Cochrane has decided to temporarily withdraw a review of exercise therapies for the illness variously known as ME, CFS, ME/CFS and CFS/ME. The review reported that exercise therapy is effective in treating the illness—a finding that has provided unwarranted support for recommendations that patients should undergo the intervention known as graded exercise therapy. Yet Cochrane has found merit in complaints about serious scientific missteps and has asked the review team to respond accordingly.
Supporters of the approach to treatment endorsed by the Cochrane review have portrayed the decision for temporary withdrawal as a loss for science and an unfortunate capitulation to pressure from a vocal patient lobby. But patients have criticized the review not because they harbor anti-scientific views or are prejudiced against psychiatry. Rather, they have expressed reasonable and convincing concerns about the poor methodological choices made by the reviewers, who to date have not offered robust explanations.
We therefore believe it is important to voice our support for Cochrane’s effort to seek clarity on the issues raised not only by patients but by many others as well, including scientists, clinicians and academics. Here are some key reasons why we agree with Cochrane’s decision:
1) The PACE trial, the largest of the eight studies included in the Cochrane review, has been internationally discredited because of its outcome-switching and many other flaws. Yet the review rated the trial as being at “low risk” of reporting bias. In a recent open letter to The Lancet, more than 100 experts, including many of us, expressed concern about PACE’s “unacceptable methodological lapses.”
2) Like PACE, the other studies in the Cochrane review are open label trials relying on subjective outcomes. Trials with this design are fraught with bias, which is why they are no longer considered as reliable evidence for making decisions and developing recommendations for biomedical treatment. The review ignored objective outcomes from exercise interventions, which have generally failed to confirm subjective reports of benefits.
3) Five of the studies included in the Cochrane review used the Oxford criteria, a case definition that only requires six months of unexplained fatigue to render a diagnosis. This case definition generates heterogeneous samples that likely include many people suffering from undiagnosed depression, anxiety disorders and other fatiguing conditions rather than the devastating illness in question. When the US Agency for Healthcare Research and Quality removed Oxford criteria studies from its own analysis, the agency found no evidence to support recommendations for graded exercise therapy. This re-analysis also reported more harms among those assigned to such treatment than among those in the comparison groups.
4) Six of the studies included in the Cochrane review tested graded exercise therapy as a treatment for the illness. This intervention has been predicated on the theory that the ongoing symptoms are not caused by underlying pathophysiological processes but by a fear of activity, which in turn leads to sedentary behavior and severe deconditioning. Yet there is no legitimate scientific evidence to support this theory. A 2015 report from the US Institute of Medicine (now the National Academy of Medicine) concluded that ME/CFS is not driven by psychological factors; biomedical research from major medical centers in the US, UK, Australia and elsewhere supports that conclusion.
5) Given the many methodological and scientific problems with the Cochrane review, its conclusion that exercise therapy is effective cannot be taken at face value. This is of particular concern because it is widely accepted that the cardinal symptom of the illness is post-exertional malaise, or what the Institute of Medicine report called “exertion intolerance.” In other words, patients can suffer prolonged relapses even after engaging in minor physical activities, suggesting that graded exercise therapy is contra-indicated and could cause harm.
The reviewers need to provide substantive and satisfactory answers to Cochrane’s legitimate methodological and scientific questions. If they are unable or unwilling to do so, the review should be permanently withdrawn.
Vincent R. Racaniello, PhD
Professor of Microbiology and Immunology
Columbia University
New York, New York, USA
Host of Virology Blog
Christopher Armstrong, PhD
Bio21 Molecular Science & Biotechnology Institute
Department of Biochemistry and Molecular Biology
University of Melbourne
Melbourne, Victoria, Australia
James N. Baraniuk, MD
Professor of Medicine
Georgetown University
Washington, DC, USA
Lucinda Bateman, MD
Medical Director
Bateman Horne Center
Salt Lake City, Utah, USA
Jonas Bergquist, MD, PhD
Professor of Analytical Chemistry and Neurochemistry
Biomedical Centre
Uppsala University
Uppsala, Sweden
Charlotte Blease, PhD
Fulbright and Marie Curie Research Fellow
General Medicine and Primary Care
Beth Israel Deaconess Medical Center
Harvard Medical School
Boston, Massachusetts, USA
School of Psychology
University College Dublin
Dublin, Ireland
Bela Chheda, MD
Center for Complex Diseases
Mountain View, California, USA
Member, The ME/CFS Collaborative Research Center at Stanford
Palo Alto, California, USA
Joan Crawford CEng, MSc MA
Counselling Psychologist – Chronic Pain Management Service, NHS, UK
Private psychology practice – Chester UK.
Chair – Chester ME self help group (MESH), UK
Todd E. Davenport, PT, DPT, MPH, OCS
Professor & Program Director
Thomas J. Long School of Pharmacy & Health Sciences
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
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
Rebecca Goldin, PhD
Professor of Mathematics
George Mason University
Fairfax, Virginia, USA
Alan Gurwitt, MD
Clinician in Private Practice (retired)
Associate Clinical Professor
Yale Child Study Center (retired)
New Haven, Connecticut, USA
Associate Clinical Professor
University of Connecticut Dept of Psychiatry (retired)
Storrs, Connecticut, USA
Lecturer, Harvard Medical School (retired)
Boston, Massachusetts, USA
Paul M. Guyre, PhD
Professor of Microbiology and Immunology
Geisel School of Medicine at Dartmouth
Hanover, New Hampshire, USA
Maureen Hanson, PhD
Liberty Hyde Bailey Professor
Department of Molecular Biology and Genetics
Cornell University
Ithaca, New York, USA
H. Craig Heller, PhD
Professor of Biology
Stanford University
Stanford, California, USA
Brian M. Hughes, PhD, FPsSI
Professor of Psychology
National University of Ireland Galway
Galway, Ireland
David L. Kaufman, MD
Center for Complex Diseases
Mountain View, California, USA
Member, The ME/CFS Collaborative Research Center at Stanford
Palo Alto, California, USA
Betsy Keller, PhD, FACSM
Professor of Exercise & Sport Sciences
Ithaca College
Ithaca, New York, USA
Eliana Mattos Lacerda
Assistant Professor of Epidemiology
Clinical Research Department
Faculty of Infectious and Tropical Diseases
London School of Hygiene and Tropical Medicine
London, England, UK
Bruce Levin, PhD
Professor of Biostatistics
Columbia University
New York, New York, USA
Susan Levine, MD
Clinician in Private Practice
New York, New York
Visiting Fellow
Cornell University
Ithaca, New York, USA
Alan R. Light, PhD
Professor of Anesthesiology
Professor of Neurobiology and Anatomy
University of Utah
Salt Lake City, Utah, USA
Ami Mac, MD
Director of Translational Medicine
Stanford Genome Technology Center
Palo Alto, Michigan, USA
David F. Marks, PhD
Editor
Journal of Health Psychology
& Health Psychology Open
London, England, UK
Marlon Maus, MD, DrPH, FACS
DrPH Program Director
School of Public Health
University of California, Berkeley
Berkeley, California, USA
Neil R McGregor, BDS, MDSc, PhD
Clinical Associate Professor
Faculty of Medicine, Dentistry and Health Sciences
Bio21 Molecular Science & Biotechnology Institute
University of Melbourne.
Melbourne, Victoria, Australia
Patrick E. McKnight, PhD
Associate 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
Director, Palo Alto Medical Foundation Toxoplasma Serology Laboratory
National Reference Center for the Study and Diagnosis of Toxoplasmosis
Palo Alto, California, USA
Elisa Oltra, PhD
Professor of Molecular and Cellular Biology
Catholic University of Valencia School of Medicine
Valencia, Spain
Roshini C. Pinto-Powell, MD, FACP
Associate Professor of Medicine and Medical Education
Associate Dean of Students and Admissions
Co-director of On Doctoring
Co-director of Geriatrics and Ambulatory Medicine
Geisel School of Medicine at Dartmouth
Hanover, New Hampshire, USA
Deborah Rose, MD
Emeritus Adjunct Assistant Clinical Professor of Psychiatry
Stanford University School of Medicine
Stanford, California, USA
Peter C. Rowe, MD
Professor of Pediatrics
Johns Hopkins University School of Medicine
Baltimore, Maryland, 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
Gold Coast, Queensland, Australia
Philip B. Stark, PhD
Professor of Statistics
University of California, Berkeley
Berkeley, California, USA
Leonie Sugarman, PhD
Emeritus Associate Professor of Applied Psychology
University of Cumbria
Carlisle, England, UK
Ronald G. Tompkins, MD, ScD
Sumner M Redstone Professor of Surgery
Harvard Medical School
Boston, Massachusetts, USA
David Tuller, DrPH
Senior Fellow in Public Health and Journalism
Center for Global Public Health
School of Public Health
University of California, Berkeley
Berkeley, California, USA
Mark VanNess, PhD
Professor of Health, Exercise & Sports Sciences
University of the Pacific
Stockton, California, USA
Workwell Foundation
Ripon, California, USA
Wenzhong Xiao, PhD
Assistant Professor of Bioinformatics
Harvard Medical School
Boston, Massachusetts, USA
Carolyn Wilshire, PhD
Senior Lecturer
School of Psychology
Victoria University of Wellington
Wellington, New Zealand
Comments
35 responses to “A Statement in Support of Cochrane”
Simply amazing. Just what the doctor ordered. Thank you!!
All of the work that has gone into this is VERY much appreciated! Thank you!
This letter is timely & underscores the need for well executed studies. It is important to continue to advocate for diagnostic tests and clinical trials to evaluate the efficacy of all interventions. The current portrayal of “angry patient advocates” as the cause of the temporary removal of the review is a weak attempt to blame the patient versus diagnose and treat ME.
Fake news. Please leave ME out of this. The review doesn’t mention it anywhere.
Many thanks to each and every one of you.
I am now 71 and have had this illness for 53 years (waxing and waning; now mostly bed-bound) and you give me hope that the eye-rolling and stigma I’ve encountered may end before I’m gone.
Please note that Ronald Tompkins is Sumner M Redstone Professor of Surgery (not Summer – the season).
you only have to look at gkbrown to know exercise is toxic for g93.3 post viral sufferers
a dr had me walking 10 klm a day our staggering a better discription
this resulted in open heart surgery to replace an Aorta valve riddled with infection burn holes and a brain MRI with the arc pure white except for the left side 20% the reserve brain the nuero psychiatrist explained to me
Thank you!
People with ME/CFS fulfilling the CCC /ICC and IOM criteria, are unfortunately harmed by aerobic excersize that trespass their individual limits.
It led me to relapse, going from a light form of the disease (70-80% activity level) working full time in decades, to a very limited life with about 15-20 % activity level, where can hardly care for my self.
We need rewievs based on good solid science, and on patients diagnosed with the Canadian Concensus Criteria (CCC) or International concensus criteria (ICC).
Smart job shoring up the defenses David.
Simply excellent!
Yesssssss! Huge thanks to David Tuller and to all the signatories.
Thanks for all of the signatories for so quickly speaking out about this.
As if it wasn’t bad enough that Larun failed to correct her work after being informed of such serious problems in the comments submitted by Tom Kindlon and Robert Courtney, that she has now responded to Cochrane’s editorial decision to withdraw her work by aiding in a smear campaign against patients indicates unfit a person she was to do this work.
Whether she’s unable to understand the problems with her review, and so feels genuinely aggrieved at ‘unjust’ criticism, or else is just cynically placing her own short-term self-interest above the importance of rigorous standards for systematic reviews, I’m very grateful for the work that went into ensuring Cochrane’s leadership finally recognised that they could just accept the weak and evasive responses she had provided, and that they needed to take action themselves by withdrawing the review.
Well done and thank you all.
Was the Virology Blog established as part of a conspiracy?
Those desperate anti science patient activists that are bullying the poor Biopsychsocial researchers into CFS, they even managed to disguise themselves as respected PhDs and Proffessors at major academic institutes. The lengths they will go to, concealing their major disabling illness, studying and researching for twenty, thirty, forty years or more, infiltrating medicine and academia just because they fear the stigma of a psychiatric diagnosis.
The paranoia of people with chronic fatigue is such that they started planning this major international undercover operation over thirty years before the publication of PACE and the Cochrane Reviews of GET and CBT with the deliberate intent of libelling and bullying the authors. Thank goodness we have people like Prof Blakemoor and such as the SMC that can see through their evil anti science machinations.
Well done to Reuters for coming to the defence of the BPS martyrs and exposing this evil plot where millions of dollars of research funding has been syphoned off into thousands of biomedical research studies in so many universities designed with the sole purpose of undermining these true believers.
Fortunately our heroes of true science have built impenetrable defences around their minds by refusing to read any of this false research and by steadfastly declining to engage with any of the beguiling false criticisms designed to distract them from the true path.
A very clear and succinct summing up of the situation with the Cochrane review, thank you
Hope, this gives me hope that science will shine through the dark cloud of devastation we have lived with.
Thank you David and all those that signed this support to Cpochrane,
Giving us this hope is a most wonderful gift.
Here here
I thank Dr. Tuller, Tom Kindlon, the late Robert Courtney, Mary Dimmock, and a host of others for all their hard advocacy work on this project. I actually appreciate the positive reinforcement given by the signers of the letter to Cochrane. Their (Cochrane’s) decision to withdraw the ME/cfs treatment review until all the expert criticisms about it are satisfactorily answered is a good thing. (I’m hoping there will be no “backsliding” on their decision under pressure from newly distraught colleagues–who seem unaccustomed to having their scientific work critiqued by others. )
Next, I’m looking forward to the positive reinforcement to be given to the Lancet, PLOS, and other journals when they retract anything associated with the PACE study, as well as to the developers of UK’s NICE guidelines (and other national medical guidance boards) when they remove GET and CBT as “treatments” for ME/cfs. Not only am I ready for the (genuine) apology tour, I’d be willing to hand out positive vibes as the tour makes its way from coast to coast and across both big ponds separating new world from old.
Support from professionals continues to be essential, so thank you very much!
With your help, we can overcome the constant misrepresentations by the PACE authors.
Thank you for your well written blog. Your posts are easy to understand and impossible for them to argue against
Thank you for your hard work. You are making a difference.
Great to see all this support! Thanks to all involved in getting us here.
You nailed it, David!! Enormous thanks to you & all the signatories for having our backs, & fighting in our corner. I’m aghast at the lengths the BPS proponents will go to support what is known to be flawed, & causes those with ME (CFS) harm, & often, deterioration. To fight tooth & nail against millions of severely ill patients, & to continue with their smear campaigns against us, is beyond comprehension.
To those out there who support them without knowing the facts, please research it thoroughly before you side with them. There is a LOT to this story, & it’s worth looking into if you seek truth & justice. It is a huge medical scandal, & history will judge them harshly. 23+ years with a severe & hugely debilitating disease leaves one beyond weary of it all. But to then have to fight against all this too, is enough to make some give up. And, sadly, many have. It may be too late for me, but for the sake of the younger ones, & the dear children with ME, I hope this nightmare ends very soon.
Thank you so much to Dr Tuller and all the signatories, for standing up for science.
Thank you David for all your work on this. Let’s hope health science journalists in the UK will pick up on this scandal.
Thank you so much for such a great letter. Well written and the arguments are explained in a clear manner.
Thank you David for the work you have done for PWME is much appreciated and it give me hope for my future Thanks to all the other amazing signatories too. Thank you, thank you, thank you.
Thank you from the bottom of my heart.
I’d like to offer my heartfelt gratitude to the signatories. It is very low that proponents of PACE must mischaracterise their opponents in order to try to win the debate.
Thank you! To every signatory and to David Tuller. My son is 14 and has had this disease for 2 years – you all give us hope.
Thank you for standing up for science!
Useful thanks. What appears to be missing is a register of people with ME harmed by GET. Whilst I understand the difficulties of reliable diagnostics for PWME a register of people harmed by GET and some account of health before and after would possibly be helpful in getting a more reliable idea of this evidence. How can this be effectively pursued in different countries please?
Peter Trewhitt’s comment here is very irrational. It comes off as conspiratorial or as satire. He thinks patients have went to great lengths to get PhDs to push their “biased” views. To him bias simply means having personal experience with something you study. If this where true it would mean people with spinal code injuries cannot study the spinal cord.
I’ve had CFS since my late teens and I am not an anti-science person. I have a pretty good understanding of science that is applied to everyday issues such as being able to identify pseudoscience an consider myself a pro-science skeptic. I am pro-vax, pro-GMO, I don’t believe in alternative medicine and I believe in anthropogenic climate change. I don’t believe in chronic lyme disease, EMF sensitivity syndrome or MCS which are actual fake diseases. I hate to see CFS lumped in with conditions like this.
The stigma and fear of being diagnosed with mental illness is real, but it’s stronger in the US and not all sufferers live there. I believe someone can have co-morbid mental illness with CFS. I myself have a neurodevelopmental condition called Non-verbal learning disability and OCD and I am not ashamed of it nor am I anti-psychiatry like a scientologist or something.
We need to have a compassionate attitude towards people who have been tricked by quacks! The skeptic blog Debunking Denialism has written about this on his blog. Of course some CFS sufferers will be drawn into alt med because of desperation but so are many cancer patients and there aren’t many cancer denialists in any professional setting. https://debunkingdenialism.com/2018/05/28/people-who-fell-for-quackery-dont-deserve-death/
Sometimes it is really hard to suffer both mental illness and CFS, because it makes it easy for Biopsychsocial model people like you to dismiss the physical symptoms of my illness. CBT would be fine if it didn’t make faulty assumptions in the case of PACE inspired recommendations on how CFS is psychogenic. In fact CBT that went off a premise that the disease is biomedical in origin and helping people cope with how much it can change your life in limiting ways would be great! But those psychologists are rare and even rarer in psychiatry.
It causes severe emotional distress to deal with CFS denialist medical professionals. Especially ones to do with mental health. I’d be happy to see a counselor again for OCD and getting an updated psychoeducational assessment for my learning disability! But seeing a counselor now would be hard once I tell them my full circumstances including having CFS. I do not deny the effectiveness of psychiatric medication and CBT for many mental illnesses! It has saved my life. But some of it when applied to CFS sufferers can actually make us worse.
The whole stereotyping of CFS sufferers as angry, mean, bad people is really unfair. I’ve even seen cancer patients mad/frustrated that there are not more options! It’s a normal reaction to being sick, I think.
I admit I get annoyed at the ME people who think that the cause of CFS has been known for decades when the cause is still unknown and don’t want to be associated with the term CFS nor those patients because of the trauma of being disbelieved. It’s clear they just want ME for the Latin name and they crave being taken seriously, which I do not blame them for. There’s no point in having a Latin name with a very descriptive meaning for a disease we are still trying to figure out what causes it and how it works.
Well-written letter! I’d be happy if the PACE stuff was taken out of medical guidelines. It does a number on one’s mental health to not have your physical suffering validated. These people who deny this do not care how much they damage patients mental health and well-being by their denial.
Even my boyfriend who has Crohn’s was accused by a psychiatrist of having anorexia nervosa before he was diagnosed! He actually just had nausea that made it hard for him to eat. Many people can tell you the insulting bullcrap they have went through til they got their diagnosis but for us there is no end to it because of no biomedical test.
If Peter is not a troll, he is an buttmad researcher who has had his psychogenic CFS research challenged.
Sorry for any typos, I am just too tired to edit it but I tried to make sense.
Thank you for another very clear and well argued article. Thanks to David and the superb researchers now working on ME, we are finally emerging from the darkness.
By the way, Peter Trewhitt’s comments are firmly tongue-in-cheek – I found them very funny!
Chthonic Countenance, sorry that I caused confusion. My intention was to point out the ludicrous nature of the GET/CBT appologists attempt to divert attention from the failings in their science by inventing the unjustified narrative of anti science patients harassing and bullying them. To point out, as David says elsewhere, these supposed scientists are behaving more like a cult or ideological extremists.
My preposterous suggestion that such as the signatories of this letter were people with a major disabling illness disguised for thirty or forty years was to stress how idiotic it is to continue this abuse of patient advocates and patient scientists when also there is an international swelling of academics, clinicians and charities raising the same concerns.
I have had ME/CFS for over twenty five years and would not intentionally cause distress to anyone with this horrid condition.
It is encouraging that Cochrane has smelled a rat. I hope this well-constructed and well-supported letter will stiffen their resolve so that the review is permanently withdrawn now. More alarming is the willingness of Reuters to act as lap-dog to the BPS lobby and smear patients. They used to be a reliable news agency.