An open letter to Psychological Medicine about “recovery” and the PACE trial

Sir Robin Murray and Dr. Kenneth Kendler
Psychological Medicine
Cambridge University Press
University Printing House
Shaftesbury Road
Cambridge CB2 8BS
UK

Dear Sir Robin Murray and Dr. Kendler:

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Sincerely,

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

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

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

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

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

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

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

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

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

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

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

Derek Enlander, MD
New York, New York, USA

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Frans Visser, MD
Cardiologist
Stichting Cardiozorg
Hoofddorp, Netherlands

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

William Weir, FRCP
Infectious Disease Consultant
London, UK

John Whiting, MD
Specialist Physician
Private Practice
Brisbane, Australia

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

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

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

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

 

ME/CFS Patient Organizations

25% ME Group
UK

Emerge Australia
Australia

European ME Alliance:

Belgium ME/CFS Association
Belgium

ME Foreningen
Denmark

Suomen CFS-Yhdistys
Finland

Fatigatio e.V.
Germany

Het Alternatief
Netherlands

Icelandic ME Association
Iceland

Irish ME Trust
Ireland

Associazione Malati di CFS
Italy

Norges ME-forening
Norway

Liga SFC
Spain

Riksföreningen för ME-patienter
Sweden

Verein ME/CFS Schweiz
Switzerland

Invest in ME Research
UK

Hope 4 ME & Fibro Northern Ireland
UK

Irish ME/CFS Association
Ireland

Massachusetts CFIDS/ME & FM Association
USA

ME Association
UK

ME/cvs Vereniging
Netherlands

National ME/FM Action Network
Canada

New Jersey ME/CFS Association
USA

Pandora Org
USA

Phoenix Rising
International membership representing many countries

Solve ME/CFS Initiative
USA

Tymes Trust (The Young ME Sufferers Trust)
UK

Wisconsin ME and CFS Association
USA

[1] White PD, Goldsmith K, Johnson AL, et al. 2013. Recovery from chronic fatigue syndrome after treatments given in the PACE trial. Psychological Medicine 43(10): 2227-2235.

[2] White PD, Goldsmith KA, Johnson AL, et al. 2011. Comparison of adaptive pacing therapy, cognitive behaviour therapy, graded exercise therapy, and specialist medical care for chronic fatigue syndrome (PACE): a randomised trial. The Lancet 377: 823–836

[3] Racaniello V. 2016. An open letter to The Lancet, again. Virology Blog, 10 Feb. Available at: http://www.virology.ws/2016/02/10/open-letter-lancet-again/ (accessed on 2/24/17).

[4] White PD, Sharpe MC, Chalder T, et al. 2007. Protocol for the PACE trial: a randomised controlled trial of adaptive pacing, cognitive behaviour therapy, and graded exercise, as supplements to standardised specialist medical care versus standardised specialist medical care alone for patients with the chronic fatigue syndrome/myalgic encephalomyelitis or encephalopathy. BMC Neurology 7: 6.

[5] Tuller D. 2015. Trial by error: the troubling case of the PACE chronic fatigue syndrome trial. Virology Blog, 21-23 Oct. Available at: http://www.virology.ws/2015/10/21/trial-by-error-i/ (accessed on 2/24/17)

[6] Wilshire C, Kindlon T, Matthees A, McGrath S. 2016. 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. Fatigue: Biomedicine, Health & Behavior; published online 14 Dec. Available at: http://www.tandfonline.com/doi/full/10.1080/21641846.2017.1259724 (accessed on 2/24/17)

[7] PACE Participants Newsletter. December 2008. Issue 3. Available at: http://www.wolfson.qmul.ac.uk/images/pdfs/participantsnewsletter3.pdf (accessed on 2/24/17).

[8] Sharpe M, Chalder T, Johnson AL, et al. 2017. Do more people recover from chronic fatigue syndrome with cognitive behaviour therapy or graded exercise therapy than with other treatments? Fatigue: Biomedicine, Health & Behavior; published online 15 Feb. Available at: http://www.tandfonline.com/doi/full/10.1080/21641846.2017.1288629 (accessed on 2/24/17).

[9] Green CR, Cowan P, Elk R. 2015. National Institutes of Health Pathways to Prevention Workshop: Advancing the research on myalgic encephalomyelitis/chronic fatigue syndrome. Annals of Internal Medicine 162: 860-865.

Comments on this entry are closed.

  • Alex Young

    In terms of contrary research that is not aimed at PACE trial critique, I suggest looking at the exercise research of Light and Light, and the Workwell foundation, but there is much more. Ask about these on any large ME forum and someone should be able to point to topic threads or direct links.

  • Dominique

    Thank you so much for your continued efforts to expose the PACE trial as the fraudulent research it is and seek justice for millions worldwide who continue to be harmed in so many ways by it. I can only hope that your efforts attract the attention and support of the wider scientific community. The PACE trial is surely is equal to any current affront to published (and/or retracted) science compounded as it is by the significant impact on society. Due the influence of this trial, I am one of the aforementioned millions subjected to medical neglect and even derision. I am literally rotting away on a couch (others in their beds), unable to work and too sick to advocate for change or anything else really.

  • Milo Paradiso

    Thank you for your efforts. Psychology Medicine needs to do the right thing here for the sake of science and the medical profession.

  • Firestormm

    I am also grateful to those who compiled and signed this letter which is another terrific attempt to highlight bad scientific practices. That it is ME/CFS we are dealing with shouldn’t really matter. Bad science is bad science and should be treated accordingly – in this case with a retraction.
    I don’t think we should forget that the PACE Trial itself was published after the NICE Clinical Guideline in the UK established CBT and GET as treatment recommendations for ME/CFS along with Graded Activity Management. Severely affected patients were not considered appropriate candidates for GET. Of course, and as NICE itself would say, these were ever only guidelines and as many patients have found, the application of the recommendations leaves a lot to be desired in clinical practice.
    But the findings from the PACE Trial – which remains regrettably the largest trial ever carried out in the UK for ME/CFS – have been widely influencial and were used by NICE to reinforce their recommendations at the time of review.
    All I want is good science for my disease. As for treatments, I simply want ones that are backed by good science and that offer a good chance of improving my health – not ones that have been mis-sold, are inappropriate and can lead to relapse.
    Many thanks again for taking this action. It really means a great deal to me.

  • Antithesis

    Thank you.

  • Action CIND

    Thank you to all that have signed this letter. Let hope it gets retracted.

    We add our support and if possible our signature to the letter.

    Alison Rae
    Board Chair and CEO
    Action CIND
    Canada

  • 1989

    Love and respect to the authors and the signatories of this letter. The fraudulent mess that is “the PACE trial” is not only ridiculously bad science, but it’s suggested methods have in fact caused irreversible HARM to countless patients. It mustn’t be allowed to cause more.

    The paper should be retracted. Now.

  • Beth Nielson

    Tweeted by @TomKindlon “If anyone else would like to sign this, email me
    at tomkindlon [at] Hotmail [dot] com and I will pass it on to David
    Tuller.”

  • Beth Nielson

    “Think of Madoff or Enron in charge of a disease.”

    #PACEtrial #CDC30YRS #MEclinics #OutcomeSwitching #CheaperThanResearch #FollowTheMoney

    ~Fibro ’73 ME/CFS ’79 Twitter

  • Beth Nielson

    @GQ, your comment is in moderation so I cannot reply to it but I agree, the misconduct of the PACE trial authors and peer review process and implementation of GET/CBT that harm patients rises to the breaking of the Declaration of Helsinki.

    Also, let’s not forget that the Oxford Criteria does not choose ME/CFS patients so I suspect the small “valid” percentages of “recovery” were due to those who did not have the disease. http://me-pedia.org/wiki/How_have_selection_bias_and_disease_misclassification_undermined_the_validity_of_myalgic_encephalomyelitis/chronic_fatigue_syndrome_studies%3F

  • Nita Dozer Thatcher

    A HUGE Thank You to every Hero listed here. Your efforts are deeply appreciated by everyone with ME/CFS. Thank you, Prof, Racaniello for helping to get the word out!

  • Art Vandelay

    Thank you to everyone involved. The pseudo-scientific nonsense of PACE (and indeed, the pseudo-science that makes up much of psychiatry) must be torn down.

  • C’est la même

    It’s easy. Get your friends (who also like to fudge their thresholds) to review the paper without any criticism.

  • C’est la même

    This is post publication peer review in action.

    Dr. Robin Murray and Dr. Kenneth Kendler must respond.

  • A.B.

    Read http://iom.nationalacademies.org/Reports/2015/ME-CFS.aspx by the US Institute of Medicine. In particular the post-exertional malaise (PEM) section. There is objective evidence that exertion leads to an increase in physical and cognitive impairment. Research is moving so fast at the moment that the report from 2015 is already missing important information. Since then more PEM studies have come out, and about 7 studies have reported hypometabolism and energy production problems at a cellular level.

    It is also worth noting that CBT/GET research is usually performed on a patient sample that may not even meet commonly accepted definitions of CFS! In simple words, they use a fringe definition of CFS that is considered flawed and may include people that have a different fatiguing illness. For this reason a federal report says that there’s little evidence that CBT/GET even work: https://www.healthrising.org/blog/2016/08/18/federal-report-says-almost-no-evidence-cbtget-work-chronic-fatigue-syndrome-mecfs/

  • A.B.

    CBT/GET also don’t lead to an increase in activity levels (or other objective markers of health such as employment). You can see this in the PACE trial and other studies.

  • Aaron C

    Thank you to everyone who signed–the groundswell of support, especially from those outside of the tiny bubble of ME/CFS specialists, is truly touching.

    Maybe once this farce is torn down we will have an easier time getting funding for well-designed biomedical research.

  • Sam Perry

    Thank you to the people that signed this, it’s appalling how badly conducted the pace study was.

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  • Rogerblack

    I thank all of the researchers and others involved in making this happen.
    (Apart from White et al).
    Psych research in principle has so much to offer people with ME/CFS – if only they diddn’t go down the ridiculous rabbit-hole of it being a cure.
    Much valuable work could have been done on the psychological effects of ME/CFS way before the recent biomedical work became possible.
    Even just creating a sane questionnaire for people with physical issues to assess mental state would have been a positive for other research.

    Alas, the field as a whole went off after tiny effect sizes in badly organised and run interventions and made overblown claims about them and ruined lives.

  • So Ph

    yay!

  • acacia1

    Karla, unfortunately, there is little direct evidence collected on harm of GET, some of this is listed below. But, PACE itself found that there is little benefit when an objective measure, the 6 minute walking test is used. This is shown up in a set of letters to Psychological Medicine and includes the authors’ lame response where they unwittingly? confirm that PACE did little good.
    http://www.meassociation.org.uk/2013/07/pace-trial-letters-and-reply-journal-of-psychological-medicine-august-2013/

  • Mithriel

    I became ill in 1968 and in all these long years there has been little progress for people with ME. The psychosocial model has lead to no alleviation of illness for patients despite decades of claims for how well it works. I have lain in bed while careers have been built on my misfortune. They have had their chance but modern scientific tools are now managing to untangle the biochemistry of ME in a way that matches my experience and that research over the years has hovered round.

    I finally feel there is hope.

    It was frustrating that the flaws that were so obvious to me did not seem apparent to anyone outside the ME community but now honourable and intelligent people have looked and are doing something about it and I am so very grateful to them.

  • Valentijn

    Wiborg 2010 and any other trials with actometers or other objective outcomes (work, benefits, education, etc) prove that GET results in no real improvements. Patients report less fatigue after being told to ignore symptoms, but it isn’t reflected by reality.

  • Luise

    “I have lain in bed while careers have been built on my misfortune.” This is exactly how i feel! Thank you for putting it into words.

  • JustinReilly

    An excellent letter. Thank you so much to the authors and all signatories!!

  • Noreen Murphy

    Sincerest thanks to all the distinguished scientists/researchers who signed this letter. Your support means so much to the M.E. community which has endured decades of abuse and neglect, with the PACE trial also preventing decades of proper biomedical research into M.E.

    I cannot understand how a paper which has been shown to be flawed and fraudulent is not automatically retracted from all medical journals? I certainly do not understand how the PACE paper made it into them in the first place (except maybe because of influence, cronyism and corruption?).

    The day of bad “science” is long over. The day of fraudsters harming patients to further their careers, pockets and collars should never have existed in the first place, nor should it have been allowed or tolerated. Our hope is that, once this house of cards has fallen, biomedical research will be funded and a treatment found.

    Hopefully Psychological Medicine will do the right thing now and retract this paper. Then, hopefully, other ethical medical journals will follow its lead.

    Many, many thanks again and thank you Dr. Racaniello for posting on your blog.

  • Katy Bruce

    A really huge thank you to all involved in this. You are our heroes & so many of us are enormously grateful to very one of you.

  • Wendy Boutilier

    Thank you, all of you, for standing with us and believing in us. It gives us hope on those devastating days when we have to shut everything out just to survive. Some of us are lucky because we have found ME friendly doctors willing to learn with us. I have shared all of David Tuller’s links to Canada’s Minister of Health and I have received a heart felt warm response. I will add this to the file.
    David – you have taught us how to advocate in a smart way and we appreciate you more than I can put in words.

  • Jan

    Heartfelt thanks to all who have taken the time, and for some, the courage to sign, you will never know just how much gratitude there is from a truly desperate patient community. A patient community treated appallingly by much of the medical establishment in the UK, The US, Canada, Australia and Europe, and no doubt countless other countries, due to these and similar studies. No objective measures are ever used, (or results never made public) and we’ve never heard of a single patient who has recovered using these techniques. I am truly ashamed that these studies originate in my country and have been exported throughout the world.

    So many millions must have been saved by the insurance companies refusing to pay out, not to mention millions of pounds of benefits denied by governments across the world. It has been a witch hunt and many, many have taken their lives due to the utter despair from sheer lack of hope.

    How was this ever allowed to happen 30 years ago? How can psychiatrists suddenly ‘claim’ an illness, decide without evidence that it’s ‘all in the mind’, even back then there was enough biomedical research showing evidence of severe abnormalities? Around 9000 studies have shown that this is a physical illness. Yet so many continue to die, so many are confined to darkened rooms, and the rest are left suffering an illness with a shockingly low quality of life decade, after decade with no hope of treatment. So much needless suffering due to the opinions of a few psychiatrists who have caused this illness to be denied research funding, unless it is heading in their direction.

    We have suffered enough.

  • KME

    Thank you to all of the signatories above – it means a huge amount to those of us whose ME has deteriorated due to GET, CBT and other biopsychosocial school principles.

    PACE author Michael Sharpe was quoted in Science Magazine as saying “It’s sometimes quite hard to understand what motivates the very vocal minority that gets so
    upset about this apparently benign bit of moderately helpful treatment” http://www.sciencemag.org/news/2015/10/criticism-mounts-long-controversial-chronic-fatigue-study

    Thanks for letting the world know that this is about an international community of scientists, clinicians and patient advocates legitimately questioning the science of “treatments” that are experienced by the majority of patients as ineffective and harmful.

    For those who want to know more about patients’ experiences
    of GET and CBT, see the ME Association’s extensive patient survey:

    http://www.meassociation.org.uk/wp-content/uploads/2015-ME-Association-Illness-Management-Report-No-decisions-about-me-without-me-30.05.15.pdf

    See the Institute of Medicine’s 2015 report for the low-down on research into ME/CFS:

    https://www.ncbi.nlm.nih.gov/books/NBK274235/pdf/Bookshelf_NBK274235.pdf

  • Margaret Smith

    I agree with what you say Jan. But I would just add that the thing that always seems to be left out of the financial aspect of the equation, is the cost to the economy of thousands of missing employees from the workplace (patients and their family/carers) and the extra burden on the health services all due to the missing and severely neglected millions of patients.

  • Karla

    Thanks for this!

  • Karla

    Thank you – I’ll follow up on these.

  • Karla

    Thank you!

  • Karla

    I’ll look into these trials – thanks for pointing me in this direction!

  • Margaret Smith

    Can’t tell you how grateful I am to the people who have drafted and signed this letter. It makes such a heart warming change to see so many representatives of honest and true science and medicine speak out against the poor research and science of PACE and the huge amounts of damage it has gone on to cause amongst the ME community in particular, but also the scientific community.

    People have suffered not just directly from the affects of GET in particular, but also indirectly from the impact of society’s subsequent reaction to this condition. The financial, physical, emotional and psychological damage that PACE has been responsible for is immeasurable.

    In addition the damage that PACE has done to the reputation of scientific research is worrying. How are people supposed to trust research if this is the way it is allowed to be carried out and implemented irrespective of professional challenges to it.

    Thank you so, so much to those who are now prepared to speak out in this way and hopefully put things back on track for the much beleaguered ME community and the reputation of scientific research.

  • Sheila Campbell

    Here’s the Editorial Board of Psychological Medicine:

    https://www.cambridge.org/core/journals/psychological-medicine/information/editorial-board

    Professor Michael Sharpe, Professor Simon Wessely, Professor Matthew Hotopf and Professor Carmine Pariante are all members.

  • Barry

    Very sincere thanks to the many high-integrity scientists who have signed this letter. PACE is a disgrace, and the ongoing detriment caused by its reported outcomes and its investigators’ dogma, piles disgrace onto disgrace. Hopefully, history will show this letter to be a watershed; the point at which the PACE investigators could no longer dismiss informed constructive criticism as inconsequential.

  • Agapanthus

    To everyone who has put this together & had the courage to sign it. My gratitude is beyond words.

    90% of the people i tell about the PACE flaws look at me like i just said the moon landings were a conspiracy. They think I’m misguided, or that its a ‘patients vs science’ situation. That we’re not clever enough to understand the science & dont want to accept it because it doesnt fit with what we want to be true.
    But today I have printed out this letter & am very much looking forward to saying “see, look, it’s not just me, not just patients, it’s a lot of eminent scientists & drs”. Which will help me enormously, even if it doesnt change anything. -At least when i try to explain why i’m not doing CBT/GET I will have some credible opinion to back me up & in an easy to read, succinct manner.
    Brilliantly done.

    I dont think PT will listen & i dont expect them to retract it. But it will make it a *little more difficult for Wessely/White et al’s narrative (that it’s a small group of abusive patients who’re ‘attacking’ them because they dont want to ‘accept the stigma of being mentally ill’) to stand unchallenged.
    Mind you they will definitely start stepping up the spin of “these poor dear drs, they’ve been misled by patients & dont understand the nuances of the science, they should be stopped because they are not helping patients but instead are enabling & encouraging their faulty cognitions”.

    You are all heroes in my opinion & will be viewed as such by history. Thank you again.

  • Garrett Wilkinson

    Fraudulent studies like the pace trial should never be published. Papers like this will erode the credibility of all published studies. This is not only a fight for myalgic encephalitis, it is a fight for science itself. Special interest groups have no place in science. Thank you to all of the signatories.

  • Thank you to the authors of the letter and to all the signatories.

    As a science teacher (prior to being hit with ME) I am very surprised that these basic errors of trial design were able to slip through to the point of publication. The fact that the authors of the PACE trial papers don’t recognise that their errors render their conclusions void, is also of huge concern.

    I hope this PACE paper will now be swiftly retracted,and that the other PACE papers will also be held to rigorous scrutiny.

  • chrisd87

    Many thanks to everyone who signed. Particular thanks to those from the UK who have shown bravery in signing this.

  • Orla Pwme

    Thank you to all the scientists and clinicians, other professionals and patient groups who signed this letter.

  • Robert McMullen

    Sincere thanks to all the signatories.

  • Steve Hawkins

    Many thanks to all for keeping up the pressure. It really is astonishing, just how shameless these people are, and how little the publishers care about maintaining scientific respectability.

  • JustinReilly

    Stand Up For Science!
    Why is it vital this article be immediately retracted? Because it is theoretically impossible for the “therapy” touted by this article, “Graded Exercise Therapy,” NOT to exacerbate the disease.

    The most glaring example of fraud in the article: Some patients whose disease was worsened by the “therapy” were declared “cured” by the study authors! Scientific fraud does not get any more blatant than this.

    If you are a medical professor or other medical doctor, I urge you to sign this demand; you will be helping to save lives of patients vicitimized by insurers who push this therapy. If the medical and scientific communities do not stand up to such blatant fraud, the public’s trust in medicine and science will continue to erode to untenable levels. Please contact me on facebook or David Tuller if you wish to support.

    If you are a journalist, you can help by covering the fraud.

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