Trial By Error: Letter to British Journal of Sports Medicine from CPET Experts

By David Tuller, DrPH

Last October, the British Journal of Sports Medicine published a short paper that was essentially a summary of Cochrane’s systematic review of graded exercise for chronic fatigue syndrome (as Cochrane calls the illness). This systematic review is problematic for a number of reasons—not least of which is that it includes the debunked PACE trial and other Oxford criteria studies.

The Oxford case definition does not require any symptoms besides fatigue for diagnosis—including the cardinal symptom of post-exertional malaise. Studies that rely on Oxford criteria samples do not represent the experiences of patients with more narrowly defined disease. Systematic reviews of flawed trials produce flawed results.

In response to the BJSM article, the experts on post-exertional malaise from University of the Pacific and the Workwell Foundation wrote a letter to the journal that has not yet been published. These investigators have documented this symptom through use of the two-day CPET test, which measures the impact of exercise. They wanted to register their evidence-based opposition to the recommendation for GET. Since the letter makes valuable points and will be useful for those seeking to rebut the BJSM paper’s fallacious claims about exercise, I am happy to post it below.

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Dear Editor,

We are writing in response to the article, Exercise therapy is a beneficial intervention for chronic fatigue syndrome (PEDro synthesis), by Dannaway et al. and published on October 5, 2017 [1]. We are opposed to graded exercise therapy as a treatment for ME/CFS as recommended in this article. Our experiences working with ME/CFS patients are that graded exercise – particularly aerobic exercise–not only fails to improve function, it is detrimental to the health of patients.

The rationale behind using GET as treatment for ME/CFS is that it can reverse a cycle of inactivity and deconditioning, and subsequently reduce the fatigue and disability associated with this disease [2,3]. However, it seems counterintuitive at best to employ exercise as treatment when the hallmark of ME/CFS is a distinctive post-exertional malaise or PEM, whereby even trivial mental or physical exertion can cause a worsening of symptoms and reduced function [4]. As further noted in the 2015 National Academy of Medicine (NAM, previously called the Institute of Medicine) report, ME/CFS is a complex, multi-system disease accompanied by neurological, immunological, autonomic, and energy metabolism impairments [5]. It is not deconditioning nor are its symptoms explained by inactivity. As noted by NAM chair Dr. Ellen Clayton, the debility in ME/CFS is much greater than would be seen with deconditioning [6].

Scientific studies published by our group and other researchers have demonstrated that aerobic exercise exacerbates symptoms [7,8,9], a conclusion supported by the 2015 NAM report. This abnormal physiological response to exertion is so distinctive that many ME/CFS researchers, including the National Institute of Health’s Intramural Study [10] and Cornell’s Collaborative ME/CFS Research Center [11], use exercise, not as a therapeutic intervention, but as a way to exacerbate the illness so that it can be studied.

Studies evaluating the use of graded exercise therapy (GET) to treat ME/CFS have been criticized in part for including patients with other fatiguing conditions [12]. This led the US Agency for HealthCare Research and Quality (AHRQ) to conclude in its evidence review that once these studies were excluded there was insufficient evidence of efficacy for GET [13]. Beyond lack of efficacy there is also concern about the harm done by GET. AHRQ reported that GET was “associated with higher numbers of reported adverse events [14].” A 2017 review of patient surveys by Geraghty concurred, stating GET “brings about large negative responses in patients [15].”

In addition to research, our team has also worked for years with therapeutic exercise strategies in an attempt to help ME/CFS patients. We have tried to incorporate aerobic exercise training as a re-conditioning strategy for ME/CFS patients but it simply does not work. To the contrary, in nearly all cases, patient symptoms heighten after exercise [16].

Our research and clinical experiences engender a certain skepticism toward findings from the recent GETSET study, as expressed by experienced physical therapist Dr. Todd Davenport [17]. Further, the Centers for Disease Control and Prevention have recently removed recommendations for GET from their ME/CFS website [18].

Given what is known about the biology of ME/CFS, avoiding aerobic exercise and limiting aerobic activity whenever possible seems a more reasonable approach. This minimizes risk of relapse, the detrimental effects of which can persist for prolonged periods. Our position is that patients’ first-hand experiences can provide better evidence-based support to develop therapeutic interventions that help rather than harm. The goal of therapeutic exercise for ME/CFS patients should be to increase activity levels while reducing fatigue. We believe this is best achieved by training the anaerobic energy system, i.e., improving the body’s tolerance for and ability to clear lactate while increasing ATP in resting muscle [19].

This letter is motivated by concern about the potential harm to ME/CFS patients from aerobic exercise recommended by otherwise well-intentioned health care professionals. The views expressed here echo real-life experiences of many ME/CFS patients, which we feel, are well-supported by the scientific literature.

J. Mark VanNess, Ph.D.
Department of Health and Exercise Science
University of the Pacific
Stockton, California
Corresponding author. Email: mvanness@pacific.edu

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

Christopher R. Snell, PhD
Scientific Director
Workwell Foundation
Ripon, California

Staci Stevens, MA
Founder, Exercise Physiologist
Workwell Foundation
Ripon, CA

Conflicts of Interest:
None declared

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References

1. Dannaway J, New CC, New CH, et al Exercise therapy is a beneficial intervention for chronic fatigue syndrome (PEDro synthesis). Br J Sports Med Published Online First: 05 October 2017. doi: 10.1136/bjsports-2017-098407

2. Burgess M, Chalder T. PACE Manual for Therapists. Cognitive Behavioral Therapy for CFS/ME. MREC Version 2. PACE Trial Management Group. November 2004. http://www.wolfson.qmul.ac.uk/images/pdfs/3.cbt-therapist-manual.pdf

3. Bavinton J, Darbishire L, White PD. “PACE Manual for Therapists. Graded Exercise Therapy for CFS/ME.” MREC Version 2. PACE Trial Management Group. November 2004. https://www.wolfson.qmul.ac.uk/images/pdfs/5.get-therapist-manual.pdf

4. Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness. National Academy of Medicine. February 10, 2015. http://www.nationalacademies.org/hmd/Reports/2015/ME-CFS.aspx Page 86.

5. Ibid. Page 71-139

6. Tucker, M. IOM Gives Chronic Fatigue Syndrome a New Name and Definition. Medscape. February 10, 2015. http://www.medscape.com/viewarticle/839532 Page 86.

7. Davenport T, Stevens S, VanNess M, Snell C, Little T. Conceptual Model for Physical Therapist Management of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis. Physical Therapy, April 1, 2010. Volume 90 (4) 602–614. https://doi.org/10.2522/ptj.20090047

8. Davenport TE, Stevens SR, Baroni K, Van Ness M, Snell CR. “Diagnostic accuracy of symptoms characterizing chronic fatigue syndrome.” Disabil Rehabil September 2011; 33(19-20): 1768-75. PMID: 21208154 http://dx.doi.org/10.3109/09638288.2010.546936

9. VanNess JM, Stevens SR, Bateman L, Stiles TL, Snell CR. “Post-exertional malaise in women with chronic fatigue syndrome.” J Women’s Health (Larchmt) February 2010; 19(2): 239-44. http://dx.doi.org/10.1089/jwh.2009.1507

10. NIH Intramural Study on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. National Institutes of Health. https://mecfs.ctss.nih.gov/

11. Ramanujan, K. $9.4M NIH grant funds chronic fatigue syndrome center. Cornell Chronicle. September 27, 2017. http://news.cornell.edu/stories/2017/09/94m-nih-grant-funds-chronic-fatigue-syndrome-center

12. U.S. Agency for Healthcare Quality and Research. “Diagnosis and Treatment of Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome.” Evidence Report/Technology Assessment Number 219. U.S. Agency for Healthcare Quality and Research. December 9, 2014. Updated July 28, 2016. AHRQ Pub. No. 15-E001-EF https://ahrq-ehc-application.s3.amazonaws.com/media/pdf/chronic-fatigue_research.pdf Page 1

13.Ibid. Page 11

14. Ibid. Page vi.

15. Geraghty K, Hann M, Kurtev A. Myalgic encephalomyelitis/chronic fatigue syndrome patients’ reports of symptom changes following cognitive behavioural therapy, graded exercise therapy and pacing treatments: Analysis of a primary survey compared with secondary surveys. Journal of Health Psychology. August 29, 2017. http://journals.sagepub.com/eprint/hWSxVIBTzDtqisvafkhE/full

16. Chu L, Bateman L, Davenport T, Stein E, Stevens S. Treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Ann Intern Med. December 2015. 163(11):887. http://annals.org/aim/article/2473522/treatment-myalgic-encephalomyelitis-chronic-fatigue-syndrome

17. Davenport T. Another False Start” in ME/CFS Clinical Trials: The GETSET Study. Workwell Foundation. 2017. http://www.workwellfoundation.org/wp-content/uploads/2017/07/GETSET-Trial-in-MECFS-L1.pdf

18. CDC ME/CFS Website. Treatments. Centers for Disease Control and Prevention. Updated July 3, 2017. https://www.cdc.gov/me-cfs/treatment/index.html

19. Davenport T, Stevens S, VanNess M, Snell C, Little T. Conceptual Model for Physical Therapist Management of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis. Physical Therapy, April 1, 2010. Volume 90 (4) 602–614. https://doi.org/10.2522/ptj.20090047

Comments on this entry are closed.

  • Sleepyblondie 5 February 2018, 5:58 pm

    Thank you. This is a never ending battle to stop medical professionals from harming us and I am so grateful that you listen and help to speak for us

  • Star Man 5 February 2018, 5:59 pm

    “Our experiences working with ME/CFS patients are that graded exercise –
    particularly aerobic exercise–not only fails to improve function, it is
    detrimental to the health of patients.”

    Thank you to the University of the Pacific and the Workwell Foundation for this letter. The lack of effectiveness and potential potential for harm from GET need to be continually pointed out until doctors take notice.

    Hopefully one day soon, healthcare providers (such as Kaiser Permanente and its 12 million members), will stop recommending GET for their ME/CFS patients.

  • Peter Trewhitt 5 February 2018, 6:05 pm

    Thank you for publishing this clear and concise account of why aerobic exercise is contra indicated in ME/CFS and why the studies advocating GET are profoundly flawed. It is a great shame it was not published in the BJSM.

    Let’s hope this Blog series is read by the clinicians and researchers that continue to advocate GET.

  • Robert McMullen 5 February 2018, 6:11 pm

    Excellent letter. Many thanks to all.

  • Wendy Boutilier 5 February 2018, 6:13 pm

    The review was funded by £206,000 (US$304,087 ) from the UK National Institute for Health Research.

    What could possibly go wrong when the Heroes of the the PACE Trial Study – the UK Psychiatric Collaborative wrote the Cochrane Protocol for people with Chronic Fatigue Syndrome as well as for people with Myalgic Encephalomyelitis ????

    Every other country adopted it without question.

  • Fiona 5 February 2018, 6:22 pm

    Terrific letter from Workwell/UoP – it encapsulates a lot of what this disease is, and explains clearly why aerobic exercise is bad news for PWME. Thanks for publishing!

  • mesupport 5 February 2018, 6:29 pm

    The Cochrane review appears in the Common Mental Disorders Group totally ignoring WHO G93.3 classification as a neurological condition.

  • Wendy Boutilier 5 February 2018, 7:14 pm

    Canada turned down an ME Study a couple of years ago because the Cochrane Review suggests GET and CBT. They felt we didn’t need another “fatigue” Study.

  • tomkindlon 5 February 2018, 9:28 pm

    Very good letter.

    Small point: I am surprised to see the “ibid” format being used. I’m not sure I have ever seen it used in the many hundreds of medical and scientific papers I have read. I have certainly not used it in the letters I have had published.

  • JustinReilly 6 February 2018, 12:41 am

    Very cogent letter. Thanks for posting!

  • Olivia Beatty 6 February 2018, 3:18 am

    Apparently the German equivalent of UK NICE has just approved CBT/GET as the recommended treatment in it’s recent review.

  • Valentijn 6 February 2018, 4:26 am

    Simon Wessely was one of the founders of that Cochrane group. No doubt the intent was to prevent honest and impartial review from other groups better suited to handling a disease with neurological, muscular, and immunological components.

  • pinklil 6 February 2018, 6:11 am

    This is a very useful tack in as much as it both highlights the prejudices of the Cochrane review and hopefully piques the interest of a discipline which I have long felt might be very curious to investigate this disease more closely. In the same way Cheney had problems convincing his cardiologist peers that people with ME could have a positive bubble test, whilst simultaneously appearing to be hale and hearty on the usual bank of hospital cardio tests, until those cardiologist peers had seen the evidence with their own eyes, maybe sports scientists could be encouraged to look at the impaired physiology of people with ME using the technologies at their disposal and thus also believe what VanNess et al have described here? They might be able to elucidate extra fundamental flaws in the way people with this disease use, or don’t use, energy.
    I suppose how the BJSM react to this letter rather depends on how open minded they are to the scientific method and proper scientific enquiry rather than, possibly, toeing a line handed to them by others with a vested interest in maintaining the status quo & who would prefer a discipline such as ‘sports medicine’ (with its bias toward *objective* measurements 😉 ) to not interfere and threaten their subjective, un-blinded junk-science ‘data base’.

  • Anton Mayer 6 February 2018, 7:51 am

    Thank you for this letter. Can anyone summarize how one can train the anaerobic energy system?

  • disqus_joh5XNAv6w 6 February 2018, 8:19 am

    “This is a very useful tack in as much as it both highlights the
    prejudices of the Cochrane review and hopefully piques the interest of a
    discipline which I have long felt might be very curious to investigate
    this disease more closely.” _ I agree and suggest this is offered to the NICE SCoping Exercise?

  • pinklil 6 February 2018, 9:13 am

    Good idea.

  • leelaplay 6 February 2018, 3:10 pm

    Anton, Workwell has a number of publications and videos that address this linked to on their site.

  • leelaplay 6 February 2018, 3:19 pm

    Thank you Workwell and David for this letter. Well done. I hope that the BJSM has the ethics to publish it soon. If not, is there another avenue to get it published now that pubmed commons is no longer publishing comments?