 per cent deterioration. These findings are better than our primary survey findings for CBT/GET benefit (1/10 vs 3/10), but similarly show a pattern that GET brings about a worsening in symptom experience for at least 5 out of every 10 patients, with PT benefiting far more patients by a large margin (8/10).

Table
Table 4. Summary of key symptom change data from ME/CFS patient surveys (2000–2015).

Table 4. Summary of key symptom change data from ME/CFS patient surveys (2000–2015).

CBT: cognitive behavioural therapy; GET: graded exercise therapy; ME: myalgic encephalomyelitis; PT: pacing therapy.

All percentages rounded to closest round number/some crossover between respondent numbers.

View larger version
Discussion
CBT is offered to patients based on a model of dysfunctional illness beliefs (Deary et al., 2007; Sharpe, 2010) and rests on a theory that ME/CFS is perpetuated by such factors (Moss-Morris et al., 2003). In our primary survey, patients were split on the appropriateness of CBT, with over half finding it inappropriate (46% appropriate/partly appropriate) to their needs. Findings from our patient survey and secondary survey analysis show that CBT has little impact on symptom improvement for approximately 70–90 per cent of patients, raising questions about the utility of the CBT model of ME/CFS. For those who benefit from CBT, CBT may be an adjunct therapy that helps ME/CFS patients deal with the emotional distress of illness, the anxiety generated by suffering troubling physical symptoms, and the secondary depression that is associated with most chronic illnesses (Harris, 2012). Our data indicate that CBT therapists who regard ME/CFS as a physical illness are more likely to have a better chance of helping patients improve symptoms and relieve distress, compared to those who view the illness as psychological.

GET fails to help the majority of ME/CFS patients improve symptoms and has a marked negative impact on approximately 50 per cent of patients. GET also had a marked negative impact on perceived degree of illness severity, particularly for those with severe to very severe presentations, with 21 per cent more patients reporting being more severely afflicted after GET. Not surprisingly, 78 per cent of patients in our survey reported GET not to be appropriate to their needs. The beliefs of GET therapists have an effect on outcomes, with 80 per cent of patients reporting no benefit if the therapist believed ME/CFS to be a psychological illness. This evidence contrasts with RCTs that report benefits using GET in CFS (Moss-Morris et al., 2005; White et al., 2011). The high rate of adverse symptom reactions to GET observed in our survey and secondary survey analysis may well be connected to the advice of therapists to continue exercising even if symptoms worsen, with pushing ‘beyond limits’ a key feature of GET (Bavinton et al., 2004). While physiological deconditioning is important to combat in chronic illness, alternative physical rehabilitative therapies may need to be developed and tested that take account of ME/CFS-specific features, including orthostatic intolerance (Frith et al., 2014) and symptom flare post-exertion (Twisk and Geraghty, 2015).

Pacing alone brought about the greatest positive impact on symptom experience with 44 per cent of patients reporting improvement, compared with 8 per cent in CBT and 12 per cent in GET treatment. Following PT, 14 per cent reported worsening symptoms, compared with 18 per cent in CBT and 74 per cent in GET, making pacing the least negative treatment approach. Much more detailed empirical research is needed to qualify these findings. PT is overwhelmingly favoured by patients (84% finding it appropriate/partly appropriate) and has a moderate impact on reducing the degree of illness severity. Secondary surveys show that 82 per cent of patients report improvement with PT, compared with 35 per cent in CBT or 28 per cent in GET. The beneficial outcomes of pacing were strongly correlated with the beliefs of the therapists, with 53 per cent of patients reporting benefit if the therapist believed ME/CFS to be a physical illness, compared to just 5 per cent if the therapist believed ME/CFS to be psychological. Unlike CBT and GET, that are interventions to emerge from a theoretical model of ME/CFS (Deary et al., 2007; Surawy et al., 1995), pacing is less of a formal therapy and more of a personal approach to energy management practised by ME/CFS sufferers. The benefit of PT may relate to the way in which it allows a sufferer to adapt to the illness and work within limits, while testing boundaries. This approach is less invasive than CBT or GET programmes and may be more appropriate for the most severely afflicted. It is worthwhile remembering that most RCTs of CBT/GET only recruit participants well enough to attend clinics (mild to moderate cases).

Benchmarking key findings
Findings from our primary and secondary survey analysis conflict with numerous RCTs that report CBT and GET to be superior and safe treatments for ME/CFS (e.g. PACE trial). However, the PACE trial has attracted much criticism (Kindlon, 2011b). Reanalysis of data from PACE reveals alterations to methods that make CBT and GET appear more beneficial than would have been the case if the original protocol had been adhered to (Goldin, 2016). Detractors point to the way in which recovery was operationally defined as not requiring return to normal, or near normal, levels of physical activity (Geraghty, 2016; Wilshire et al., 2016). A Cochrane review of CBT in CFS found that 40 per cent of CFS patients report a reduction in self-rated fatigue following CBT, with 26 per cent improving in usual care, a differential of only 14 per cent added benefit of CBT above standard care using subjective measures. Price et al. (2008) concluded that the benefits of CBT are not sustained over the long term and that there is little evidence of improvements in physical function following CBT. Moss-Morris et al. (2005) observed a decrease in self-rated fatigue in CFS using GET, but Wiborg et al. (2010) observed that reduced fatigue did not correlate with an increase in physical activity measured objectively with actometers. Other RCTs have found no substantive benefits using CBT or GET (Núñez et al., 2011; Wearden et al., 2010). A Cochrane review of non-pharmacological interventions for functional syndromes, including CFS, noted multiple methodological concerns in psychotherapy trials, including high drop-out rates and selective biases in sampling (Van Dessel et al., 2014). ME/CFS is difficult to diagnose and it is speculated that clinical trials often involve volunteer bias and include patients with psychiatric illnesses and milder cases. These patients may respond better to CBT or GET than patients with more moderate-to-severe cases that are captured by surveys.

Negative responses in context
A Cochrane review of exercise therapy for CFS found that exercise therapy did not have a detrimental impact on primary outcomes (Larun et al., 2016), but this finding is based on limited reporting of serious adverse reactions (SARs), from just one study. The largest RCT (PACE) found little evidence of serious adverse effects, with just two SARs reported in the GET group (Dougall et al., 2014). The FINE trial (Wearden et al., 2010) also found no SARs using CBT/GET. In contrast, a detailed report on harms in ME/CFS treatment (Kindlon, 2011a) found that 51 per cent of patients surveyed (range, 28%–82%; n = 4338) reported that GET worsened their health, while 20 per cent (range, 7%–38%; n = 1808) reported some adverse reaction to CBT. Our survey findings of high negative responses to GET are inconsistent with RCTs that report no substantial adverse outcomes using CBT/GET to treat ME/CFS, but are consistent with Kindlon (2011a) and mirror the findings from a detailed epidemiological study by Nacul et al. (2011) who found that 81 per cent of ME/CFS patients reported fatigue after exercise (>24 hours), 72 per cent had an intolerance to exercise and 69 per cent had malaise after exertion (>24 hours). A recent meta-synthesis of seven relevant clinical studies found that acute exercise increases fatigue in ME/CFS patients, particularly after 4 hours (Loy et al., 2016). Physiological reasons for exercise intolerance and post-exertional malaise in ME/CFS include cellular events and immune activation events (Twisk and Geraghty, 2015).

In clinical trials, certain treatment biases may partly account for differences in reports of harms/negative responses in patient surveys that canvass sufferers from patient organisations and community settings (Lilienfeld et al., 2014). In RCTs, manualised CBT/GET instructs patients to view negative experiences as unhelpful (White et al., 2007); thus, the patient is asked to ignore or dismiss adverse reactions to treatments. In addition, patients undertaking treatments may be reluctant to report all harms to therapists, given the ‘therapeutic relationship’, even if harms occur (Blease, 2015). Scott and Young (2016) stated that current methods for recording the negative effects of psychotherapies are insufficient. A systematic review of treatments for ME/CFS (Smith et al., 2015) suggests harms in GET are poorly reported in exercise trials with little subgroup analysis. This might help explain why RCTs of CBT or GET for ME/CFS find no major adverse effects; yet, patient surveys consistently find sizeable negative responses to CBT and GET. Drop-out rates in CBT treatment for CFS range from 20 to 42 per cent (Malouff et al., 2008; Price et al., 2008). These patients may make up part of those responding to surveys of these treatments.

Kathryn Dickenson left an annotation ()

Link to Alem Matthees response to QMUL's refusal to release a small percentage of the subjective data.

https://valerieeliotsmith.files.wordpres...

IN THE FIRST-TIER TRIBUNAL (INFORMATION RIGHTS) EA/2015/0269
BETWEEN:
QUEEN MARY UNIVERSITY OF LONDON
(Appellant)
And
THE INFORMATION COMMISSIONER
(First Respondent)
MR ALEM MATTHEES
(Second Respondent)
ALEM MATTHEES' MAIN RESPONSE

Dear Queen Mary, University of London FOI,
I refer to the statement made by QMUL in it's response to my request for information on how the university
calculated that it would take more than 18 hours to provide the various narrowed requests for objective data from the PACE trial i.e. FOI request 2017/F294.

QMUL stated as follows:
"It does not matter how little data is requested (or how small the file may be); at the current time Queen Mary University of London does not have the ability to provide such information without exceeding the appropriate limit."

Please explain if/how the above statement pertains to this request for less than 100kB of data ( a small table) of data of the STEP test results at baseline and 52 weeks.

Yours sincerely,

Kathryn Dickenson

Dear Queen Mary, University of London FOI,

I am seeking clarification of your position in relation to my request for a small amount of objective data from the PACE trial.

Has the person who is the authorised delegate, for internal review decisions, refused to provide the data requested?

In the event that the internal review decision had not been made, I bring it to the attention of QMUL that:

1/ A claim that it will take more than 18 hours to upload the PACE, STEP data to the "What do they know?" website, is at odds with the ease and speed of modern day data transfer. A data file this small, will upload in a matter of minutes. The information has already been located as per QMUL advised on this website, on 5 June 2017.

2/ The claim that it is too onerous, to provide the data requested, is also at odds with the fact that the University of Manchester, speedily and readily, provided a similar volume and type of data from PACE's sister trial.

The University of Manchester's file of the STEP data is 37kB in size. It is estimated, that the requested QMUL STEP data file, to be less than 100kB in size (PACE had twice as many participants but only the baseline and 52 week data points are requested).

3/ A striking feature of the FINE trial raw data is that 50% of the participants, appear to have been so adversely affected by doing the baseline STEP test, and or the "treatment" regimes, that they did not do subsequent STEP tests.

It is anticipated that the raw data, from PACE trial objective results, may demonstrate a similar deterioration in participants health, after a STEP test. As an exacerbation of symptoms and deterioration of health in response to physical exertion is a key diagnostic feature of the disease chronic fatigue syndrome. Deterioration after exercise is widely reported by patients, biomedical researchers and exercise physiologists and any persons who have patients physiological, biomedical and subjective responses in the hours/days after exercise beyond that patients "usual" activity.

Is the fact that the objective data from the PACE trial has not been released to date because the objective findings are at odds with the PACE authors beliefs and at odds with the wishes of the insurance industry funding these authors?

In the alternative, I am left wondering, why it is not in the best interests of QMUL, to make all the objective data from the PACE trial freely available, to independent researchers, the UK tax payer, the NHS, NICE, the Department of Health, the Department of Work and Pensions and patients.

Yours sincerely,

Kathryn Dickenson

Dear Queen Mary, University of London FOI,

Please find attached a summary of my attempts to obtain the objective data from the PACE trial. Unfortunately some of the formatting is lost when it is uploaded.

Please advise if you find any errors or mistakes in this summary as I will be providing the same to the Information Commissioner.

Yours sincerely,

Kathryn Dickenson

FOI requests for PACE objective raw data.

Quick Summary
Reference numbers and links to the website, What do they know? Following the website can get a tad confusing, as on the website the requests are siloed into threads, and there is some cross over between threads. Also QMUL, did not recognise the unique nature of the threads and at times, provided responses that crossed threads.
This summary is provided with each entry in date order and cross-referenced back to the FOI thread it is found on the “What do they know?” website.
6 May 2017, FOI 2017/F158 -KD Submitted an FOI request via What do they know? QMUL gave this request the reference number FOI 2017/F158.
The request is entitled: CFS - PACE trial objective data enable comparison with patients own objective data. https://www.whatdotheyknow.com/request/c....
6 June 2017 KD narrowed the request and removed the information that QMUL stated that they did not hold most of the information and that given the time already taking ascertaining what they held it would be to onerous for QMUL to provide the information.
8 June 2017 KD narrowed the request yet again.
QMUL refused the request.
13 June 2017, FOI 2017/F158 (b) -KD Submitted a narrowed, FOI request via the website What do they know?
Request entitled: CFS - a small % of the objective physical and physiological data from PACE trial
Link to the request:
https://www.whatdotheyknow.com/request/c...
QMUL said that they were treating it as a continuation of the previous request. KD refers to it by the reference number FOI 2017/F248 (b). The request was refused and is currently with internal review.
27 July 2017, FOI 2017/F158 (c) KD submitted a narrowed, FOI request via What do they know?
Entitled: CFS - a small % of the objective physical and physiological data from PACE trial (6 minute walk test already in public domain).
Link to the request:
https://www.whatdotheyknow.com/request/c...
KD refers to this request as FOI 2017/F158 (c)
No response to this request was received from QMUL. The request was withdrawn on 19 August 2017, as it did not fufil its intended purpose of clarifying the FOI status.
On 21 August 2017, ie after the request was withdrawn, QMUL advised that it was refusing the request as the amount of data requested was too onerous.
7 August 2017, FOI 2017/F158 (d) FOI 2017/F255, KD submitted a narrowed FOI request via What do they know?
Entitled: CFS- a request for even less objective info from the PACE trial just the STEP test results at baseline and 52 weeks
Link to the request:
https://www.whatdotheyknow.com/request/c...
KD has used the reference number FOI 2017/F158(d) to refer to this request, however on 17 August 2017 QMUL gave the narrowed request a new reference number i.e. FOI 2017/F255. QMUL refused the request on the basis that the request is a narrowing of the request FOI 2017/F158(b), and hence overlaps with it. The refused request is with QMUL internal review.
6 September 2017, FOI 2017/F294
KD requested information on how QMUL determined that it would take more than 18 hours to obtain the information requsted.
Request entitled: “CFS- the volume of objective data was narrowed down many times how was it determined it would take more than 18 hours to provide the data”
Link to the request
https://www.whatdotheyknow.com/request/c...
--------------------------------------------------------------------------------------------------------------

Full Timeline – ONLY the request for OBJECTIVE data from the PACE trial
-new FOI requests are highlighted in yellow an annotations are partially greyed
FOI request lodged via the website, What do they know?
6 May 2017- FOI 2017/F158
CFS - PACE trial objective data enable comparison with patients own objective data. https://www.whatdotheyknow.com/request/c....
“Dear Queen Mary, University of London,
I am writing to request the release of the objective physiological and physical data, collected during the PACE trial, and at follow up. This data was collected according to the procedures detailed in the PACE trial manual and the trial protocol published in the BMC in 2007 and follow up papers.
It is appropriate to release this data since, the State, and taxpayers, ultimately fund clinical research for the benefit of patients, so it’s important patients are provided with accurate, reliable information on the effectiveness of any proclaimed treatments.
This is particularly imperative in cases such as the PACE trial, where the beliefs and claims made by the authors, their colleagues and the insurance industry appear to be at odds, with the patient experience of living with the disease, biomedical research findings, physiological findings and those of CFS clinicians based outside the mental health field.
There is no evidence that the disclosure of the trial’s objective raw data will prejudice to QMUL’s research programme, reputation, or funding streams. In the contrary, it could be claimed, that the non-release of the data, may look like an attempt to hide scientific findings from scrutinty and be harmful to the universities reputation.
I request this data so that myself and other independent researchers may determine the effect of PACE-style GET, CBT, APT and SMC on reducing physiological/physical dysfunction in patients with CFS.
I request, that the data is provided in a manner that enables me to distinguish between data from patients with CFS and those with mental health disorders, since these 3 patient cohorts were included in the PACE trial:
(i) Patients diagnosed with CFS and no mental health disorders
(ii) Patients diagnosed with psychiatric disorder
(iii) Patients diagnosed with depressive disorder
This separation of patient streams is necessary as the mixing of patients diagnosed with psychiatric and depressive disorders and “pure” CFS patients, may severely affect the results and compromise the conclusions. Other, authors have found that CFS and mental health disorders respond very differently and in opposite directions to exertion and exercise and in fact this difference may be used, in part, to distinguish between the disease CFS and mental health disorders [1]. In addition, the recent Centre for Disease Control multi-site clinical study, found severe physiological and biological abnormalities in patients with CF, yet these very ill patients had good mental and emotional health [2].
QMUL is aware that the objective raw data, may be anonymised to the extent that the risk of identification is remote. The release of some of the subjective PACE trial raw data and the raw data from PACE’s sister trial, the FINE trial has not led to the identification of any patient/s.
In contrast to the subjective observations favoured by the PACE authors, patients are documenting objective improvements in their health and the release of the objective data will enable them to compare their progress using other management techniques such as flexible pacing and pacing assisted by a heart rate monitor to the PACE trial findings.
Patients appear to be benefiting from findings of the Workwell Foundation [3], the International Consensus Criteria [4] and exercise physiological principles used for other categories of severely ill patients, such as those with congestive heart disease. These ideas are largely consistent with the ideas of the UK CFS doctors achieving positive outcomes such as Dr. Nigel Speight, Dr. Sarah Myhill, Dr. Peter Smith.
Ironically one of the PACE authors Peter White, published a paper on the successful use of a physiologically based exercise program in 1997 [5]. It is not clear why physiologically guided programs were dropped. Replacement of physiologically based programs, with uncontrolled programs where CFS patients are told to ignore their symptoms, and exercise despite worsening health appears to have been detrimental to CFS patients. Patients report worsening of health and unsustainable increases in activity that lead to a severe worsening of health, on these programs.
Many patients are now wearing continuous heart rate monitors and are identifying and quantifying severely abnormal heart rate drops and rises, in response to everyday activities. Many patients find that they need to REDUCE their activity levels, in the first instance to enable sustainable health improvements in the longer term.
The release of the objective data from the 5 million pound PACE trial will enable independent researchers and patients to compare their own findings and data with that measures during the trial.
In order to ease the burden of staff and not requiring them to do any calculations themselves once the relevant data is located and retrieved. I would like to request the data on the following selection of assessments, as detailed in the published protocol [6] and the PACE, GET manual version 7, MREC Version 2; 16/11/04 [7].
I seek the data for all 640 individual PACE Trial participants, for which the requested data exists, in a spreadsheet or equivalent file with separate columns for each variable/descriptor and the three clinical groups of patients as described above be provided separately.
MEASURE
Actometer results (BMC reference 18)
VO2 max (manual page 40)
TUAG (timed up and go. Chair-stand-walk 3 metres-turn- walk back -sit down (manual page 88)
Sit-stand test (count number in one minute – manual page 88))
2-minute walk (manual page 88)
6 minute walk objective measure of recovery (BMC reference 31)
Self-paced step. Test of fitness (BMC reference 43)
Exercise and activity scale (BMC reference 36)
For each physiological measure I require, The time, End heart rate and Borg measure. (Borg Scale of perceived physical exertion [BMC reference 44], is used to measure effort with exercise.)
I request, the information for each of the time periods, that the PACE authors specified they would collect, objective measurements of physical functioning, as follows:
Baseline (PACE manual)
After randomisation (BMC)
10 weeks
12 weeks (authors response to review)
Mid assessment (PACE manual)
24 weeks
Final assessment (PACE manual)
39 weeks
One year follow up
2.5 year follow up
I look forward to your response.
Yours faithfully,
Kathryn Dickenson
[1] Eleanor Stein Assessment and Treatment of Patients with ME/CFS: Clinical Guidelines for Psychiatrists.http://sacfs.asn.au/download/guidelines_...
[2] Multi-Site Clinical Assessment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (MCAM): Design and Implementation of a Prospective/Retrospective Rolling Cohort Study. Unger ER, Lin JS, Tian H, Natelson BH, Lange G, Vu D, Blate M, Klimas NG, Balbin EG, Bateman L, Allen A, Lapp CW, Springs W, Kogelnik AM, Phan CC, Danver J, Podell RN, Fitzpatrick T, Peterson DL, Gottschalk CG, Rajeevan MS; MCAM Study Group. Am J Epidemiol. 2017 Apr 15;185(8):617-626. doi: 10.1093/aje/kwx029.
[3] Conceptual model for physical therapist management of chronic fatigue syndrome/myalgic encephalomyelitis. Davenport TE1, Stevens SR, VanNess MJ, Snell CR, Little T. Phys Ther. 2010 Apr;90(4):602-14. doi: 10.2522/ptj.20090047. Epub 2010 Feb 25.
http://www.workwellfoundation.org/resear...
[4] Myalgic encephalomyelitis: International Consensus Criteria
Authors B. M. Carruthers, M. I. van de Sande, et al Journal of Internal Medicine
First published: 22 August 2011 DOI: 10.1111/j.1365-2796.2011.02428.x
http://www.investinme.org/Documents/Guid...
[5] Physiotherapy. Graded Exercise Therapy for Chronic Fatigue Syndrome
Dr Peter D White Vanessa AB Naish2 DOI: http://dx.doi.org/10.1016/S0031-9406(05)...
[6] GET manual version 7, MREC Version 2; 16/11/04 – pages 40- 88
[7] BMC Neurology Study protocol Open Access 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 Peter D White*1, Michael C Sharpe2, Trudie Chalder3, Julia C DeCesare4, Rebecca Walwyn5 and the PACE trial group. BMC Neurology2007 DOI: 10.1186/1471-2377-7-6 © White et al; licensee BioMed Central Ltd. 200 Received: 30 October 2006 Accepted: 08 March 2007 Published: 08 March 2007
[8] Author's response to reviews Title: 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 Authors: Peter D White, Michael C Sharpe, Trudie Chalder ) =Julia C DeCesare, Rebecca Walwyn Version: 2 Date: 24 January 2007 Author's response to reviews: see over
Outcome will be assessed at 12, 24, and 52 weeks after randomisation. Two primary outcomes of self rated fatigue and physical function will assess differential effects of each treatment on these measures. Secondary outcomes include …..objective measures of physical activity, fitness.
https://static-content.springer.com/open...
Yours faithfully,
Kathryn Dickenson”

8 May 2017 - QMUL Acknowledge receipt of the request of 6 May.
“We acknowledge receipt of your request and will respond as soon as we can.”

21 May 2017 KD added annotation FOI 2017/F158 (a) thread
Cite this as: BMJ 2015;350:h227
Tom Kinlon

Tackling fears about exercise is important for ME treatment, analysis indicates. Objective measures found a lack of improvement for CBT & GET in the PACE Trial: subjective improvements may simply represent response biases or placebo effects in this non-blinded trial.
This BMJ article and a flurry of articles in the lay media this week followed the publication in Lancet Psychiatry of an analysis of the mediators of change in the important PACE Trial, a chronic fatigue syndrome (CFS) trial which cost UK taxpayers £5 million[1,2]. What seems to have been lost in the coverage is that, although there were some modest improvements in the self-report measures, there was an almost complete absence of improvements in objectively measured outcomes for cognitive behavioural therapy (CBT) and graded exercise therapy (GET) compared to the control group (specialist medical care only (SMC)).
This is a non-blinded trial, where participants were told CBT and GET had previously been found to be effective in CFS and other conditions[3,4]: one way to look at the mediation results for subjective measures when there was a lack of objective improvements is that they may merely tell us how response biases and/or placebo effects are mediated[5].

The focus on subjective measures in some CFS studies was previously criticised in a systematic review published back in 2001 (long before the PACE Trial started)[6]. They suggested instead "a more objective measure of the effect of any intervention would be whether participants have increased their working hours, returned to work or school, or increased their physical activities."

The model presented for cognitive behaviour therapy (CBT) in the PACE Trial manuals posits that the impairments and symptoms are reversible with the therapy[3,7]. However, the latest paper shows that fitness, as measured by a step test, didn't improve following CBT[2]. An earlier PACE Trial publication reported that the addition of CBT to SMC did not result in an improvement in 6-minute walking test scores compared to SMC alone[8].

The PACE Trial was part funded by the UK Department of Work and Pensions, a rare move for them, presumably done due to an expectation that the therapies would improve measures of employment and levels of benefit receipt. However, again CBT brought about no improvement using objective measures, such as days of employment lost, levels of disability benefits received and levels of receipt of insurance payments[9].

These results are in line with earlier studies of CBT. For example, an analysis of three randomized controlled trials of CBT interventions for CFS found no improvement in objectively measured activity, despite participants reporting a reduction in (self-reported) fatigue and (sometimes) functional impairments[10]. Similar results were found in another uncontrolled trial where changes in objectively measured activity did not predict fatigue levels, and objectively measured activity on completion remained low compared to population norms[11]. An uncontrolled study found improvements in self-reported physical functioning and fatigue were reported despite a numerical decrease in (objectively measured) activity[12]. In another study, the level of self-reported cognitive impairment in CFS patients decreased significantly after CBT, however, cognition had not improved when it was measured objectively using neuropsychological test performance[13].

It is unsurprising that 15 sessions of CBT (and the associated homework exercises and management program) might alter how participants respond to self-report questionnaires. A PACE Trial manual itself says "the essence of CBT is helping the participant to change their interpretation of symptoms": this could lead to altered or biased fatigue scores, one of the two primary outcome measures[14]. Also, one of the aims of CBT (for CFS) has been said to be "increased confidence in exercise and physical activity"[15]. The possible responses for the other primary outcome measure, the SF-36 physical functioning subscale, are "yes, limited a lot", "yes, limited a little" and "no, not limited at all" to questions on a range of physical activities. Such responses could be easily be artificially altered following a therapy like CBT for CFS.

The results were not that different with the GET cohort in the PACE Trial. Again the manuals predicted that the impairments and symptoms are reversible using the intervention[4,15]. The model said there was no reason participants should not be able to get back to full functioning. Deconditioning was posited to be an important maintaining factor. However, GET did not result in an improvement in fitness, as measured by the step test. GET did result in a small improvement on the six minute walking test to a final distance of 379 metres, or 35 metres more than the SMC-only group[7]. However, as Knoop and Wiborg commented in an accompanying editorial in Lancet Psychiatry: "an increase in distance walked during a test situation without an increased fitness suggests that patients walk more because of a change in cognitive processes (eg, daring to do more or an increased self-efficacy with respect to activity), not because of a change in physiological capacity”[16]. The result remained very poor given that normative data would suggest a group of similar age and gender should walk an average of 644 or so metres[17]. The distance walked remained comparable to people with many serious conditions[18-21], and considerably worse than the distance walked by healthy elderly adults[22,23], despite the PACE trial cohort having a mean age of only 40[8]. Also, to be allowed entry into CFS research studies such as the PACE Trial one can not have a range of chronic illnesses so with genuine recovery one would expect results comparable to healthy people[8].

As with CBT, measures relating to employment showed no improvement following GET in days of work missed, which remained very high, nor a reduction in levels of benefits (financial support from the state) or payments from insurance companies[9].

These results are in line with an audit of Belgian rehabilitation centres for CFS offering CBT and GET[24-26]. Some improvements in subjective measures were found, but there was no improvement in the results of the exercise test and hours in employment actually decreased.

Probably the main contribution of the PACE Trial has been to add to a growing body of evidence that while CBT and GET for CFS have resulted in some changes on subjective measures, they haven't lead to improvements on objective measures.

References: …….
21 May 2017 annotation FOI 2017/F158
http://journals.sagepub.com/doi/full/10....

PACE trial claims for recovery in myalgic encephalomyelitis/chronic fatigue syndrome – true or false?

It’s time for an independent review of the methodology and results
Charles Bernard Shepherd
First Published April 9, 2017
PACE trial claims for recovery in myalgic encephalomyelitis/chronic fatigue syndrome ; true or false? It's time for an independent review of the methodology and results

The PACE trial set out to discover whether cognitive behaviour therapy and graded exercise therapy are safe and effective forms of treatment for myalgic encephalomyelitis/chronic fatigue syndrome. It concluded that these interventions could even result in recovery.

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

Keywords activity, behavioural medicine, chronic fatigue syndrome, cognitive behaviour therapy, dissatisfaction, efficacy, exercise, graded exercise therapy
Keith Geraghty’s (2016) editorial has identified and discussed most of the key reasons why both the PACE trial methodology and the results are not regarded as reliable.

PACE – an acronym for Pacing, graded Activity, and Cognitive behaviour therapy, a randomised Evaluation – compared the effectiveness of four separate inteventions: specialist medical care (SMC) to SMC plus adaptive pacing therapy, cognitive behaviour therapy and graded exercise therapy in patients with myalgic encephalomyelitis/chronic fatigue syndrome. However, those involved in the PACE trial have responded by stating that these criticisms are based on misunderstandings and misrepresentations (White, 2017).

I would like to use this commentary to examine controversies surrounding how two of the PACE trial interventions – cognitive behaviour therapy (CBT) and graded exercise therapy (GET) – originated, why the PACE trial was bound to run into difficulties, and why the patient community is so at odds with the medical establishment over their promotion of CBT and GET.

As a physician who has spent much of the past 35 years helping patients with myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS), I have a strong desire to find safe, acceptable and effective forms of treatment that are aimed at the underlying disease process – rather than just trying to relieve some of the key symptoms. The same position is taken by most ME/CFS patients.

However, uncertainties and disagreements among doctors and patients as to how we should name, define and diagnose this illness, what causes it and how it should be managed make this a very challenging task.

The failure to accept that ME/CFS is a very heterogeneous condition in both clinical presentations and underlying disease mechanisms has meant that the two ‘rehabilitative’ approaches to management – CBT and GET – which were assessed in the PACE trial have become the only forms of treatment for ME/CFS recommended by NICE (National Institute for Health and Clinical Excellence, 2011). At the same time, CBT and GET are consistently rejected by a substantial proportion of people with ME/CFS for being either ineffective (in the case of CBT) or harmful (in the case of GET).

This conflict over the management of ME/CFS largely dates back to a decision taken in the 1980s to rename and redefine what had previously been known as ME as CFS. By relaxing the diagnostic criteria, CFS brought in a much wider group of people who had some form of undiagnosed chronic fatigue that, in some cases, primarily involved psychological or psychiatric factors.

Based on a new and seriously flawed hypothesis that CFS was largely being maintained by abnormal illness beliefs and behaviours, along with inactivity and deconditioning, CBT and GET became the two main recommended forms of treatment in both the United Kingdom and the United States.

Prior to publication of the PACE trial results, a small number of clinical trials had supported the use of CBT and GET, almost all of which had been carried out by health professionals who promoted a psychosomatic model of causation and management. However, patient survey evidence, as collected by the ME Association (ME Association, 2015) along with most other patient surveys (Kindlon and Baldwin, 2015), told a very different story. The majority of people with ME/CFS consistently reported that CBT was ineffective. And around 50 per cent consistently reported that GET had made their condition worse.

The largest and most recent ME Association survey (ME Association, 2015) of patient evidence on the acceptability, efficacy and safety of CBT, GET and Pacing involved 1428 respondents. In this case, 73 per cent of respondents reported that CBT had no effect on their symptoms and 74 per cent reported that their symptoms were made worse by GET.

Surveys carried out by patient support groups have a number of limitations and these are listed in detail in section 6 of The ME Association survey results. In particular, it should be noted that people who belong to patient support groups, or use their websites, are going to produce a bias towards those who have been ill for a longer period of time and/or have a more severe form of illness. At the same time, those who have recovered, or have largely recovered, are less likely to belong to a support group or take part in surveys. So the respondents in these sort of surveys are not necessarily a representative sample of the whole ME/CFS population who have tried these therapies.

And while entry to this survey was on the basis of having a diagnosis of ME/CFS, we did not collect any clinical details or contact the health professional involved for confirmation.

So the PACE trial was essentially set up to provide robust evidence of both safety and efficacy for graded activity (i.e. GET), CBT and a modified version of pacing known as adaptive pacing. But PACE was a study that selected patients using a flawed diagnostic criteria (i.e. Oxford) and only assessed a limited number of subjective outcome measures focusing on fatigue and disability – a design that required strict vigilance in order to prevent the possibility of bias. Not surprisingly, PACE met with widespread criticism right from the very start.

The MEA argued that PACE was not taking account of the clinical heterogeneity of the illness and was ignoring the complex interaction between central (brain) and peripheral (muscle) factors in the causation of fatigue in ME/CFS.

With specific reference to graded exercise, muscle performance and the observation that exercise often makes symptoms worse, Brown et al. (2015) have used magnetic resonance spectroscopy to demonstrate that there are at least two muscle phenotypes involved in ME/CFS. This finding, along with other research evidence on abnormal exercise physiology (VanNess et al., 2003), that is not consistent with a deconditioning/inactivity model of causation, emphasises the need to fully characterise muscle phenotypes, as well as muscle biochemical abnormalities, before generically prescribing exercise as an effective intervention.

The MEA therefore argued that PACE was unlikely to tell us anything we did not already know from previous clinical trials involving CBT and GET. The charity also argued that PACE was a colossal waste of money that should be far better spent on much needed biomedical research – which the main funder of PACE, the Medical Research Council, had always been reluctant to do.

When the first PACE trial results were published (White et al., 2011), they once again failed to convince people with ME/CFS that CBT and GET were the most effective ways of managing everyone with mild or moderate ME/CFS.

But it was the follow-up paper on recovery in Psychological Medicine (White et al., 2013) – where it was claimed that CBT and GET led to ‘recovery’ in 22 per cent – that really intensified the debate into the methodology of the trial, the way recovery had been defined, and the manner in which the results were portrayed to clinicians, patients and the media. Key criticisms included the following:

Recovery figures were based on a definition of recovery that differed from that specified in the trial protocol. In fact, the final definition of recovery was so lax that on some criteria it was possible to score below the level required for entry to the trial, yet still be counted as ‘recovered’.

Participants were not even asked whether they had recovered in relation to normal aspects of daily living.

Information on overall receipt of state sickness or disability benefits failed to support a recovery – with the PACE trial cost analysis study (McCrone et al., 2012) reporting: ‘Receipt of benefits due to illness or disability increased slightly from baseline to follow-up’.

Information on return to some form of meaningful employment or education status was never sought. This was dismissed by the investigators as not being relevant.

Information on ability to mobilise failed to support a recovery. Overall results for all treatments relating to changes in the 6-minute walking test from baseline to 52 weeks did not represent a return to normal levels of activity. In fact, data for all the treatment groups at 52 weeks indicated that they were below the 402 m achieved by patients with class three heart failure. In addition, rejecting the use of electronic activity monitors meant no objective assessment of mobility was carried out.

The term ‘recovery’ implies a sustained return towards symptom-free health along with the ability to repeatedly and reliably participate in all aspects of normal life – employment, education, social activities and so on. Without this information, it was impossible to conclude that any of the patients in the PACE trial had usefully recovered.

Not surprisingly, criticism of the PACE trial continued and intensified. There was a debate in the House of Lords (UK House of Lords, 2013) and 36 academics and clinicians signed an open letter to The Lancet (ME Association, 2016) calling for an independent re-analysis of the data.

Several requests by academics, clinicians and patients asked for unpublished data to be made available so that it could be subjected to independent analysis. These demands were consistent with the growing acceptance by the scientific community that there should be far more transparency in clinical trials, including the sharing of data. The investigators refused to give way even when asked to do so by the Information Commissioner. Queen Mary University of London, which oversaw the trial, then spent almost £250,000 of public money on legal fees by taking the case to an appeal tribunal – which they lost.

When the unpublished PACE trial data was re-analysed by Wilshire et al. (2017), the authors found that if recovery was defined according to the original trial protocol, recovery rates in the CBT and GET groups were low and not significantly higher than in the control group (4%, 7% and 3%, respectively). The authors concluded, The claim that patients can recover as a result of CBT and GET is not justified by the data, and is highly misleading to clinicians and patients considering these treatments.

I conclude with some observations on what we can learn from the mistakes of the PACE trial. Because if lessons are not learned, distrust of the medical and scientific community by the people with ME/CFS will only continue and intensify.

This is not an argument with psychiatry. Mental and physical illness are equally real and horrible. As with any long-term illness, some people with ME/CFS will develop comorbid depression and other mental health problems – where CBT can be of help alongside good quality general management. The argument here is with a flawed model of causation assuming efficacy for CBT and GET while taking no significant account of varying clinical presentations and disease pathways.

First, on behalf of all the journals that have so far published 16 papers from the trial, The Lancet must now set up an independent re-analysis of the PACE trial data, along with appropriate sensitivity analysis. This re-analysis should be carried out by well respected independent reviewers with expertise in statistics and study design. If any results are found to be significantly inaccurate or unreliable, the possibility of a retraction will have to be considered.

Second, if a drug treatment was found to be making a significant proportion of people worse, as is the case with patient evidence relating to the use of GET, the treatment would be withdrawn and would not form part of a NICE recommendation. As there is now both consistent and extensive patient evidence relating to the harmful effects of GET, the NICE guideline recommendation on GET must be reviewed as a matter of urgency. The generic prescribing of progressive and inflexible exercise programmes is not an acceptable form of treatment for people with ME/CFS.

Third, the enormous amount of public money spent by the Medical Research Council and Department of Work and Pensions on funding the PACE trial, along with legal costs met by Queen Mary University of London in appealing against the Freedom of Information requests, merits a formal inquiry, possibly at a parliamentary level.

Finally, there is a desperate need for clinical trials of activity management that examine the heterogeneity of ME/CFS, the fact that underlying disease processes involve both central and peripheral fatigue, and the consistent evidence from patients that inflexible or progressive exercise programmes aggravate symptoms in the majority of patients who come under the ME/CFS umbrella.

Declaration of conflicting interests The author(s) declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article.

Funding The author(s) received no financial support for the research, authorship and/or publication of this article.

References …….

21 May 2017 annotation on the FOI 2017/F158 thread left by KD
http://www.virology.ws/2017/03/13/an-ope...

An open letter to Psychological Medicine about “recovery” and the PACE trial
13 MARCH 2017
Sir Robin Murray and Dr. Kenneth Kendler
Psychological Medicine
Cambridge University Press
University Printing House
Shaftesbury Road
Cambridge CB2 8BS
UK

Dear Sir Robin Murray and Dr. Kendler:

In 2013, Psychological Medicine published an article called “Recovery from chronic fatigue syndrome after treatments given in the PACE trial.”[1] In the paper, White et al. reported that graded exercise therapy (GET) and cognitive behavioural therapy (CBT) each led to recovery in 22% of patients, compared with only 7% in a comparison group. The two treatments, they concluded, offered patients “the best chance of recovery.”

PACE was the largest clinical trial ever conducted for chronic fatigue syndrome (also known as myalgic encephalomyelitis, or ME/CFS), with the first results published in The Lancet in 2011.[2] It was an open-label study with subjective primary outcomes, a design that requires strict vigilance to prevent the possibility of bias. Yet PACE suffered from major flaws that have raised serious concerns about the validity, reliability and integrity of the findings.[3] Despite these flaws, White et al.’s claims of recovery in Psychological Medicine have greatly impacted treatment, research, and public attitudes towards ME/CFS.

According to the protocol for the PACE trial, participants needed to meet specific benchmarks on four different measures in order to be defined as having achieved “recovery.”[4] But in Psychological Medicine, White et al. significantly relaxed each of the four required outcomes, making “recovery” far easier to achieve. No PACE oversight committees appear to have approved the redefinition of recovery; at least, no such approvals were mentioned. White et al. did not publish the results they would have gotten using the original protocol approach, nor did they include sensitivity analyses, the standard statistical method for assessing the impact of such changes.

Patients, advocates and some scientists quickly pointed out these and other problems. In October of 2015, Virology Blog published an investigation of PACE, by David Tuller of the University of California, Berkeley, that confirmed the trial’s methodological lapses.[5] Since then, more than 12,000 patients and supporters have signed a petition calling for Psychological Medicine to retract the questionable recovery claims. Yet the journal has taken no steps to address the issues.

Last summer, Queen Mary University of London released anonymized PACE trial data under a tribunal order arising from a patient’s freedom-of-information request. In December, an independent research group used that newly released data to calculate the recovery results per the original methodology outlined in the protocol.[6] This reanalysis documented what was already clear: that the claims of recovery could not be taken at face value.

In the reanalysis, which appeared in the journal Fatigue: Biomedicine, Health & Behavior, Wilshire et al. reported that the PACE protocol’s definition of “recovery” yielded recovery rates of 7 % or less for all arms of the trial. Moreover, in contrast to the findings reported in Psychological Medicine, the PACE interventions offered no statistically significant benefits. In conclusion, noted Wilshire et al., “the claim that patients can recover as a result of CBT and GET is not justified by the data, and is highly misleading to clinicians and patients considering these treatments.”

In short, the PACE trial had null results for recovery, according to the protocol definition selected by the authors themselves. Besides the inflated recovery results reported in Psychological Medicine, the study suffered from a host of other problems, including the following:

*In a paradox, the revised recovery thresholds for physical function and fatigue–two of the four recovery measures–were so lax that patients could deteriorate during the trial and yet be counted as “recovered” on these outcomes. In fact, 13 % of participants met one or both of these recovery thresholds at baseline. White et al. did not disclose these salient facts in Psychological Medicine. We know of no other studies in the clinical trial literature in which recovery thresholds for an indicator actually represented worse health status than the entry thresholds for serious disability on the same indicator.

*During the trial, the authors published a newsletter for participants that included glowing testimonials from earlier participants about their positive outcomes in the trial.[7] An article in the same newsletter reported that a national clinical guidelines committee had already recommended CBT and GET as effective; the newsletter article did not mention adaptive pacing therapy, an intervention developed specifically for the PACE trial. The participant testimonials and the newsletter article could have biased the responses of an unknown number of the two hundred or more people still undergoing assessments—about a third of the total sample.

*The PACE protocol included a promise that the investigators would inform prospective participants of “any possible conflicts of interest.” Key PACE investigators have had longstanding relationships with major insurance companies, advising them on how to handle disability claims related to ME/CFS. However, the trial’s consent forms did not mention these self-evident conflicts of interest. It is irrelevant that insurance companies were not directly involved in the trial and insufficient that the investigators disclosed these links in their published research. Given this serious omission, the consent obtained from the 641 trial participants is of questionable legitimacy.

Such flaws are unacceptable in published research; they cannot be defended or explained away. The PACE investigators have repeatedly tried to address these concerns. Yet their efforts to date—in journal correspondence, news articles, blog posts, and most recently in their response to Wilshire et al. in Fatigue[8]—have been incomplete and unconvincing.

The PACE trial compounded these errors by using a case definition for the illness that required only one symptom–six months of disabling, unexplained fatigue. A 2015 report from the U.S. National Institutes of Health recommended abandoning this single-symptom approach for identifying patients.[9] The NIH report concluded that this broad case definition generated heterogeneous samples of people with a variety of fatiguing illnesses, and that using it to study ME/CFS could “impair progress and cause harm.”

PACE included sub-group analyses of two alternate and more specific case definitions, but these case definitions were modified in ways that could have impacted the results. Moreover, an unknown number of prospective participants might have met these alternate criteria but been excluded from the study by the initial screening.

To protect patients from ineffective and possibly harmful treatments, White et al.’s recovery claims cannot stand in the literature. Therefore, we are asking Psychological Medicine to retract the paper immediately. Patients and clinicians deserve and expect accurate and unbiased information on which to base their treatment decisions. We urge you to take action without further delay.

Sincerely,

Dharam V. Ablashi, DVM, MS, Dip Bact
Scientific Director
HHV-6 Foundation
Former Senior Investigator
National Cancer Institute
National Institutes of Health
Bethesda, Maryland, USA

James N. Baraniuk, MD
Professor, Department of Medicine
Georgetown University
Washington, D.C., USA

Lisa F. Barcellos, MPH, PhD
Professor of Epidemiology
School of Public Health
California Institute for Quantitative Biosciences
University of California, Berkeley
Berkeley, California, USA

Lucinda Bateman, MD
Medical Director
Bateman Horne Center
Salt Lake City, Utah, USA

Alison C. Bested, MD, FRCPC
Clinical Associate Professor
Faculty of Medicine
University of British Columbia
Vancouver, British Columbia, Canada

Molly Brown, PhD
Assistant Professor
Department of Psychology
DePaul University
Chicago, Illinois, USA

John Chia, MD
Clinician and Researcher
EVMED Research
Lomita, California, USA

Todd E. Davenport, PT, DPT, MPH, OCS
Associate Professor
Department of Physical Therapy
University of the Pacific
Stockton, California, USA

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

Simon Duffy, PhD, FRSA
Director
Centre for Welfare Reform
Sheffield, UK

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

Derek Enlander, MD
New York, New York, USA

Meredyth Evans, PhD
Clinical Psychologist and Researcher
Chicago, Illinois, USA

Kenneth J. Friedman, PhD
Associate Professor of Physiology and Pharmacology (retired)
New Jersey Medical School
University of Medicine and Dentistry of New Jersey
Newark, New Jersey, USA

Robert F. Garry, PhD
Professor of Microbiology and Immunology
Tulane University School of Medicine
New Orleans, Louisiana, USA

Keith Geraghty, PhD
Honorary Research Fellow
Division of Population Health, Health Services Research & Primary Care
School of Health Sciences
University of Manchester
Manchester, UK

Ian Gibson, PhD
Former Member of Parliament for Norwich North
Former Dean, School of Biological Sciences
University of East Anglia
Honorary Senior Lecturer and Associate Tutor
Norwich Medical School
University of East Anglia
Norwich, UK

Rebecca Goldin, PhD
Professor of Mathematics
George Mason University
Fairfax, Virginia, USA

Ellen Goudsmit, PhD, FBPsS
Health Psychologist (retired)
Former Visiting Research Fellow
University of East London
London, UK

Maureen Hanson, PhD
Liberty Hyde Bailey Professor
Department of Molecular Biology and Genetics
Cornell University
Ithaca, New York, USA

Malcolm Hooper, PhD
Emeritus Professor of Medicinal Chemistry
University of Sunderland
Sunderland, UK

Leonard A. Jason, PhD
Professor of Psychology
DePaul University
Chicago, Illinois, USA

Michael W. Kahn, MD
Assistant Professor of Psychiatry
Harvard Medical School
Boston, Massachusetts, USA

Jon D. Kaiser, MD
Clinical Faculty
Department of Medicine
University of California, San Francisco
San Francisco, California, USA

David L. Kaufman, MD
Medical Director
Open Medicine Institute
Mountain View, California, USA

Betsy Keller, PhD
Department of Exercise and Sports Sciences
Ithaca College
Ithaca, New York, USA

Nancy Klimas, MD
Director, Institute for Neuro-Immune Medicine
Nova Southeastern University
Director, Miami VA Medical Center GWI and CFS/ME Program
Miami, Florida, USA

Andreas M. Kogelnik, MD, PhD
Director and Chief Executive Officer
Open Medicine Institute
Mountain View, California, USA

Eliana M. Lacerda, MD, MSc, PhD
Clinical Assistant Professor
Disability & Eye Health Group/Clinical Research Department
Faculty of Infectious and Tropical Diseases
London School of Hygiene & Tropical Medicine
London, UK

Charles W. Lapp, MD
Medical Director
Hunter-Hopkins Center
Charlotte, North Carolina, USA
Assistant Consulting Professor
Department of Community and Family Medicine
Duke University School of Medicine
Durham, North Carolina, USA

Bruce Levin, PhD
Professor of Biostatistics
Columbia University
New York, New York, USA

Alan R. Light, PhD
Professor of Anesthesiology
Professor of Neurobiology and Anatomy
University of Utah
Salt Lake City, Utah, USA

Vincent C. Lombardi, PhD
Director of Research
Nevada Center for Biomedical Research
Reno, Nevada, USA

Alex Lubet, PhD
Professor of Music
Head, Interdisciplinary Graduate Group in Disability Studies
Affiliate Faculty, Center for Bioethics
Affiliate Faculty, Center for Cognitive Sciences
University of Minnesota
Minneapolis, Minnesota, USA

Steven Lubet
Williams Memorial Professor of Law
Northwestern University Pritzker School of Law
Chicago, Illinois, USA

Sonya Marshall-Gradisnik, PhD
Professor of Immunology
Co-Director, National Centre for Neuroimmunology and Emerging Diseases
Griffith University
Queensland, Australia

Patrick E. McKnight, PhD
Professor of Psychology
George Mason University
Fairfax, Virginia, USA

Jose G. Montoya, MD, FACP, FIDSA
Professor of Medicine
Division of Infectious Diseases and Geographic Medicine
Stanford University School of Medicine
Stanford, California, USA

Zaher Nahle, PhD, MPA
Vice President for Research and Scientific Programs
Solve ME/CFS Initiative
Los Angeles, California, USA

Henrik Nielsen, MD
Specialist in Internal Medicine and Rheumatology
Copenhagen, Denmark

James M. Oleske, MD, MPH
François-Xavier Bagnoud Professor of Pediatrics
Senator of RBHS Research Centers, Bureaus, and Institutes
Director, Division of Pediatrics Allergy, Immunology & Infectious Diseases
Department of Pediatrics
Rutgers New Jersey Medical School
Newark, New Jersey, USA

Elisa Oltra, PhD
Professor of Molecular and Cellular Biology
Catholic University of Valencia School of Medicine
Valencia, Spain

Richard Podell, MD, MPH
Clinical Professor
Department of Family Medicine
Rutgers Robert Wood Johnson Medical School
New Brunswick, New Jersey, USA

Nicole Porter, PhD
Psychologist in Private Practice
Rolling Ground, Wisconsin, USA

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

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

Anders Rosén, MD
Professor of Inflammation and Tumor Biology
Department of Clinical and Experimental Medicine
Division of Cell Biology
Linköping University
Linköping, Sweden

Peter C. Rowe, MD
Professor of Pediatrics
Johns Hopkins University School of Medicine
Baltimore, Maryland, USA

William Satariano, PhD
Professor of Epidemiology and Community Health
University of California, Berkeley
Berkeley, California, USA

Ola Didrik Saugstad, MD, PhD, FRCPE
Professor of Pediatrics
University of Oslo
Director and Department Head
Department of Pediatric Research
University of Oslo and Oslo University Hospital
Oslo, Norway

Charles Shepherd, MB, BS
Honorary Medical Adviser to the ME Association
Buckingham, UK

Christopher R. Snell, PhD
Scientific Director
WorkWell Foundation
Ripon, California, USA

Donald R. Staines, MBBS, MPH, FAFPHM, FAFOEM
Clinical Professor
Menzies Health Institute Queensland
Co-Director, National Centre for Neuroimmunology and Emerging Diseases
Griffith University
Queensland, Australia

Philip B. Stark, PhD
Professor of Statistics
University of California, Berkeley
Berkeley, California, USA

Eleanor Stein, MD, FRCP(C)
Psychiatrist in Private Practice
Assistant Clinical Professor
University of Calgary
Calgary, Alberta, Canada

Staci Stevens, MA
Founder, Exercise Physiologist
Workwell Foundation
Ripon, California, USA

Julian Stewart, MD, PhD
Professor of Pediatrics, Physiology and Medicine
Associate Chairman for Patient Oriented Research
Director, Center for Hypotension
New York Medical College
Hawthorne, NY, USA

Leonie Sugarman, PhD
Emeritus Associate Professor of Applied Psychology
University of Cumbria
Carlisle, UK

John Swartzberg, MD
Clinical Professor Emeritus
School of Public Health
University of California, Berkeley
Berkeley, California, USA

Ronald G. Tompkins, MD, ScD
Summer M Redstone Professor of Surgery
Harvard Medical School
Boston, Massachusetts, USA

David Tuller, DrPH
Lecturer in Public Health and Journalism
University of California, Berkeley
Berkeley, California, USA

Rosemary A. Underhill, MB, BS, MRCOG, FRCSE
Physician and Independent Researcher
Palm Coast, Florida, USA

Rosamund Vallings, MNZM, MB, BS
General Practitioner
Auckland, New Zealand

Michael VanElzakker, PhD
Research Fellow, Psychiatric Neuroscience Division
Harvard Medical School & Massachusetts General Hospital
Instructor, Tufts University Psychology
Boston, Massachusetts, USA

Mark VanNess, PhD
Professor of Health, Exercise & Sports Sciences
University of the Pacific
Stockton, California, USA
Workwell Foundation
Ripon, California, USA

Mark Vink, MD
Family Physician
Soerabaja Research Center
Amsterdam, Netherlands

Frans Visser, MD
Cardiologist
Stichting Cardiozorg
Hoofddorp, Netherlands

Tony Ward, MA (Hons), PhD, DipClinPsyc
Registered Clinical Psychologist
Professor of Clinical Psychology
School of Psychology
Victoria University of Wellington
Wellington, New Zealand
Adjunct Professor, School of Psychology
University of Birmingham
Birmingham, UK
Adjunct Professor, School of Psychology
University of Kent
Canterbury, UK

William Weir, FRCP
Infectious Disease Consultant
London, UK

John Whiting, MD
Specialist Physician
Private Practice
Brisbane, Australia

Carolyn Wilshire, PhD
Senior Lecturer
School of Psychology
Victoria University of Wellington
Wellington, New Zealand

Michael Zeineh, MD, PhD
Assistant Professor
Department of Radiology
Stanford University
Stanford, California, USA

Marcie Zinn, PhD
Research Consultant in Experimental Electrical Neuroimaging and Statistics
Center for Community Research
DePaul University
Chicago, Illinois, USA
Executive Director
Society for Neuroscience and Psychology in the Performing Arts
Dublin, California, USA

Mark Zinn, MM
Research Consultant in Experimental Electrophysiology
Center for Community Research
DePaul University
Chicago, Illinois, USA

ME/CFS Patient Organizations

25% ME Group
UK

Emerge Australia
Australia

European ME Alliance:

Belgium ME/CFS Association
Belgium

ME Foreningen
Denmark

Suomen CFS-Yhdistys
Finland

Fatigatio e.V.
Germany

Het Alternatief
Netherlands

Icelandic ME Association
Iceland

Irish ME Trust
Ireland

Associazione Malati di CFS
Italy

Norges ME-forening
Norway

Liga SFC
Spain

Riksföreningen för ME-patienter
Sweden

Verein ME/CFS Schweiz
Switzerland

Invest in ME Research
UK

Hope 4 ME & Fibro Northern Ireland
UK

Irish ME/CFS Association
Ireland

Massachusetts CFIDS/ME & FM Association
USA

ME Association
UK

ME/cvs Vereniging
Netherlands

National ME/FM Action Network
Canada

New Jersey ME/CFS Association
USA

Pandora Org
USA

Phoenix Rising
International membership representing many countries

Solve ME/CFS Initiative
USA

Tymes Trust (The Young ME Sufferers Trust)
UK

Wisconsin ME and CFS Association
USA

References………
21 May 2017 annoation
Kathryn Dickenson left an annotation (21 May 2017)
http://www.thelancet.com/pdfs/journals/l...

Correspondence
www.thelancet.com/psychiatry Vol 3 February 2016

PACE: CBT and GET are not rehabilitative therapies
In a recent Article Michael Sharpe and colleagues report on findings of a follow-up study of the PACE trial of proposed rehabilitative interventions for chronic fatigue syndrome: graded
exercise therapy (GET) and cognitive behavioural therapy (CBT). Their main finding is that the beneficial effects of CBT and GET were maintained at follow-up (median: 2·5 years). Both CBT and GET have been qualified by the PACE trial investigators as “moderately effective treatments”.2

However, looking at the data of the follow-up study1 and other PACE trial studies,2,3 CBT and GET do not qualify as rehabilitative therapies for chronic fatigue syndrome or myalgic
encephalomyelitis, as defined by the London criteria.1

First, the PACE trial investigated the effects of CBT and GET in chronic fatigue, as defined by the Oxford criteria, not in chronic fatigue syndrome, let alone myalgic encephalomyelitis,
as defined by the Ramsay criteria.

The Oxford criteria have been criticised often. For that reason “consensus groups and researchers should consider retiring the Oxford case definition”.4

Second, the positive effect of CBT and GET in subjective measures, fatigue and physical functioning, cannot be qualified as sufficient.

Mean short form-36 physical functioning scores in the CBT group (62·2) and the GET group (59·8) at follow-up were below the inclusion cutoff score for the PACE trial (≤65)3
and far below the objective for recovery as defined in the PACE protocol (≥85).5

The mean fatigue scores in the CBT group (18·4) and GET group (19·1) were above subnormal (<18)4 and far above the entry criterion for the PACE trial
(>12, recalculated)3 and the recovery criterion in the PACE protocol (≤6).5

Third, the PACE trial follow-up study1 concluded that outcomes with specialist medical care alone or adaptive pacing therapy (APT) were similar to CBT and GET at follow-up. The authors suggest that ”it is important to note that many of the participants had received additional treatment for CFS since completing the trial”. Looking at the data,1 23 (20%) of the patients in the specialist medical care arm received an adequate number of sessions (n=10) of CBT after the PACE trial and 14 (12%) received GET, while 20 (17%)
of the patients in the APT group received CBT and 7 (6%) received GET afterwards. This finding implies that the vast majority of patients improved subjectively by specialist medical
care and APT to the same level as by CBT and GET, without any additional therapies, including CBT and GET, or by other therapies.1
Finally, looking at subjective outcomes at follow-up1 and objective outcomes in earlier studies, such as physical fitness,2 return to employment,3 social welfare benefits,3
and health-care usage,3 CBT and GET, like specialist medical care and APT, cannot be qualified as effective.

In conclusion, CBT and GET are moderately effective in subjective terms in chronic fatigue, but looking at the patients studied and the (subjective and objective) outcomes of the PACE trial,1,3–5 CBT and GET do not meet the requirements for rehabilitative or effective therapies for chronic fatigue syndrome, let alone myalgic encephalomyelitis.

I am associated with a Dutch ME/CFS patient foundation in a voluntary (non-paid) capacity.
Frank Twisk
[email address]

Research, ME-de-patiënten Foundation, Limmen,
1906HB, Netherlands
References……

22 May 2017 annotation FOI 2017/F158

http://journals.sagepub.com/doi/pdf/10.1...

David Tuller on the PACE trial authors failure to address flaws in the trial.

https://doi.org/10.1177/1359105317703788
Journal of Health Psychology 1–5

Other commentaries in this Special Section focus on specific methodological aspects of the PACE trial. (The study’s full name: “Comparison of adaptive pacing therapy, cognitive behaviour therapy, graded exercise therapy, and specialist medical care for chronic fatigue syndrome: A randomised trial.”)
I would like to examine how the PACE investigators, in their response to the troubling questions about their research raised in Geraghty’s editorial (Geraghty, 2016), have strategically avoided providing direct answers (White et al., 2017). Instead, they have provided non-answers—persuasive-sounding arguments that fall apart quickly under scrutiny. This approach is consistent with their earlier efforts to rebut legitimate criticism.
The PACE investigators note that they have “repeatedly addressed” the various concerns about the trial, citing journal correspondence as well as popular forums such as blog posts and news articles. A review of some of these publications confirms their point. But “addressing” concerns is not the same as offering credible explanations, and the investigators have failed this test each time they have responded.

24 May 2017 KD left an annotation on the thread FOI 2017/F158 which is a link to the USA Centre for disease control website.
The USA Centre for Disease Control

https://www.cdc.gov/features/cfsawarenes...

24 May 2017 KD left an annotation on the thread FOI 2017/F158
The Invest in ME Research 2017. IIMEC12 Pre-conference dinner. David Tuller will be our guest presenter.
David Tuller DrPh, is academic coordinator of University of California Berkeley's joint masters program in public health and journalism. He was a reporter and editor for 10 years at the San Francisco Chronicle, served as health editor at Salon.com and frequently writes about health for The New York Times.

David's presentation - #TearItUp - will include his work in exposing the flaws in the PACE Trial.
His analysis of the PACE (Comparison of adaptive pacing therapy, cognitive behaviour therapy, graded exercise therapy, and specialist medical care for chronic fatigue syndrome) Trial, and its aftermath, will probably be seen as a pivotal moment when the history of research into ME is written.

By bringing investigatory and scientific analysis to the PACE Trial and exposing and documenting the faults in what has taken place with this trial David Tuller has also brought awareness to how research into ME has been so flawed in the past.

The results of his thorough journalism has brought hope to people with ME and their families who have long called for independent review of the PACE trial, and related research.

David Tuller received the Special Service Award at the October 2016 IACFS/ME conference in Fort Lauderdale, USA and this high-quality and dedicated journalism will surely receive more awards in the future.

References for David Tuller …….
1 June 2017 KD left an annotation on the thread for information request FOI 2017/F158
Key websites:
Press & research
Added in 2017

TED TALK: Jen Brea describes the obstacles she’s encountered in seeking treatment for her condition: What happens when you have a disease doctors can’t diagnose

PIP INVESTIGATION: Assessment reports show widespread dishonesty by nurses

BBC: Research in Norwich could offer ME/CFS breakthrough: Researchers in Norwich are teaming up with researchers from Norway to collaborate on ME/CFS research
Jennifer Brea’s Sundance Winner “Unrest” Acquired by PBS: PBS has bought the U.S. broadcast rights to “Unrest”
The ‘all in the mind’ myth of ME/CFS: From Nursing in Practice – 27 June 2016

PACE Trial latest | MEA to pay for open access to independent reanalysis paper: PACE Trial latest-MEA to pay for open access to independent reanalysis paper

Novel Gene Variants in ME/CFS and Fibromyalgia: From the Bateman Horne Centre Feb 2017

Queensland Scientists Make Chronic Fatigue Syndrome Research Breakthrough: Minister describes a small study showing link to abnormal immune system cells

Centre for Welfare reform essay: In the Expectation of Recovery

Ronald W. Davis, Research update Feb 21st 2017: Significant breakthroughs towards understanding the molecular mechanisms of the disease.. now ready for testing
Ronald W. Davis, PhD, Scientific Advisory Board Director: About Professor Davis

Severe ME left me in a world of pain and darkness. 26 years on, why is it still so poorly understood?: Article on Open Democracy

Pathological mechanisms in ME from Bergen research group : A new study, partly funded by the Kavli Trust
Webinar led by Anthony L. Komaroff, MD, professor of medicine at Harvard Medical School: Useful overview of the state of ME science from late 2016

Impressions from IACFS/ME 2016 : Take-home messages from this conference?

Dr. Mark Van Ness, “Expanding Physical Capability in ME/CFS” Part 1 (of 2) : First of a two-part 2016 ME awareness presentation

Dr. Mark Van Ness, “Expanding Physical Capability in ME/CFS” Part 2 (of 2) : Second of a two-part 2016 ME awareness presentation
Workwell Foundation : Latest news

Added to our website in 2016
Health rising: The IACFS/ME Preconference: ME/CFS and GWI – The Complex Neuroinflammatory Conditions
Open Medicine Foundation: UPDATED: Metabolic Features of Chronic Fatigue Syndrome – Q & A with Robert Naviaux, MD

Open Medicine Foundation: Ronald W. Davis, PhD, Scientific Advisory Board Director

Invest In ME charity discuss the MEGA study, and the Omega counter petition: Find out more about objections to this proposed UK study

From 2015 – but worth watching: scientist dad searches for cure for ill son

Dr Lucinda Bateman from the Bateman Horne Center USA: Global report of progress lecture

Part 1 of three talks given at the Watershed in Bristol: Prof. Mark VanNess on exercise and CFS/ME

Part 2 of three talks given at the Watershed in Bristol: Dr. Nigel Speight on exercise and CFS/ME

Part 3 of three talks given at the Watershed in Bristol: Erina Bowman on exercise and ME/CFS
Workwell Foundation USA: Staci Stevens & Mark VanNess video’s
US Neuroscientist says exercise worsens ME/CFS Symptoms: Prof. J. Mark VanNess from the Californian University of the Pacific

The National Academies of SCIENCES, ENGINEERING, MEDICINE, USA: Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness

Virology blog: Trial By Error, Continued: The Real Data

PLOS blog: Before you enroll your child in the MAGENTA chronic fatigue syndrome study: Issues to be considered
A thoughtful piece relating to education, sick children, and the attitudes of the state: Independent Living and Education

Naviaux’s Metabolism Paper: Researcher at Uni of California publishes a ‘landmark’ paper
US Representatives support letter to NIH in USA for ME/CFS research: 55 members of Congress have signed the letter…

ME Research UK’s Forward ME Group meeting minutes: Reports on their meeting in the House of Lords

ME Research UK publishes a magazine called Breakthrough: Features updates on projects funded by the charity

Parliamentary Question regarding steps to be taken to encourage research into ME: 13th Sept 2016 – politician asks the question..

The Lancet rejects Scientists’ Pace Letter: Update on the letter written to the Lancet by 43 scientists

Soft Tissue Therapy for Fibromyalgia: Clinical trial recruiting participants

Timeline, Torture and Tragedy: Valerie Eliot Smith writes about the case of Karina
FREE Karina: The tragic and ongoing case of Karina Hansen in Denmark
PIP assesment: Dept for Work and Pensions

QMUL RELEASES THE PACE DATA: ME ACTION reports:

Hyperbaric oxygen use in fibromyalgia: Does HBO reduce the symptoms of ME/CFS and firbomyalgia?:

Posts by Valerie Eliot Smith who writes about Law and Health: Here you can see a variety of posts written by Valerie on the subject of QMUL, PACE and the law:

Article in the Proceedings of the National Academy of Sciences of the USA: Metabolic Features of chronic fatigue syndrome:

Article in the Proceedings of the National Academy of Sciences of the USA: Metabolic Features of chronic fatigue syndrome:

Trial By Error, Continued: My questions for Lancet Editor Richard Horton: By David Tuller, DrPH written 1-9-16:

Hope for CFS: Article by Julie Rehmeyer who is also making a documentary about ME/CFS called Canary in a Coal Mine:

Tribunal orders University to release data: From the BMJ news Hub, reported on ME Association website:

You look too well presented to be sick: Poem written after rising a government agency…:
Research paper about Leptin and Fibromyalgia: Association of Leptin with Body Pain in Women:

Invest in ME Research International ME Conference – 2nd June 2017: Running ME Biomedical Research conferences since 2006:

ME Association article: Tribunal orders release of PACE Trial data (courtesy of Valerie Eliot Smith)

Occupy ME article: AHRQ Evidence Review Changes its Conclusions

ME Association article: Tribunal orders university to release data from PACE chronic fatigue study- from BMJ news hub

The Information Tribunal – Government website: The QMUL appeal of 20-22 April 2016 – details of the appeal.

The Centre For Welfare Reform, article: Major breakthrough on PACE trial

USA TODAY. New research sheds light on mysterious fibromyalgia
Columbia Magazine. New hope for those with chronic fatigue syndrome

Occupy ME. Exercise Testing and Using a Heart Rate Monitor

Scientifically Redefining ME/CFS. The Other MEGA Chronic Fatigue Syndrome (ME/CFS) Project: Dr. Hornig Talks

Harvard and Tufts neuroscientist Dr. Michael Van ElZakker shares his fascinating new paper Chronic Fatigue from Vagus Nerve Infection:

A Psychoneuroimmunological Hypothesis. His hypothesis proposes that an infection of the vagus nerve can cause greatly exaggerated chronic sickness responses like fatigue, pain and more. Research paper

Vincent Racaniello speaks to guest journalist David Tuller about the flaws in the UK’s PACE trial, and the efforts to have the trial data release. Excellent for practitioners in the NHS and the general public to listen to, if you wish to be informed. Interview
Invest In ME event. Conference 2016

GMC impose conditions on Dr Speight’s licence to practice. ME Association reports..

Nigel Speight speaks at the Watershed in Bristol. Advisor to ME charities speaks.

New research on Fibro pain. USA Today – report.

The Big Sleep for ME. Invest in ME charity annual event

Search for aetiology of ME/CFS. Search for a rational diagnostic system.

Scientists find clues into cognitive dysfunction in CFS. Research from Columbia University USA.

USA. National Institute for Health – ME news release from 29-10-15. NIH Take action…

Missing Millions international protest – London event. Evening standard report
BBC Radio Bristol programme. The truth about living with ME – 3 women’s stories

ME related petition on a UK government website. Invest more money into scientific research to find the cause of ME/CFS

ME Association CBT, GET, PACING REPORT. No decisions about me – without me
A hard hitting article about what lies behind the attack on disability benefits. The Misleading Research at the Heart of Disability Cuts

Guardian article titled: Is chronic fatigue syndrome finally being taken seriously?
Virtual protest: Missing Millions

Dr Speight speaks at Bristol Watershed
2 June 2017 KD left an annotation on the FOI 2017/F158 thread
http://journals.sagepub.com/doi/10.1177/...

Relevant article regarding PACE

Once again, the PACE authors respond to concerns with empty answers
David Tuller
Abstract
In their response to Geraghty, the PACE investigators state that they have “repeatedly addressed” the various methodological concerns raised about the trial.
While this is true, these responses have repeatedly failed to provide satisfactory explanations for the trial’s very serious flaws.
This commentary examines how the current response once again demonstrates the ways in which the investigators avoid acknowledging the obvious problems with PACE and offer non-answers instead—arguments that fall apart quickly under scrutiny.
2 June 2017 KD left an annotation on the FOI 2017/F158 thread
David Tuller - podcast regarding the flaws and faults with PACE and the FOI release ordered by the First Tribunal and International and Worldwide concern about the trial.

No statistical recovery and subjective outcome only. No verifiable objective data released.

http://www.microbe.tv/twiv/twivs-tuller3/

David Tuller returns to discuss the continuing saga of the UK’s PACE trial for chronic fatigue syndrome, including the accusation that he is engaging in libelous blogging.
3 June 2017 – KD sent a reminder to QMUL FOI 2017/F158
“Dear QM FOI Enquiries,
I refer to my request for a copy of non-identified objective data, from the 5 million pound PACE study.
I am writing to remind you that it is nearly a month since I wrote to you and to advise that I have attached a series of annotations to my request.
The annotations highlight some of the problems with the PACE trial. They help explain the need for transparency and perusal of the objective outcome data from the PACE trial by independent scientists including but not limited to exercise physiologists, exercise cardiologists, exercise neuroscientists.
Independent scientists are those who are NOT connected to, or chosen by the PACE principal investigators Peter White, Michael Sharpe, Trudi Chaldler their adviser Simon Wessley, ardent supporter Ester Crawley or persons who may be unduly under the influence of these mental health professionals.
Further, given that the insurance industry directly benefits from the PACE authors misleading claims it is essential that independent scientists, NOT connected to the insurance industry are able to review the raw data.
I look forward to your response.
Yours sincerely,
Kathryn Dickenson”

5 June 2017 - QMUL refused the request and issued a refusal notice under s.17.FOI 2017/F158
“ FOI 2017/F158

Dear Kathryn Dickenson

Thank you for your email of 6^th May.
Firstly, not all of the information you have requested is held. Many of
the measures specified seem to be based on being listed in the trial’s
manuals. However, this has no bearing on what was measured in the trial
and you should refer to the protocol. We do not hold data on VO2 max,
TUAG, sit-stand test, 2 minute walk. We hold the actometer measures, but
only at baseline, not at the other time points requested. The only measure
for which we hold Borg and end heart rate is the step test. There are no
data measured direct after randomisation, at 10 weeks, separately at mid
assessment (this is the 12 week data), separately at the final assessment
(this is the 52 week data) or 39 week time points. No exercise data were
measured at long term follow-up, so these data are not held.”
“With regards to the rest of the data that we do hold, we estimate - given
the time already expended ascertaining what is held as well - that to
provide all of the information would exceed the appropriate limit. as
defined by the Freedom of Information and Data Protection (Appropriate
Limit) Regulations 2004. For your information this is £450, calculated as
the estimated cost of one person spending 18 hours in determining whether
the information is held, then locating, retrieving and extracting the
information. Section 12 of the Freedom of Information Act 2000 therefore
makes provision for public authorities to refuse such requests.

If you are dissatisfied with this response, you may ask QMUL to conduct a
review of this decision. To do this, please contact the College in
writing (including by fax, letter or email), describe the original
request, explain your grounds for dissatisfaction, and include an address
for correspondence. You have 40 working days from receipt of this
communication to submit a review request. When the review process has
been completed, if you are still dissatisfied, you may ask the Information
Commissioner to intervene. Please see [1]www.ico.org.uk for details.
Yours sincerely

Paul Smallcombe
Records & Information Compliance Manager

References
Visible links
1. http://www.ico.org.uk/”

6 June 2017 FOI 2017/F158– KD narrowed the information request and removed the information that QMUL stated that they did not hold.
“Dear QM FOI Enquiries,
I note your advice that the protocols described in the PACE manual, have “no bearing on what was measured in the trial”.
“On the basis of your advice I have modified my information request to the information that QMUL states was measured, and make the following amendments, to my request for objective physiological/physical data :
1/ Actometer results (BMC reference 18) – QMUL advise that the actometer results were only measured at baseline. Request raw data actometer, baseline measurements.
2/ VO2 max (manual page 40) - QMUL advise this is not held.
3/ TUAG (timed up and go. Chair-stand-walk 3 metres-turn- walk back -sit down (manual page 88) - QMUL advise this is not held.
4/ Sit-stand test (count number in one minute – manual page 88)) - QMUL advise this is not held - QMUL advise this is not held.
5/ 2-minute walk (manual page 88)- QMUL advise this is not held.
6/ 6 minute walk objective measure of recovery (BMC reference 31) – Request raw data.
7/ Self-paced step. Test of fitness (BMC reference 43) - QMUL advise have Borg test (scale of perceived exertion) and end heart rate – Request raw data.
8/ Exercise and activity scale (BMC reference 36) – Request raw data.
9/ For each physiological measure I require, The time, End heart rate and Borg measure. (Borg Scale of perceived physical exertion [BMC reference 44], is used to measure effort with exercise.) QMUL advise that the “only measure for which we hold Borg and end heart rate is the step test” – Request raw data for the heart rate and Borg measure for the step test.
Time periods, that the PACE authors specified they would collect, objective measurements of physical functioning:
10/ Baseline (PACE manual) – request the raw data
After randomisation (BMC) – QMUL advise this measurement did not take place.
10 weeks - QMUL advise this measurement is the 12 week data.
11/ 12 weeks (authors response to review) – request the raw data
Mid assessment (PACE manual) - QMUL advise was not measured
12/ 24 weeks - request the raw data
13/ Final assessment (PACE manual) – request the raw data
14/ 39 weeks - QMUL advise data was not measured at this time point.
15/ 52 week data - QMUL advise this measurement time point is the same as the 39 week time point and the final assessment time point.
16/ One year follow up - request the raw data.
17/ 2.5 year follow up - QMUL advise that data was not obtained at long term follow up.
Hence my modified request is as follows:
i/ Actometer results (BMC reference 18) – raw data actometer, baseline measurements.
ii/ 6 minute walk objective measure of recovery (BMC reference 31).
iii/ Self-paced step. Test of fitness (BMC reference 43), including the Borg test (scale of perceived exertion) and end heart rate.
iv/ Exercise and activity scale (BMC reference 36).
At the specified time periods, that the PACE authors specified they would collect the data:
v/ Baseline
vi/ 12 weeks
vii/ 24 weeks
viii/ Final assessment – 52 week/39 week time point
ix/ One year follow up
I request, that the data is provided in a manner that enables me to distinguish between data from patients with CFS and those with mental health disorders:
(i) Patients diagnosed with CFS and no mental health disorders
(ii) Patients diagnosed with psychiatric disorder
(iii) Patients diagnosed with depressive disorder”
Yours sincerely
Kathryn Dickenson”

8 June 2017 FOI 2017/F158 (a) thread – QMUL clarified that the refusal applied to the modified request
“Dear Kathryn Dickenson
You do not appear to have understood our response. Where we do hold data, this has been refused under s.12 of the Freedom of Information Act.
Please accept our email of 5th June as a refusal notice under s.17.
Yours sincerely
Queen Mary University of London”
8 June 2017 FOI 2017/F158– KD thanked QMUL for responding
“Dear QM FOI Enquiries,
Thank you, for getting back to me.
Yours sincerely,
Kathryn Dickenson”

8 June 2017
KD narrowed the request, thread FOI 2017/F158(a)– reducing the number of time points requested, and removing the separation of patients into mental health and non-mental health patients requested, the third version of the request
“Dear QM FOI Enquiries,
Thank you for your assistance, further to your comments, I have reduced my information request to asking for even less information.
I have reduced my information request to asking for even less information.
I have reduced the number of time points, removed the request for the exercise and activity scale data and removed, the request for a copy of the data in a format that separated the patients without depressive or psychiatric disorders from those with the mental health issues.”
My reduced information request is as follows:
i/ Actometer results (BMC reference 18) – raw data actometer, baseline measurements.
ii/ 6 minute walk objective measure of recovery (BMC reference 31).
iii/ Self-paced step. Test of fitness (BMC reference 43), including the Borg test (scale of perceived exertion) and end heart rate.
At the specified time periods, that the PACE authors specified they would collect the data:
iv/ Baseline
v/ Final assessment – 52 week/39 week time point
Yours sincerely,
Kathryn Dickenson”
13 June 2017 lodged a new request via the website, What do they know? KD refers to this request as FOI 2017/F158(b) and on the What do they know? Website this request is started on a new thread.
The FOI request is entitled: CFS - a small % of the objective physical and physiological data from PACE trial.
The link to the website is:
https://www.whatdotheyknow.com/request/c...
“Dear Queen Mary, University of London,
I refer to FOI 2017/F158, which details why I am requesting the release of some of the objective, physiological and physical raw data from the PACE trial and contains links to letters/articles written by expert scientists, about the misleading claims made by PACE trial authors.
I have amended my request in response to your claim that it would cost more than 450 pounds to provide the objective data requested in FOI 2017/F158, and hence refusal of the request.
In this amended request, I have reduced or removed, the following items:
(a) the number of time points;
(b)exercise and activity scale data;
(c)physical and physiological data specified in version 7 of the PACE manual, but not directly specified, in the 2007, published protocol
(d) data that separates patients with depressive or psychiatric disorders from those without mental health issues , who "just" have CFS.
(e) VO2 max test results (which you advise were not obtained)
My amended information request is as follows:
i/ Actometer results (BMC reference 18) – raw data actometer, baseline measurements.
ii/ 6 minute walk objective measure of recovery (BMC reference 31).
iii/ Self-paced step. Test of fitness (BMC reference 43), including the Borg test (scale of perceived exertion) and end heart rate.
This information is requested for two of the specified time periods:
iv/ Baseline
v/ Final assessment – 52 week/39 week time point
Yours faithfully,
Kathryn Dickenson”

13 June 2017 - Lodged on the FOI 2017/F158 (a), “What do they know?” thread but actually chasing a response to the request lodged on the FOI 2017/F158(b0 thread.
– KD chased up an acknowledgement that QMUL had received the narrowed request as follows:
“Dear QM FOI Enquiries,
I refer to my amended FOI request in which I significantly reduced the amount of information requested.
I have not received a response.
Is QMUL proceeding with the amended FOI request?
Yours sincerely,
Kathryn Dickenson”

13 June 2017 FOI 2017/F158 (a)– QMUL responded to KD’s chase up of a response to the request actually lodged on the “What do they know?” thread, FOI2017/F158 (b).
“Dear Kathryn Dickenson
We are proceeding with this request now that it has been narrowed. We will be in touch in due course.
Yours sincerely
Queen Mary University of London”

14 June 2017 – KD advises on the original information request thread i.e. FOI 2017/F158(a)
“Dear QM FOI Enquiries,
After I didn't receive a response to my reduced request for information. I submitted a fresh request. In part as it appears quite likely that this FOI could follow the footsteps of Alem Mattews one and end up before the Information Commissioner, in which case it might be clearer to have the request as a "fresh start".
Hence, I refer you to my request entitled:
"CFS - a small % of the objective physical and physiological data from PACE trial
Yours sincerely,
Kathryn Dickenson”
# No further entries are made on the thread 2017/F158(a)

15 June 2017 – KD writes to QMUL to clarify on the thread FOI 2017/F158 (b)
“Dear Queen Mary, University of London,
To clarify this request is a narrowing of FOI 2017/F158, which QMUL refused on the basis that:
i) the PACE trial authors did not obtain the data from all the objective outcome measures specified in the PACE manual (version 7),
ii) it would cost more than 450 pound, to provide a copy of the raw data from the objective outcome measures, that PACE authors did collect.
I have marked FOI 2017/F158, as refused, as per QMUL's advice. I was advised that it was prudent to start afresh, in order to avoid any legal debate about whether a refused request could be subsequently, narrowed and restarted.
Note the reasons for requesting this data (i.e. non vexatious) and links to relevant research and expert comment detailed in FOI 2017/F158, also relate to this narrowed request.
I look forward to your response.
Yours faithfully,
Kathryn Dickenson”

11 July 2017 – KD advises that the response for FOI 2017/F158 (b) is due.
“Dear Queen Mary, University of London,
I am writing to remind QMUL that it has a legal obligation to respond promptly to a request and that a response to this request is due by 11 July 2017, at the latest.
Yours faithfully,
Kathryn Dickenson”
12 July 2017 – KD advises that the response for FOI 2017/F158 (b) is overdue:
“Dear Queen Mary, University of London,
I am writing to remind QMUL that by law, public authorities must respond promptly to requests for information, requested under the FOI Act and that legally you must respond within 20 working days.
Your response to this request is overdue.
Please advise when a response will be forthcoming.
Yours faithfully,
Kathryn Dickenson”

13 July 2017 – KD requests an internal review for FOI 2017/F158 (b), as the due date has past:
“Dear Queen Mary, University of London,
Please pass this on to the person who conducts Freedom of Information reviews.
I am writing to request an internal review of Queen Mary, University of London's handling of my FOI request 'CFS - a small % of the objective physical and physiological data from PACE trial'.
QMUL has not responded to my request for this data that was collected by the PACE trial principal investigators Micheal Sharpe, Peter White and Trudi Chaldler, under the guidance of the principal adviser Simon Wessley. Nor has QMUL responded to my emails chasing up a response.
A full history of my FOI request and all correspondence is available on the Internet at this address: https://www.whatdotheyknow.com/request/c...
Note that this request for a small % of the objective data from the 5 million pound PACE trial, was drafted after my request for all of the objective trail data was refused on the basis of cost.
Yours faithfully,
Kathryn Dickenson”

15 July 2017 – KD details why she needs the objective data, i.e. for a submission regarding the NICE Guidelines on the What do they know thread, FOI 2017/F158 (b)
“Dear Queen Mary, University of London,
I am concerned that your failure to respond this request and to my original request for all the objective physical and physiological data, promptly and within 20 days, is putting the health of CFS patients at risk UK wide.
QMUL must be aware of the dichotomy between UK mental health "experts" proclaiming CFS to be a mental health disease and graded exercise therapy (GET) to be safe and the USA , patients and exercise physiologists who on the basis of objective research findings, patients and patient carers reports have found GET to be extremely harmful.
The USA Centre for Disease Control's is so concerned about the negative impact of GET on the health of patients with CFS (and its lack of effectiveness) that it has removed all reference to GET from its website.
The requested information is required urgently, as the time frame for stakeholders to make a submission substantiating why NICE should overturn its decision not to up date its guideline for CFS is only a few days.
I will bring the fact that QMUL's failure to comply with its legal obligations to respond to requests as required by law has serious health implications for patients and hence tax payers to the attention of the Information Commissioner and hold QMUL responsible for all legal costs associated with this matter.
Yours faithfully,
Kathryn Dickenson”
15 July 2017 -annotation added by KD on FOI 2017/F158(b)
Cognitive behaviour therapy and objective assessments in chronic fatigue syndrome

Graham McPhee

Abstract Most evaluations of cognitive behavioural therapy to treat people with chronic fatigue syndrome/myalgic encephalomyelitis rely exclusively on subjective self-report outcomes to evaluate whether treatment is effective. Few studies have used measures appropriate to assessing whether cognitive behavioural therapy changes in more objective measures. A review of studies incorporating objective measures suggests that there is a lack of evidence that cognitive behavioural therapy produces any improvement in a patient’s physical capabilities or other objective measures such as return to work. Future studies of chronic fatigue syndrome/myalgic encephalomyelitis should include some objective assessments as primary outcomes. If this is to include activity monitors, we first need a sound baseline dataset.
Journal of Health Psychology 1-6
2017
DOI:10.1177/1359105317707215
Journals.sagepub.com/home/hpo

16 July 2017 annotation added
Kathryn Dickenson left an annotation (16 July 2017)
Graham McPhee requested the objective data from PACE via a FOI request, QMUL responded advising that his request was vexatious. QMUL's response to my original request for all the objective data was to say the provision of the data would cost more than 450 pounds.

16 July 2017 -annotation added) on thread FOI 2017/F158(b)
Future studies of chronic fatigue syndrome/myalgic encephalomyelitis should include some objective assessments as primary outcomes. If this is to include activity monitors, we first need a sound baseline dataset.
Journal of Health Psychology 1-6
2017
DOI:10.1177/1359105317707215
Journals.sagepub.com/home/hpo

20 July 2017 – KD chases up a response to her request for an internal review on thread FOI 2017/F158 (b)
“Dear Queen Mary, University of London,
I have referred your no response to this request for Internal Review as you will be aware.
I will lodge a complainant with the Information Commissioner in relation to the failure of QMUL to comply with its legal obligations under the FOI Act, i.e. the requirement to response promptly and within 20 days of the request.
Yours faithfully,
Kathryn Dickenson”

20 July 2017 – QMUL responses to being chased up for a lack of response to the request for an internal review on thread FOI 2017/F158 (b)
“Dear Kathryn Dickenson
We are planning to respond to this request and apologise for the delay.
Yours sincerely
Queen Mary University of London”

21 July 2017 – KD advises QMUL on the FOI 2017/F158 (b) thread as follows:
“Dear Queen Mary, University of London FOI,
I have previously detailed why delays in the provision of the objective raw data from the PACE trial, may adversely affect chronic fatigue syndrome (CFS) patients ie the data is required for a submission to NICE.
The use of graded exercise therapy (GET) and cognitive behavior therapy (CBT) as described in the PACE trial as "treatments" for CFS, have been rejected by the USA Centre for Disease Control (CDC). It is expected that the objective raw data will substantiate the view of the CDC.
The non-release of the objective raw data from the UK tax payer funded the 5 million pound study enables the PACE authors, to continue to peddle their false belief that GET and/or CBT result in improved health in patients with CFS throughout the UK.
QMUL appear to be complicit in perpetuating the PACE authors misleading claims.
Since your apology appears to be merely a delaying tactic, I need to proceed with lodging a complaint to the Information Commissioner.
Yours sincerely,
Kathryn Dickenson”

21 July 2017 annotation added)
Another ‘False Sart’ in ME/CFS Clinical Trials: The GETSET Study by Todd Davenport, Associate Professor and Program Director, Department of Physical Therapy, University of the Pacific.

I am a physical therapist, and movement is my medicine. Some people might need more movement, in the form of an exercise program, while some people might need less movement, in the form of a pacing program.

I rely on scientific studies to help me decide who might benefit from which kind of treatment. Science helps me assign probabilities to outcomes, which I can then use to work with my patients collaboratively to establish the best possible treatment program to help them meet their goals. Reliable data from valid scientific studies can help me be more confident as a clinician that the decisions I make together with my patients actually will help them.

After starting my research career conducting clinical studies related to other fatiguing health conditions, I’ve now worked in the field of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) for over 10 years. During that time, I’ve been fortunate to work with a caring and dedicated group of scientists and advocates.

To say that the body of intervention studies in ME/CFS has involved disappointingly (and sometimes breathtakingly!) poor science is an understatement. The trend of poorly designed intervention studies, most recently headlined by the PACE trial, has just led to reinforcement of erroneous perceptions about ME/CFS without providing the tools necessary for clinicians like me to help ameliorate the devastating impact of ME/CFS on real peoples’ lives. So, it was with great interest that I read the GETSET study, which was recently
published in the Lancet.

All the things that made me uneasy as a physical therapist about the PACE trial are back, now in the form of a study involving a slick self-help guide. It’s the same confirmation bias of telling folks to move in the context of a graded exercise program, and then having them parrot back the study hypothesis on standardized questionnaires. It’s the same absence of objective activity measures that result in the same self-fulfilling prophecy of telling people to move more, and then declaring victory when some of them are actually able to
do it. It’s the same disregard for foundational scientific evidence of aerobic system compromise, immune activation, and other forms of organic pathophysiology in favor of a behavioral approach to ‘tell the tired people to move more.’

http://www.workwellfoundation.org/wp-con...

25 July 2017 – QMUL advises FOI 2017/F158 (b)
“Dear Kathryn Dickenson
Thank you for your email. We have not treated this as a new request but
rather as a narrowing of your request received on 08/05/2017, which was
initially refused on 05/06/2017. I apologise for the slight delay in
responding.
You have requested:
i/ Actometer results (BMC reference 18) – raw data actometer, baseline
measurements.
ii/ 6 minute walk objective measure of recovery (BMC reference 31).
iii/ Self-paced step. Test of fitness (BMC reference 43), including the
Borg test (scale of perceived exertion) and end heart rate.
This information is requested for two of the specified time periods:
- Baseline
- Final assessment – 52 week/39 week time point
The 6 minute walking test measures are attached as these are already in
the public domain.
I am afraid that the rest of your request remains impossible to fulfil
without exceeding the appropriate limit as defined by the Freedom of
Information and Data Protection (Appropriate Limit) Regulations 2004. For
your information this is £450, calculated as the estimated cost of one
person spending 18 hours in determining whether the information is held,
then locating, retrieving and extracting the information. Section 12 of
the Freedom of Information Act 2000 therefore makes provision for public
authorities to refuse such requests. The extraction and analysis required
must be done by a statistician and QMUL does not employ one for PACE.

If you are dissatisfied with this response, you may ask QMUL to conduct a
review of this decision. To do this, please contact the College in
writing (including by fax, letter or email), describe the original
request, explain your grounds for dissatisfaction, and include an address
for correspondence. You have 40 working days from receipt of this
communication to submit a review request. When the review process has
been completed, if you are still dissatisfied, you may ask the Information
Commissioner to intervene. Please see [1]www.ico.org.uk for details.
Yours sincerely
Paul Smallcombe
Records & Information Compliance Manager
References
Visible links
1. http://www.ico.org.uk/”
NOTE: QMUL advised that “ The extraction and analysis required
must be done by a statistician and QMUL does not employ one for PACE.
However, at no time have I requested any analysis to be carried out, I have merely sought raw data. In fact, my request specifically states that “in order to ease the burden of staff and not requiring them to do any calculations themselves once the relevant data is located and retrieved”

25 July 2017 – KD refutes the reasons for refusing the request in the thread FOI 2017/F158 (b)
“Dear QM FOI Enquiries,
My original request, (your reference number FOI 2017/F158) was made on 5 May 2017 - refused on 8 June 2017, due a claim that it would cost more than 450 pounds to provide the information.
On 13 June 2017, I submitted a narrowed request, which I will refer to as FOI 2017/F158 (b) - refused on 25 July 2017, due a claim that it would cost more than 450 pounds to provide the information.
None of the information, that was not already in the public domain, has been provided, nor has QMUL responded promptly to the request/s.
I contend that some of the 5 million pounds of tax payers money, spent on the PACE trial, would have included putting the actometer and the self paced STEP test results into a table.
As illustrated by the table of the 6 minute walking test data, (that QMUL provided as it was already in the public domain), the information requested is not onerous, and is merely the content of two small tables.
I contend that locating, retrieving and extracting the table of results, will not cost more than 450 pounds i.e. take more than 18 hours.
I contend that the claim QMUL by staff that they can not find these tables in less than 18 hours is preposterous.
I contend that a willing person, could find the data in minutes, if not seconds.
I suggest that a search entry such as "Peter White", "PACE trial", "actometer results" "STEP test results" in the QMUL database would quickly locate the data.
I request that QMUL, complies with its legal obligation to the UK tax payers, and promptly provides the following information:
i/ Actometer results (BMC reference 18) – raw data actometer, baseline
measurements.
ii/ Self-paced step. Test of fitness (BMC reference 43), including the
Borg test (scale of perceived exertion) and end heart rate.
This information is requested for two of the specified time periods:
- Baseline
- Final assessment – 52 week/39 week time point
As detailed in previous correspondence, the non-provision of objective data from the PACE trial is harmful to people with chronic fatigue syndrome (CFS) and the release of this data is in the public interest.
Yours sincerely,
Kathryn Dickenson”

27 July 2017 annotation FOI 2017/F158 (b)
No confidence’: Charities reject NICE ‘no update’ proposal for ME/CFS guideline
Support for CBT and GET, the treatments in question, is largely due to the claimed results of the UK PACE Trial. However, 42 experts wrote an open letter accusing the researchers of that trial of bias and misrepresentation.

‘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,’ says the letter published at Virology.

Invest in ME Research also rejects the trial’s claims, saying, ‘The PACE Trial is null science, bad science, discredited science, its worth is only to demonstrate how research should not be conducted.’

After a Freedom of Informational tribunal ruled that the authors of the PACE Trial had to publish their raw data, unusual changes to trial outcome measures were discovered, and the data was reanalysed by a number of different parties. Critics of the PACE Trial and GETSET trial have pointed out that only a small number of patients seem to improve with these treatments, and that a significant number report getting worse, especially after GET.

An open critique of the PACE Trial was also published by Rebecca Goldin, the director of Stats.org and Professor of Mathematical Sciences at George Mason University. Goldin writes, ‘The question of how all this happened and how the criticism is being handled have sent shockwaves through medicine. The results from PACE (including these) have been published in prestigious journals and influenced public health recommendations around the world; and yet, unraveling this design and the characterization of the outcomes of the trial has left many people, including me, unsure this study has any scientific merit. How did the study go unchallenged for five years?’

ME Action wrote, ‘We would like to make clear that our concerns about methodology extend beyond the PACE trial to include the entire body of GET/CBT research, where it relies on the flawed combination of unblinded randomisation and subjective outcomes (Helmfrid, 2016). We ask that such clinical trials be excluded or downgraded.’

http://vadamagazine.com/news/no-confiden...

27 July 2017 KD left a further annotation on the thread FOI 2017/F158 (b)
The NICE guideline for CFS/ME is not fit for purpose and needs a complete revision

“I think that the single most damaging misconception perpetrated on ME patients is
the idea that deconditioning is the problem and that exercise is the antidote.
“I have seen many people now, well-motivated, who have made themselves much
worse with exercise, often on the advice of their GPs who have been gullible enough to
swallow the deconditioning hypothesis.
“I think this needs to be properly emphasised with NICE, otherwise their advice
concerning graded exercise will always be assumed to be "exercise to fitness" which
is always destructive.
“Sadly, the people who get worse with exercise, because they exceed their anaerobic
threshold on multiple occasions with further reduction of the latter, are then assumed
to be imagining their disability and treated accordingly. It would be farcical if it wasn't
so serious.”

27 July 2017 – KD advises QMUL that she will amend the request on the thread FOI 2017/F158 (b), remove the request for the 6 minute walking test information and submot a new information request on a new thread on the website “What do they know?”>
“Dear QM FOI Enquiries,
To avoid future confusion if the case goes to the First Tribunal, I've been advised to mark this request refused as per the advice from QMUL and submit an amended request, without the request for the 6 minute walking test as that information is in the public domain.
Yours sincerely,
Kathryn Dickenson
Linked to:
FOI 2017/F158
Links to previous requests, annotations and history:
https://www.whatdotheyknow.com/request/c...
https://www.whatdotheyknow.com/request/c...
30 July 2017 A Baldwin left an annotation on the thread FOI 2017/F158 (c)
In a response to Anna Wood's FoI concerning the mean 6mwt distances for people who they claimed were recovered QMUL claimed that it would take them over 18 hours to calculate.

After the release of data for Mr Matthees's FoI it tool me about an hour to calculate these values. Most of that time was taken working out how they had changed the Oxford definition within the recovery paper to include additional thresholds.

27 July 2017 KD lodged a new and narrowed information request via the website, What do they know and gave it the reference number FOI 2017/F158 (c)
The new request is entitled:
CFS - a small % of the objective physical and physiological data from PACE trial (6 minute walk test already in public domain) https://www.whatdotheyknow.com/request/c...
“I refer to:
1/ My original request: (your reference number FOI 2017/F158) which was made on 5 May 2017 and refused on 8 June 2017, due a claim that it would cost more than 450 pounds to provide the information.
2/ My second request for small % of the information: (my reference FOI 2017/F158 (b)) made on 13 June 2017 and refused on 25 July 2017, due a claim that it would cost more than 450 pounds to provide the information.
3/ This third request: (my reference FOI 2017/F158 (c)), it is largely the same as request 2/ however I am not requesting the 6 minute walk test results, as these results are in the public domain.
I request that QMUL, complies with its legal and moral obligation to UK tax payers and CFS patients, and promptly provides the following information from the PACE trial:

27 July 2017 annotation FOI 2017/F158 (c)
THE PACE TRIAL: THE MAKINGS OF A MEDICAL SCANDAL

Special issue on the PACE trial, Vol 22, No 9, Aug 2017.
Publication date 31 July 2017
http://journals.sagepub.com/toc/hpqa/cur...
28 July 2017 annotation FOI 2017/F158 (c)
PACE-gate Papers

http://journals.sagepub.com/action/doSea...
29 July 2017.. KD advises FOI 2017/F158 (c)
“I am writing to put on record the small size of the file/s containing the objective actometer and STEP test results from the PACE trial as detailed in requests FOI 2017/F158, FOI 2017/F158 (b) and FOI 2017/F158 (c).
Depending on how the data has been tabulated there may be 1-4 tables of data.
It is estimated that these files will be less than 20 Kb in size each and hence easily copied and transposed digitally.
The size of the data files is estimated, based on the fact that the table for the PACE trial 6 minute walking test data, is is 1.7 kB in size.
The information is likely to be stored, in files near the PACE trial 6 minute walking test data and easy to locate.
The claim made in response to FOI 2017/158 (b) that it would take more than 18 hours to locate and provide copies of this information is rejected.
For clarity I have resubmitted this request, with the request for the 6 minute walking test data deleted, since this data is in the public domain.
I refer this narrowed request as FOI 2017/158 (c).
It is nearly 3 months since my request for objective information from the 5 million pound, PACE trial, was first made.”
31 July 2017 annotation FOI 2017/F158 (c)
PACE-gate

Last ditch attempt to block publication of special issue of Journal of Health Psychology foiled

by James C Coyne July 30, 2017

Publication of the special issue of Journal of Health Psychology will go forward as planned on Monday July 31.
31 July 2017 annotation FOI 2017/F158 (c)
Journal of Health Psychology

David F Marks First Published July 31, 2017 Editorial

Download PDFPDF download for Special issue on the PACE Trial Article information

Abstract
We are proud that this issue marks a special contribution by the Journal of Health Psychology to the literature concerning interventions to manage adaptation to chronic health problems. The PACE Trial debate reveals deeply embedded differences between critics and investigators. It reveals an unwillingness of the co-principal investigators of the PACE trial to engage in authentic discussion and debate. It leads one to question the wisdom of such a large investment from the public purse (£5million) on what is a textbook example of a poorly done trial.
31 July 2017 annotation FOI 2017/F158 (c)
https://jcoynester.wordpress.com/2017/08...

QUICK THOUGHTS
One of James C. Coyne's Blogs

The unfolding story of removal of data from a PLOS One article
31 July 2017 - KD advises FOI 2017/F158 (c)
“Please advise if QMUL intends to respond to this request and if so by what date.
As per the previous FOI requests, I am adding comments on and publications relating to the PACE-gate trial, in the annotations section of my request.
When adding an annotation to this request, I noticed a typo...the size of the file containing the 6 minute walk test data is actually 17 kB.”
1 August 2017 FOI 2017/F158 (c)

Scientists trade insults over myalgic encephalomyelitis (ME) study

1 August 2017 – KD advises on the FOI 2017/F158 (b) thread that I am not sure of the most appropriate way forward, in order to minimise confusion, with different threads in existence:
“Dear QM FOI Enquiries,
I am not sure which is the most appropriate way forward with this request and have submitted a narrowed request given that some of the 6 minute walking test data is in the public domain. I am also detailing the need for an internal review here.
The claim by QMUL that it would take more than 18 hours and cost more than 450 pounds to provide the information requested in FOI 2017/F158 (b), is at odds with reality.
The volume of information requested is less than one gigabyte and is most likely located in a file adjacent or near the 6 minute walking trial data.
My interest in the objective data, is because patients are using bio feed back such as continuous heart rate monitoring, and following the Workwell video's to improve their quality of life.
I want to see how the PACE trial objective outcomes compare to the scientific and physiologically based methods being used successfully by patients worldwide.
The PACE trial for all its flaws and faults did collect some objective data from 640 patients with CFS. This data does not appear to be being collected by NHS clinics hence is not able to be obtained elsewhere.
The 6 minute walking test data showed that after a year of the PACE GET, the patients could walk on average an extra 30 metres, this result appears to be significantly less than the results being obtained by individualised, physiologically based programs.
It is not onerous for QMUL to produce the requested data , it might take a couple of minutes to locate the file and a couple more minutes to upload the data to this website.
It is in the tax payers and patients interests to facilitate open and honesty in scientific research and to cease protecting those whose agenda is at odds with scientific progress, regardless of the human cost of their false belief systems.
Yours sincerely,
Kathryn Dickenson”

10 August 2017 – KD chases up a response to her information request. The chase up is lodged on the thread FOI 2017/F158 (b) but it should. have been lodged on the thread FOI 2017/F185 (c)
“Dear QM FOI Enquiries,
The Information Commisioner's office advises that it is reasonable to expect a response to a request for an internal review within 20 days of the request being made.
It is now over 3 months since I first lodged a request for the release of objective data from the PACE trial with QMUL.
It is nearly 2 months since I lodged this narrowed request with QMUL.
Does QMUL intend to respond to this request for an internal review? If so when? If not why not?
Yours sincerely,
Kathryn Dickenson”

7 August 2017 KD submitted a further narrowing of the information request via the website What do they know? This request was referred to by KD as FOI 2017/F158 (d), however subsequently QMUL gave it a unique reference number i.e. FOI 2017/F255
Entitled: CFS- a request for even less objective info from the PACE trial just the STEP test results at baseline and 52 weeks
Link to the website: https://www.whatdotheyknow.com/request/c...
“ Dear Queen Mary, University of London,
I have narrowed my request further, I am only requesting the:
i/ Self-paced step. Test of fitness (BMC reference 43), including the
Borg test (scale of perceived exertion) and end heart rate.
This information is requested for two of the specified time periods:
- Baseline
- Final assessment – 52 week/39 week time point
The amount of data I have requested is tiny and is likely to be less than 200 Kb in size.
In support of this request refer to:
1/ My original request: (your reference number FOI 2017/F158) which was made on 5 May 2017 and refused on 8 June 2017, due a claim that it would cost more than 450 pounds to provide the information.
2/ My second request for small % of the information: (my reference FOI 2017/F158 (b)) made on 13 June 2017 and refused on 25 July 2017, due a claim that it would cost more than 450 pounds to provide the information.
3/ My third request: (my reference FOI 2017/F158 (c)), made on 27 July 2017, is largely the same as FOI 2017/F158 (b) however I excluded the 6 minute walk test results, as these results are in the public domain. I've not received a response to this request.
4/ This is my fourth request: (my reference FOI 2017/F158 (d). I have removed the request for the actometer data. This data is of limited use. QMUL only measured the physical activity of the trial participants at baseline and not, as is normal scientific practice, also at the end of the trial. From memory, the reason given by Peter White, Trudi Chaldler, Micheal Sharpe and Simon Wessley, for this omission is that it was too onerous, for the trial participants, to wear a 28g actometer for a week, post "treatment". This claim is at odds with the fact that the participants, were healthy enough to wear a 28g actometer for a week pre-"treatment". This claim is also at odds with the fact that surveyed patients have stated that GET (74%) and CBT (14%) made them sicker, some severely, yet none appear to have ever stated that the wearing of a 28g actometer, adversely affects their health.”…
…”The provision of the data requested will help patients who are using heart rate based monitoring to pace effectively, as touched on in the NICE Guidelines. Given the lack of guidance in UK literature many patients are relying on the work of USA exercise physiologists such as Prof. Mark Van Ness, Todd Davenport, Staci Stevens (Workwell Foundation and associated Universities) to manage their activity levels, and to ensure that they rest adequately. Many patients struggle with staying below 50% of their age predicted maximum heart rate, doing their activities of daily living e.g. rolling over in bed, walking to the toilet, dressing etc...but are improving by ensuring that they spend most of their day in the "resting heart rate zone".
For these patients the provision of the objective data will enable them to compare their progress from following USA protocols, with the treatment regimes carried out by the 4 arms of the PACE trial.
Yours faithfully,
Kathryn Dickenson
FOI 2017/F158
Links to previous requests, annotations and history:
https://www.whatdotheyknow.com/request/c...
https://www.whatdotheyknow.com/request/c...
https://www.whatdotheyknow.com/request/c...

8 August 2017 KD left an annontation on the FOI 2017/F255 thread

Trial by Error: Retired PACE Investigator Peter White and Swiss Re
7 AUGUST 2017
By David Tuller, DrPH

On November 17, 2015, a few weeks after publication of my 15,000-word investigation of the PACE trial, I posted a blog about a talk Peter White gave to Swiss Re employees on the findings from his bogus study. Professor White, of course, was the lead PACE investigator and also served–and apparently still serves–as “chief medical officer” for the insurance company.

Swiss Re has released information about its 2017 “insurance medicine summit,” to be held this coming November. Not surprisingly, Professor White is on the schedule. Although he has retired from his academic position, he apparently continues his work promoting his egregious research to insurers. His talk is called “Burn out, vital exhaustion and chronic fatigue syndrome: Old wine in new bottles?” Presumably he will once more be discussing the false PACE trial results and perhaps the campaign of “harassment” that he claims angry patients have waged against him.

It cannot be repeated often enough that the tribunal decision from last summer, which ordered the release of the raw trial data, dismissed the claims of harassment as baseless. The tribunal found that the only credible evidence of such behavior was that Professor Trudie Chalder was once heckled during a lecture. However, the tribunal’s scathing decision hasn’t prevented these dishonest researchers from continuing their disinformation campaign against the patient community.

Given Professor White’s ongoing role with the Swiss Re, I decided to repost the 2015 blog below. Shortly after I initially posted the blog, the insurance company removed from its website the article touting Professor White’s presentation. Therefore, in this version, I am linking instead to a screen-shot of the “disappeared” page. (Thanks, Anil van der Zee!)

**********

Trial by Error, Continued: PACE Team’s Work for Insurance Companies Is “Not Related” to PACE. Really?

By David Tuller, DrPH

In my initial story on Virology Blog, I charged the PACE investigators with violating the Declaration of Helsinki, developed in the 1950s by the World Medical Association to protect human research subjects. The declaration mandates that scientists disclose “institutional affiliations” and “any possible conflicts of interest” to prospective trial participants as part of the process of obtaining informed consent.

The investigators promised in their protocol to adhere to this foundational human rights document, among other ethical codes. Despite this promise, they did not tell prospective participants about their financial and consulting links with insurance companies, including those in the disability sector. That ethical breach raises serious concerns about whether the “informed consent” they obtained from all 641 of their trial participants was truly “informed,” and therefore legitimate.

The PACE investigators do not agree that the lack of disclosure is an ethical breach. In their response to my Virology Blog story, they did not even mention the Declaration of Helsinki or explain why they violated it in seeking informed consent. Instead, they defended their actions by noting that they had disclosed their financial and consulting links in the published articles, and had informed participants about who funded the research–responses that did not address the central concern.

“I find their statement that they disclosed to The Lancet but not to potential subjects bemusing,” said Jon Merz, a professor of medical ethics at the University of Pennsylvania. “The issue is coming clean to all who would rely on their objectivity and fairness in conducting their science. Disclosure is the least we require of scientists, as it puts those who should be able to trust them on notice that they may be serving two masters.”

In their Virology Blog response, the PACE team also stated that no insurance companies were involved in the research, that only three of the 19 investigators “have done consultancy work at various times for insurance companies,” and that this work “was not related to the research.” The first statement was true, but direct involvement in a study is of course only one possible form of conflict of interest. The second statement was false. According to the PACE team’s conflict of interest disclosures in The Lancet, the actual number of researchers with insurance industry ties was four—along with the three principal investigators, physiotherapist Jessica Bavington acknowledged such links.

But here, I’ll focus on the third claim–that their consulting work “was not related to the research.” In particular, I’ll examine an online article posted by Swiss Re, a large reinsurance company. The article describes a “web-based discussion group” held with Peter White, the lead PACE investigator, and reveals some of the claims-assessing recommendations arising from that presentation. White included consulting work with Swiss Re in his Lancet disclosure.

The Lancet published the PACE results in February, 2011; the undated Swiss Re article was published sometime within the following year or so. The headline: “Managing claims for chronic fatigue the active way.” (Note that this headline uses “chronic fatigue” rather than “chronic fatigue syndrome,” although chronic fatigue is a symptom common to many illnesses and is quite distinct from the disease known as chronic fatigue syndrome. Understanding the difference between the two would likely be helpful in making decisions about insurance claims.)

The Swiss Re article noted that the illness “can be an emotive subject” and then focused on the implications of the PACE study for assessing insurance claims. It started with a summary account of the findings from the study, reporting that the “active rehabilitation” arms of cognitive behavioral therapy and graded exercise therapy “resulted in greater reduction of patients’ fatigue and larger improvement in physical functioning” than either adaptive pacing therapy or specialist medical care, the baseline condition. (The three intervention arms also received specialist medical care.)

The trial’s “key message,” declared the article, was that “pushing the limits in a therapeutic setting using well described treatment modalities is more effective in alleviating fatigue and dysfunction than staying within the limits imposed by the illness traditionally advocated by ‘pacing.’”

Added the article: “If a CFS patient does not gradually increase their activity, supported by an appropriate therapist, then their recovery will be slower. This seems a simple message but it is an important one as many believe that ‘pacing’ is the most beneficial treatment.”

This understanding of the PACE research—presumably based on information from Peter White’s web-based discussion—was wrong. Pacing is not and has never been a “treatment.” It is also not one of the “four most commonly used therapies,” as the newsletter article declared, since it has never been a “therapy” either. It is a self-help method practiced by many patients seeking the best way to manage their limited energy reserves.

The PACE investigators did not test pacing. Instead, the intervention they dubbed “adaptive pacing therapy” was an operationalized version of “pacing” developed specifically for the study. Many patients objected to the trial’s form of pacing as overly prescriptive, demanding and unlike the version they practiced on their own. Transforming an intuitive, self-directed approach into a “treatment” administered by a “therapist” was not a true test of whether the self-help approach is effective, they argued–with significant justification. Yet the Swiss Re article presented “adaptive pacing therapy” as if it were identical to “pacing.”

The Swiss Re article did not mention that the reported improvements from “active rehabilitation” were based on subjective outcomes and were not supported by the study’s objective data. Nor did it report any of the major flaws of the PACE study or offer any reasons to doubt the integrity of the findings.

The article next asked, “What can insurers and reinsurers do to assist the recovery and return to work of CFS claimants?” It then described the conclusions to be drawn from the discussion with White about the PACE trial—the “key takeaways for claims management.”

First, Swiss Re advised its employees, question the diagnosis, because “misdiagnosis is not uncommon.”

The second point was this: “It is likely that input will be required to change a claimant’s beliefs about his or her condition and the effectiveness of active rehabilitation…Funding for these CFS treatments is not expensive (in the UK, around £2,000) so insurers may well want to consider funding this for the right claimants.”

Translation: Patients who believe they have a medical disease are wrong, and they need to be persuaded that they are wrong and that they can get better with therapy. Insurers can avoid large payouts by covering the minimal costs of these treatments for patients vulnerable to such persuasion, given the right “input.”

Finally, the article warned that private therapists might not provide the kinds of “input” required to convince patients they were wrong. Instead of appropriately “active” approaches like cognitive behavior therapy and graded exercise therapy, these therapists might instead pursue treatments that could reinforce claimants’ misguided beliefs about being seriously ill, the article suggested.

“Check that private practitioners are delivering active rehabilitation therapies, such as those described in this article, as opposed to sick role adaptation,” the Swiss RE article advised. (The PACE investigators, drawing on the concept known as “the sick role” in medical sociology, have long expressed concern that advocacy groups enabled patients’ condition by bolstering their conviction that they suffered from a “medical disease,” as Michael Sharpe, another key PACE investigator, noted in a 2002 UNUMProvident report. This conviction encouraged patients to demand social benefits and health care resources rather than focus on improving through therapy, Sharpe wrote.)

Lastly, the Swiss Re article addressed “a final point specific to claims assessment.” A diagnosis of chronic fatigue syndrome, stated the article, provided an opportunity in some cases to apply a mental health exclusion, depending upon the wording of the policy. In contrast, a diagnosis of myalgic encephalomyelitis did not.

The World Health Organization’s International Classification for Diseases, or ICD, which clinicians and insurance companies use for coding purposes, categorizes myalgic encephalomyelitis as a neurological disorder that is synonymous with the terms “post-viral fatigue syndrome” and “chronic fatigue syndrome.” But the Swiss Re article stated that, according to the ICD, “chronic fatigue syndrome” can also “alternatively be defined as neurasthenia which is in the mental health chapter.”

The PACE investigators have repeatedly advanced this questionable idea. In the ICD’s mental health section, neurasthenia is defined as “a mental disorder characterized by chronic fatigue and concomitant physiologic symptoms,” but there is no mention of “chronic fatigue syndrome” as a discrete entity. The PACE investigators (and Swiss Re newsletter writers) believe that the neurasthenia entry encompasses the illness known as “chronic fatigue syndrome,” not just the common symptom of “chronic fatigue.”

This interpretation, however, appears to be at odds with an ICD rule that illnesses cannot be listed in two separate places—a rule confirmed in an e-mail from a WHO official to an advocate who had questioned the PACE investigators’ argument. “It is not permitted for the same condition to be classified to more than one rubric as this would mean that the individual categories and subcategories were no longer mutually exclusive,” wrote the official to Margaret Weston, the pseudonym for a longtime clinical manager in the U.K. National Health Service.

Presumably, after White disseminated the good news about the PACE results at the web-based discussion, Swiss Re’s claims managers felt better equipped to help ME/CFS claimants. And presumably that help included coverage for cognitive behavior therapy and graded exercise therapy so that claimants could receive the critical “input” they needed in order to recognize and accept that they didn’t have a medical disease after all.

In sum, contrary to the investigators’ argument in their response to Virology Blog, the PACE research and findings appear to be very much “related to” insurance industry consulting work. The claim that these relationships did not represent “possible conflicts of interest” and “institutional affiliations” requiring disclosure under the Declaration of Helsinki cannot be taken seriously.

Update 11/17/15 12:22 PM: I should have mentioned in the story that, in the PACE trial, participants in the cognitive behavior therapy and graded exercise therapy arms were no more likely to have increased their hours of employment than those in the other arms. In other words, there was no evidence for the claims presented in the Swiss Re article, based on Peter White’s presentation, that these treatments were any more effective in getting people back to work.

The PACE investigators published this employment data in a 2012 paper in PLoS One. It is unclear whether Peter White already knew these results at the time of his Swiss Re presentation on the PACE results.

Update 11/18/15 6:54 AM: I also forgot to mention in the story that the three principal PACE investigators did not respond to an e-mail seeking comment about their insurance industry work. Lancet editor Richard Horton also did not respond to an e-mail seeking comment.
11 August 2017 KD requests an internal review of the request on the FOI 2017/F158 (b) thread.
“Dear Queen Mary, University of London,
Please pass this on to the person who conducts Freedom of Information reviews.
I refer to my request an internal review of Queen Mary, University of London's handling of my FOI request 'CFS - a small % of the objective physical and physiological data from PACE trial' , submitted 13 June 2017.
I refer QMUL to the What do you know website:
"Internal reviews should be quick. If one takes longer than 20 working days then the authority should write and let you know, and it should never take longer than 40 working days (see this good practice guide). You will then either get the information that you originally requested, or you will be told that the review upholds the original decision."
A full history of my FOI request and all correspondence is available on the Internet at this address: https://www.whatdotheyknow.com/request/c...
Yours faithfully,
Kathryn Dickenson”
11 August 2017 KD left an annotation on the FOI 2017/F158 (b) thread
Kathryn Dickenson left an annotation (11 August 2017)
PACE authors are not the only ones who drop objective measures of the trial participants physical functioning ( actometer /actigraph results). The PACE authors colleagues in the Netherlands did the same and this paper details how subjective results are over inflated and no borne out by the objective findings.

http://www.mdpi.com/2076-328X/7/3/52/htm
Open Access
Behavioral Sciences 2017, 7(3), 52; doi: 10.3390/bs7030052
Review
FITNET’s Internet-Based Cognitive Behavioural Therapy Is Ineffective and May Impede Natural Recovery in Adolescents with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. A Review
Simin Ghatineh 1 and Mark Vink 2,*
1 Biochemist, London TW11, UK
2 Soerabaja Research Center, 1096 HH Amsterdam, The Netherlands
* Correspondence:
Received: 6 April 2017 / Accepted: 2 August 2017 / Published: 11 August 2017
Abstract: The Dutch Fatigue In Teenagers on the interNET (FITNET) study claimed that after 6 months, internet based cognitive behaviour therapy in adolescents with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), led to a 63% recovery rate compared to 8% after usual care, and that this was maintained at long term follow up (LTFU). Our reanalysis shows that their post-hoc definition of recovery included the severely ill, the unblinded trial had no adequate control group and it used lax selection criteria as well as outcomes assessed via questionnaires rather than objective outcomes, further contributing to exaggerated recovery figures. Their decision not to publish the actometer results might suggest that these did not back their recovery claims. Despite these bias creating methodological faults, the trial still found no significant difference in recovery rates (“~60%”) at LTFU, the trial’s primary goal. This is similar to or worse than the documented 54–94% spontaneous recovery rates within 3–4 years, suggesting that both FITNET and usual care (consisting of cognitive behaviour and graded exercise therapies) are ineffective and might even impede natural recovery in adolescents with ME/CFS. This has implications for the upcoming costly NHS FITNET trial which is a blueprint of the Dutch study, exposing it to similar biases.

15 August 2017 – QMUL requests clarification on the FOI 2017/F158 (b) thread
“Dear Kathryn Dickenson
Please clarify that you wish QMUL to carry out an internal review of this request despite the fact that you have subsequently submitted a new request, which narrows the original.
We have presumed that the latter request superseded this one, with the effect that this one has been withdrawn.
Yours sincerely
Paul Smallcombe
Queen Mary University of London”

15 August 2017 – KD advises on the FOI 2017/F158 (b) thread
“Dear Queen Mary, University of London FOI,
I apologise for any confusion, I would like all the information requested.
The reason that, I narrowed the request was to obtain at least some of the information, within a reasonable time frame.
To date, I have not received any information.
We are talking about a few tiny tables of data of only a few hundred kilobytes.
Yours sincerely,
Kathryn Dickenson”

15 August 2017 KD left an annotation on the FOI 2017/F255 thread.
“Dr Naviaux, during Open Medicine Foundation ME/CFS symposium Q&A:
"We consider autism and MECFS as part of the same biologic and physiologic spectrum. The things that differ are the fact that in one case, autism, the triggers were encountered - and may in fact be genetic - early in life in critical neuro-development. Then in MECFS the triggers are encountered later in life and lead to this outcomes of this syndrome, Many of the same genetic predispositions, the genes that come up, predispose to autism and to MECFS. The other interesting thing is that it's a common observation in autism but not made enough of yet in patients with MECFS, but I find it to be true, is that the people who are affected are among our generations best and brightest. These are individuals who are born with unique gifts - the ability to sense the world in novel ways, that we "normal" human beings are not able to. To sense subtle differences in the social network and groups of people that children with autism as well as children and adults with MECFS can sense. The ability to actually see colour more vividly, to smell things more vividly, to taste more vividly. You know these are actually created by cellular differences that create unique vulnerabilities, and those vulnerabilities then lead to this sequence of pathogenesis that we now call ME/CFS. "

16 August 2017 – QMUL advises as follows on the FOI 2017/F158 (b) thread
“FOI 2017/F248

Dear Kathryn Dickenson

Thank you for your reply. It is not altogether clear when overlapping
requests are received before we have had an opportunity to respond.

Given your reply, please confirm that you wish to withdraw the request
made in your email of 7^th August at 1.30a.m. Or do you wish us to refuse
that under s.14(2) of the Freedom of Information Act 2000, since it
repeats in part what you have requested in the present request, in order
to close that one? We have received at least 16 emails from you since May
and in some cases you have requested internal reviews only to put in a
narrowed request, or before the time for compliance has been reached. We
currently have two open requests from you: this one due on 25^th August
and the one of 7^th of this month due on 5^th September.

Please clarify that by 'all the information requested' you are referring
to your email of 27^th July, which QMUL has assigned the reference above,
if you wish for us to deal with this one.

Yours sincerely

Paul Smallcombe”

16 August 2017 – KD advises on the FOI 2017/F158 (b) thread
“Dear QM FOI Enquiries,
I request all the information that I have asked for. I apologise for the confusion, I am profoundly ill with ME/CFS and have the physical and physiological abnormalities detailed, in the International Consensus Criteria 2011 and the Canadian Consensus Criteria 2003, this adversely impacts on my cognition, especially after exertion.
In my opinion instead of prevaricating and debating the semantics of my request, if QMUL was acting in good faith. you would take a few minutes, to upload the requested information, to this website.
It would be much appreciated if the broadest list of information was provided.
Yours sincerely,
Kathryn Dickenson”

17 August 2017 – QMUL (on the thread that KD allocated the QMUL reference number FOI 2017/F158 (d)) advises that in its records this thread has the reference number FOI 2017/F255 i.e. unlike previous narrowing of the FOI request in which QMUL kept the same reference number.
“FOI 2017/F255

Thank you for your email of 7th August where you requested:
‘Self-paced step. Test of fitness (BMC reference 43), including the Borg
test (scale of perceived exertion) and end heart rate.

This information is requested for two of the specified time periods:
- Baseline
- Final assessment – 52 week/39 week time point’

As per the correspondence here:
[1]https://www.whatdotheyknow.com/request/c...,
for the sake of completeness this request is refused under s.14(2) of the
Freedom of Information Act 2000 as it is a repeat of part of the request
made on 27th July, found at the previous link.

Please accept this as a refusal notice.”
18 August 2017- KD seeks an internal review of the decision to refuse FOI 2017/F255 as detailed on the FOI 2017/F255 thread:
“Dear Queen Mary, University of London,
Please pass this on to the person who conducts Freedom of Information reviews.
I am writing to request an internal review of Queen Mary, University of London's handling of my FOI request 'CFS- a request for even less objective info from the PACE trial just the STEP test results at baseline and 52 weeks'.
I request a review of the decision, to refuse the release of the information request.
I agree that the request is a narrowing down of the information sought in the previous request.
QMUL refused to release the accelerometer and STEP test results, on the basis that the 2 pages of data sought were too onerous and would take more than 18 hours to find, locate and upload to this website.
I narrowed the request to just the STEP test results as any objective data would be better than none. To date the only objective data released by QMUL is the 6 minute walking data and 28% of the final test results are missing.
I put it to QMUL that given the misleading claims made by PACE authors, the flaws and faults in the trial that they have refused to address in any meaningful manner that it is negligent to continue to hide objective data, from the UK tax payer, independent researchers and patients.
A full history of my FOI request and all correspondence is available on the Internet at this address: https://www.whatdotheyknow.com/request/c...
I trust that QMUL will comply with its legal obligation to respond promptly and provide the 2 pages of data sought (estimated).”
18 August 2017 Kathryn Dickenson left an annotation PACE update
http://www.virology.ws/2017/08/14/trial-...

Trial by Error: My E-Mail Exchange With NICE Chief Executive
14 AUGUST 2017
By David Tuller, DrPH

On Friday, I had an e-mail exchange with Sir Andrew Dillon, chief executive of the NICE Guidance Executive. The other seven Guidance Executive members are various directors within the NICE hierarchy, including the communications director. This group will make the final decision about whether to accept the provisional decision of a NICE surveillance review team to leave as is CG53, the guidance for CFS/ME released in 2007. (I have written about the NICE review process on CG53 here, here and here.)

That ten-year-old CFS/ME guidance recommends treatment with graded exercise therapy and cognitive behavior therapy. NICE reaffirmed the guidance after the 2011 publication of the first PACE results, which were taken as evidence that these treatments were effective. As part of the current review process, NICE provided stakeholders with a two-week window last month to submit comments about the provisional decision not to change CG53. Not surprisingly, this recommendation has alarmed many patients and advocates.

I didn’t expect to get answers to my questions from the Guidance Executive, but I felt an obligation to pose them anyway, given the importance of the issues. In fact, Sir Andrew responded to my e-mail within an hour. He explained that no comments would be forthcoming while the Guidance Executive was reviewing the situation. I have posted his response below my initial e-mail.

**********

Sir Andrew Dillon
Chief Executive
National Institute for Health and Care Excellence

Dear Sir Andrew:

I am a journalist and public health researcher at the University of California, Berkeley. I have reported on the current review of CG53, the NICE guidance for CFS/ME, for the science site Virology Blog, which is hosted by Professor Vincent Racaniello, a microbiologist at Columbia University. I have previously reported for Virology Blog on the PACE trial and other issues related to graded exercise therapy and cognitive behavior therapy. Earlier this year, I co-authored a commentary about the serious problems with PACE for the Sunday opinion section of The New York Times.

In my role as a journalist covering this issue, I have some questions for you and the other members of the NICE Guidance Executive about the decision-making process concerning the provisional recommendation to make no changes to CG53:

1) For many years, the U.S. Centers for Disease Control recommended GET and CBT as treatments, citing PACE. In late June or early July, the agency removed all references to these therapies from its main pages on the illness. Does the Guidance Executive plan to consult with American public health officials about what prompted this major “dis-endorsement” of these two therapies that NICE continues to promote?

2) In 2015, both the U.S. National Institutes of Health and the Institute of Medicine (now the National Academy of Medicine) released reports on the illness (they call it ME/CFS). These reports both concluded that it is a serious organic disease involving pathophysiological processes and not a psychological or psychiatric disorder—a determination that would have significant impact on treatment options. Does the Guidance Executive plan to consider these two reports and consult with any of the members of the panels that wrote them?

3) Other fields of medicine have abandoned the use of the trial design favored in this entire body of research, including PACE: open-label studies with subjective outcomes. That’s because other fields of medicine recognize that the combination of those two features in one study inherently produces bias. Does the Guidance Executive share these concerns about results from open-label studies with subjective outcomes, or does it believe that such studies can produce reliable and unbiased evidence suitable for clinical decision-making?

4) In PACE and other studies from this field, objective measures have largely failed to support the subjective results that have generated claims of “recovery” or significant clinical improvement. Does this pattern of sharp contradiction between objective and subjective results raise questions for the Guidance Executive about whether patients are objectively getting better?

5) In the 2011 Lancet paper, 13 % of the PACE participants had already met one of the study’s outcome thresholds at trial entry—that is, although assessed as “disabled” enough in physical function to qualify for the study, they were also found to be “within normal range” for physical function, before any treatment at all. In the 2013 Psychological Medicine paper, the same 13 % were already “recovered” for physical function at baseline, before any treatment at all—that is, they were simultaneously “disabled” for physical function and “recovered” for physical function. These facts were not included in the published papers but emerged later through a patient’s freedom-of-information request. Does the Guidance Executive have confidence in the reported results of a study in which a significant minority of participants have already met a key outcome threshold at baseline? If so, can the Guidance Executive point to other studies in the clinical trial literature in which a significant number of participants have already met a key outcome threshold at baseline? Does the Guidance Executive believe that the published PACE papers should have mentioned the fact that a signifiant minority of participants had already met a key outcome threshold at baseline?

6) In February 2016, forty-two leading scientists and clinicians signed an open letter to The Lancet in which they outlined the methodological lapses of the PACE trial, stated unequivocally that “such flaws have no place in published research,” and demanded an independent investigation. In March 2017, more than 100 experts signed an open letter to Psychological Medicine, asking the journal to retract immediately its core finding that GET and CBT helped patients “recover.” Does the Guidance Executive plan to review these open letters and consult with any of the signatories–from Columbia, University College London, Harvard, Stanford, Berkeley, etc.—about their reasons for publicly dismissing the PACE findings as invalid?

7) Both GET and CBT, as described in PACE and other studies from this field of research, involve telling participants that the treatments can reverse the illness and return them to a state of health. Is the Guidance Executive concerned that telling study participants repeatedly about the effectiveness of the treatments could bias their responses, augmenting any bias already inherent in open-label studies with subjective outcomes?

8) Some defenders of PACE note that CBT is also recommended for patients with cancer and other chronic diseases. But the approach advocated in PACE and related studies is not the kind of CBT focused on helping patients adapt to the reality of their illness. Rather, this form of CBT is specifically designed to alleviate patients of their purportedly “unhelpful” beliefs of having an ongoing medical disease that can be exacerbated by activity and exercise. Is the Guidance Executive aware of this critical distinction between CBT as normally administered in the case of other chronic illnesses and the adapted form of CBT investigated in PACE and other studies in this field?

9) The PACE trial used the Oxford criteria to identify participants. This case definition requires only six months of unexplained fatigue, so its use could result in the selection of participants with depression or other unidentified fatiguing illnesses. Some of these other illnesses might resolve spontaneously or respond to behavioral and psychological interventions like GET and CBT. In fact, the NIH report noted that using the broad Oxford case definition could “impair progress and cause harm,” and recommended that it be “retired.” Is the Guidance Executive concerned that populations derived using the Oxford criteria might contain many participants experiencing prolonged fatigue for a range of reasons unrelated to the illness being investigated? Is the Guidance Executive concerned that such heterogeneity in study samples could lead to erroneous findings about treatments?

10) The U.S. Agency for Healthcare Research and Quality found evidence to support GET and CBT for ME/CFS in its review of multiple studies. However, when the agency subsequently removed Oxford criteria studies from this analysis, it found no evidence that GET provided any benefits and almost no evidence that CBT provided benefits. Is the Guidance Executive considering this AHRQ re-analysis in its decision-making? Does the Guidance Executive plan to consult with officials at the agency to discuss why they conducted this re-analysis and how it subsequently led them to downgrade their assessments of the therapies?

11) The surveillance review team cites Cochrane reviews of GET and CBT to support the recommendation to leave the 2007 guidance as is. Many of the trials included in these Cochrane reviews rely on a broad case definition like the Oxford criteria. Is the Guidance Executive comfortable relying on Cochrane reviews for confirmation of controversial findings when the reviews themselves include the studies that feature the methodological problems being questioned? Will the Guidance Executive consider asking Cochrane to follow the lead of American public health officials and conduct a re-analysis of its GET and CBT reviews with Oxford criteria studies removed from the sample?

12) In the PACE trial protocol, the investigators promised to follow the Declaration of Helsinki, which requires researchers to tell prospective participants about “any possible conflicts of interest.” The three main PACE investigators have had longstanding relationships with insurance companies, advising them to offer GET and CBT to claimants diagnosed with the illness. Yet the investigators did not tell prospective PACE participants about these extensive consulting and financial links with insurance companies or include the information in consent forms. Is the Guidance Executive concerned that this clear violation of the investigators’ protocol promise to disclose “any possible conflicts of interest” to prospective participants means that they did not obtain properly “informed” consent? Does the Guidance Executive believe it should base clinical guidelines on studies that have not obtained properly “informed” consent?

13) More than 15,000 people signed the ME Association’s online petition outlining their concerns with the 2007 guidance and their objection to the provisional decision to leave it unchanged. Is it unusual for that many people to sign a petition protesting a NICE guidance?

14) Surveys of patients who have undergone GET have routinely found that more patients report harms from the intervention than benefits. In making its decision, does the Guidance Executive plan to consider these reports based on the clinical experiences of patients receiving GET in the real world?

15) The conduct and findings of the PACE trial have become a worldwide controversy. The study has been presented as a paragon of bad science at conferences of epidemiologists and statisticians and in graduate-level seminars. Leading scientists and clinicians have publicly denounced the trial’s perplexing irregularities. The CDC has removed references to PACE and has dropped the associated treatment recommendations. In making its decision about the 2007 guidance, does the Guidance Executive plan to consider that large segments of the scientific and public health worlds have already rejected the evidence base for GET and CBT as interventions for CFS/ME, ME/CFS, or whatever the disease entity is called? Given the public health stakes involved, will the Guidance Executive consider commissioning a more extensive, authoritative, independent and unbiased review of the evidence–and perhaps even a review in which the reviewers read the actual studies on which they are basing their recommendations, and not just the study abstracts?

I have other questions, but will leave it at that for now. I would be delighted should you and/or other members of the Guidance Executive choose to respond.

Kind regards–David

David Tuller, DrPH
Senior fellow in public health and journalism
Center for Global Public Health
School of Public Health
University of California, Berkeley

**********

Sir Andrew’s réponse to me:

Dear Dr Tuller,

Thank you for your enquiry.

It looks like you are aware that we have recently concluded a public consultation about our provisional decision on the review of this clinical guideline. We are in the process of reviewing the results of that consultation and will make our final decision in due course. We will make that decision public, together with any other statements we think will be helpful to contextualise it. Until then, we don’t intend to respond to enquiries about the provisional decision. It may be that our final decision, when placed in the public domain, will help you with some of your questions, but if not, we will endeavour to answer them as best we can at that time.

Yours sincerely,

Andrew Dillon
Chief Executive
National Institute for Health and Care Excellence
10 Spring Gardens | London | SW1A 2BU | United Kingdom

19 August 2017 – KD withdraws the FOI 2017/F158 (c) request thread for the following reasons:
“I sent this request to QMUL with the intent of clarifying the status of my "narrowing" of requests for objective data from the PACE trial.
I now think it clearer to leave FOI 2017/F158 (b) and FOI 2017/F158 (c) standing.
Please withdraw this request.”
19 August 2017 KD publishes an error correction of the withdrawal made on the FOI 2017/F158 (c) request thread, and clarifies as follows:
“Requests FOI 2017/F158 (b) and FOI 2017/F158 (d) are still standing.”

20 August 2017 KD asked QMUL to respond promptly on the FOI 2017/F255 thread as follows:
“Dear QM FOI Enquiries,
To aid you with understanding this request for information I have compiled the attached document, which demonstrates the repeated narrowing of my request of objective physical and physiological data collected by the PACE trial authors.
The annotations have not been provided to QMUL, and are available in full on the website, What do they know?
I remind QMUL that the FOI act requires a prompt response to requests.
On 5 June 2017 in its refusal response to the original request of 6 May 2017, QMUL acknowledged the fact that it holds the data requested. It is estimated that the volume of data in this drastically narrowed request, is contained within a 2 page, less than 100 kB table and it is at odds with the FOI Act to claim that it is onerous to provide a document of this tiny size.
I would appreciate a copy of the information by return.
Yours sincerely,
Kathryn Dickenson
FOI requests for PACE objective raw data.
Summary
Reference numbers and links to the website, What do they know?
FOI 2017/F158 - 6 May 2017-KD Submitted an FOI request via What do they know? QMUL gave it the reference number FOI 2017/F158.
Request entitled: CFS - PACE trial objective data enable comparison with patients own objective data. https://www.whatdotheyknow.com/request/c....
6 June 2017 KD narrowed the request and removed the information that QMUL stated that they did not hold most of the inform…….”
The summary is not included here……but can be accessed online.
20 August 2017 – Dear QM FOI Enquiries,
As QMUL is aware I have narrowed this request down further this is because as explained to QMUL, in previous correspondence, I require the data urgently as information for a submission to NICE regarding their decision not to update their 2007 Guideline for CFS.
The QMUL claim that it has not had "an opportunity to respond", is at odds with its legal obligation to respond promptly. On 5 June 2017, QMUL advised that it had ascertained that it holds the data requested, when responding to my original request of 6 May 2017.
It is now more than 70 days since this narrowed request, of data that QMUL has determined that it holds, was lodged on 13 June 2017. In my opinion is ample time for QMUL, to comply, with its legal obligation to provide information to the public.
It is not as if the volume of data I have requested is onerous. I estimate the data to be around 2-4 (at most) pages of information, less than 100 kB, as per the 6 minute walking test data was a 17 kB file, a 3 column table that bleed onto a second page.
I have attached a summary of the information regarding my request for objective data from the PACE trial. The full information e.g working links to the annotations are available on the What do they know? website.
Yours sincerely,
Kathryn Dickenson
FOI requests for PACE objective raw data.
Summary
Reference numbers and links to the website, What do they know?
FOI 2017/F158 - 6 May 2017-KD Submitted an FOI request via What do they know? QMUL gave it the reference number FOI 2017/F158.
Request entitled: CFS - PACE trial objective data enable comparison with patients own objective data. https://www.whatdotheyknow.com/request/c....
6 June 2017 KD narrowed the request and removed the information that QMUL stated that they did not hold most of the information and that given the time already taking ascertaining what they held it would be to onerous for QMUL to provide the information.
8 June 2017 KD narrowed the request yet again.
QMUL refused the request.
FOI 2017/F158 (b) 13 June 2017-KD Submitted a narrowed, FOI request via the website What do they know?
Request entitled: CFS - a small % of the objective physical and physiological data from PACE trial
Link to the request:
https://www.whatdotheyknow.com/request/c...
QMUL said that they were treating it as a continuation of the previous request. KD refers to it by the reference number FOI 2017/F248 (b). The request was refused currently with internal review
FOI 2017/F158 (c) 27 July 2017 KD submitted a narrowed, FOI request via What do they know?
Entitled: CFS - a small % of the objective physical and physiological data from PACE trial (6 minute walk test already in public domain).
Link to the request:
https://www.whatdotheyknow.com/request/c...
KD refers to this request as FOI 2017/F158 (c)
No response to this request was received from QMUL. The request was withdrawn on 19 August 2017, as it did not fufil its intended purpose of clarifying the FOI status.
FOI 2017/F158 (d) FOI 2017/F255 7 August 2017, KD submitted a narrowed FOI request via What do they know?
Entitled: CFS- a request for even less objective info from the PACE trial just the STEP test results at baseline and 52 weeks
Link to the request:
https://www.whatdotheyknow.com/request/c...
KD has used the reference number FOI 2017/F158(d) to refer to this request, however on 17 August 2017 QMUL gave the narrowed request a new reference number i.e. FOI 2017/F255. QMUL refused the request on the basis that the request is a narrowing of the request FOI 2017/F158(b), and hence overlaps with it. The refused request is with QMUL internal review
--------------------------------------------------------------------------------------------------------------
Timeline

Kathryn Dickenson left an annotation on the FOI 2017/F255 thread.
http://journals.sagepub.com/doi/pdf/10.1...

Journal of Health Psychology
2017, Vol. 22(9) 1181–1186

A review of studies incorporating objective measures suggests that
there is a lack of evidence that cognitive behavioural therapy produces any improvement in a patient’s
physical capabilities or other objective measures such as return to work.
I
21 August 2017 - FOI 2017/F255 thread
Kathryn Dickenson left an annotation on the FOI 2017/F255 thread.
PACE and NICE are very light on how to exercise despite the fact that patients are having good results by following UK experts work. One only has to look to the experts revered by patients to find out how to effectively manage this disease.

Dr Sarah Myhill is one such doctor, Dr Nigel Speight another. In the USA Prof Mark Van Ness, Todd Davenport, Staci Stevens, Dr Nancy Klimas. In Canda Dr Alison Bested. In Australia Prof Sonya Marshall-Gradnisk, Prof Don Staines, Dr Don Lewis.

http://www.drmyhill.co.uk/wiki/Exercises...

Exercise - the right sort in Chronic Fatigue Syndrome
My view is that CFSs are on the same energy spectrum, but the opposite end, to elite athletes. The processes and principles for improving energy efficiency apply equally to both. See Exercise - the right sort.
In CFS the first step is to put in place all the necessary dietary, nutritional and detox mechanisms so that your mitochondria are working efficiently. At this point clinically you should be feeling absolutely fine doing absolutely nothing . Until this point is achieved one dare not exercise because this will just cause massive tissue damage! Indeed we already know this – CFS is characterised by running a high cell free DNA which is a measure of tissue damage.
Please see Pattern of recovery, where the stages of recovery are explained in more detail. Read this page in detail BEFORE attempting any of the exercise regimes mentioned here.
However once you feel absolutely fine doing very little, and your mitochondrial tests, cell free DNA and antioxidant status are all improved, ideally normalised, together with any other problems that you know about, then the principles should be as per Exercise - the right sort.
These exercises are about increasing the numbers of mitochondria. This is equivalent to upgrading your car from a 500cc Deux Cheveaux ( as here) to a Rolls Royce V8 ! ( see here!) So first you have to get your mitochondria working well, then you need to increase their numbers.

21 August 2017 KD wrote this on the thread FOI 2017/F158 (b) clarified the request history as follows:
“Dear QM FOI Enquiries,
As QMUL is aware I have narrowed this request down further this is because as explained to QMUL, in previous correspondence, I require the data urgently as information for a submission to NICE regarding their decision not to update their 2007 Guideline for CFS.
The QMUL claim that it has not had "an opportunity to respond", is at odds with its legal obligation to respond promptly. On 5 June 2017, QMUL advised that it had ascertained that it holds the data requested, when responding to my original request of 6 May 2017.
It is now more than 70 days since this narrowed request, of data that QMUL has determined that it holds, was lodged on 13 June 2017. In my opinion is ample time for QMUL, to comply, with its legal obligation to provide information to the public.
It is not as if the volume of data I have requested is onerous. I estimate the data to be around 2-4 (at most) pages of information, less than 100 kB, as per the 6 minute walking test data was a 17 kB file, a 3 column table that bleed onto a second page.
I have attached a summary of the information regarding my request for objective data from the PACE trial. The full information e.g working links to the annotations are available on the What do they know? website.
Yours sincerely,
Kathryn Dickenson
FOI requests for PACE objective raw data.
Summary
Reference numbers and links to the website, What do they know?
FOI 2017/F158 - 6 May 2017-KD Submitted an FOI request via What do they know? QMUL gave it the reference number FOI 2017/F158.
Request entitled: CFS - PACE trial objective data enable comparison with patients own objective data. https://www.whatdotheyknow.com/request/c....
6 June 2017 KD narrowed the request and removed the information that QMUL stated that they did not hold most of the information and that given the time already taking ascertaining what they held it would be to onerous for QMUL to provide the information.
8 June 2017 KD narrowed the request yet again.
QMUL refused the request.
FOI 2017/F158 (b) 13 June 2017-KD Submitted a narrowed, FOI request via the website What do they know?
Request entitled: CFS - a small % of the objective physical and physiological data from PACE trial
Link to the request:
https://www.whatdotheyknow.com/request/c...
QMUL said that they were treating it as a continuation of the previous request. KD refers to it by the reference number FOI 2017/F248 (b). The request was refused currently with internal review
FOI 2017/F158 (c) 27 July 2017 KD submitted a narrowed, FOI request via What do they know?
Entitled: CFS - a small % of the objective physical and physiological data from PACE trial (6 minute walk test already in public domain).
Link to the request:
https://www.whatdotheyknow.com/request/c...
KD refers to this request as FOI 2017/F158 (c)
No response to this request was received from QMUL. The request was withdrawn on 19 August 2017, as it did not fufil its intended purpose of clarifying the FOI status.
FOI 2017/F158 (d) FOI 2017/F255 7 August 2017, KD submitted a narrowed FOI request via What do they know?
Entitled: CFS- a request for even less objective info from the PACE trial just the STEP test results at baseline and 52 weeks
Link to the request:
https://www.whatdotheyknow.com/request/c...
KD has used the reference number FOI 2017/F158(d) to refer to this request, however on 17 August 2017 QMUL gave the narrowed request a new reference number i.e. FOI 2017/F255. QMUL refused the request on the basis that the request is a narrowing of the request FOI 2017/F158(b), and hence overlaps with it. The refused request is with QMUL internal review
--------------------------------------------------------------------------------------------------------------
Timeline………………”

21 August 2017 – FOI 2017F255 thread
QMUL advised KD that it would not carry out an internal review of the information request on the FOI 2017/F255 thread as follows:
“Dear Kathryn Dickenson
We will not be carrying out an internal review of this request because, as already explained, it has been refused as repeated, since it consists of a smaller part of a wider request to which we intend to respond by 25th August 2017. Please await our response to that.
Yours sincerely
Queen Mary University of London
(F255)”

21 August 2017 - FOI 2017/F255 thread
(which she had referred to prior to the unique reference number being given as FOI 2017/F158 (d), as follows:
“Dear Queen Mary, University of London FOI,
Thank you for your advice that QMUL will respond to my request for the actometer (only obtained at baseline) and STEP data (baseline and 52 weeks), that was submitted on 13 June 2017, by 25 August 2017, and has the reference number FOI 2017/F158 (b) .
In the event that QMUL refuses my request of 13 June 2017, I request that the internal review of this decision proceeds and I do not accept that the clock has stopped on this narrowed request i.e. FOI 2017/F158 (d) FOI 2017/F255”

21 August 2017 – FOI 2107/F158(b) thread
KD responded to QMUL’s refusal to carry out an internal review that is documented on the FOI 2017/F255 thread
“Dear QM FOI Enquiries,
I note the advice received from QMUL provided in response to the narrowed request, i.e. actometer data not requested (QMUL reference FOI 2017/F255), that it will respond to this request for the actometer and STEP data, by the end of this week i.e. Friday 25 August 2017.
Yours sincerely,
Kathryn Dickenson”

23 August 2017 FOI 2017/F158 (c) thread.
”FOI 2017/F248
Dear Kathryn Dickenson
Thank you for your email of 27th July, where you asked for the following
i/ Actometer results (BMC reference 18) – raw data actometer, baseline measurements.
ii/ Self-paced step. Test of fitness (BMC reference 43), including the Borg test (scale of perceived exertion) and end heart rate.
This information is requested for two of the specified time periods:
- Baseline
- Final assessment – 52 week/39 week time point
I am afraid that we estimate to provide the information would exceed the appropriate limit as defined by the Freedom of Information and Data Protection (Appropriate Limit) Regulations 2004. For your information this is £450, calculated as the estimated cost of one person spending 18 hours in determining whether the information is held, then locating, retrieving and extracting the information. Section 12 of the Freedom of Information Act 2000 therefore makes provision for public authorities to refuse such requests. As the Chief Investigator has retired we have no one qualified to locate, retrieve and extract the information requested.
If you are dissatisfied with this response, you may ask QMUL to conduct a review of this decision. To do this, please contact the College in writing (including by fax, letter or email), describe the original request, explain your grounds for dissatisfaction, and include an address for correspondence. You have 40 working days from receipt of this communication to submit a review request. When the review process has been completed, if you are still dissatisfied, you may ask the Information Commissioner to intervene. Please see www.ico.org.uk for details.
Yours sincerely
Paul Smallcombe
Records & Information Compliance Manager”

30 August 2017 on the FOI 2017/255 thread KD repeated her request for an internal review of the narrowed information request, made on this thread.
“Dear Queen Mary, University of London,
Please pass this on to the person who conducts Freedom of Information reviews.
I am writing to request an internal review of Queen Mary, University of London's handling of my FOI request 'CFS- a request for even less objective info from the PACE trial just the STEP test results at baseline and 52 weeks i.e. FOI2017/F255.
As QMUL is aware this request is a narrowing of the narrowing of request FOI 2017/F158 (b), as described in the FOI request submitted on 13 June 2017, on this website. Approximately 1/2 of the data, that was requested on that date is now requested.
I trust that QMUL will respond promptly, as per its legal obligation under the FOI Act.
A full history of my FOI request and all correspondence is available on the Internet at this address: https://www.whatdotheyknow.com/request/c...

25 August 2017 – on the FOI 2107/F158(b) thread
“Dear QMUL FOI Enquiries,
I refer to my request of 5 May 2017 requesting the objective data from the PACE trial and subsequent correspondence.
On 13 June 2017-KD, I submitted a narrowed, FOI request to QMUL, via the website. "What do they know?".
The request is entitled: CFS - a small % of the objective physical and physiological data from PACE trial
Link to the request:
https://www.whatdotheyknow.com/request/c...
QMUL said that they were treating this request as a continuation of the request submitted on 6 May 2017. I refer to it by the reference number FOI 2017/F248 (b), as on the website it appears in a separate thread to the original request. The request was refused and I was advised that a response from the internal review panel, would be provided by 25 August 2017.
No response has been received.
Please provide the response from QMUL's internal review team to this request by return.
Yours sincerely,
Kathryn Dickenson”

25 August 2017 – on the FOI 2107/F158(b) thread KD wrote:
“Dear QM FOI Enquiries,
I am writing to remind QMUL that the reply to this internal review is long overdue and QMUL has not complied with its undertaking to respond by 25 August 2017.
I trust that QMUL will respond by return.
Yours sincerely,
Kathryn Dickenson”

29 August 2017 – on the FOI 2107/F158(b) thread QMUL wrote:
“Dear Kathryn Dickenson
It appears that you are confused as to our reply of 21st August 2017 in which reference was made to a response being made by 25th August to a request. That response was made on 23rd August (with our ref. FOI 2017/F248) here: https://www.whatdotheyknow.com/request/c.... It is not clear to us why you marked this as withdrawn.
The attached will hopefully clarify for you the requests we have received from you related to the PACE trial, with dates, reference numbers and responses. We do not believe that any have been late or are currently
outstanding because we have taken the view that new requests submitted have superseded previous ones. Please confirm the request on which you would like QMUL to carry out an internal review.
Yours sincerely
Paul Smallcombe
Queen Mary University of London”
QMUL provided the following table:
Date Received Reference No. Source Nature of query Deadline Date Date Resolved Response/Resolution Comments (if applicable)
2017-05-05 2017/F155 Kathryn Dickenson PACE trial: raw data from objective measures (actometer, VO2 max, TUAG, sit-stand test, 2 minute walk, 6 minute walk) at specified periods of time for each individual participant 2017-06-05 2017-05-05 Withdrawn by requester
2017-05-08 2017/F158 Kathryn Dickenson PACE trial: raw data from objective measures (actometer, VO2 max, TUAG, sit-stand test, 2 minute walk, 6 minute walk) at specified periods of time for each individual participant per their diagnosis criteria 2017-06-06 2017-06-05 Some information not held, some refused under s.12 exceeds appropriate limit Expansion of 2017/F155.
Narrowed on 08/06 to Actometer
results, 6 minute walk objective
measure of recovery, self-paced
step at both baseline and final assessment.
Replied again 25/07, refused under s.12
2017-06-06 2017/F187 Kathryn Dickenson PACE trial: information stating that certain physiological data was not to be collected 2017-07-04 2017-07-03 Information not held
2017-07-05 2017/F219 Kathryn Dickenson PACE trial: a copy of the undertakings/agreements that were made by QMUL in order to be granted funding. Limited to the physical/physiological research assessment measures to be collected at the beginning and end of the trial 2017-08-02 2017-07-18 Refused under s.21 accessible by other means
2017-07-27 2017/F248 Kathryn Dickenson PACE trial: Actometer results, Self-paced step at both baseline and final assessment 2017-08-25 2017-08-23 Refused under s.12 exceeds appropriate limit
2017-08-07 2017/F255 Kathryn Dickenson PACE trial: Self-paced step data. Test of fitness, including the Borg test (scale of perceived exertion) and end heart rate at baseline and final assessment 2017-09-05 2017-08-17 Refused under s.14(2) repeated Further narrowing of 2017/F248

29 August 2017 - FOI thread 2017/F158(b) KD wrote to QMUL as follows:
“Dear Queen Mary, University of London FOI,
What caused the confusion is that QMUL gave separate requests the same FOI reference number and treated them as the same request.
This resulted in QMUL "seeing" the FOI requests differently from how they are recorded on the "What do you know?" website.
QMUL has been persistently, tardy and failed to comply with its legal responsibility to respond promptly.
I note your refusal.
Yours sincerely,
Kathryn Dickenson”
No further correspondence on this What do they know? Thread.

5 September 2017 on the FOI 2017/255 thread
Kathryn Dickenson left an annotation
Myalgic encephalomyelitis/chronic fatigue syndrome patients’ reports of symptom changes following cognitive behavioural therapy, graded exercise therapy and pacing treatments: Analysis of a primary survey compared with secondary surveys

Keith Geraghty, Mark Hann, Stoyan Kurtev First Published August 29, 2017 Research Article

Journal of Health Psychology
Abstract
Cognitive behavioural therapy and graded exercise therapy are promoted as evidence-based treatments for myalgic encephalomyelitis/chronic fatigue syndrome. This article explores patients’ symptom responses following these treatments versus pacing therapy, an approach favoured by many sufferers. We analyse data from a large cross-sectional patient survey (n = 1428) and compare our findings with those from comparable patient surveys (n = 16,665), using a mix of descriptive statistics and regression analysis modelling. Findings from analysis of primary and secondary surveys suggest that cognitive behavioural therapy is of benefit to a small percentage of patients (8%–35%), graded exercise therapy brings about large negative responses in patients (54%–74%), while pacing is the most favoured treatment with the lowest negative response rate and the highest reported benefit (44%–82%). ……

5 September 2017 – KD lodges an annotation on the FOI 2017/F255 thread
Kathryn Dickenson left an annotation with the link to the tribunal’s decision relating to the request for some of the subjective data from the PACE trial.
Link to Alem Matthees response to QMUL's refusal to release a small percentage of the subjective data.

https://valerieeliotsmith.files.wordpres...

IN THE FIRST-TIER TRIBUNAL (INFORMATION RIGHTS) EA/2015/0269
BETWEEN:
QUEEN MARY UNIVERSITY OF LONDON
(Appellant)
And
THE INFORMATION COMMISSIONER
(First Respondent)
MR ALEM MATTHEES
(Second Respondent)
ALEM MATTHEES' MAIN RESPONSE

6 September 2017- KD lodges FOI 2017/F294
KD lodges a request for “CFS- the volume of objective data was narrowed down many times how was it determined it would take more than 18 hours to provide the data.” QMUL give the request the reference number. FOI 2017/F294
Link to the request: https://www.whatdotheyknow.com/request/c...
“Dear Queen Mary, University of London,
I refer to my request for a copy of the objective raw data from the PACE trial as submitted on the website "What do they know? " that QMUL gave the reference number FOI2017/F158. On 5 June 2017, QMUL advised that it had located the data requested.
I request a copy of the calculations made/information used to determine that it would take QMUL more than 18 hours (more than 450 pounds) to provide a copy of the data on or after each time the original request was narrowed as detailed below.
Yours faithfully,
Kathryn Dickenson
History of narrowing the request.
1. 6 May 2017-KD Submitted an FOI request via What do they know? QMUL gave it the reference number FOI 2017/F158.
The request is entitled: CFS - PACE trial objective data enable comparison with patients own objective data. https://www.whatdotheyknow.com/request/c....
QMUL refused the request, for two reasons, one, the researchers never collected more than ½ of the objective data described in the PACE manual and secondly that the volume of objective raw data obtained by the PACE authors, would take more than 18 hours and cost more than 450 pounds, to provide to the tax payer
2. 6 June 2017 KD narrowed the request and removed the information that QMUL stated that they did not hold. QMUL said that given the time already taking ascertaining what information they already held, it would still be too onerous for QMUL to provide the lesser amount of objective data requested.
3. 8 June 2017 KD narrowed the request yet again, QMUL again refused the request on the basis that the volume of material sought was still too great.
4. 13 June 2017- (FOI 2017/F1589 (b)) KD narrowed the request even further and QMUL refused the request on the basis that the volume of material sought was still too great.
5. 27 July 2017 (FOI 2017/F1589 (c))KD submitted a further narrowed request and QMUL refused the request on the basis that the volume of material sought was still too great.”
7 September 2017
QM FOI Enquires Queen Mary, University of London acknowledges the request for information FOI 2017/F294,
“We acknowledge receipt of your request and will respond as soon as we can.”

15 September 2017 QMUL refuses information request FOI 2017/F294, as stated on the FOI 2017/F2934 thread on the “What do they know?” website.
QMUL responded to the request for information on calculating that it would take more than 18 hours to provide the objective information from the PACE trial, stating:
“ FOI 2017/F294

Dear Kathryn Dickenson
Queen Mary University of London has used s.12 of the Freedom of
Information Act 2000 on three occasions in relation to requests made by
yourself.

We have based this on a reasonable estimate of where and how the
information from the PACE trial is believed to be held and the time it
would take one person, with no prior knowledge, locating, retrieving and
extracting the relevant information. However, we have not recorded any
actual calculations, therefore the information you have requested is not
held. It does not matter how little data is requested (or how small the
file may be); at the current time Queen Mary University of London does not
have the ability to provide such information without exceeding the
appropriate limit.
If you are dissatisfied with this response, you may ask QMUL to conduct a
review of this decision. To do this, please contact the College in
writing (including by fax, letter or email), describe the original
request, explain your grounds for dissatisfaction, and include an address
for correspondence. You have 40 working days from receipt of this
communication to submit a review request. When the review process has
been completed, if you are still dissatisfied, you may ask the Information
Commissioner to intervene. Please see [1]www.ico.org.uk for details.
Yours sincerely

Paul Smallcombe
Records & Information Compliance Manager

References
Visible links
1. http://www.ico.org.uk/”

18 September 2017 KD seeks an internal review of QMUL’s refusal FOI 2017/F294 for how it determined that it could not possibly provide any objective data as follows:
“Dear QM FOI Enquiries,
I request a review of QMUL's decision NOT to release the calculations that form the grounds for its repeated claims, that it is too onerous to release objective data, from the PACE raw trial, despite my repeated narrowing of my request.
QMUL is reminded, that the decision by QMUL, to continue to hide the objective data from this trial, has serious health implications, for millions of people with the disease chronic fatigue syndrome (CFS) in the UK. This is because in the UK, the health care of people with CFS is based on the PACE authors beliefs and claims, which still form the basis of the NICE Guidelines. The recent review of the NICE CFS Guideline is based on partially completed questionaire's by seven unidentified personal (David Tullers email exchange with NICE: http://www.virology.ws/2017/08/14/trial-... .
In contrast the USA, after a million dollar review, of more than 9 thousand research papers, about the disease (https://www.cdc.gov/me-cfs/index.html) has determined, that to date there is no treatment and no cure for CFS. Note, in the USA scientists and CFS experts, have a positive and productive relationship with CFS patients, and are carrying out serious biomedical research into the disease in a wide range of disciplines. This in contrast to in the UK where a small number of extremely vocal mental health experts appear to have hijacked the disease and when asked to justify their beliefs and claims, hide behind the non-provision of data, subjective surveys, non-specific questions that ignore the core/key diagnostic symptoms of post exertional exacerbation of symptoms after exertion (often delayed) and even
unsubstantiated/disputed claims of harassment (rejected as spurious by the First Tribunal judge that ordered the release of a small volume of subjective data).
The USA government, has rejected the PACE authors claims of the effectiveness of GET and CBT for treating CFS. The controversial and widely disputed beliefs of the PACE authors, form no part of USA health policies and guidelines for CFS. In contrast claims made by the PACE authors, continue to form the basis of the NICE Guidelines for CFS, despite the failure of the authors to satisfactorily explain the documented flaws and faults in their work (http://www.meassociation.org.uk/2017/07/....
I put it to QMUL, that the decision not to release the data, has a serious impact on UK CFS patients, their families, and the health care system and as such either is, or needs to be clearly documented and the calculations and associated information on which this decision is made clearly delineated. It beggars belief that such a serious decision is made on an unsubstantiated and undocumented whim. If this is in fact the reality, then I request that QMUL reviews its decision/s to not release the data on the basis that the non-release of the data is unsubstantiated.
It appears that the university has been stringing me along for months and has never intended to provide me with any of the information I am seeking . QMUL stated as follows:
" It does not matter how little data is requested (or how small the file may be); at the current time Queen Mary University of London does not have the ability to provide such information without exceeding the appropriate limit." This statement presumably relates to the fact that the volume of information specified in the narrowed requests was less than 100 kB in size and consisting of a small table of a few pages of results. This statement by QMUL appears to make it clear that the university has never intended to comply with its legal obligation for transparency and the release of data requested under the FOI Act, when the request relates to the PACE trial.
I seek a copy of all documentation, relating to the claims by Paul Smallcombe and QMUL that the release of the PACE objective data will take more than 18 hours/cost more than 450 pounds to provide
Yours sincerely,
Kathryn Dickenson”
18 September 2017
18 September 2017- annotation on FOI 2017/F294 “What do they Know?” thread
http://www.virology.ws/2017/08/14/trial-...

Trial by Error: My E-Mail Exchange With NICE Chief Executive
14 AUGUST 2017
By David Tuller, DrPH

On Friday, I had an e-mail exchange with Sir Andrew Dillon, chief executive of the NICE Guidance Executive. The other seven Guidance Executive members are various directors within the NICE hierarchy, including the communications director. This group will make the final decision about whether to accept the provisional decision of a NICE surveillance review team to leave as is CG53, the guidance for CFS/ME released in 2007. (I have written about the NICE review process on CG53 here, here and here.) That ten-year-old CFS/ME guidance recommends treatment with graded exercise therapy and cognitive behavior therapy. NICE reaffirmed the guidance after the 2011 publication of the first PACE results, which were taken as evidence that these treatments were effective. As part of the current review process, NICE provided stakeholders with a two-week window last month to submit comments about the provisional decision not to change CG53. Not surprisingly, this recommendation has alarmed many patients and advocates.

I didn’t expect to get answers to my questions from the Guidance Executive, but I felt an obligation to pose them anyway, given the importance of the issues. In fact, Sir Andrew responded to my e-mail within an hour. He explained that no comments would be forthcoming while the Guidance Executive was reviewing the situation. I have posted his response below my initial e-mail.

**********

Sir Andrew Dillon
Chief Executive
National Institute for Health and Care Excellence

Dear Sir Andrew:

I am a journalist and public health researcher at the University of California, Berkeley. I have reported on the current review of CG53, the NICE guidance for CFS/ME, for the science site Virology Blog, which is hosted by Professor Vincent Racaniello, a microbiologist at Columbia University. I have previously reported for Virology Blog on the PACE trial and other issues related to graded exercise therapy and cognitive behavior therapy. Earlier this year, I co-authored a commentary about the serious problems with PACE for the Sunday opinion section of The New York Times.

In my role as a journalist covering this issue, I have some questions for you and the other members of the NICE Guidance Executive about the decision-making process concerning the provisional recommendation to make no changes to CG53:

1) For many years, the U.S. Centers for Disease Control recommended GET and CBT as treatments, citing PACE. In late June or early July, the agency removed all references to these therapies from its main pages on the illness. Does the Guidance Executive plan to consult with American public health officials about what prompted this major “dis-endorsement” of these two therapies that NICE continues to promote?

2) In 2015, both the U.S. National Institutes of Health and the Institute of Medicine (now the National Academy of Medicine) released reports on the illness (they call it ME/CFS). These reports both concluded that it is a serious organic disease involving pathophysiological processes and not a psychological or psychiatric disorder—a determination that would have significant impact on treatment options. Does the Guidance Executive plan to consider these two reports and consult with any of the members of the panels that wrote them?

3) Other fields of medicine have abandoned the use of the trial design favored in this entire body of research, including PACE: open-label studies with subjective outcomes. That’s because other fields of medicine recognize that the combination of those two features in one study inherently produces bias. Does the Guidance Executive share these concerns about results from open-label studies with subjective outcomes, or does it believe that such studies can produce reliable and unbiased evidence suitable for clinical decision-making?

4) In PACE and other studies from this field, objective measures have largely failed to support the subjective results that have generated claims of “recovery” or significant clinical improvement. Does this pattern of sharp contradiction between objective and subjective results raise questions for the Guidance Executive about whether patients are objectively getting better?

5) In the 2011 Lancet paper, 13 % of the PACE participants had already met one of the study’s outcome thresholds at trial entry—that is, although assessed as “disabled” enough in physical function to qualify for the study, they were also found to be “within normal range” for physical function, before any treatment at all. In the 2013 Psychological Medicine paper, the same 13 % were already “recovered” for physical function at baseline, before any treatment at all—that is, they were simultaneously “disabled” for physical function and “recovered” for physical function. These facts were not included in the published papers but emerged later through a patient’s freedom-of-information request. Does the Guidance Executive have confidence in the reported results of a study in which a significant minority of participants have already met a key outcome threshold at baseline? If so, can the Guidance Executive point to other studies in the clinical trial literature in which a significant number of participants have already met a key outcome threshold at baseline? Does the Guidance Executive believe that the published PACE papers should have mentioned the fact that a signifiant minority of participants had already met a key outcome threshold at baseline?

6) In February 2016, forty-two leading scientists and clinicians signed an open letter to The Lancet in which they outlined the methodological lapses of the PACE trial, stated unequivocally that “such flaws have no place in published research,” and demanded an independent investigation. In March 2017, more than 100 experts signed an open letter to Psychological Medicine, asking the journal to retract immediately its core finding that GET and CBT helped patients “recover.” Does the Guidance Executive plan to review these open letters and consult with any of the signatories–from Columbia, University College London, Harvard, Stanford, Berkeley, etc.—about their reasons for publicly dismissing the PACE findings as invalid?

7) Both GET and CBT, as described in PACE and other studies from this field of research, involve telling participants that the treatments can reverse the illness and return them to a state of health. Is the Guidance Executive concerned that telling study participants repeatedly about the effectiveness of the treatments could bias their responses, augmenting any bias already inherent in open-label studies with subjective outcomes?

8) Some defenders of PACE note that CBT is also recommended for patients with cancer and other chronic diseases. But the approach advocated in PACE and related studies is not the kind of CBT focused on helping patients adapt to the reality of their illness. Rather, this form of CBT is specifically designed to alleviate patients of their purportedly “unhelpful” beliefs of having an ongoing medical disease that can be exacerbated by activity and exercise. Is the Guidance Executive aware of this critical distinction between CBT as normally administered in the case of other chronic illnesses and the adapted form of CBT investigated in PACE and other studies in this field?

9) The PACE trial used the Oxford criteria to identify participants. This case definition requires only six months of unexplained fatigue, so its use could result in the selection of participants with depression or other unidentified fatiguing illnesses. Some of these other illnesses might resolve spontaneously or respond to behavioral and psychological interventions like GET and CBT. In fact, the NIH report noted that using the broad Oxford case definition could “impair progress and cause harm,” and recommended that it be “retired.” Is the Guidance Executive concerned that populations derived using the Oxford criteria might contain many participants experiencing prolonged fatigue for a range of reasons unrelated to the illness being investigated? Is the Guidance Executive concerned that such heterogeneity in study samples could lead to erroneous findings about treatments?

10) The U.S. Agency for Healthcare Research and Quality found evidence to support GET and CBT for ME/CFS in its review of multiple studies. However, when the agency subsequently removed Oxford criteria studies from this analysis, it found no evidence that GET provided any benefits and almost no evidence that CBT provided benefits. Is the Guidance Executive considering this AHRQ re-analysis in its decision-making? Does the Guidance Executive plan to consult with officials at the agency to discuss why they conducted this re-analysis and how it subsequently led them to downgrade their assessments of the therapies?

11) The surveillance review team cites Cochrane reviews of GET and CBT to support the recommendation to leave the 2007 guidance as is. Many of the trials included in these Cochrane reviews rely on a broad case definition like the Oxford criteria. Is the Guidance Executive comfortable relying on Cochrane reviews for confirmation of controversial findings when the reviews themselves include the studies that feature the methodological problems being questioned? Will the Guidance Executive consider asking Cochrane to follow the lead of American public health officials and conduct a re-analysis of its GET and CBT reviews with Oxford criteria studies removed from the sample?

12) In the PACE trial protocol, the investigators promised to follow the Declaration of Helsinki, which requires researchers to tell prospective participants about “any possible conflicts of interest.” The three main PACE investigators have had longstanding relationships with insurance companies, advising them to offer GET and CBT to claimants diagnosed with the illness. Yet the investigators did not tell prospective PACE participants about these extensive consulting and financial links with insurance companies or include the information in consent forms. Is the Guidance Executive concerned that this clear violation of the investigators’ protocol promise to disclose “any possible conflicts of interest” to prospective participants means that they did not obtain properly “informed” consent? Does the Guidance Executive believe it should base clinical guidelines on studies that have not obtained properly “informed” consent?

13) More than 15,000 people signed the ME Association’s online petition outlining their concerns with the 2007 guidance and their objection to the provisional decision to leave it unchanged. Is it unusual for that many people to sign a petition protesting a NICE guidance?

14) Surveys of patients who have undergone GET have routinely found that more patients report harms from the intervention than benefits. In making its decision, does the Guidance Executive plan to consider these reports based on the clinical experiences of patients receiving GET in the real world?

15) The conduct and findings of the PACE trial have become a worldwide controversy. The study has been presented as a paragon of bad science at conferences of epidemiologists and statisticians and in graduate-level seminars. Leading scientists and clinicians have publicly denounced the trial’s perplexing irregularities. The CDC has removed references to PACE and has dropped the associated treatment recommendations. In making its decision about the 2007 guidance, does the Guidance Executive plan to consider that large segments of the scientific and public health worlds have already rejected the evidence base for GET and CBT as interventions for CFS/ME, ME/CFS, or whatever the disease entity is called? Given the public health stakes involved, will the Guidance Executive consider commissioning a more extensive, authoritative, independent and unbiased review of the evidence–and perhaps even a review in which the reviewers read the actual studies on which they are basing their recommendations, and not just the study abstracts?

I have other questions, but will leave it at that for now. I would be delighted should you and/or other members of the Guidance Executive choose to respond.

Kind regards–David

David Tuller, DrPH
Senior fellow in public health and journalism
Center for Global Public Health
School of Public Health
University of California, Berkeley

**********

Sir Andrew’s réponse to me:

Dear Dr Tuller,

Thank you for your enquiry.

It looks like you are aware that we have recently concluded a public consultation about our provisional decision on the review of this clinical guideline. We are in the process of reviewing the results of that consultation and will make our final decision in due course. We will make that decision public, together with any other statements we think will be helpful to contextualise it. Until then, we don’t intend to respond to enquiries about the provisional decision. It may be that our final decision, when placed in the public domain, will help you with some of your questions, but if not, we will endeavour to answer them as best we can at that time.

Yours sincerely,

Andrew Dillon
Chief Executive
National Institute for Health and Care Excellence
10 Spring Gardens | London | SW1A 2BU | United Kingdom

19 September 2017 - FOI 2017/F255
KD sought advice from QMUL, on the FOI 2017/F255 thread, in relation to a statement made by QMUL on the What do they know?, thread relating to her request for information, on how the University determined how long it would take to provide the objective data requested i.e information request FOI 2017/F294. As follows:
“Dear Queen Mary, University of London FOI,
I refer to the statement made by QMUL in it's response to my request for information on how the university
calculated that it would take more than 18 hours to provide the various narrowed requests for objective data from the PACE trial i.e. FOI request 2017/F294.
QMUL stated as follows:
"It does not matter how little data is requested (or how small the file may be); at the current time Queen Mary University of London does not have the ability to provide such information without exceeding the appropriate limit."
Please explain if/how the above statement pertains to this request for less than 100kB of data ( a small table) of data of the STEP test results at baseline and 52 weeks.
Yours sincerely,
Kathryn Dickenson”

24 September 2017 - FOI 2017/F255 thread

“Dear Queen Mary, University of London FOI,
I am seeking clarification of your position in relation to my request for a small amount of objective data from the PACE trial.
Has the person who is the authorised delegate, for internal review decisions, refused to provide the data requested?
In the event that the internal review decision had not been made, I bring it to the attention of QMUL that:
1/ A claim that it will take more than 18 hours to upload the PACE, STEP data to the "What do they know?" website, is at odds with the ease and speed of modern day data transfer. A data file this small, will upload in a matter of minutes. The information has already been located as per QMUL advised on this website, on 5 June 2017.
2/ The claim that it is too onerous, to provide the data requested, is also at odds with the fact that the University of Manchester, speedily and readily, provided a similar volume and type of data from PACE's sister trial.
The University of Manchester's file of the STEP data is 37kB in size. It is estimated, that the requested QMUL STEP data file, to be less than 100kB in size (PACE had twice as many participants but only the baseline and 52 week data points are requested).
3/ A striking feature of the FINE trial raw data is that 50% of the participants, appear to have been so adversely affected by doing the baseline STEP test, and or the "treatment" regimes, that they did not do subsequent STEP tests.
It is anticipated that the raw data, from PACE trial objective results, may demonstrate a similar deterioration in participants health, after a STEP test. As an exacerbation of symptoms and deterioration of health in response to physical exertion is a key diagnostic feature of the disease chronic fatigue syndrome. Deterioration after exercise is widely reported by patients, biomedical researchers and exercise physiologists and any persons who have patients physiological, biomedical and subjective responses in the hours/days after exercise beyond that patients "usual" activity.
Is the fact that the objective data from the PACE trial has not been released to date because the objective findings are at odds with the PACE authors beliefs and at odds with the wishes of the insurance industry funding these authors?
In the alternative, I am left wondering, why it is not in the best interests of QMUL, to make all the objective data from the PACE trial freely available, to independent researchers, the UK tax payer, the NHS, NICE, the Department of Health, the Department of Work and Pensions and patients.
Yours sincerely,
Kathryn Dickenson”

Kathryn Dickenson left an annotation ()

https://www.statnews.com/2017/09/25/chro...

Why did it take the CDC so long to reverse course on debunked treatments for chronic fatigue syndrome?

By JULIE REHMEYER and DAVID TULLER
SEPTEMBER 25, 2017

After years of resisting pleas from patients, advocates, and clinicians, the CDC quietly dropped its recommendations for debunked treatments for chronic fatigue syndrome, which included graded exercise and psychotherapy
For years, people with chronic fatigue syndrome have wrangled with the Centers for Disease Control and Prevention over information on the agency’s website about this debilitating illness. The website highlighted two treatments that became the de facto standards of care: a gradual increase in exercise and a form of psychotherapy known as cognitive behavioral therapy. The problem was that the evidence doesn’t support these treatments.
This summer, after years of resisting pleas from patients, advocates, and clinicians, the CDC quietly dropped the treatment recommendations from its website. Its decision represents a major victory for the patient community — and for science. But the country’s lead public health agency still has a long way to go to meet its responsibilities to the estimated 1 million Americans with this disease.
Exercise and psychotherapy might sound like the most benign of recommendations. But the hallmark symptom of chronic fatigue syndrome (also called myalgic encephalomyelitis, or ME/CFS) is that overexertion triggers relapses that can leave patients much, much sicker, as the Institute of Medicine documented in a landmark 2015 report. So a steady increase in activity can easily cause further harm, not benefit. In multiple surveys, more patients report getting worse, not better, from these “graded exercise” programs.

The theory underlying the two discarded treatments arose in earlier decades when the medical and scientific communities largely dismissed the devastating illness as illusory or psychological. According to that theory, such patients harbor mistaken beliefs that they suffer from an actual physical disease. As a result, they remain sedentary out of a misguided fear that activity will make them worse. They then develop severe deconditioning, perpetuating their symptoms.

Bad science misled millions with chronic fatigue syndrome. Here’s how we fought back
However, more recent studies from Stanford, Columbia, Cornell and elsewherehave demonstrated that ME/CFS patients suffer from immunological, neurological, and other systemic dysfunctions. And scientists have reported that the bodies of ME/CFS patients generate energy inefficiently if they push beyond their limited capacities.

Moreover, the key piece of evidence the CDC once cited to support its recommendations of exercise and psychotherapy has been debunked.

That evidence was a multimillion-dollar British study called the PACE trial, the largest ever of the illness. The first results appeared in the Lancet in 2011, with other findings published in Psychological Medicine in 2013 and many other journals. But the trial had a host of flaws that render its reported results nonsensical and uninterpretable. Most remarkably, the investigators relaxed their outcome measures so dramatically during the trial that participants could deteriorate during treatment on the key measure of physical functioning and still be declared “recovered.” Because of these changes, the findings were far more impressive than those the investigators would have obtained using the methods they originally proposed, as reanalyses of the trial data have shown.

The larger scientific community is up in arms over the problems with PACE. Earlier this year, more than 100 experts signed an open letter to Psychological Medicine (orchestrated and signed by one of us [DT]) stating that the trial’s flaws “are unacceptable in published research” and “cannot be defended or explained away.” The letter requested immediate retraction of the claim that patients “recovered” from the treatments. The journal refused the request.

Yet the trial and its claims remain hugely influential. In the U.S., Kaiser Permanente, the Mayo Clinic, and WebMD all continue to promote the therapies. So does UpToDate, a popular decision-making tool for clinicians. In the United Kingdom, graded exercise and cognitive behavior therapy continue to be the most widely offered treatments for the illness through the National Health Service system.

However, the country’s National Institute for Health and Care Excellence, which creates clinical guidelines that are widely followed, recently announced that it will be conducting a “full update” of its current recommendations, citing the CDC’s decision as one reason for the update.
NIH launches study seeking answers on chronic fatigue syndrome

Despite the significance of the changes, few medical professionals are aware the CDC has dropped the exercise and psychotherapy recommendations. Nor do they know about the extreme care with which people with ME/CFS need to regulate their activity. If your doctor were to diagnose you with this condition today, the odds are good that you’d be advised to exercise your way out of it and to consult a psychotherapist.

While the CDC deserves credit for having removed information based on bad science, that alone is not enough. The agency must also undo the damage it has caused.
First, the CDC needs to acknowledge that it got things wrong. So far, the agency has stated in response to questions that the changes were made because “there has been confusion about what we recommend related to exercise and therapy,” and the agency had not intended to recommend the PACE trial treatments despite using identical terminology. Given that ME/CFS advocates lobbied the CDC for years specifically about the problems with recommending these therapies, that explanation is hard to take seriously. An honest acknowledgement of error will go far toward re-establishing trust with the ME/CFS patient community.

Second, the CDC must actively disseminate the news that it no longer recommends these two ineffective and possibly harmful therapies and that no legitimate evidence supports their use. This should be part of a muscular plan, coordinated with the National Institutes of Health and other agencies, to counter the prevalent myths about ME/CFS among doctors, other health care providers, and the general public.

Third, the agency needs to reach out directly to health care and medical organizations, such as Kaiser Permanente and the Mayo Clinic, to urge them to stop recommending the treatments and ensure that the information they provide is truly up to date. That outreach should include the UK’s National Institute for Health and Care Excellence.

For decades, the ME/CFS patient community has been waiting for the CDC to get this right. The agency has finally taken a step in the right direction. Now it needs to redouble its efforts to find legitimate answers to the many outstanding questions about the illness and to investigate treatments that might actually work.

Julie Rehmeyer is a contributing editor to Discover magazine and author of “Through the Shadowlands: A Science Writer’s Odyssey into an Illness Science Doesn’t Understand,” a memoir describing the science, history, and politics of chronic fatigue syndrome. David Tuller is a senior fellow in public health and journalism at the Center for Global Public Health at the University of California, Berkeley. Members of the ME/CFS patient community generously donated to a crowdfunding campaign in support of Tuller’s position at Berkeley.

Kathryn Dickenson left an annotation ()

A video explaining PACE recovery rates as per PACE authors

https://www.youtube.com/watch?v=d_7J5ELj...

Dear Queen Mary, University of London FOI,
I repeat my request for an acknowledgement from QMUL, that the university is going to conduct an internal review of this request.
Yours sincerely,

Kathryn Dickenson

QM FOI Enquiries, Queen Mary, University of London

Dear Kathryn Dickenson

 

QMUL has completed its internal review. The reviewer has concluded that
Section 12 has been correctly applied for the following reasons:

 1. The data relating to the PACE trial is extensive and it would not be
straightforward to access, locate and extract the information
requested;
 2. The process of finding and providing the data requested would require
a considerable level of expertise and knowledge of the PACE trial and
its data;
 3. QMUL does not currently employ any staff with sufficient skills and
experience to fulfil point 2 above;
 4. Whilst the request appears to be small and the requester has sought to
narrow it, considering all of the above reasons together, providing
the information would exceed the appropriate limit defined by the
Freedom of Information and Data Protection (Appropriate Limit)
Regulations 2004.

 

You have the right to complain further to the Information Commissioner,
please see [1]www.ico.org.uk for details.

 

Yours sincerely

 

Paul Smallcombe

Records & Information Compliance Manager

 

PS - Please note that this review actually applies to FOI 2017/F248:

I request that QMUL, complies with its legal and moral obligation to UK
tax payers and CFS patients,  and promptly provides the following
information from the PACE trial:

i/ Actometer results (BMC reference 18) – raw data actometer, baseline
measurements.

ii/ Self-paced step. Test of fitness (BMC reference 43), including the
Borg test (scale of perceived exertion) and end heart rate.

This information is requested for two of the specified time periods:

- Baseline

- Final assessment – 52 week/39 week time point

References

Visible links
1. http://www.ico.org.uk/

Kathryn Dickenson

Dear QM FOI Enquiries,
Seriously?
Yours sincerely,

Kathryn Dickenson

Kathryn Dickenson

Dear Queen Mary, University of London,

Please pass this on to the person who conducts Freedom of Information reviews.

I am writing to request an internal review of Queen Mary, University of London's handling of my FOI request 'CFS- a request for even less objective info from the PACE trial just the STEP test results at baseline and 52 weeks'.

It appears that the main problem for QMUL, is that since Peter White suddenly retired (the day before the release of the PACE subjective data), it does not have any staff with the expertise and knowledge of the PACE trial. This problem can be easily solved, as myself and many other ME/CFS patients have considerable knowledge and a high level of expertise about the PACE trial and its data. Many of us were also scientists and researchers before getting ill and we have the expertise that you say is lacking in your current staff. We are happy to volunteer out expertise, to help your staff, find and identify the PACE data.

1. “The data relating to the PACE trial is extensive”
Those of us with knowledge about the data relating to the PACE trial, are aware that in fact, very little objective data was collected and there are not extensive results. As, QMUL has previously advised, most of the objective data specified in the PACE manual, was not collected by Principal Investigators. The only objective data collected was the actigraph, STEP and 6- minute walk test data. Some of the 6 minute walk test data is already, in the public domain and not requested here.
The STEP test results are just numerical results, for a maximum of 641 participants, of a file size less than 100kB.
The University of Manchester released the objective raw results from the PACE sister trials, immediately on request. It is not clear why QMUL is unable to do the same.

2. “it would not be straightforward to access”
I’m not sure what you mean, when you say that the data is not straightforward to access. Could you please explain what you mean.

3. it would not be straightforward “to locate”
Again, I’m not sure what you mean, when you say that the data is not straightforward to locate. Could you please explain what you mean.

4. it would not be straightforward to “extract the information”
I don’t want or expect QMUL, to take the time and effort required to extract the information specified in this request. To the contrary, I would prefer the full set of objective data. I am happy with the provision of the raw objective in the format that it is currently being held by QMUL.

5. The “process of finding and providing the data requested would require
a considerable level of expertise” ?
I’m not sure what you mean by considerable expertise. Is this expertise about the PACE trial or data management expertise? I am sure that I can find a volunteer patient who before getting ill with ME/CFS worked in data management at a University. You may not be aware but ME/CFS is a common disease affecting many thousands of people and hence we have a wide range of expertise in our community.

6. The process of finding and providing the data requested would require “knowledge of the PACE trial and its data”
I’m not sure what you mean when you say that the process of finding and providing the data requires specific knowledge of the PACE trial and its data? Is this knowledge about the trial itself and or knowledge about finding data in general? Either way I am sure that the patient community can help QMUL.

7. QMUL does not currently employ any staff with sufficient skills and
experience to fulfil point 2 above; ie The process of finding and providing the data requested would require would require a considerable level of expertise and knowledge of the PACE trial and its data.
I’m a bit confused by the need to have people with a considerable level of expertise and knowledge of the PACE trial to identify objective raw data from the STEP test and the actigraph. STEP tests are routinely used in sports and exercise medicine and I am sure that your colleagues will be able to help you -http://www.whri.qmul.ac.uk/about-us/418-....
In the alternative, myself and many ME/CFS patients, have considerable knowledge and a high level of expertise of the PACE trial and its data. We are happy to help your staff find and provide the data.

A full history of my FOI request and all correspondence is available on the Internet at this address: https://www.whatdotheyknow.com/request/c...

Yours sincerely,

Kathryn Dickenson

Queen Mary, University of London FOI, Queen Mary, University of London

Dear Kathryn Dickenson,

QMUL has concluded its procedures. If you remain dissatisfied, then your next step is to contact the Information Commissioner's Office.

Yours sincerely

Queen Mary University of London

Kathryn Dickenson

Dear Queen Mary, University of London FOI,

Request now with the Office of the Information Commissioner.

Yours sincerely,

Kathryn Dickenson

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