We don't know whether the most recent response to this request contains information or not – if you are George Jenson please sign in and let everyone know.

CFS correspondence on the Department's view of the PACE trial

We're waiting for George Jenson to read recent responses and update the status.

Dear Department of Health,

I am seeking information on:

1/ the departments view of the problems raised about the PACE trial- detailed below.
2/ the departments view of the responses to the reanalysis of the PACE raw data, which found CBT and GET to be ineffective on self reporting, subjective measures.

(NB On objective measures little effect was found e.g. after a year of treatment severely disabled patients were still severely ill although able to walk on average an extra 38 metres.)

Yours faithfully,

George Jenson

Quotes from PACE trial critics - source MEpedia

Vincent Racaniello
Vincent Racaniello is a virologist at Columbia University in New York in the United States.
"This is a flawed study, it has to be fixed and people are being harmed by it."[168]
"... multiple flaws that are inexcusable."[168]

Trevor Butterworth
Trevor Butterworth is the Editor of 'Sense About Statistics', an online collaboration between the American Statistical Association and Sense About Science USA.[169]
"...the way PACE was designed and redesigned means it cannot provide reliable answers to the questions it asked. There is really not a lot that can be said to mitigate that; it’s a terminal prognosis."

Professor James Coyne
Professor Coyne is Professor of Health Psychology, University Medical Center, Groningen and University of the Netherlands; Distinguished Visiting Professor at the Institute for Health Policy, Rutgers, the State University of New Jersey; and Professor Emeritus of Psychology in the Department of Psychiatry, University of Pennsylvania. He is one of the most cited psychologists in the academic literature.

"The data presented are uninterpretable. We can temporarily suspend critical thinking and some basic rules for conducting randomized trials (RCTs), follow-up studies, and analyzing the subsequent data. Even if we do, we should reject some of the interpretations offered by the PACE investigators as unfairly spun to fit what [is] already a distorted positive interpretation of the results."[60]

"The self-report measures do not necessarily capture subjective experience, only forced choice responses to a limited set of statements."[60]

"One of the two outcome measures, the physical health scale of the SF-36 requires forced choice responses to a limited set of statements selected for general utility across all mental and physical conditions."[60]

"The validity [of the] other primary outcome measure, the Chalder Fatigue Scale depends heavily on research conducted by this investigator group and has inadequate validation of its sensitivity to change in objective measures of functioning."[60]

Professor Coyne gave a public talk criticising the PACE trial in Edinburgh in November 2015. Video footage is available[75][76][77], as are a slide show[78], a full[170] and an edited transcript[171][172] and an audio recording.[173]

He spoke again about the PACE study in Belfast in February 2016 where he described it as "a wasteful trainwreck of a study".[174][175]

Professor Coyne has questioned whether the PACE trial paper could ever have been properly peer-reviewed, given the large number of study authors and the small world of British science.[176]

Professors James Coyne and Keith Laws
Professor Coyne and Professor Laws of the University of Hertfordshire have criticised, in a joint letter to Lancet Psychiatry, the long-term follow-up analysis of the PACE trial that was published in 2015.[177] Referring to the results of the study as a whole, they said:

"There are no group differences, and the overall mean short-form 36 (SF-63) physical functioning score is less than 60. It is useful to put this number in context. 77% of the PACE trial participants were women, and the mean age of the trial population was 38 years, with no other disabling medical conditions. Patients with lupus have a mean physical functioning score of 63, patients with class II congestive heart failure have a mean score lower than 60, and normal controls with no long-term health problems have a mean score of 93."

Professor Ronald Davis
Professor Ronald Davis is a world-famous geneticist at Stanford University, known for work that enabled the Human Genome Project.
“I’m shocked that the Lancet published it... The PACE study has so many flaws and there are so many questions you’d want to ask about it that I don’t understand how it got through any kind of peer review.”[22]

Emeritus Professor Jonathan Edwards
Professor Edwards, of University College London, is internationally known for his pioneering work in establishing B-cell depletion therapy as an effective treatment for rheumatoid arthritis.

“It’s a mass of un-interpretability to me…All the issues with the trial are extremely worrying, making interpretation of the clinical significance of the findings more or less impossible.”[22]
Professor Rebecca Goldin

Professor Goldin is Professor of Mathematical Sciences at George Mason University and Director of STATS.org (USA).[47]

"The PACE design changed so significantly as to leave many wondering whether there is value in the study itself."

"It seems that the best we can glean from PACE is that study design is essential to good science, and the flaws in this design were enough to doom its results from the start."

Dr Ellen Goudsmit
Dr Goudsmit is a retired health psychologist who has published a number of criticisms of the PACE trial.

"The PACE trial was scientifically extremely poor"[178]
"A treatment like GET is simply not appropriate for a disease like ME which is linked to infection and metabolic abnormalities. Given the close relationship between exertion and symptoms, it follows that asking a patient to increase their activity levels is as logical as advising smokers with lung cancer to gradually increase the number of cigarettes they smoke"[179]

Professor Leonard Jason
Leonard Jason is a professor of psychology at DePaul University in Chicago, Illinois, and director of its Center for Community Research.

“The PACE authors should have reduced the kind of blatant methodological lapses that can impugn the credibility of the research, such as having overlapping recovery and entry/disability criteria.”[22]

Professor Bruce Levin
Professor Levin is a professor of biostatistics at Columbia University and an expert in clinical trial design.

“To let participants know that interventions have been selected by a government committee ‘based on the best available evidence’ strikes me as the height of clinical trial amateurism.”[22]

Professor Arthur Reingold
Professor Reingold is Head of Epidemiology at the University of California, Berkeley.
“Under the circumstances, an independent review of the trial conducted by experts not involved in the design or conduct of the study would seem to be very much in order.”[22]

Dr. Charles Shepherd
Dr Shepherd, medical advisor to the ME Association, has criticised the trial's long-term follow-up analyses:

"Without robust objective evidence relating to improvement and recovery, the ME patient community will continue to regard the PACE trial as a tremendous waste of research funding money".[180]

Dr David Tuller
Dr Tuller is is academic coordinator of the 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. He has written extensively about the PACE trial.[91]

"The study included a bizarre paradox: participants’ baseline scores for the two primary outcomes of physical function and fatigue could qualify them simultaneously as disabled enough to get into the trial but already 'recovered' on those indicators–even before any treatment. In fact, 13 percent of the study sample was already 'recovered' on one of these two measures at the start of the study."[22]

"In the middle of the study, the PACE team published a newsletter for participants that included glowing testimonials from earlier trial subjects about how much the 'therapy' and 'treatment' helped them. The newsletter also included an article informing participants that the two interventions pioneered by the investigators and being tested for efficacy in the trial, graded exercise therapy and cognitive behavior therapy, had been recommended as treatments by a U.K. government committee 'based on the best available evidence.' The newsletter article did not mention that a key PACE investigator was also serving on the U.K. government committee that endorsed the PACE therapies."[22]

"The PACE team changed all the methods outlined in its protocol for assessing the primary outcomes of physical function and fatigue, but did not take necessary steps to demonstrate that the revised methods and findings were robust, such as including sensitivity analyses. The researchers also relaxed all four of the criteria outlined in the protocol for defining 'recovery.' They have rejected requests from patients for the findings as originally promised in the protocol as 'vexatious.'"[22]

"The PACE claims of successful treatment and 'recovery' were based solely on subjective outcomes. All the objective measures from the trial—a walking test, a step test, and data on employment and the receipt of financial information—failed to provide any evidence to support such claims. Afterwards, the PACE authors dismissed their own main objective measures as non-objective, irrelevant, or unreliable."[22]

"In seeking informed consent, the PACE authors violated their own protocol, which included an explicit commitment to tell prospective participants about any possible conflicts of interest. The main investigators have had longstanding financial and consulting ties with disability insurance companies, having advised them for years that cognitive behavior therapy and graded exercise therapy could get claimants off benefits and back to work. Yet prospective participants were not told about any insurance industry links and the information was not included on consent forms. The authors did include the information in the 'conflicts of interest' sections of the published papers."[22]

"The Lancet Psychiatry follow-up had null findings: Two years or more after randomization, there were no differences in reported levels of fatigue and physical function between those assigned to any of the groups... Yet the authors, once again, attempted to spin this mess as a success."[181]

"This study is a piece of crap"[168]

Dr David Tuller and Julie Rehmeyer
Public health expert Dr Tuller and ME/CFS patient Julie Rehmeyer are both journalists who have written critically about the PACE authors' claims regarding the safety of Graded exercise therapy:[65]

"The study’s primary case definition for identifying participants, called the Oxford criteria, was extremely broad; it required only six months of medically unexplained fatigue, with no other symptoms necessary. Indeed, 16% of the participants didn’t even have exercise intolerance—now recognized as the primary symptom of ME/CFS".

"After the trial began, the researchers tightened their definition of harms, just as they had relaxed their methods of assessing improvement."

"[T]he study was unblinded, so both participants and therapists knew the treatment being administered. Many participants were probably aware that the researchers themselves favored graded exercise therapy and another treatment, cognitive behavior therapy, which also involved increasing activity levels. Such information has been shown in other studies to lead to efforts to cooperate, which in this case could lead to lowered reporting of harms."

Julie Rehmeyer
"... one of the most damaging cases of bad statistical practice that I have personally encountered in my years as a journalist"[182]
"... an object lesson in how our systems can break down. In this case there were serious breakdowns statistically, scientifically, journalistically and in public health."[182]

Dr Michael VanElzakker
"Subjective measures of sick people before & after they are repeatedly told 'You're not sick' is a social psych study, not a clinical trial."[183]

"In 5 years, the UK medical establishment's obdurateness on ME/CFS and PACE will be taught in medical schools as a cautionary tale."[183]

"The PACE trial is a classic case of bad science - researchers are determined to support their theory, even if the data do not."[183]

Analysis by "citizen-scientists"
Several patients and other interested parties have produced critiques of PACE's statistical analyses and trial methodology.

Robert Courtney
Mr Courtney has written a number of published letters in the medical journals, criticising PACE.
"Chalder and colleagues acknowledge that the trial outcomes do not support the hypothetical deconditioning model of GET for chronic fatigue syndrome".[184]
Peter Kemp[edit]
Peter Kemp has written a detailed critique of the study.[185]

Angela Kennedy[edit]
Angela Kennedy has made specific critiques of PACE regarding the following areas:[186]
Serious risks to clinical patient safety caused by unsound claims made about the efficacy of CBT and GET following the PACE trial;
Gross discrepancies between research and clinical cohorts, and how clinical patients (and the physiological dysfunction associated with them) appear to have been actively excluded from PACE and other research by the research group involved in PACE, which has, ironically, caused serious resulting risks to clinical patient safety in the UK in particular;
Related to the above, gross discrepancies in how various sets of patient criteria were used (and/or rejected), including but not limited to a changing of the London criteria by PACE authors from its original state, a set of criteria which was already controversial and problematic to start with for a number of reasons;
Failure of the PACE trial authors to acknowledge the range and depth of scientific literature documenting serious physiological dysfunction in patients given diagnoses of ME or CFS, and how CBT and GET approaches may endanger patients in this context;
The inclusion of major mental illnesses in the research cohort;
The distortion by PACE trial researchers of 'pacing' from an autonomous flexible management strategy for patients into a therapist led Graded Activity approach;
The post hoc dismissal of adverse outcomes as irrelevant to the trial, in direct contradiction to what is scientifically known about the physiological dysfunctions of people given diagnoses of Myalgic Encephalomyelitis or Chronic Fatigue Syndrome;
The instability of 'specialist medical care' as a treatment category, and the lack of any sound category of 'control' group.

Tom Kindlon
Mr Kindlon is a patient and Vice-Chairman of the Irish ME Association. He has published extensive criticism of the PACE trial. In 2011 he published a paper on harms associated with Graded exercise therapy.[64]
Graham McPhee and Tom Kindlon[edit]
Mr. McPhee and Mr. Kindlon and others have collaborated on a set of explanatory videos about flaws in PACE's statistical analyses:
The PACE Race
60 - The new 75
Not so bad
The force of LOGic
Tom Kindlon has also written a large number of letters and comments that have been published in medical journals in response to the published papers.
Among many other published letters that have been critical of the trial, many are from people who have identified themselves as patients. For example, most of the letters published by The Lancet criticising the 2011 PACE paper were from patients or representatives of patients' groups.[187][188][189]
MEAction[edit]
MEAction has published an overview of PACE and its flaws, produced by patients.[190]
Frank Twisk[edit]
Dutch patient Frank Twisk of the ME-de-patiënten Foundation has also published criticism of the PACE trial.[191]
"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".
"[T]he 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)".
"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".
"[L]ooking at subjective outcomes at follow-up and objective outcomes in earlier studies, such as physical fitness, return to employment, social welfare benefits, and health-care usage, CBT and GET, like specialist medical care and APT, cannot be qualified as effective".
Janelle Wiley and Graham McPhee[edit]
Janelle Wiley and Graham McPhee also collaborated with others to create a website summarising their critique of the trial.

Dear Department of Health,

FYI the PACE trial reanalysis has just been published as per the abstract found below.

Yours faithfully,

George Jenson

Journal
Fatigue: Biomedicine, Health & Behavior
Can patients with chronic fatigue syndrome really recover after graded exercise or cognitive behavioural therapy? A critical commentary and preliminary re-analysis of the PACE trial
Carolyn Wilshire, Tom Kindlon, Alem Matthees & Simon McGrath
Pages 1-14 | Received 07 Jul 2016, Accepted 06 Nov 2016, Published online: 14 Dec 2016

ABSTRACT
BACKGROUND: Publications from the PACE trial reported that 22% of chronic fatigue syndrome patients recovered following graded exercise therapy (GET), and 22% following a specialised form of CBT. Only 7% recovered in a control, no-therapy group. These figures were based on a definition of recovery that differed markedly from that specified in the trial protocol.
PURPOSE: To evaluate whether these recovery claims are justified by the evidence.
METHODS: Drawing on relevant normative data and other research, we critically examine the researchers’ definition of recovery, and whether the late changes they made to this definition were justified. Finally, we calculate recovery rates based on the original protocol-specified definition.
RESULTS: None of the changes made to PACE recovery criteria were adequately justified. Further, the final definition was so lax that on some criteria, it was possible to score below the level required for trial entry, yet still be counted as ‘recovered’. When recovery was defined according to the original protocol, recovery rates in the GET and CBT groups were low and not significantly higher than in the control group (4%, 7% and 3%, respectively).
CONCLUSIONS: 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.

Do Not Reply, Department of Health

Our ref: DE-1063443  

 

Dear Mr Jenson,

 

Thank you for your correspondence of 13 December about chronic fatigue
syndrome/myalgic encephalomyelitis (CFS/ME), the PACE trial and graded
exercise therapy (GET).  I have been asked to reply.

The Freedom of Information Act only applies to recorded information such
as paper or electronic archive material.  As your correspondence asked for
general information, rather than requesting recorded information or
documentation, it did not fall under the provisions of the Act.

           

The PACE trial undertaken by Queen Mary University of London was the
largest ever trial of treatments for CFS/ME and was funded by the Medical
Research Council, a non-departmental public body funded through the
Government’s science and research budget.  The first results from the
trial were published in 2011 in The Lancet, and a number of other
evaluations based on the trial have been published since. 

 

The trial provided evidence that both cognitive behavioural therapy (CBT)
and GET were moderately effective when provided alongside specialist
medical care (SMC) and were better than adaptive pacing therapy or SMC
alone in improving both symptoms and disability.  All the treatments were
found to be safe without any serious reactions to treatments in any of the
treatment groups.  Where patients deteriorated during the trial, this was
as a result of a serious life event or infection that prompted a relapse. 
In 2013, a follow-up study, looking at recovery after one year, was
published.  This study supported the findings that CBT and GET were
therapies most likely to lead to recovery.

 

Following a number of requests to the chief investigators of the PACE
trial for the public release of data from the study, the Information
Commissioner ruled that the Wolfson Institute at Queen Mary University of
London should release this data. 

 

The Wolfson Institute provided trial data to a member of the public, and
subsequently analysis of the data was published on a blog.  The analysis
has not been validated by publication in a peer reviewed journal or other
means.

 

The National Institute for Health and Care Excellence (NICE) is
responsible for deciding whether guidance on CFS/ME should be updated.  If
you consider that the guidance should be updated to reflect new evidence,
you may therefore wish to contact NICE directly.  The contact details are:

 

National Institute for Health and Care Excellence
10 Spring Gardens
London SW1A 2BU

 

Email: [1][email address]

 

I hope this reply is helpful.

 

Yours sincerely,
 
James Shewbridge
Ministerial Correspondence and Public Enquiries
Department of Health

 

-------------------------------------------------------------------------------------------------------------------------

Please do not reply to this email. To contact the Department of Health,
please visit the [2]Contact DH section on Gov.uk

To receive news about DH: [3]sign up to our monthly newsletter

 

show quoted sections

Incoming and outgoing e-mail messages are routinely monitored for
compliance with the Department of Health's policy on the use of electronic
communications. For more information on the Department of Health's e-mail
policy click here http://www.dh.gov.uk/terms

--------------------------------------------------------------------------

This email was scanned by the Symantec virus scanning service and was
certified virus free.
Communications may be automatically logged, monitored and/or recorded for
legal purposes.

References

Visible links
1. mailto:[email address]
2. https://www.gov.uk/government/organisati...
3. http://r1.surveysandforms.com/4c3zqo08-a...

Dear Department of Health,

I refer to your claim that the PACE trial authors claimed that PACE style GET and PACE style CBT were moderately effective on the basis of subjective criteria. This claim was made by the PACE authors but is not substantiated by the analysis of their own data in accordance with their own published trial protocol. The claim relied on weakening the outcome criteria so much that 13% of the persons sick enough to enter the trial were subsequently classified as recovered on 2 of the outcome criteria.

A reanalysis of a small amount of the raw data (released by order of the first tribunal) found PACE style GET and CBT to be ineffective and even the PACE authors claims were never backed up by their objective evidence. After a year of PACE- style GET particpants on average could walk a further 33 meters and remained as severely ill as patients with stage 3 congestive heart disease.

I request recorded/written information that the Department of Health has on how it views the PACE trial authors claims given the misleading claims made by the PACE authors.

Yours faithfully,

George Jenson

Results of Reanalysis
Virology blog published the re-analysis on 21 September No ‘Recovery’ in PACE Trial, New Analysis Finds and concluded " The results should put to rest once and for all any question about whether the PACE trial’s enormous mid-trial changes in assessment methods allowed the investigators to report better results than they otherwise would have had. While the answer was obvious from Dr. Tuller’s reporting, the new analysis makes the argument incontrovertible."
The full re-analysis was published as 'A preliminary analysis of ‘recovery’ from chronic fatigue syndrome in the PACE trial using individual participant data' and was conducted by Alem Matthees, Tom Kindlon, Carly Maryhew, Philip Stark and Bruce Levin and stated "This re-analysis demonstrates that the previously reported recovery rates were inflated by an average of four-fold.".

On 19 August 2016 The Centre for Welfare Reform also published an update, to its earlier 64 page report from April 2016, called Major breakthrough on PACE trial[221].

'A critical commentary and preliminary re-analysis of the PACE trial' was published in December 2016 in the Journal of 'Fatigue: Biomedicine, Health & Behavior' by Dr Carolyn Wilshire, Tom Kindlon, Alem Matthees and Simon McGrath which found that "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"[222] [223].

'A Rejoinder to Sharpe, Chalder, Johnson, Goldsmith and White' was published by Dr Carolyn Wilshire, Tom Kindlon and Simon McGrath in response to the PACE authors reply to their original publication [224].

Wilshire et al disproved again the PACE trials misleading claims as recovery was a strong claim and did not adhere to the core meaning of the word, no evidence that the original protocol specified definition was too stringent and absolute recovery rates from other studies were not legitimate source of support for the recovery definition used. It reinforced the original conclusion that "The PACE trial provides no evidence that CBT and GET can lead to recovery from CFS. The recovery claims made in the PACE trial are therefore misleading for patients and clinicians".

Instead of engaging with critics by releasing other additional requests for data, the PACE trial authors updated their guidelines in January 2017 for those requesting access to the PACE trial data which further restricted access by requiring "formal agreement" with "precise analytic plans, and plans for outputs" [225].

Prof James Coyne commented that it is "a ruse to trap the unwary in endless haggling and appeal, while protecting the PACE investigators from the independent reanalysis of the claims, which they have already declared poses a reputational risk to them". [226]

Results of Reanalysis
Virology blog published the re-analysis on 21 September No ‘Recovery’ in PACE Trial, New Analysis Finds and concluded " The results should put to rest once and for all any question about whether the PACE trial’s enormous mid-trial changes in assessment methods allowed the investigators to report better results than they otherwise would have had. While the answer was obvious from Dr. Tuller’s reporting, the new analysis makes the argument incontrovertible."

FreedomofInformation, Department of Health

1 Attachment

Dear Mr Jenson

 

Please find our reply attached (FOI 1085858).

 

Yours sincerely

Dorothy Crowe

Freedom of Information

Department of Health

 

 

show quoted sections

Incoming and outgoing e-mail messages are routinely monitored for
compliance with the Department of Health's policy on the use of electronic
communications. For more information on the Department of Health's e-mail
policy click here http://www.dh.gov.uk/terms

--------------------------------------------------------------------------

This email was scanned by the Symantec virus scanning service and was
certified virus free.
Communications may be automatically logged, monitored and/or recorded for
legal purposes.

Dear FreedomofInformation,
Your response to my request was that "DH does not hold this information, as DH has not outlined its own view of the PACE trial
authors. To establish that this information is not held, I contacted the relevant policy officials" This response is at odds with the serious systemic problems in the PACE trial authors claims and at odds with common sense.
The PACE trials faults and flaws are widely critiqued and NO answers satisfactorily addressing these problems have been provided.
I can not accept that the DoH has no correspondence or information on this issue given its severe impact on the lives of patients with ME/CFS in the UK.
Hence I request a review of this decision.

Yours sincerely,

George Jenson

Sehdev, Harish, Department of Health

Dear Mr Jenson,

Thank you for your request of an internal review into the handling of FOI 1085858.

I have accepted your request and will endeavour to get back to you within 20 working day, in this case by 4 August 2017.

Thanks
Harish

Harish Sehdev
Deputy Head of Freedom of Information
Department of Health, Room G18, Richmond House,
79 Whitehall, SW1A 2NS
Follow us on Twitter @DHgovuk

show quoted sections

Dear Sehdev, Harish,
I am still waiting for information held by the Department of Health on its view of the PACE trial.

As the Department of Health will be aware the USA has firmly rejected the flawed and fault ridden PACE trial, and the misleading claims by the PACE authors.
The USA National Institute for health is carrying out comprehensive biomedical studies into the disease and thousands of papers have been published on various biomedical abnormalities.

The Centre for Disease Control has removed all reference to PACE "treatments" ie GET (graded exercise theraphy) and CBT (cognitive behaviour theraphy) from its website and recommendations.

On 31 July the Journal of Health Psychology devoted a chapter to the PACE trial and noted the lack of authentic discussion and debate by the co-principal investigators.

The health of people with chronic fatigue syndrome - myalgic encephalomyelitis is extremely poor with many severely disabled for decades. It is estimated that 33% commit suicide and only 4% recover, the prevalence is estimated at 1%.

Given the enormous cost of the disease to the Department of Health and the UK tax payer, I am certain that information must be to hand on the PACE trial that forms the basis of "medical treatment" offered to patients in the UK.

It is more than 20 days after the date on which you said you would get back to me.

Yours sincerely,

George Jenson

Critique of PACE
"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"

Article Information
Volume: 22 issue: 9, page(s): 1103-1105
Article first published online: July 31, 2017;Issue published: August 1, 2017
DOI: https://doi.org/10.1177/1359105317722370
David F Marks

FreedomofInformation, Department of Health

Dear Mr Jenson,

I apologise for the delay in getting back to you, unfortunately we require more time to complete your requested review.

I will keep you updated.

Kind regards,

Harish Sehdev
Deputy Head of Freedom of Information
Department of Health, Room G18, Richmond House,
79 Whitehall, SW1A 2NS
Follow us on Twitter @DHgovuk

Dear Sehdev

I note that the Department of Health's response is still in progress.

It is of great concern that UK research into the disease chronic fatigue syndrome is extremely flawed and unsubstantiated claims are made by UK "PACE" mental health research professionals that are at odds with biomedical researchers and objective science.

One of the PACE authors claims is that exercise is not harmful to people with the disease, this claim is unsubstantiated by their research. The PACE trial did not look at the key distinguishing symptom of the disease i.e. an abnormal and delayed exacerbation of symptoms after exertion.

The claim by PACE authors that exercise, as per the PACE model, is safe, is not based on objective data of physiological or biomedical changes in patients pre/post exercise nor did the PACE authors have the trial participants keep a record of their symptoms after exercise.

The PACE authors claims of exercise not having the potential to greatly harm patients is at odds with both the patients lived experiences and the findings of physiological and biomedical scientists in the patients response to exercise. A summary of a few papers is listed here: https://paradigmchange.me/me/exercise/

I look forward to receipt of the information held by the DoH in relation to the PACE trial.

Kind regards

George Jenson

An exercise challenge test used for diagnosis.

One of the critical diagnostic criteria for myalgic encephalomyelitis (M.E.) is intolerance of abnormally small amounts of activity or exercise.
By definition, M.E. patients experience “post-exertional relapse” (also sometimes called “post-exertional malaise” or “post-exertional neuroimmune exhaustion”), with their condition getting measurably worse following activity or exercise.

In more severe cases of the illness, relapse can occur for days or weeks following even brief mild activity.
Dozens of studies have looked at this abnormal response to exercise, uncovering numerous physiological abnormalities.

M.E. patients experience abnormally increased inflammation, oxidative stress, C4a complement levels and intramuscular acidosis after exercise. For them, exercise also results in abnormal gene and heat shock protein expression, decreased cerebral oxygenation, lowered mitochondrial ATP, and extended abnormal pH.

Most people get a variety of positive effects from exercise, including increased energy, better sleep and decreased sensitivity to pain. M.E. patients get the opposite: increased fatigue, insomnia, higher levels of pain, and other negative symptoms.

Especially in the first years of the illness, M.E. patients often try to be active at a higher level than their bodies can tolerate. This usually leads to a “push-crash” pattern: a burst of activity is followed by an extended period of relapse and recovery.

Thus, a challenge for M.E. patients is how to remain even a little active without experiencing repeated “crashes.”
Following is a list (in reverse chronological order) of peer-reviewed articles from medical journals on the phenomenon of exercise intolerance in myalgic encephalomyelitis and the broader condition of chronic fatigue syndrome.

The two-day exercise test discussed in some of these journal articles is now widely accepted as a good diagnostic for ME/CFS and has been helpful in allowing many patients to be approved for disability benefits.

Shukla SK, Cook D, Meyer J, Vernon SD, Le T, Clevidence D, Robertson CE, Schrodi SJ, Yale S, Frank DN. Changes in Gut and Plasma Microbiome following Exercise Challenge in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). PLoS One. 2015 Dec 18;10(12):e0145453. PMID: 26683192Following maximal exercise challenge, there was an increase in relative abundance of 6 of the 9 major bacterial phyla/genera in ME/CFS patients from baseline to 72 hours post-exercise compared to only 2 of the 9 phyla/genera in controls (p = 0.005). There was also a significant difference in clearance of specific bacterial phyla from blood following exercise with high levels of bacterial sequences maintained at 72 hours post-exercise in ME/CFS patients versus clearance in the controls. These findings suggest a role for an altered gut microbiome and increased bacterial translocation following exercise in ME/CFS patients.
Nijs J, Nees A, Paul L, De Kooning M, Ickmans K, Meeus M, Van Oosterwijck J. Altered immune response to exercise in patients with chronic fatigue syndrome/myalgic encephalomyelitis: a systematic literature review. Exerc Immunol Rev. 2014;20:94-116. PMID: 24974723 A literature review suggested that compared to the normal response of the immune system to exercise as seen in healthy subjects, patients with CFS have a more pronounced response in the complement system (i.e. C4a split product levels), oxidative stress system (i.e. enhanced oxidative stress combined with a delayed and reduced anti-oxidant response), and an alteration in the immune cells’ gene expression profile (increases in post-exercise interleukin-10 and toll-like receptor 4 gene expression), but not in circulating pro- or anti-inflammatory cytokines. This provided evidence for an altered immune response to exercise in patients with CFS.

Keller BA, Pryor JL, Giloteaux L. Inability of myalgic encephalomyelitis/chronic fatigue syndrome patients to reproduce VO₂peak indicates functional impairment. J Transl Med. 2014 Apr 23;12:104. PMID: 24755065 This study of repeat cardiopulmonary exercise tests showed that ME/CFS participants were unable to reproduce most physiological measures at both maximal and ventilatory threshold intensities during a CPET performed 24 hours after a prior maximal exercise test.

Vermeulen RC, Vermeulen van Eck IW. Decreased oxygen extraction during cardiopulmonary exercise test in patients with chronic fatigue syndrome. J Transl Med. 2014 Jan 23;12:20. PMID: 24456560 Low oxygen uptake by muscle cells was found to cause exercise intolerance in a majority of CFS patients, indicating insufficient metabolic adaptation to incremental exercise. The high increase of the cardiac output relative to the increase of oxygen uptake argued against deconditioning as a cause for physical impairment in these patients.

Learmonth YC, Paul L, McFadyen AK, Marshall-McKenna R, Mattison P, Miller L. McFarlane NG. Short-term effect of aerobic exercise on symptoms in multiple sclerosis and chronic fatigue syndrome: a pilot study. Int J MS Care. 2014 Summer;16(2):76-82. PMID: 25061431 Undertaking 15 minutes of moderate-intensity aerobic cycling exercise had no significant adverse effects on pain or function in people with MS and CFS (with a Karnofsky score of 50-80) within a 24-hour time period.

Snell CR, Stevens SR, Davenport TE, Van Ness JM. Discriminative validity of metabolic and workload measurements for identifying people with chronic fatigue syndrome. Phys Ther. 2013 Nov;93(11):1484-92. PMID: 23813081 The objective of this study was to determine the discriminative validity of objective measurements obtained during cardiopulmonary exercise testing to distinguish participants with CFS from participants who did not have a disability but were sedentary. The lack of any significant differences between groups for the first exercise test would appear to support a deconditioning hypothesis for CFS symptoms. However, the results from the second test indicated the presence of CFS-related postexertion fatigue.

Strahler J, Fischer S, Nater UM, Ehlert U, Gaab J. Norepinephrine and epinephrine responses to physiological and pharmacological stimulation in chronic fatigue syndrome. Biol Psychol. 2013 Sep;94(1):160-6. PMID: 23770415 The researchers found evidence of altered sympathetic-neural and sympathetic adrenomedulla reactivity in CFS. Exercise stress revealed a subtle catecholaminergic hyporeactivity in CFS patients.
Kishi A, Togo F, Cook DB, Klapholz M, Yamamoto Y, Rapoport DM, Natelson BH. The effects of exercise on dynamic sleep morphology in healthy controls and patients with chronic fatigue syndrome. Physiol Rep. 2013 Nov;1(6):e00152. PMID: 24400154 Exercise promoted transitions to deeper sleep stages and inhibited transitions to lighter sleep stages for controls and CFS, but CFS also reported increased fatigue and continued to have REM sleep disruption.
Nakamura T, Schwander S, Donnelly R, Cook DB, Ortega F, Togo F, Yamamoto Y, Cherniack NS, Klapholz M, Rapoport D, Natelson BH. Exercise and sleep deprivation do not change cytokine expression levels in patients with chronic fatigue syndrome. Clin Vaccine Immunol. 2013 Nov;20(11):1736-42. PMID: 24027260
The researchers conducted repeat blood sampling for cytokine levels from healthy subjects and CFS patients during both postexercise and total sleep deprivation nights and assayed for protein levels in the blood samples, mRNA activity in peripheral blood lymphocytes (PBLs), and function in resting and stimulated PBLs. They found that these environmental manipulations did not produce clinically significant upregulation of proinflammatory cytokines.
White AT, Light AR, Hughen RW, Vanhaitsma TA, Light KC. Differences in metabolite-detecting, adrenergic, and immune gene expression after moderate exercise in patients with chronic fatigue syndrome, patients with multiple sclerosis, and healthy controls. Psychosom Med. 2012 Jan;74(1):46-54. PMID: 22210239 Postexercise mRNA increases in metabolite-detecting receptors were unique to patients with CFS, whereas both patients with MS and patients with CFS showed abnormal increases in adrenergic receptors. Among patients with MS, greater fatigue was correlated with blunted immune marker expression.
Cook DB, Stegner AJ, Nagelkirk PR, Meyer JD, Togo F, Natelson BH. Responses to exercise differ for chronic fatigue syndrome patients with fibromyalgia. Med Sci Sports Exerc. 2012 Jun;44(6):1186-93. PMID: 22157881 The purpose of the present study was to examine cardiac and perceptual responses to steady-state submaximal exercise in CFS patients and healthy controls. The CFS + FM group exhibited an exercise response characterized by higher stroke index, ventilatory equivalents for oxygen and carbon dioxide and rating of perceived exertion, lower systolic blood pressure, and similar HR responses compared to controls.
Jammes Y, Steinberg JG, Delliaux S. Chronic fatigue syndrome: acute infection and history of physical activity affect resting levels and response to exercise of plasma oxidant/antioxidant status and heat shock proteins. J Intern Med. 2011 Nov 24. PMID: 22112145 The presence of stress factors in the history of CFS patients is associated with severe oxidative stress and the suppression of protective HSP27 and HSP70 responses to exercise.
Jones DE, Hollingsworth KG, Jakovljevic DG, Fattakhova G, Pairman J, Blamire AM, Trenell MI, Newton JL. Loss of capacity to recover from acidosis on repeat exercise in chronic fatigue syndrome: a case-control study. Eur J Clin Invest. 2011 Jun 10. PMID: 21749371 CFS patients exhibit “profound abnormality in bioenergetic function.” When they exercise at the level of normal people, they demonstrate increased intramuscular acidosis that does not decrease normally with repeated exercise. Compared to normal people, it also takes four times as long for their pH to return to baseline after exercise.
Nijs J, Meeus M, Van Oosterwijck J, Ickmans K, Moorkens G, Hans G, De Clerck LS. In the mind or in the brain? Scientific evidence for central sensitisation in chronic fatigue syndrome. Eur J Clin Invest. 2011 Jul 2. PMID: 21793823 CFS patients suffer from hyperresponsiveness of the central nervous system to various stimuli, including heat, mechanical pressure, electrical stimulation and histamine. Exercise worsens this tendency.
Light AR, Bateman L, Jo D, Hughen RW, Vanhaitsma TA, White AT, Light KC. Gene expression alterations at baseline and following moderate exercise in patients with Chronic Fatigue Syndrome and Fibromyalgia Syndrome. J Intern Med. 2011 May 26. PMID: 21615807. CFS patients exhibited two different abnormal responses to exercise. Some patients demonstrated abnormal increases in mRNA for sensory and adrenergic receptors and a cytokine, resulting in fatigue or pain. A second group demonstrated abnormal decreases in adrenergic α-2A receptor’s transcription. None of the normal patients in the study showed these responses, and the authors thus suggest that this finding has the potential of serving as a biomarker for the disease.
Davenport TE, Stevens SR, Baroni K, Van Ness M, Snell CR. Diagnostic accuracy of symptoms characterising chronic fatigue syndrome. Disabil Rehabil. 2011 Jan 6. PMID: 21208154 Presence of just three measures (fatigue, sleep and pain) was effective in predicting exercise intolerance — a definitional indicator of CFS status.
Vermeulen RC, Kurk RM, Visser FC, Sluiter W, Scholte HR. Patients with chronic fatigue syndrome performed worse than controls in a controlled repeated exercise study despite a normal oxidative phosphorylation capacity. J Transl Med. 2010 Oct 11;8:93. CFS patients reached the anaerobic threshold and the maximal exercise at a much lower oxygen consumption than the controls, and this worsened in the second test. This implies an increase of lactate, the product of anaerobic glycolysis, and a decrease of the mitochondrial ATP production in the patients.
Meeus M, Ickmans K, De Clerck LS, Moorkens G, Hans G, Grosemans S, Nijs J. Serotonergic descending inhibition in chronic pain: design, preliminary results and early cessation of a randomized controlled trial. In Vivo. 2011 Nov-Dec;25(6):1019-25. PMID: 22021700. The authors administered the antidepressant citalopram to CFS patients and then had them perform a submaximal exercise protocol, preceded and followed by an assessment of endogenous pain inhibition. Significant negative effects were observed in all patients and the authors decided that proceeding with the study would be unethical.
Meeus M, Roussel NA, Truijen S, Nijs J. Reduced pressure pain thresholds in response to exercise in chronic fatigue syndrome but not in chronic low back pain: an experimental study. J Rehabil Med. 2010 Oct;42(9):884-90. PMID: 20878051. CFS patients show hyperalgesia and abnormal central pain processing during submaximal aerobic exercise.
Meeus M, van Eupen I, van Baarle E, De Boeck V, Luyckx A, Kos D, Nijs J. Symptom fluctuations and daily physical activity in patients with chronic fatigue syndrome: a case-control study. Arch Phys Med Rehabil. 2011 Nov;92(11):1820-6. PMID: 22032215. The more that patients with CFS are sedentary and the better activity is dispersed, the fewer symptoms and variations they experience on the same and next day. Inversely, more symptoms and variability is experienced when patients were more active that day or the previous day.
Suárez A, Guillamo E, Roig T, Blázquez A, Alegre J, Bermúdez J, Ventura JL, García-Quintana AM, Comella A, Segura R, Javierre C. Nitric Oxide Metabolite Production During Exercise in Chronic Fatigue Syndrome: A Case-Control Study. J Womens Health (Larchmt). 2010 May 14. PMID: 20469961. CFS patients had a higher increase in nitric oxide metabolites after exercise than did controls.
Nijs J, Van Oosterwijck J, Meeus M, Lambrecht L, Metzger K, Frémont M, Paul L. Unravelling the nature of postexertional malaise in myalgic encephalomyelitis/chronic fatigue syndrome: the role of elastase, complement C4a and interleukin-1beta. J Intern Med. 2010 Apr;267(4):418-35. PMID: 20433584. Following exercise, complement C4a levels go up more in CFS patients than in healthy people.
Maes M, Twisk FN. Chronic fatigue syndrome: Harvey and Wessely’s (bio)psychosocial model versus a bio(psychosocial) model based on inflammatory and oxidative and nitrosative stress pathways. BMC Med. 2010 Jun 15;8:35. PMID: 20550693. The authors describe how physiological abnormalities related to inflammatory, immune, oxidative and nitrosative pathways interfere with exercise tolerance in CFS.
Jones DE, Hollingsworth KG, Taylor R, Blamire AM, Newton JL. Abnormalities in pH handling by peripheral muscle and potential regulation by the autonomic nervous system in chronic fatigue syndrome. J Intern Med. 2010 Apr;267(4):394-401. PMID: 20433583. CFS patients displayed abnormalities in recovery of intramuscular pH, related to autonomic dysfunction, following exercise.
White AT, Light AR, Hughen RW, Bateman L, Martins TB, Hill HR, Light KC. Severity of symptom flare after moderate exercise is linked to cytokine activity in chronic fatigue syndrome. Psychophysiology. 2010 Mar 4. PMID: 20230500. CFS patients often display negative responses to exercise, as a result of abnormal inflammatory cytokine activity.
Robinson M, Gray SR, Watson MS, Kennedy G, Hill A, Belch JJ, Nimmo MA. Plasma IL-6, its soluble receptors and F2-isoprostanes at rest and during exercise in chronic fatigue syndrome. Scand J Med Sci Sports. 2010 Apr;20(2):282-90. PMID: 19422646. CFS patients have higher levels of F(2)-isoprostanes, an indicator of oxidative stress, after exercise.
Van Oosterwijck J, Nijs J, Meeus M, Lefever I, Huybrechts L, Lambrecht L, Paul L. Pain inhibition and postexertional malaise in myalgic encephalomyelitis/chronic fatigue syndrome: an experimental study. J Intern Med. 2010 Sep;268(3):265-78. PMID: 20412374. Healthy subjects are able to tolerate a higher level of pain following exercise, while CFS patients are able to tolerate a lower level of pain following exercise.
Brown M, Khorana N, Jason LA. The role of changes in activity as a function of perceived available and expended energy in nonpharmacological treatment outcomes for ME/CFS. J Clin Psychol. 2010 Oct 25. PMID: 20976708. CFS patients who were within their energy envelope before treatment showed more improvement in physical functioning and fatigue compared with those outside of their energy envelope.
VanNess JM, Stevens SR, Bateman L, Stiles TL, Snell CR. Postexertional malaise in women with chronic fatigue syndrome. J Womens Health (Larchmt). 2010 Feb;19(2):239-44. PMID: 20095909. Following an exercise test, all the normal sedentary controls recovered quickly (within 24-48 hours) while none of the CFS patients did. Symptoms the patients reported after the test included fatigue, light-headedness, muscular/joint pain, cognitive dysfunction, headache, nausea, physical weakness, trembling/instability, insomnia and sore throat/glands.
Light AR, White AT, Hughen RW, Light KC. Moderate exercise increases expression for sensory, adrenergic, and immune genes in chronic fatigue syndrome patients but not in normal subjects. J Pain. 2009 Oct;10(10):1099-112. PMID: 19647494. After sustained moderate exercise, CFS patients showed greater increases than control subjects in gene expression for metabolite detecting receptors ASIC3, P2X4, and P2X5, for SNS receptors alpha-2A, beta-1, beta-2, and COMT and IS genes for IL10 and TLR4. This correlated with an exacerbation in their symptoms.
Twisk FN, Maes M. A review on cognitive behavioral therapy (CBT) and graded exercise therapy (GET) in myalgic encephalomyelitis (ME) / chronic fatigue syndrome (CFS): CBT/GET is not only ineffective and not evidence-based, but also potentially harmful for many patients with ME/CFS. Neuro Endocrinol Lett. 2009;30(3):284-99. PMID: 19855350. The authors discuss how the use of exercise therapy in CFS may be harmful to patients.
Maes M. Inflammatory and oxidative and nitrosative stress pathways underpinning chronic fatigue, somatization and psychosomatic symptoms. Curr Opin Psychiatry. 2009 Jan;22(1):75-83. PMID: 19127706. The authors review recent findings on inflammatory and oxidative and nitrosative stress (IO&NS) pathways in CFS and suggest that for these patients, exercise can be a trigger factor causing damage.
Sorensen B, Jones JF, Vernon SD, Rajeevan MS. Transcriptional control of complement activation in an exercise model of chronic fatigue syndrome. Mol Med. 2009 Jan-Feb;15(1-2):34-42. PMID: 19015737. Mannan-binding lectin serine protease 2 (MASP2) was higher than normal following exercise in CFS patients, and this seems related to the phenomenon of post-exertional malaise.
Jammes Y, Steinberg JG, Delliaux S, Brégeon F. Chronic fatigue syndrome combines increased exercise-induced oxidative stress and reduced cytokine and Hsp responses. J Intern Med. 2009 Aug;266(2):196-206. PMID: 19457057. CFS patients have more severe and longer oxidative stress following exercise, and this may result from delayed and insufficient heat shock proteins protecting the cells.
Paul L, Rafferty D, Marshal R. Physiological cost of walking in those with chronic fatigue syndrome (CFS): a case-control study. Disabil Rehabil. 2009;31(19):1598-604. PMID: 19848558. Compared to controls walking at the same speed, CFS patients had a lower gross and net oxygen uptake and suffered a higher physiological cost.
Maes M, Twisk FN. Chronic fatigue syndrome: la bête noire of the Belgian health care system. Neuro Endocrinol Lett. 2009;30(3):300-11. PMID: 19855351. In case reports, the authors show that Belgian patients who received Graded Exercise Therapy in fact suffered from disorders of the inflammatory/oxidative/nitrosative stress pathways, including intracellular inflammation, an increased translocation of gram-negative enterobacteria (leaky gut), autoimmune reactions and damage by O&NS. They suggest that exercise was inappropriate treatment and recommend policy changes.
Jason L, Benton M, Torres-Harding S, Muldowney K. The impact of energy modulation on physical functioning and fatigue severity among patients with ME/CFS. Patient Educ Couns. 2009 Nov;77(2):237-41. PMID: 19356884. CFS patients who were able to keep their expended energy close to available energy (i.e. were able to stay within their “energy envelope”) experienced significant improvements in physical functioning and fatigue severity.
Weinstein AA, Drinkard BM, Diao G, Furst G, Dale JK, Straus SE, Gerber LH. Exploratory analysis of the relationships between aerobic capacity and self-reported fatigue in patients with rheumatoid arthritis, polymyositis, and chronic fatigue syndrome. PM R. 2009 Jul;1(7):620-8. PMID: 19627955. Patients with CFS have significantly decreased aerobic capacity. Self-reports of physical activity predicted VO(2peak), and may be used as an indicator of activity-based aerobic capacity. Self-reports of fatigue, however, did not correlate with VO(2peak) and hence are assessing something other than an index of aerobic capacity.
Thambirajah AA, Sleigh K, Stiver HG, Chow AW. Differential heat shock protein responses to strenuous standardized exercise in chronic fatigue syndrome patients and matched healthy controls. Clin Invest Med. 2008 Dec 1;31(6):E319-27. PMID: 19032901. Heat shock protein expression following exercise is abnormal in CFS, suggesting an abnormal response to oxidative stress. This has potential of serving as a biomarker.
Patrick Neary J, Roberts AD, Leavins N, Harrison MF, Croll JC, Sexsmith JR. Prefrontal cortex oxygenation during incremental exercise in chronic fatigue syndrome. Clin Physiol Funct Imaging. 2008 Nov;28(6):364-72. PMID: 18671793. Decreased cerebral oxygenation and blood flow may make contribute to the reduced exercise abilities in CFS.
Nijs J, Almond F, De Becker P, Truijen S, Paul L. Can exercise limits prevent post-exertional malaise in chronic fatigue syndrome? An uncontrolled clinical trial. Clin Rehabil. 2008 May;22(5):426-35. PMID: 18441039. Limiting both the intensity and duration of exercise prevents important health status changes following a walking exercise in people with CFS, but was unable to prevent short-term symptom increases.
Nijs J, Zwinnen K, Meeusen R, de Geus B, De Meirleir K. Comparison of two exercise testing protocols in patients with chronic fatigue syndrome. J Rehabil Res Dev. 2007;44(4):553-9. PMID: 18247252. CFS patients engaging in a stepwise exercise protocol had lower mechanical efficiency (ratio peak workload/peak oxygen uptake) than those engaging in a linear exercise protocol.
Nijs J, Demol S, Wallman K. Can submaximal exercise variables predict peak exercise performance in women with chronic fatigue syndrome? Arch Med Res. 2007 Apr;38(3):350-3. PMID: 17350488. This study aimed at examining whether physiological exercise variables at the submaximal level, defined as 75% of the age-predicted target heart rate, are able to predict peak exercise performance in women with chronic fatigue syndrome (CFS).
Yoshiuchi K, Cook DB, Ohashi K, Kumano H, Kuboki T, Yamamoto Y, Natelson BH. A real-time assessment of the effect of exercise in chronic fatigue syndrome. Physiol Behav. 2007 Dec 5;92(5):963-8. PMID: 17655887. CFS patients experienced increased physical symptoms after exercise, on average with a five-day delay. Psychological symptoms and cognitive functioning did not change after exercise.
Nijs J, Meeus M, De Meirleir K. Chronic musculoskeletal pain in chronic fatigue syndrome: recent developments and therapeutic implications. Man Ther. 2006 Aug;11(3):187-91. PMID: 16781183. CFS sufferers respond to incremental exercise with a lengthened and accentuated oxidative stress response, explaining muscle pain, postexertional malaise, and the decrease in pain threshold following graded exercise in CFS patients.
Cook DB, Nagelkirk PR, Poluri A, Mores J, Natelson BH. The influence of aerobic fitness and fibromyalgia on cardiorespiratory and perceptual responses to exercise in patients with chronic fatigue syndrome. Arthritis Rheum. 2006 Oct;54(10):3351-62. PMID: 17009309. In the overall sample, there were no significant differences in cardiorespiratory parameters between the CFS only group and the controls. However, the CFS plus FM group exhibited lower ventilation, lower end-tidal CO2, and higher ventilatory equivalent of carbon dioxide compared with controls, and slower increases in heart rate compared with both patients with CFS only and controls. Peak oxygen consumption, ventilation, and workload were lower in the CFS plus FM group. Subjects in both the CFS only group and the CFS plus FM group rated exercise as more effortful than did controls.
Nijs J, Meeus M, McGregor NR, Meeusen R, de Schutter G, van Hoof E, de Meirleir K. Chronic fatigue syndrome: exercise performance related to immune dysfunction. Med Sci Sports Exerc. 2005 Oct;37(10):1647-54. PMID: 16260962. There appears to be an association between intracellular immune deregulation and exercise performance in patients with CFS.
Jammes Y, Steinberg JG, Mambrini O, Brégeon F, Delliaux S. Chronic fatigue syndrome: assessment of increased oxidative stress and altered muscle excitability in response to incremental exercise. J Intern Med. 2005 Mar;257(3):299-310. PMID: 15715687. Following exercise, CFS patients have lengthened and accentuated oxidative stress together with marked alterations of the muscle membrane excitability.
Nijs J, De Meirleir K. Impairments of the 2-5A synthetase/RNase L pathway in chronic fatigue syndrome. In Vivo. 2005 Nov-Dec;19(6):1013-21. PMID: 16277015. The 2′-5′ oligoadenylate (2-5 A) synthetase/RNase L pathway in CFS patients appears to be both upregulated and deregulated, and this seems to be related to performance during a graded exercise stress test.
Black CD, McCully KK. Time course of exercise induced alterations in daily activity in chronic fatigue syndrome. Dyn Med. 2005 Oct 28;4:10. PMID: 16255779. CFS patients who attempt to increase their activity by participating in a daily walking program have a difficult time maintaining that increase over time and usually compensate by reducing other activity.
Bazelmans E, Bleijenberg G, Voeten MJ, van der Meer JW, Folgering H. Impact of a maximal exercise test on symptoms and activity in chronic fatigue syndrome. J Psychosom Res. 2005 Oct;59(4):201-8. PMID: 16223622. After exercise, CFS patients reported fatigue for an additional two days, compared to two hours for matched sedentary controls.
Snell CR, Vanness JM, Strayer DR, Stevens SR. Exercise capacity and immune function in male and female patients with chronic fatigue syndrome (CFS). In Vivo. 2005 Mar-Apr;19(2):387-90. PMID: 15796202. Abnormal immune activity related to oxidative stress, nitric oxide related toxicity and hyperactivation of Rnase-L is related to exercise intolerance in CFS patients.
Whistler T, Jones JF, Unger ER, Vernon SD. Exercise responsive genes measured in peripheral blood of women with chronic fatigue syndrome and matched control subjects. BMC Physiol. 2005 Mar 24;5(1):5. PMID: 15790422. Following an exercise challenge, CFS patients differed from controls on a variety of genes, including chromatin and nucleosome assembly, cytoplasmic vesicles, membrane transport and G protein-coupled receptor ontologies. Differences in ion transport and ion channel activity were evident at baseline and exaggerated after exercise.
Nijs J, De Meirleir K. Prediction of peak oxygen uptake in patients fulfilling the 1994 CDC criteria for chronic fatigue syndrome. Clin Rehabil. 2004 Nov;18(7):785-92. PMID: 15573835. A technique to predict peak oxygen uptake in CFS patients was developed.
Whiteside A, Hansen S, Chaudhuri A. Exercise lowers pain threshold in chronic fatigue syndrome. Pain. 2004 Jun;109(3):497-9. PMID: 15157711. During exercise, normal people have higher pain thresholds and CFS patients have lower pain thresholds.
Nijs J, Vanherberghen K, Duquet W, De Meirleir K. Chronic fatigue syndrome: lack of association between pain-related fear of movement and exercise capacity and disability. Phys Ther. 2004 Aug;84(8):696-705. PMID: 15283620. This study shows a lack of correlation between kinesiophobia (fear of movement) and exercise capacity, activity limitations, or participation restrictions, at least in patients with CFS who are experiencing widespread muscle or joint pain.
Siemionow V, Fang Y, Calabrese L, Sahgal V, Yue GH. Altered central nervous system signal during motor performance in chronic fatigue syndrome. Clin Neurophysiol. 2004 Oct;115(10):2372-81. PMID: 15351380. CFS involves altered central nervous system signals in controlling voluntary muscle activities, especially when the activities induce fatigue.
McCully KK, Smith S, Rajaei S, Leigh JS Jr, Natelson BH. Muscle metabolism with blood flow restriction in chronic fatigue syndrome. J Appl Physiol. 2004 Mar;96(3):871-8. PMID: 14578362. CFS patients have evidence of hyperemic flow and reduced oxygen delivery, but this does not seem to result in disturbed muscle metabolism.
Nijs J, De Meirleir K, Wolfs S, Duquet W. Disability evaluation in chronic fatigue syndrome: associations between exercise capacity and activity limitations/participation restrictions. Clin Rehabil. 2004 Mar;18(2):139-48. PMID: 15053122. These results suggest a moderate association between exercise capacity and activity limitations/participation restrictions in patients with CFS. The observed correlations lack strength to predict activity limitations/ participation restriction based on exercise capacity parameters.
Sorensen B, Streib JE, Strand M, Make B, Giclas PC, Fleshner M, Jones JF. Complement activation in a model of chronic fatigue syndrome. J Allergy Clin Immunol. 2003 Aug;112(2):397-403. PMID: 12897748. Exercise challenge induced significant increases of the complement split product C4a, but not C3a or C5a, at 6 hours after exercise only in the CFS group. This has potential of serving as a biomarker.
Vanness JM, Snell CR, Strayer DR, Dempsey L 4th, Stevens SR. Subclassifying chronic fatigue syndrome through exercise testing. Med Sci Sports Exerc. 2003 Jun;35(6):908-13. PMID: 12783037. Severely affected CFS patients are more impaired during exercise stress tests in terms of peak systolic blood pressure and peak heart rate.
Snell CR, Vanness JM, Strayer DR, Stevens SR. Physical performance and prediction of 2-5A synthetase/RNase L antiviral pathway activity in patients with chronic fatigue syndrome. In Vivo. 2002 Mar-Apr;16(2):107-9. PMID: 12073768. Seventy-three CFS patients performed a graded exercise test to voluntary exhaustion. Forty-six patients had elevated RNase L levels. The elevated RNase L group had a lower peak V02 and duration than the normal group, but a higher KPS. Both Rnase L and exercise intolerance have potential as biomarkers for CFS.
Ohashi K, Yamamoto Y, Natelson BH. Activity rhythm degrades after strenuous exercise in chronic fatigue syndrome. Physiol Behav. 2002 Sep;77(1):39-44. PMID: 12213500. CFS patients had an abnormal lengthening (P < .05) of mean circadian period (MCP) after exercise that was longer than 24 hours.

Farquhar WB, Hunt BE, Taylor JA, Darling SE, Freeman R. Blood volume and its relation to peak O(2) consumption and physical activity in patients with chronic fatigue. Am J Physiol Heart Circ Physiol. 2002 Jan;282(1):H66-71. PMID: 11748048. CFS patients tend to have low blood volume and low peak oxygen consumption, and this seems to be related to their exercise intolerance.

Inbar O, Dlin R, Rotstein A, Whipp BJ. Physiological responses to incremental exercise in patients with chronic fatigue syndrome. Med Sci Sports Exerc. 2001 Sep;33(9):1463-70. PMID: 11528333. CFS patients demonstrated significantly lower cardiovascular as well as ventilatory values at peak exercise, compared with the control group.

Jason LA, Melrose H, Lerman A, Burroughs V, Lewis K, King CP, Frankenberry EL. Managing chronic fatigue syndrome: overview and case study. AAOHN J. 1999 Jan;47(1):17-21. PMID: 10205371. The basic principles of envelope theory are explained. By not overexerting themselves, people with CFS can avoid the setbacks and relapses that commonly occur in response to overexertion while increasing their tolerance to activity.

McCully KK, Natelson BH. Impaired oxygen delivery to muscle in chronic fatigue syndrome. Clin Sci (Lond). 1999 Nov;97(5):603-8; discussion 611-3. PMID: 10545311. Compared to healthy controls, CFS patients suffered abnormally reduced time constant of oxygen delivery and oxidative metabolism following exercise.

Mullis R, Campbell IT, Wearden AJ, Morriss RK, Pearson DJ. Prediction of peak oxygen uptake in chronic fatigue syndrome. Br J Sports Med. 1999 Oct;33(5):352-6. PMID: 10522640. Using a simple to administer maximal exercise test on a cycle ergometer, it is possible to predict accurately the VO2peak of a patient with CFS from peak work rate alone. This value can then be used as an aid to setting appropriate exercise intensity for a rehabilitation programme.

Paul L, Wood L, Behan WM, Maclaren WM. Demonstration of delayed recovery from fatiguing exercise in chronic fatigue syndrome. Eur J Neurol. 1999 Jan;6(1):63-9. PMID: 10209352. Throughout a period of exercise, patients were able to exercise less than controls. Recovery was prolonged in the patient group, however, with a significant difference compared to initial amount of exercise being evident during the recovery phase after exercise (P = 0.001) and also at 24 h (P < 0.001). These findings support the clinical complaint of delayed recovery after exercise in patients with CFS.

LaManca JJ, Sisto SA, DeLuca J, Johnson SK, Lange G, Pareja J, Cook S, Natelson BH. Influence of exhaustive treadmill exercise on cognitive functioning in chronic fatigue syndrome. Am J Med. 1998 Sep 28;105(3A):59S-65S. PMID: 9790484. After a physically demanding exercise, CFS subjects demonstrated impaired cognitive processing compared with healthy individuals.

Blackwood SK, MacHale SM, Power MJ, Goodwin GM, Lawrie SM. Effects of exercise on cognitive and motor function in chronic fatigue syndrome and depression. J Neurol Neurosurg Psychiatry. 1998 Oct;65(4):541-6. PMID: 9771781. After exertion, patients with chronic fatigue syndrome showed a greater decrease than healthy controls on everyday tests of focused and sustained attention, as well as greater deterioration than depressed patients on the focused attention task.

Lane RJ, Barrett MC, Woodrow D, Moss J, Fletcher R, Archard LC. Muscle fibre characteristics and lactate responses to exercise in chronic fatigue syndrome. J Neurol Neurosurg Psychiatry. 1998 Mar;64(3):362-7. PMID: 9527150. Muscle histometry in patients with chronic fatigue syndrome generally did not show the changes expected as a result of inactivity. However, patients with abnormal lactate responses to exercise had a significantly lower proportion of mitochondria rich type 1 muscle fibres.
Fischler B, Dendale P, Michiels V, Cluydts R, Kaufman L, De Meirleir K. Physical fatigability and exercise capacity in chronic fatigue syndrome: association with disability, somatization and psychopathology. J Psychosom Res. 1997 Apr;42(4):369-78. PMID: 9160276. The authors present evidence against an association in CFS between avoidance of physically demanding tasks and early anaerobic metabolism during effort.
Kent-Braun JA, Sharma KR, Weiner MW, Massie B, Miller RG. Central basis of muscle fatigue in chronic fatigue syndrome. Neurology. 1993 Jan;43(1):125-31. Voluntary activation of the tibialis was significantly lower in CFS patients during maximal sustained exercise.
Wong R, Lopaschuk G, Zhu G, Walker D, Catellier D, Burton D, Teo K, Collins-Nakai R, Montague T. Skeletal muscle metabolism in the chronic fatigue syndrome. In vivo assessment by 31P nuclear magnetic resonance spectroscopy. Chest. 1992 Dec;102(6):1716-22. PMID: 1446478. CFS patients reach exhaustion much more rapidly than normal subjects, at which point they also have relatively reduced intracellular concentrations of ATP. These data suggest a defect of oxidative metabolism with a resultant acceleration of glycolysis in the working skeletal muscles of CFS patients.
Montague TJ, Marrie TJ, Klassen GA, Bewick DJ, Horacek BM. Cardiac function at rest and with exercise in the chronic fatigue syndrome. Chest. 1989 Apr;95(4):779-84. PMID: 2924607. Patients with chronic fatigue syndrome have normal resting cardiac function but a markedly abbreviated exercise capacity characterized by slow acceleration of heart rate and fatigue of exercising muscles long before peak heart rate is achieved.

George Jenson left an annotation ()

http://www.virology.ws/2017/07/31/trial-...
NICE bases it's Guideline on partially completed Q and A forms by seven "unknown" mental health workers, no references to published literature, no biomedical evidence reviewed, no review of faults/flaws in PACE trial authors work. UK mental health workers claim harassment despite it never being proven and the claims being rejected by the FOI first tribunal.

In contrast the USA bases its Guidelines on a comprehensive study costing over 1 million dollars, a detailed review of 9,000 published articles, the panel of experts are known and their work is fully referenced. The USA ME/CFS experts and researchers widely report enjoying working with the patients.

Trial by Error: NICE Rejects My FOI Request
31 JULY 2017
By David Tuller, DrPH

The National Institute for Health and Care Excellence, the U.K. organization that develops clinical guidelines for medical conditions, has rejected my freedom-of-information request for the names of the experts involved in the reassessment of the guidance for the illness it calls CFS/ME. This isn’t surprising, since the agency also recently rejected similar requests from the Countess of Mar and the ME Association. However, NICE’s response to the FOI request, which I received on Friday, contains some useful information and clarifies the decision-making process. I have included the NICE response below, but here are some key observations.

The 2007 guidance, called CG53, endorsed cognitive behavior therapy and graded exercise therapy as the treatments of choice. According to the FOI response, the surveillance team that drew up the recently published “consultation document,” which recommends no change in this guidance, includes four NICE staffers: a technical analyst, a technical adviser, a clinical adviser and an associate director. In developing their proposal, they consulted with seven “topic experts”–three psychiatrists, two neurologists, a pediatrician and a patient representative. The surveillance team’s provisional decision to leave the guidance as is triggered this month’s two-week period for receiving comments from stakeholders. The final call will now be made by a group of eight top NICE employees, collectively called the “guidance executive.” Among the eight are Sir Andrew Dillon, NICE’s chief executive; Mark Baker, director of the Centre for Clinical Practice; and communications director Jane Gizbert.

According to the FOI response, four of the topic experts consulted were members of the committee that developed the guidance in 2007. That list included Professor Esther Crawley of Bristol University, who could presumably be the pediatrician among the topic experts. (For those who have not followed this saga closely, Professor Crawley falsely accused me of libeling her in two high-profile lectures this year—her inaugural address at her own institution and a talk to the British Renal Society. Despite my multiple efforts to extract an explanation from her, she has failed to provide any documentation for this ridiculous allegation.)

It is inappropriate and unsatisfactory that psychiatrists were the largest group represented among the topic experts. Apparently NICE still fails to recognize that the disease in question is most emphatically not a psychiatric or psychological disorder; the agency apparently accepts without question the specious perspective of the cabal of U.K. psychiatrists, psychologists and others who have hijacked the debate for the last three decades. The 2015 reports from the U.S. National Institutes of Health and the Institute of Medicine (now the National Academy of Medicine) authoritatively documented that ME/CFS, as American government agencies now generally call the illness, is an actual organic disease and not a figment of patients’ fevered imaginations.

The PACE/CBT/GET counter-narrative—that deconditioning alone accounts for the perpetuation of the symptoms, and that patients harbor “unhelpful beliefs” about having a medical condition—is not grounded in legitimate scientific research. Despite the desperate attempts by the PACE investigators to defend their pet theoretical framework, it is now clear to the international scientific community that the study’s reported findings in The Lancet (2011) and Psychological Medicine (2013) were wildly inflated—the result of rampant outcome-switching and other egregious methodological lapses.

In addition to PACE and other Oxford criteria studies, the NICE document cites the Cochrane reviews of CBT and GET in support of its conclusion. First of all, Cochrane includes the illness it calls CFS in its mental health disorders section, which immediately raises questions about the organization’s biased perspective. Moreover, given the inclusion of PACE and other studies using overly broad case definitions in the Cochrane analyses, the NICE consultation document is seriously misguided to cite these reviews as reliable evidence. After all, the Cochrane analyses cannot be legitimate and accurate when the studies they include are not. (I plan to take on Cochrane in an upcoming post.)

Both CBT and GET involve telling patients that these approaches will help them get better—an obvious method of biasing the results, especially given that the study was not blinded. The treatments appear to provide modest boosts in subjective measures but no long-term benefits over other treatment or management approaches. Neither PACE nor other studies from this group of researchers have documented objective improvements to match these subjective results; indeed, objective measures have consistently failed to support the claims of improvement and recovery. The significance of these salient facts appears lost on the NICE surveillance review team, which apparently suffers from the same “dysfunctional cognitions” as the PACE investigators about the efficacy of their strategy.

In normal circumstances, it might be appropriate to include committee members who worked on previous guidance as topic experts in the review process. But these are not normal circumstances. With this illness, relying on these committee members is a bad move. It stands to reason that those who developed the utterly inadequate and potentially dangerous 2007 guidance would be unwilling to challenge their own past perspective that GET and CBT are effective. This is especially true given that the PACE authors and other adherents of the biopsychosocial approach have consistently demonstrated their unwillingness to accept any criticism that challenges their viewpoint. They refuse to acknowledge, for example, that any study in which participants can meet outcome thresholds at baseline, before any treatment at all, has no place in the scientific literature, as many dozens of well-known experts have made clear in open letters to The Lancet and Psychological Medicine.

In Professor Crawley’s case, her research on the prevalence of the illness among children consistently conflates the symptom of “chronic fatigue” with “chronic fatigue syndrome.” This conflation serves to dramatically inflate the numbers of those purported to be afflicted. Her work, such as her proposal for the FITNET-NHS study of online CBT for kids, also misrepresents the NICE guidance that she herself was involved in developing, in ways that appear to render post-exertional malaise as an optional symptom rather than a required one. When called to account for these distortions, she chooses to insult her critics rather than provide satisfactory explanations of her flawed methodological choices. It is therefore highly troubling that the NICE consultation document cites FITNET-NHS as important new research that will inform future guidance.

The NICE response to my FOI request indicates that the agency reached out to the topic experts seeking their opinions on being identified. Three of them expressed concerns about having their names made public; a fourth could not be reached. The response does not indicate the answer, if any, from the remaining three; perhaps they didn’t object at all. Nevertheless, based on the responses from the three who objected, NICE has decided to keep all the names secret.

According to the NICE response, here’s why the three topic experts objected: “Reasons given include their experience, and that of other experts in the field, of being connected with this topic area. These included concerns about personal harassment, previous abuse and threats they have been subjected to when involved in work on this topic.”

It needs to be stated clearly that the PACE authors have routinely wielded this overhyped claim as a way of discrediting critics. However, the tribunal decision last summer that ordered Queen Mary University of London to release the raw trial data dismissed the claims as unfounded. The tribunal decision noted pointedly that the only reliable evidence presented to the court about such behavior involved an incident in which Professor Trudie Chalder, one of the three main PACE investigators, was heckled at a lecture. Professor Chalder herself acknowledged in her testimony at the tribunal that none of the investigators had received death threats, despite their habit of hyperventilating about the issue of abuse from patients. As has been previously documented, the wave of news stories about these purported death threats was a public relations stunt organized by the Science Media Centre.

So have some CBT/GET investigators received offensive e-mails or other communications that have upset them? I have no reason to doubt it. Perhaps some of these messages have even contained what could be construed as threats. But Professor Crawley and her colleagues have routinely deflected attention from the defects of their research by wrapping themselves in martyrdom, complaining vociferously that even the filing of freedom-of-information requests constitutes harassment—a preposterous argument, given that patients have a legal right to seek key information about publicly funded trials. And these researchers also frame accurate criticism as vexatious and illegitimate. That’s what Professor Crawley did earlier this year when she accused me of “libelous blogging” in a slide shown during her two speeches.

So despite its claims of valuing an open and transparent process, NICE is allowing the topic experts involved—including four whose names are already public as part of the 2007 guidance committee–to cloak themselves in anonymity. That is not acceptable. Given the enormous importance of this reassessment of CG53 and the huge public interest in understanding how the decisions are being made, NICE should reconsider this rejection of my request.

I am appealing to the agency to overturn its initial decision. Following the agency’s expected rejection of my appeal, I will then appeal to the Information Commissioner’s Office. Whatever the ultimate outcome of my request, the FOI response suggests that it is critical that the members of the guidance executive recognize that a pro forma ratification of the 2007 guidance will be a public relations disaster. More than 15,000 people signed the ME Association petition protesting the NICE provisional decision; that’s a lot of very, very unhappy patients. With PACE now exposed as a dishonest and even fraudulent piece of research, the ground in the debate has shifted. It is no longer time for business as usual.

**********

Here is the substantive part of the NICE response to my FOI request:

Thank you for your request for information under the Freedom of Information Act (FOIA), received at this office on 07 July 2017. You requested the following information about the review of the CFS/ME guideline (CG53):

1. The number of people on the expert panel who will review input from stakeholders
2. The number, if any, of these people who are the same as those who were on the panel that developed the 2007 guidelines
3. The names of the people on the expert panel reviewing the CFS/ME guidelines, those currently serving and those who have served in the past year.

Background

There is no expert panel which reviews input from stakeholders in our review process. You can read more about how we check that published guidelines are current and accurate in our guidelines manual.

For this review we followed the process for the 4 and 8 year checks. It includes extensive searches to identify any new primary and secondary studies, including any economic studies. The focus is on the scope of the published guideline, but any additional areas or changes in practice that are identified are also considered if they fall within the referral of the published guideline. A literature search is conducted across a range of sources. These may vary from topic to topic. They are selected according to their relevance to the topic and are based on those used in the published guideline.

Topic experts and members of the original guideline committee are asked for their opinion, in their personal capacity, on the relevance of the published guideline, recent developments in the topic area and their knowledge of any new important evidence since publication of the guideline. Guideline committees are responsible for the recommendations made and we publish the membership of them. We do not routinely publish the identities of topic experts because while they may express an opinion they are not part of the decision making body.

NICE’s surveillance review team summarises the relevant evidence and highlights any studies that may have an important impact on our recommendations. The main themes of new, relevant evidence across the guideline are also summarised, along with any other identified information (such as changes in licensing indications for a medicine or updated national policy). The surveillance team is made up of NICE employees – a Technical Analyst, Technical Adviser, Clinical Adviser and Associate Director.

The information identified as part of the surveillance review forms the basis of a review proposal for NICE’s Guidance Executive. In this case the review proposal was a public consultation document. When the information summarised in the review indicates that a ‘no update’ decision should be considered there is a 2‑week consultation with stakeholders who are registered for the published guideline.

The final decision about whether an update is need is based on a balanced assessment of new relevant evidence published since guideline publication, the views of the topic experts, feedback during consultation and other sources of information on the continued relevance of the guideline. The findings of the check on the need for an update are discussed with topic experts. All proposals go through an internal validation process (including sign‑off by the Associate Director and Director) before submission to NICE’s Guidance Executive. It is Guidance Executive that takes the decision to update the guideline or not.

Response to your request under the FOIA

Given the background above, in responding to your request, I have assumed that by ‘expert panel’ you mean the topic experts who were asked for their opinion on the relevance of the published guideline.

1. The number of people on the expert panel who will review input from stakeholders.
Seven topic experts were asked for their opinion on the relevance of the published guideline.

2. The number, if any, of these people who are the same as those who were on the panel that developed the 2007 guidelines.
Four of these people were also members of the original guideline committee.

3. The names of the people on the expert panel reviewing the CFS/ME guidelines, those currently serving and those who have served in the past year.
We hold the names of the topic experts who were asked for their opinion on the relevance of the published guideline. For your information the topic experts are from the following fields: neurology (2), psychiatry (3), paediatrics (1), patient representative (1). However, we consider that the names are exempt from disclosure under 2 sections of the FOIA. We explain these exemptions and why we have applied them below.

Section 40 – personal information

Section 40 provides an exemption from the right to know where the information requested is personal data protected by the Data Protection Act. Personal data is data that relates to a living individual who can be identified from that data. The names of these individuals is clearly personal data.

Under section 40(2) we are withholding the names of the topic experts because we consider that to release it would contravene the principles of the Data Protection Act. In reaching this decision we considered whether disclosure would be fair to the individuals concerned, the consequences of disclosure, the reasonable expectations of the individuals and any legitimate public interest in disclosing the information.

NICE does not routinely publish the names of topic experts who contribute to the review process therefore the individuals had no expectation that this information would be made public. We wrote to the topic experts to ask them if they had any objections to their identities being disclosed to the public, and if so, what those objections were. Three of them were strongly opposed to their identities being made public in this context and one could not be contacted within the time available.

Reasons given include their experience, and that of other experts in the field, of being connected with this topic area. These included concerns about personal harassment, previous abuse and threats they have been subjected to when involved in work on this topic. We were sent a link to a news story from the Guardian describing threats and abuse directed at researchers and professionals in this field.

NICE is also concerned that disclosing the identities of the topic experts would have a significant impact on our ability to get experts to contribute to our work on this topic in the future. This point was supported by Mr Justice Simon in the judicial review that followed the publication of the original guideline. While Mr Simon was referring to guideline committee members in his judgement we consider that the impact would be the same if the identities of the topic experts asked for their opinion in the review process were made public.

When individuals are members of a guideline development group (also known as a guideline committee) their identities are publicly available on our website because the membership, as a whole, is responsible for the recommendations made. As described above, in the review process, the topic experts are asked for their opinion but the review decision is taken by NICE’s Guidance Executive whose membership is publicly available on our website.

As 3 of the topic experts expressed concerns over their identities being made public and 1 could not be contacted we consider that it would not be fair to make the remaining names public as this could have the effect of unreasonably focusing activity on these individuals.

We recognise the public interest in ensuring public authorities remain transparent, accountable and open to scrutiny. We also recognise that disclosure would enable individuals to understand decisions made by public authorities in more detail, however on balance we do not consider the public interest in disclosure overrides the interest in maintaining these individuals’ privacy.

We therefore conclude it would not be fair to disclose the information under section 40(2) of the FOIA.

Section 38 – health and safety

Section 38 states that information is exempt from disclosure if its disclosure would, or would be likely to
(a) endanger the physical or mental health of any individual, or
(b) endanger the safety of any individual

The topic experts, and other experts in the same field, have specifically referenced threats and harassment they have been subject to in the past, as described above.

We have also considered if some of this information is already in the public domain because of the individuals previous work in this or other fields. As 4 of the topic experts were also on the guideline committee, their interest in this field is already in the public domain. However, in the context of the review, consultation and the campaigning activity around NICE’s proposal, we consider that releasing the information at this time would create a direct link between the experts and the review proposal and would raise their profile. Therefore disclosure at this time is likely to increase the risk that these individuals would be targeted and that this could lead to additional harm.

Mr Justice Simon also referenced unfounded allegations made against guideline committee members and his judgement stated that ‘unfounded as they were, the allegations were damaging to those against whom they were made; and were such as may cause health professionals to hesitate before they involve themselves in this area of medicine. A perception that this is an area of medicine where contrary views are not to be voiced, and where scientific enquiry is to be limited, is damaging to science and harmful to patients.’

Given the volume and nature of the correspondence (enquiries, petitions, letters, activity on message boards, Freedom of Information requests) we have received to date we are concerned that the experts may be targeted individually by any campaign and that such activity would impact on experts’ wellbeing and on their and others’ willingness to contribute to the work of NICE in the future, especially when they are not part of the decision making body.

We can’t be certain that the release of the withheld information would put the individuals at risk but we consider that there is sufficient evidence to conclude that they would be singled out for harassment, intimidation and possibly threats of violence.

This exemption is subject to the public interest test. We accept that there is significant public interest in being accountable and transparent for the decisions we take and for individuals under understand how we make our decisions. However, NICE also has a duty to protect the physical and mental wellbeing of the individuals concerned.

In this case the makeup of the decision making body, Guidance Executive, is already in the public domain. The review proposal is also publicly available and contains comprehensive discussion of the evidence including the feedback from the topic experts.

NICE operates openly and transparently. All of our guidance development processes are published in detail on the website. We believe the process and information on which the proposal is based is publicly available and subject to consultation. We consider that those with an interest in this guideline have sufficient information to be able to understand both the process and consideration of the evidence.

Given the concerns raised by the individuals and other evidence of previous incidents of experts in this field being targeted for harassment, including threats of violence, in the past we conclude that the public interest in disclosing the information does not outweigh the interest in maintaining the exemption in light of the likely risks to the health and safety of the individuals.

We therefore conclude it would not be fair to disclose the information under section 38 of the FOIA.

FreedomofInformation, Department of Health

Dear Mr Jenson,

You internal review request was previously allocated to a colleague but due to staffing issues has been escalated to me to complete. I will aim to do so within 10 working days.

I apologise for the delay incurred to date in dealing with your request.

Kind regards,
James

James Shewbridge
Freedom of Information Team
Department of Health
39 Victoria St
London SW1H 0EU

show quoted sections

FreedomofInformation, Department of Health

2 Attachments

Dear Mr Jenson,

 

I apologise for the length of time it has taken to carry out your
requested Internal Review of FOI-1085858.

 

The review is now complete. Please see the attached letter for the
outcome.

 

Your sincerely,

 

James Shewbridge

 

[1]DH.JPG James Shewbridge

Casework Manager

Department of Health, 39 Victoria Street

London SW1H 0EU

 

Further information on Freedom of Information (FOI) policy, including full
guidance on the application of exemptions, can be found on the FOI
intranet page:
[2]https://in.dh.gov.uk/how-to/manage-infor...,
or please contact any member of the FOI team directly for advice.

 

 

show quoted sections

Incoming and outgoing e-mail messages are routinely monitored for
compliance with the Department of Health's policy on the use of electronic
communications. For more information on the Department of Health's e-mail
policy click here http://www.dh.gov.uk/terms

--------------------------------------------------------------------------

This email was scanned by the Symantec virus scanning service and was
certified virus free.
Communications may be automatically logged, monitored and/or recorded for
legal purposes.

References

Visible links
2. https://in.dh.gov.uk/how-to/manage-infor...

We don't know whether the most recent response to this request contains information or not – if you are George Jenson please sign in and let everyone know.

Looking for an EU Authority?

You can request documents directly from EU Institutions at our sister site AskTheEU.org . Find out more .

AskTheEU.org