International Association for Chronic Fatigue Syndrome/ Myalgic
Encephalomyelitis (IACFS/ME)
9650 Rockville Pike
Bethesda, MD 20814
United States of America
July 25, 2018
Japan ME Association
3-11-12 Takanodai
Nerima-ku, Tokyo
177-0033 Japan
Dear Japan ME Association:
We provide this letter in response to your request for our comment on the“ME/CFS Treatment Guidelines for Japan (Draft),” which we understand iscurrently being re-evaluated. We have reviewed the English translation ofsections that you sent to us which were of the most concern to your patientassociation.
The International Association for Chronic Fatigue Syndrome/ Myalgic
Encephalomyelitis is concerned about the potential harmful impact of thisdocument on ME/CFS patients in Japan, particularly as policymakers,
government officials, medical researchers, and healthcare providers are often
unfamiliar with the symptoms and complex nature of ME/CFS.
As noted in our “Chronic fatigue syndrome/ myalgic encephalomyelitis primer forclinical practitioners: 2014 edition,” (1) ME/CFS is a serious and complex physicalillness with neurological, immunological, endocrinological, autonomic, energy
metabolism, and other physiological abnormalities. These abnormalities werealso documented in a 2015 review (2) of over 9,000+ studies by the US National
Academy of Medicine. It is not a psychiatric or psychological disorder.
Patients suffer from substantially impaired physical and/or cognitive functioning
due to severe fatigue, widespread musculoskeletal and joint pain, memory andconcentration problems, unrefreshing sleep, autonomic dysfunction, and flu-likesymptoms. A key feature of the illness is post-exertional malaise (PEM), a
worsening of symptoms following even minimal physical or cognitive exertion.
The severity and duration of PEM is often disproportionate to the precipitating
activity. For example, a short shopping trip might land a patient in bed for days.

The World Health Organization currently classifies myalgic encephalomyelitis asa disease of the central nervous system (G93.3) (1).
It is of concern to us that ME/CFS Treatment Guidelines for Japan (Draft)
discusses Graded Exercise Therapy as a recommended treatment for
ME/CFS. GET studies suffer from multiple flaws including overly broad inclusion
criteria, a paucity of objective outcome measures, questionable blinding ofparticipants, high trial participant drop-out rates, post-hoc modifications ofoutcome measures, selective outcome reporting, and poor reporting of harms.
In 2016, the United States Agency for Healthcare Research and Quality (3) rated
the evidence for GET as “Insufficient” and recommended that the broad “Oxford”
criteria used for many GET studies be retired due to its non-specific nature. Andin 2017, a re-analysis of the United Kingdom (4) multi-million-pound PACE trial
using the original outcome measures found that recovery rate with GET fell froman initially reported 22% to 4% and was not statistically significant from therecovery rate of 3% reported with usual medical care. Consequently, we areskeptical about the validity of GET trial results. The US Centers for Disease Controland Prevention came to similar conclusions in the Fall of 2017 and are currently
in the process of removing GET as a recommended treatment for ME/CFS (5).
Moreover, evidence against GET exists. Our organization does not recommend
GET because our clinician members, who have taken care of ME/CFS patients fordecades, tell us it does not work. Surveys of thousands of patients, across differentcountries, over many years, and conducted by different groups consistently findthat very few benefit substantially from GET. Instead, a mean of 50% (6) of
respondents disclosed that their health worsened with GET. Finally, physiologicalstudies support patient and clinician accounts. For example, some studies suggestthat patients have an impaired aerobic energy (7) system while others
demonstrate an abnormal immunological response (8) to exercise. (Interestingly,
the discussion sections of published GET studies rarely address this contraryevidence.) Thus, we hope that GET will not be recommended in the final versionof the document.
Further, we share your concern that because the ME/CFS Treatment Guidelines(Draft) frames behavioral approaches such as CBT, yoga, and drug treatments
such as antidepressants as blanket treatments for ME/CFS, the document may
reinforce erroneous beliefs among healthcare providers that ME/CFS itself
is a psychological or psychogenic illness that can be cured or reversed bysuch interventions. Accordingly, we believe the document should prevent any
such misunderstandings by:a) making it explicitly clear that ME/CFS is not a psychological or psychogenicillness,b) conveying that these treatments are merely supportive and not primary,curative, or disease-modifying, treatments, and should be incorporated in asimilar matter as they are for other medical conditions like cancer, heart disease,etc. (e.g., cancer patients would never be solely treated with CBT or yoga),c) emphasizing that such treatments are not mandatory for all ME/CFS patients(e.g., a patient who does not have depression as a comorbidity (depression is nota symptom of ME/CFS) should not be given antidepressants).
We hope these comments are helpful to you, the research committee, and thegovernment agencies reviewing the Draft in producing a scientifically accurate
guideline that benefits everyone.
Sincerely,Fred Friedberg, PhD and Lily Chu, MD, MSHS on behalf of theThe International Association for Chronic Fatigue Syndrome/ Myalgic
Encephalomyelitis Board
www.iacfsme.org

REFERENCES:
1. IACFS/ME Primer Writing Committee. Chronic fatigue syndrome/
myalgic encephalomyelitis primer for clinical practitioners: 2014 edition.
International Association for Chronic Fatigue Syndrome/ Myalgic
Encephalomyelitis.
https://iacfsme.org/portals/0/pdf/Primer_Post_2014_conference.pdf.
Published 2014. Accessed June 26, 2018.
2. Committee on the Diagnostic Criteria for Myalgic
Encephalomyelitis/Chronic Fatigue Syndrome. Beyond myalgic
encephalomyelitis/ chronic fatigue syndrome: redefining an illness. TheNational Academies Press.
https://www.nap.edu/read/19012/chapter/1. Published February
2015. Accessed June 26, 2018.
3. Agency for Healthcare Research and Quality. Diagnosis and treatment ofmyalgic encephalomyelitis/chronic fatigue syndrome. Agency for
Healthcare Research and Quality.
https://effectivehealthcare.ahrq.gov/sites/default/files/pdf/chronicfatigue_research.pdf. Published July 2016. Accessed June 26, 2018.
4. Wilshire C, Kindlon T, Matthees A, McGrath S. Can patients with chronic
fatigue syndrome really recover after graded exercise or cognitive
behavioural therapy? A critical commentary and preliminary re-analysisof the PACE trial. Fatigue: Biomedicine, Health & Behavior, 5:1, 43-56,
DOI: 10.1080/21641846.2017.1259724
5. Doucleff, M. For people with chronic fatigue syndrome, more exercise
isn't better. National Public Radio.
https://www.npr.org/sections/healthshots/2017/10/02/554369327/for-people-with-chronic-fatiguesyndrome-more-exercise-isnt-better. Published October 2017. Accessed
June 26, 2018.
6. Kindlon T. Reporting of harms associated with graded exercise therapy
and cognitive behavioural therapy in myalgic encephalomyelitis/chronic
fatigue syndrome. International Association for CFS/ME.
http://iacfsme.org/PDFS/Reporting-of-Harms-Associated-with-GET-andCBT-in.aspx. Published Fall 2011. Accessed June 26, 2018.
7. Tomas C, Newton J. Metabolic abnormalities in chronic fatigue
syndrome/ myalgic encephalomyelitis: a mini-review. Biochem Soc
Trans. 2018 Jun 19;46(3):547-553. doi: 10.1042/BST20170503.
8. 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.