The influence of the Cochrane review on GET

ME/CFS Skeptic

ME/CFS Skeptic

Senior Member (Voting Rights)
I thought it might be useful to get an overview of medical guidelines on ME/CFS that have been influenced by the Cochrane review on graded exercise therapy (GET).

I’m mostly interested in official government positions or influential medical authorities that have referred to the Cochrane review to (1) recommend the use of graded exercise therapy for patients with ME/CFS, (2) ignore surveys where ME/CFS patients report having been harmed by GET or (3) deflect criticism of other GET-trials such as PACE.

I’ve already given a short overview and I’ll try to update it with the information that others add to this thread. I hope that people from countries such as France, Italy, Spain, Norway Sweden, Austria etc. could have a quick look to what official government or medical guidelines in their country say and whether the Cochrane review is cited. You can search the Cochrane reference by looking for :

Larun L, Brurberg KG, Odgaard-Jensen J, Price JR. Exercise therapy for chronic fatigue syndrome. Cochrane Database Syst Rev. 2015;2:CD003200.​

The review was published in 2015 but has been amended several times since, so the year in the citation may be different.

Many thanks in advance,



Germany
In response to a parliamentary question, the German federal government referred to the Cochrane review to defend the use of graded exercise therapy for patients with CFS against criticism from patient surveys that indicate harms caused by GET.
http://dip21.bundestag.de/dip21/btd/19/126/1912632.pdf

The German College of General Practitioners and Family Physicians has published a 2018 guideline on fatigue (Müdigkeit). In the chapter on CFS, the Cochrane review is mentioned as evidence for exercise therapy.
https://www.awmf.org/uploads/tx_szleitlinien/053-002l_S3_Muedigkeit_2018-06.pdf

A 2018 guideline of the Association of the Scientific Medical Societies in Germany on Functional Disorders mentions the Cochrane review as evidence that exercise therapy is beneficial in patients with CFS.
https://www.awmf.org/uploads/tx_szleitlinien/051-001l_S3_Funktionelle_Koerperbeschwerden_2018-11.pdf

Denmark
The Danish Health Authority cited the Cochrane review to recommended graded exercise therapy for patients with CFS.
https://www.sst.dk/da/udgivelser/2018/~/media/1CE89F3206874263888BA4719419B844.ashx

Researcher Per Fink has cited the Cochrane review to argue that GET is an effective treatment for (severe) ME/CFS patients and to oppose changes to the classification of ME/CFS as a functional disorder.
https://translate.google.com/translate?sl=da&tl=en&u=https://propatienter.dk/sygdomme/muskler/1977-29-arig-kvinde-har-ligget-to-ar-i-morkt-rum-debat-i-folketinget-i-dag.html

Australia
The Cochrane review has been used by the Royal Australian College of General Practitioners to recommend graded exercise therapy for patients with CFS.
https://www.racgp.org.au/clinical-r...ded-exercise-therapy-chronic-fatigue-syndrome

The HANDI working group headed by Paul Glasziou has used the Cochrane review to promote the use of graded exercise therapy as a safe and effective treatment for patients with CFS.
https://journals.sagepub.com/doi/abs/10.1177/1755738019852393?journalCode=inoa

An ongoing Australian randomized controlled trial is testing how to educate healthcare professionals about the “level 1 evidence” for graded exercise therapy for patients with CFS, citing the 2017 Cochrane review. The intervention consists of an educational program for healthcare professionals on the use of GET For CFS. The protocol (Li et al. 2017) explains: “The intervention has been designed based on a manual developed by the research group that drew on Cochrane reviews of cognitive behaviour therapy (CBT) and graded exercise therapy (GET) interventions for CFS.”
https://bmjopen.bmj.com/content/7/5/e014133

New Zeeland
A medical educational document in ‘New Zealand doctor’ cites the Cochrane review to claim that exercise is beneficial for chronic fatigue syndrome. The document is part of PEARLS (Practical Evidence About Real Life Situations) and was developed by the Cochrane Primary Care Field, New Zealand Branch of the Australasian Cochrane Centre at the Department of General Practice and Primary Health Care, University of Auckland and funded by the Ministry of Health.
https://www.nzdoctor.co.nz/vault/pearls/exercise-beneficial-chronic-fatigue-syndrome

The UK
The NICE 2017 Surveillance report on the CG53 guideline on ME/CFS noted that “Cochrane reviews appear to support the guideline recommendations on CBT and GET.” The surveillance report concluded that a review of the guideline was not necessary, a decision that was later overruled when the majority of stakeholders argued that update was indicated.
https://www.nice.org.uk/guidance/cg...Surveillance-decision#reason-for-the-decision

When the PACE trial was criticized during a 2018 Westminster Hall debate, The Minister for Care, Caroline Dinenage, referred to the Cochrane review to defend PACE. She said: "Since 2011, PACE trial data has been shared with many independent scientists as part of normal research collaboration, including the internationally respected research organisation Cochrane, which independently validated the findings."
https://hansard.parliament.uk/commo...-4566-940D-249F5026FF73/PACETrialPeopleWithME

The Health Research Authority (HRA) cited the Cochrane review to argue that the PACE trial was high quality. In a 2019 report the HRA wrote: “The robustness of the PACE trial has been considered in a Cochrane review that classified it as high quality. This was also challenged by critics, and the author of the review responded to those criticisms. It would be as inappropriate for the regulator to disregard these indications that the trial was of high quality as to ignore the criticisms that have been expressed.” https://www.parliament.uk/documents...Research-Authority-to-Chair-re-PACE-trial.pdf

Fiona Watt, Executive Chair of the Medical Research Council, cited the Cochrane review as a reason to disagree with criticism of the PACE trial. She wrote: “While most of the criticism focuses on the PACE trial, there is a large amount of evidence from other studies that also shows CBT and graded exercise therapy (GET) can be helpful to some CFS/ME patients. Other research groups, using different study designs, have drawn similar conclusions about the benefit of these treatments. This evidence is summarised in three Cochrane reviews. Cochrane reviews are systematic reviews of primary research in human healthcare and health policy, and are internationally recognised as the gold standard in evidence-based healthcare.” https://mrc.ukri.org/news/browse/criticism-of-the-pace-trial/

Mayo Clinic US
The influential Mayo Clinic in the US currently gives CFS patients the following advice: “Gradually increasing the intensity of your exercise over time may help reduce your hypersensitivity to exercise, just like allergy shots gradually reduce a person's hypersensitivity to a particular allergen.” The main article cited by Mayo to support the use of graded exercise is the Cochrane review.
http://www.virology.ws/2018/08/06/trial-by-error-mayo-still-champions-get/

UpToDate cites the Cochrane review as evidence supporting the use of GET in CFS, but the article is cautious in its conclusions and also mentions criticism of GET trials.
https://www.uptodate.com/contents/c...ic-encephalomyelitis-chronic-fatigue-syndrome

Canada
The 2016 Clinical Practice Guidelines for ME/CFS 2016, Alberta, Canada, mentions the Cochrane review, but the guideline also discusses the methodological weakness of GET-trials and is cautious in its conclusion.
http://www.topalbertadoctors.org/download/1929/MECFS CPG.pdf?_20191017122609

A 2016 article in the Canadian Medical Association on exercise therapy for various chronic conditions, mentions the Cochrane review as evidence for exercise therapy in CFS. It writes that "there are no absolute contraindications to exercise for patients with chronic fatigue syndrome."
https://www.cmaj.ca/content/cmaj/188/7/510.full.pdf

Belgium
Minerva, a Belgium website that offers evidence-based medicine guidelines for primary care physicians used the Cochrane review to advise graded exercise therapy for patients with CFS.
http://www.minerva-ebm.be/NL/Article/2071

A government website in Belgium that that writes medical guidelines for doctors (ebpractice.net) used the Cochrane review to promote GET in ME/CFS. Recently, however, the GET review has been removed and is no longer cited. https://www.ebpnet.be/nl/Pages/default.aspx (I think the guideline is not visible for readers outside Belgium). The guideline was formulated by Duodecim, a company owned by the Finnish Medical Society that publishes information content for medical and healthcare professionals. The guideline on fatigue citing the Cochrane review might still be in use in other countries.

The Netherlands
The 2018 report of the Dutch Health Council cites the Cochrane review but argued there was insufficient reason to advise GET in the Netherlands.
https://www.gezondheidsraad.nl/documenten/adviezen/2018/03/19/me-cvs

The 2013 guideline formulated by several societies of Dutch physicians referred to the 2004 Cochrane review by Edmonds et al. to advise graded exercise therapy.
https://www.nvvg.nl/files/41/04_Richtlijn_CVS_Definitief_8_feb_2013.pdf

A controversial series of news articles by De Monitor which criticized ME/CFS patient organizations for objecting to GET/CBT cited the Cochrane review to respond to criticism of their articles.
https://demonitor.kro-ncrv.nl/artikelen/de-monitor-reageert-op-kritiek-uitzending-mecvs

Switzerland
In its overview article on chronic fatigue, the Revue médicale suisse cites the Cochrane review to recommend graded exercise therapy.
https://www.revmed.ch/RMS/2015/RMS-N-496/Syndrome-de-fatigue-chronique#anchor-B24

Sweden
The ME/CFS guideline of Region Kronoberg, references Cochrane indirectly. It reads (translated into English): "Current compilations of the state of knowledge include NICE 2007, NAS/IOM 2015, Cochrane 2017 and Swedish recommendations from SLL/viss.nu and the national clinical knowledge support. [...]" The guideline recommends graded exercise therapy but also mentions that many patients object to the therapy.
http://dokpub.regionkronoberg.se/OpenDoc.aspx?Id=146163

Norway
Several Norwegian sources refer to the Cochrane review. The Norwegian Institute of Public Health, for example, has highlighted the conclusions of the Cochrane review in this 2015 article:
https://www.fhi.no/publ/2015/bedre-...ing-for-personer-med-kronisk-utmattelsessynd/

The website Norsk Helseinformatikk, made by the same company that publishes the Electronic Guidelines for Doctors in Norway, recommends graded exercise for ME.
https://nhi.no/sykdommer/hjernenerv...om-kronisk/utmattelsessyndrom-kronisk/?page=8

It refers to an article by Kjersti Uvaag and Elin Bolle Strandhe in the Journal of the Norwegian Physiotherapist Association where the Cochrane review is used as a source.
https://oslo-universitetssykehus.no/seksjon/nasjonal-kompetansetjeneste-for-cfsme/Documents/Kronikk CFS-ME Fysioterapeuten 08-17.pdf

A 2017 open-access journal sponsored by the Norwegian Society for Psychological Science said GET is effective for CFS patients referencing the Cochrane review.
https://psykologisk.no/sp/2017/01/e1/

Professor Brun Wyller cites the Cochrane review in an overview article on ME/CFS for the Journal of the Norwegian Medical Association in 2015. The article writes: "We believe the evidence base for cognitive behavioural therapy is so solid that all patients with chronic fatigue syndrome/myalgic encephalomyelitis should be offered this treatment." This includes patients with severe ME/CFS.
https://tidsskriftet.no/en/2015/12/...tis-pathophysiology-diagnosis-and-treatment-0

Italy
A ME/CFS guideline by The Italian National Agency for Regional Healthcare Services does not mention the Cochrane review. It's possible that the guideline was written before 2015, when the update of the Cochrane review by Larun et al. was first published.
https://www.s4me.info/threads/the-influence-of-the-cochrane-review-on-get.11768/#post-208734


France
?

Spain
?

Finland
?

Other countries
?
 
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Thanks Michiel for another useful overview.

Does the Cochrane review actually differentiate between GET and any kind of exercise?

As far as I know GET isn't recommended or even offered in Germany, only any kind of exercise ("Bewegungstherapie", "Aktivierung") -- but I think the Cochrane review as well as the PACE trial are referred to not only in the parliament's recent response but also in treatment recommendations.

(Hope to be able to write more about guidelines in Germany someday.)

(Edited for clarity.)
 
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I'm not really following the situation in Italy but some guidelines were published a few years ago. I don't know if they are still considered up to date or to what degree they influence care.

The document mentions Cochrane as source of information but doesn't seem to cite the "exercise therapy for CFS" review (maybe they do and I just missed it). It mentions CBT and GET as therapy option along with pharmacological interventions.

I should mention that in Italy there doesn't seem to be a psychiatry lobby pushing for psychosomatic explanations for poorly understood conditions. I think Italians don't have the character to treat patients so poorly. In fact they abolished psychiatric hospitals in the 70's or so and I heard mostly good things from a few psychiatry patients in Italy.
 

Attachments

Michiel Tack said:
Sweden
?
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There are currently no national guidelines for ME/CFS in Sweden, nor any ME/CFS insurance medicine decision guidelines.

There are very few regional ME/CFS guidelines. One of them, Region Kronoberg, references Cochrane indirectly:

Google Translate said:
Current compilations of the state of knowledge include NICE 2007, NAS/IOM 2015, Cochrane 2017 and Swedish recommendations from SLL/viss.nu and the national clinical knowledge support. [...]

The most commonly used rehabilitation strategies are GET (Graded Exercise Therapy), APT (Adaptive Pacing Therapy), KBT (Cognitive Behavioral Therapy) and ACT (Acceptance and Commitment Therapy), where the former has strongest formal scientific support but is highly questioned, especially by patient representatives.

http://dokpub.regionkronoberg.se/OpenDoc.aspx?Id=146163
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There might be more examples, but nothing comes to mind at the moment.
 
Thanks again for your enormous work on this. I haven't been able to read everything yet, but looking forward to.

In Norway the national guidelines for CFS/ME from the Directorate of Health is from 2014. So before the Cochrane review from 2015. The guidelines mention GET and refer to among others the PACE trial and a publication by Larun from 2011 called Finding the right balance of physical activity: a focus group study about experiences among patients with chronic fatigue syndrome

Here's what I found where the Cochrane review is referred to. Will add more articles when I can dig further.

  • Kjersti Uvaag (physiotherapist) and Elin Bolle Strand (psychologist) are both working at the national competence service for CFS/ME, known for their biopsychosocial approach to ME. In 2017 they wrote a scientific article for the Journal of the Norwegian Physiotherapist Association referring among other to the Cochrane review. Hva kan fysioterapeuter bidra med for CFS/ME pasienter? (How can physiotherapists contribute to CFS/ME patients?)

  • It is referred to at Norsk Helseinformatikk, an official website about illnesses/diseases. The same company publishes the Electronic Guidelines for Doctors in Norway and is much trusted. Graded exercise is recommended for ME. Kronisk utmattelsessyndrom (2017)

  • Of course the Norwegian Institute of Public Health has several articles praising GET as ME treatment and referring to the Cochrane review. Here's one from 2015 Bedre helse med treningsbehandling for personer med kronisk utmattelsessyndrom (Better health with exercise treatment for people with chronic fatigue syndrome)

  • An open access journal sponsored by the Norwegian Society for Psychological Science published in 2017: How is it to be an adolescent living with chronic fatigue syndrome/myalgic encephalomyelitis? A narrative review (abstract in English) by L. Rødevand where GET is said to be effective with the Cochrane review as reference.

  • Professor Wyller for the Journal of the Norwegian Medical Association in 2015. This article is both in English and Norwegian. For some reason, the references are only given in the Norwegian version, but he points to among other the Cochrane review.
    Chronic fatigue syndrome/myalgic encephalomyelitis - pathophysiology, diagnosis and treatment https://tidsskriftet.no/en/2015/12/...litis-pathophysiology-diagnosis-and-treatment
 
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Thanks for your effort @Michiel Tack!

Germany

Guideline Tiredness (2018) – chapter on CFS:
Several studies have shown improvements under aerobic training [266,267] This is confirmed by a new Cochrane review [164], on which the conclusions of the Guidelines Group are essentially based.

Mehrere Studien ergaben Verbesserungen unter aerobem Training [266,267] Dies wird bestätigt durch ein neues Cochrane-Review [164], auf dem im wesentlichen die Schlussfolgerungen der Leitliniengruppe basieren.
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https://www.awmf.org/uploads/tx_szleitlinien/053-002l_S3_Muedigkeit_2018-06.pdf, page 45


Guideline Functional Disorders (2018):
The effect of activating exercises has been investigated in a large number of systematic reviews for wide areas of functional body complaints. Activating movement exercises without further treatment components ("exercise therapy") were shown to be effective for chronic fatigue syndrome (Larun et al 2016).

Der Effekt aktivierender Übungen wurde in einer großen Zahl von systematischen Übersichtsarbeiten für weite Bereiche funktioneller Körperbeschwerden untersucht. Aktivierende Bewegungs-Übungen ohne weitere Behandlungskomponente („Exercise Therapy“) erwiesen sich als wirksam für das chronische Müdigkeitssyndrom (Larun et al 2016).
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https://www.awmf.org/uploads/tx_szleitlinien/051-001l_S3_Funktionelle_Koerperbeschwerden_2018-11.pdf, pages 141 and 146
 
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For Canada I only found:

Prescribing exercise interventions for patients with chronic conditions, by the Canadian Medical Association Journal, April 2016: https://www.cmaj.ca/content/188/7/510/. Authors include Paul P. Glasziou. It includes several chronic conditions. I quote below those for CFS (no mention of ME).
The most effective type, duration and intensity of exercise for chronic fatigue syndrome are unclear. Appendix 5 describes an example of one exercise intervention (graded exercise therapy).
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The evidence comes from a recent Cochrane review (eight RCTs involving 1518 participants) of exercise therapy compared with usual care, wait list, or relaxation and flexibility training.41 There was moderate-quality evidence for the effect of exercise on fatigue, with a mean reduction of 2.8 points (95% CI 1.57 to 4.07) on a 0–33 point scale (a lower score indicates less fatigue). Studies that used other scoring for the fatigue scale had similar results (see Appendix 2). In four RCTs (involving 489 participants, with moderate-quality evidence) that measured self-perceived changes in overall health, more participants in the exercise groups reported improvement than in the control groups (RR 1.83, 95% CI 1.39 to 2.40). Two RCTs (low-quality evidence) measured sleep, with a mean sleep score of 1.5 points (95% CI 0.02 to 2.95) lower in the exercise groups, with a lower score suggesting improved sleep quality. There was also low-quality evidence (five RCTs) for the effect on physical functioning, with mean scores 13.10 points (95% CI 1.98 to 24.22) higher in the exercise therapy groups. The review authors were unable to draw conclusions about the effect of exercise therapy on QoL, pain, anxiety, depression, use of health service resources and drop-out rate.
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There are no absolute contraindications to exercise for patients with chronic fatigue syndrome.
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There is limited evidence about adverse events. In the Cochrane review,41 serious adverse reactions (worsening symptoms and deterioration in function) were only reported by one study (n = 319) but were uncommon (two participants) in both groups (RR 0.99, 95% CI 0.14 to 6.97).
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The report from the task force on environmental health published by the health ministry of Ontario cites the Cochrane review but not quite positively, http://www.health.gov.on.ca/en/comm...task_force_on_environmental_health_report.pdf:
A body of research exists on supportive (i.e., non-curative, symptom-based) therapies for both ME/CFS and FM that is large enough, for example, to have served as the basis for Cochrane Reviews of randomized clinical trials conducted on exercise therapy for ME/CFS and randomized clinical trials conducted on oral nonsteroidal anti-inflammatory medications for FM. However, no consensus exists on the effectiveness of such treatments; and they only address approaches that are supportive (versus curative, since the basic mechanisms underlying both of the conditions remain unknown).
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This search also yielded this document I was not aware of before: Care and support needs of people with chronic fatigue syndrome/myalgic encephalomyelitis in Québec (https://www.inesss.qc.ca/fileadmin/doc/AETMIS/Rapports/Autres/2010_02_monograph_en.pdf). Published in 2010. Very telling that I wrote the health ministry around 2015 and in response was referred only to a small pamphlet published by the ministry. This report clearly did not have much impact and nothing has changed since.

It was in the results because it included Cochrane as a source of documentation but does not refer to it much. It's not half bad in that there is a clear exposition of a complete breakdown of care. However there is a lot of emphasis on psychological consequences, not quite clearly enough separating that it is the direct consequence of the illness in combination with the breakdown of care.

It's useful however because it included a patient panel and there are a lot of quotes from patients.

Could be useful to some maybe? @ScottTriGuy?
 
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MSEsperanza said:
Does the Cochrane review actually differentiate between GET and any kind of exercise?
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It does, but I don't think it's all that clear. It makes a distinction between:
  • Graded exercise therapy: exercise in which the incremental increase in exercise was defined by discussion between participant and therapist
  • Exercise with pacing: exercise in which the incremental increase in exercise was defined by the participant alone
  • Anaerobic exercise: exercise requiring a high level of exertion for a short period of time, which may be gradually increased with training.
I suspect the trial by Wallman et al. is exercise with pacing and the trial by Jason et al. is anaerobic exercise. In my view all interventions in the review can be described as graded exercise therapy, as they all gradually and carefully try to increase the amount of exercise.

strategist said:
I'm not really following the situation in Italy but some guidelines were published a few years ago
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Thanks. Interesting to see that there's an extensive document on ME/CFS in Italian (although my Italian isn't good enough to read it all). I see the newest date in the references is 2012 so I suspect it was published shortly after, around that time? As you say, they used the Cochrane Library to search for sources but I don't think they refer to any of the Cochrane reviews on ME/CFS.

Sly Saint said:
might find something of interest on this thread
https://www.s4me.info/threads/cochrane-review-and-the-pace-trial.2529/

from when Bob was still with us
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Thanks, Bob understood how important the Cochrane review was. Wish I had the chance to meet him or work with him.

mango said:
There are very few regional ME/CFS guidelines. One of them, Region Kronoberg, references Cochrane indirectly:
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Thanks. I'm going to add that.
 
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Kalliope said:
Here's what I found where the Cochrane review is referred to. Will add more articles when I can dig further.
Click to expand...
Thanks Kalliope!

I've added your sources to the overview, hope my summary is ok. I'm mostly interested in the promo article by the Norwegian Institute of Public Health (NIPH), because it's a government agency.

Joh said:
Germany

Guideline Tiredness (2018) – chapter on CFS:
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Thanks Joh. I've added these. Hope my summary is ok.

rvallee said:
Prescribing exercise interventions for patients with chronic conditions, by the Canadian Medical Association Journal, April 2016: https://www.cmaj.ca/content/188/7/510/. Authors include Paul P. Glasziou. It includes several chronic conditions. I quote below those for CFS (no mention of ME).
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Thanks, I've added this article. It's quite a statement to make that "There are no absolute contraindications to exercise for patients with chronic fatigue syndrome." Again
Paul Glasziou is involved. I've not added the other sources because they do use the Cochrane review in their recommendations. Still interesting though. Perhaps we should make a separate thread with the most important guidelines/ reports in each country.

Adam pwme said:
It was mentioned in the government response to Carol Monaghans first debate.
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Thanks, I'm going to add this.
 
Michiel Tack said:
Thanks Joh. I've added these. Hope my summary is ok.
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Thanks! :) Great summary – just two tiny points: 1. The guideline Müdigkeit was published in 2018 (not 2017). 2. Just to be sure, as it might not be obvious: The Cochrane review is mentioned in a separate chapter on CFS in the guideline Müdigkeit, so the exercise recommendation is explicitly for CFS-Patients (vs: tired patients).
 
Joh said:
Thanks! :) Great summary – just two tiny points: 1. The guideline Müdigkeit was published in 2018 (not 2017). 2. Just to be sure, as it might not be obvious: The Cochrane review is mentioned in a separate chapter on CFS in the guideline Müdigkeit, so the exercise recommendation is explicitly for CFS-Patients (vs: tired patients).
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Thanks I've changed it.

I was somewhat confused because the document says: © DEGAM 2017. Sometimes there can be a delay between when a report is written and formally published. Perhaps this was the case here? The final page seems to say that the guideline was initially released in 2002 and that it was updated in November 2017.
 
Michiel Tack said:
I was somewhat confused because the document says: © DEGAM 2017. Sometimes there can be a delay between when a report is written and formally published. Perhaps this was the case here? The final page seems to say that the guideline was initially released in 2002 and that it was updated in November 2017.
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Yes, there was a delay, it was written in 2017 and published in 2018. If you check out the URL, this version was published in June 2018. It was first published in February 2018, then the Deutsche Gesellschaft für ME/CFS lodged a successful complaint about the chapter on CFS. The edited version was published in May 2018 and as the authors were so sloppy a few more corrections had to be made for the final version in June 2018.
 
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