Mary Dimmock has led the way on this issue, and is co-author of this post.
In response to requests by U.S. patient organizations and advocates, the U.S. Agency for Healthcare Research and Quality (AHRQ) has issued an Addendum to its 2014 ME/CFS evidence review. This Addendum downgrades the conclusions on the effectiveness of cognitive behavioral therapy (CBT) and graded exercise therapy (GET), and this has tremendous implications for medical education and treatment recommendations.
At Long Last, AHRQ Undertakes Reanalysis
The 2014 AHRQ evidence review had originally reported that treatment with CBT and GET improved fatigue, function, global improvements, and employment in ME/CFS patients. This conclusion was based on an analysis that combined studies using any of seven CFS and ME definitions as though they represented the same disease. We highlighted this fatal flaw in our comments on the draft evidence review. The review itself acknowledged that CFS definitions did not require hallmark symptoms of the disease, that no treatment studies used ME/CFS or ME definitions, and that the Oxford definition was so broad that it would include patients with other diseases and should be retired. The 2015 NIH Pathways to Prevention report concurred that Oxford should be retired, stating that it could “impair progress and cause harm.” And yet, the 2014 AHRQ evidence review maintained its conclusion that CBT and GET could benefit some “ME/CFS” patients, based in substantial part on studies that used the Oxford definition.
Following the publication of David Tuller’s PACE analysis in October 2015, ME organizations and advocates called on AHRQ to reanalyze the PACE trial, to analyze the results of Oxford studies separate from studies using other definitions, and to analyze CBT studies separately from other forms of counseling. Following requests in November 2015 and again in February 2016, AHRQ agreed to ask the authors to reanalyze studies by definition and to separate out CBT from other counseling studies. They declined to reanalyze the PACE trial, which they had ranked a good trial with “undetected” reporting bias.
This new analysis was published in late July as an Addendum to the original report (see pages 1-16 of the linked report). This updated review reanalyzed the effectiveness of GET, CBT, and other forms of counseling, first with Oxford studies included and then after Oxford studies were excluded. As we predicted, breaking out the Oxford studies forced a significant downgrade in the review’s conclusions.
GET is Ineffective for ME Patients
The 2014 evidence review had combined four GET studies and two other exercise studies (qigong and orthostatic training) in its analysis and concluded, “GET improved measures of fatigue, function, and clinical global impression of change compared with controls.”
The Addendum reanalyzed just the four GET studies, three of which used the Oxford definition. When all four GET studies were analyzed together, the Addendum reported a moderate strength of evidence of improved function and global improvement and low strength of evidence of improved fatigue and employment. But when Oxford studies were excluded from the analysis, the Addendum reported that there was insufficient evidence of effectiveness of GET on any outcome.
| Study Outcome | Results with Oxford Studies | Results Excluding Oxford Studies |
| Function | Moderate strength of evidence | Insufficient evidence |
| Fatigue | Low strength of evidence | Insufficient evidence |
| Quality of Life | Insufficient evidence | Insufficient evidence |
| Employment | Low strength of evidence | Insufficient evidence |
| Global Improvement | Moderate strength of evidence | Insufficient evidence |
CBT Is Barely Effective
The 2014 evidence review combined CBT and other counseling therapies in its analysis and concluded that collectively, these therapies improved fatigue, function, quality of life, and global improvement. Acknowledging that “CBT is a unique approach with disputable underlying rationale regarding the fear avoidance theory contributing to the perpetuation of symptoms in ME/CFS,” the Addendum reanalyzed the seven CBT studies separately from the other counseling studies. The Addendum also analyzed the Oxford CBT studies separately from the Fukuda CBT studies, although one study (Deale 1997, 2001) appears to have been incorrectly classified.
When all seven CBT studies were reanalyzed, the Addendum reported low strength of evidence for improved function, fatigue, and global improvement; insufficient evidence of improvement in employment; and low strength of evidence that CBT did not improve quality of life. When Oxford studies were excluded from the reanalysis, the Addendum found insufficient evidence of effectiveness of CBT on function, employment and global improvement and a low strength of evidence of improved fatigue.
| Study Outcome | Results with Oxford Studies | Results Excluding Oxford Studies |
| Function | Low strength of evidence of improvement | Insufficient evidence |
| Fatigue | Low strength of evidence of improvement | Low strength of evidence of improvement |
| Quality of Life | Low strength of evidence that CBT does not impact quality of life | Low strength of evidence that CBT does not impact quality of life |
| Employment | Insufficient evidence | Insufficient evidence |
| Global Improvement | Low strength of evidence of improvement | Insufficient evidence |
Implications and What Next
The Addendum reaches a damning conclusion, cloaked in dry language:
This addendum has delineated differences in treatment effectiveness and harms according to case definitions, highlighting studies that used the Oxford case definition and how these studies impacted our conclusions. Additionally, results of studies evaluating CBT have been considered independently from other counseling and behavioral therapies. Our sensitivity analysis would result in a downgrading of our strength of evidence on several outcomes which can be attributed to the decrease in power, dominance of one large trial, or lack of trials using criteria other than the Oxford case definition for inclusion. Blatantly missing from this body of literature are trials evaluating effectiveness of interventions in the treatment of individuals meeting case definitions for ME or ME/CFS.
In other words, there is no evidence that supports the conclusion that CBT and GET are effective treatments or ME or ME/CFS patients.
And THAT is a ground breaking conclusion.
CBT and GET still remain the most common treatment recommendations across mainstream “evidence-based” medical education today. Recommendations for CBT and GET have been based directly on Oxford studies like PACE, or indirectly through evidence reviews such as AHRQ and Cochrane that have relied heavily on Oxford studies. At the same time, these treatment recommendations have ignored numerous patient surveys that have reported harms from CBT and GET. The resultant medical education, including that from CDC and key medical education providers such as UpToDate, confuses medical providers on the nature of the disease and puts patients at significant risk of harm from inappropriate treatment.
Recommendations for CBT and GET have become so pervasive that they are also found in the educational plans of medical societies. The American Academy of Family Physicians issued a 2016 needs assessment for education of members that specified that CBT and GET “improved fatigue, work and social adjustment, anxiety, and postexertional malaise” and called out the need for more training of doctors in the use of exercise therapies.
The problem, as this reanalysis found, is that when you remove the Oxford studies, the positive effect of CBT and GET disappears. The Addendum notes that “using the Oxford case definition results in a high risk of including patients who may have an alternate fatiguing illness or whose illness resolves spontaneously with time.” CBT and GET appears to help these patients to a limited extent. However, the recommendation of either of these therapies for ME and ME/CFS patients is inappropriate.
This Addendum highlights a key issue that has perverted medical education and evidence reviews in this field for a long time. It is medically inappropriate to make recommendations for disease treatment based on studies in patients who do not have the disease. CDC, UpToDate, AAFP, and other medical education sources must change their recommendations for ME/CFS treatments. Furthermore, NIH must address the gap in treatment trials for ME and ME/CFS patients by funding intervention studies on these patients.
There is no evidence that CBT and GET are effective treatments for us, and therefore, these treatments can no longer be recommended. If CDC and others persist in recommending treatments for which there is no evidence of effectiveness in ME/CFS patients, it will not only perpetuate confusion but also put patients at risk. Such an unscientific recommendation goes against the principles of evidence-based medicine and is not accepted in other diseases. It will not be tolerated here.
Edited 8/24/16 to add: Some medical education sites may be using these terms to refer to some other form of talk therapy and “exercise,” not PACE style CBT and GET. But the ambiguity in what is actually being recommended and its expected benefit creates medical misunderstanding and a risk of harm for patients, especially given the lack of published evidence for these other approaches and the volume of evidence for PACE style CBT and GET. Recommendations for talk therapy and any kind of “exercise” or activity management must be precise in terms of the recommended approach, the expected impact and benefit, the potential harm, and any contraindications, particularly for severely ill patients.
Incredible work, ladies. Keep pushing!
What a difference!
Going from CBT and GET are recommended to
“In other words, there is no evidence that supports the conclusion that CBT and GET are effective treatments or ME or ME/CFS patients.”
The Oxford definition has never been our friend and this shows it quite clearly.
Stunning result! Congratulations!
Well done. We need NICE in the UK to review the evidence along the same lines. We could do with help to make that happen because there is even more resistance over here.
Thank you both so very much for all your hard and brilliant work on this issue. Congratulations!
Great news-the hard work that you and Mary and others have been doing seems to have been having a good effect finally! Combine this change with today’s news that a tribunal has given a ruling in support of making the PACE date public (subject doubtless to further delays and obstruction etc. ) and maybe we are really beginning to get somewhere on these issues. Thanks again for all the hard work you have been doing–though I was a bit disturbed by your comment that you wrote the previous blog in bed–take care of yourself!
Thanks Chris! And I’m ok – trying to get enough rest between tasks.
Brava!! Big news today!
Who is gathering forces to ask for next steps? Where do I sign up?
Mary is already following up with CDC. I’m sure this will be relevant to the upcoming MEAction day of protest on September 27th. I’ll share anything I learn about next steps.
In the next few weeks, I will provide a followup on CDC’s response to our request, including CDC’s use of PACE and Oxford studies.
So many great news today! Thanks Jennie and Mary.
So many great news today!
Thanks Jennie and Mary
Wow- congratulations Mary and Jennie
Fabulous work Jennie and Mary!
Thank you to two amazing women for your hard work for those of us who can not fight for ourselves!
A historic day for PwME!
Such important work you are doing; I know there will be patients all over the world rejoicing at today’s joint news about PACE and the AHRQ ruling. We will win this mighty struggle yet!
Excellent work!! Thank you both for your efforts. This is wonderful news. Between this and the decision to uphold the FOIA release of PACE data, could the ME community finally be catching a break? I certainly hope so.
Thank you for all your hard work ???? ME needed this great news!. You are the best ?? ? fantastic! ?
Mary and Jennie, what an achievement! So glad you are out there fighting the good fight. Thanks for giving us hope that change can happen!
So happy to see this!
This is terrific news! Thank you to you and Mary for your hard work on this. This is a really significant shift.
Wonderful news! Congratulations and thank you!
Big win!
Much thanks to all who worked for this. 🙂
Fantastic, way to go!!
Fantastic! Thank you Jennie, and Mary. This CBT and GET has been permeating the medical field, for all manner of patients with fatigue and/or chronic pain. It’s being recommended with absolutely NO science to back it up! I think when physicians have a difficult (as in can’t seem to get better) patient, they get frustrated and don’t need “junk” science (Pace!) as their resource!!! ? Maybe now there can be some research done that is based on true science.
Great work!
These same so called advocates have created and promoted the mixed ME/CFS
nonsense. PACE was not on ME. We have no actual ME advocacy in the US, just these fake ME groups printing the ME/CFS agenda. We will not tolerate your ME/CFS claptrap.
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Awesome!! Is this the old report and if so how do we get it replaced with the new version (with addendum)?
http://www.ncbi.nlm.nih.gov/books/NBK293916/
Thanks for highlighting that, Janine. I’ll forward to AHRQ to ensure this gets replaced everywhere.
Hi Mary,
Perfect! Please let me know when the task is done and I will retest to confirm.
Thanks again for your contributions toward highlighting the flaws of PACE and setting the record straight!! 🙂
Great work Mary and JEN .
Thank you for all you have done, starting with you chapter, I mean book :-).
Take care look forward to the CDC response.
Also the NIH and Actin secretary of hhs.
Your on a roll.
Meghan
Jennie and Mary,
Thank you for your efforts to obtain the AHRQ Evidence Review Addendum changing the conclusions on the effectiveness of CBT and GET. As you stated this has “tremendous implications for medical education and treatment recommendations.”
As you explained, the CDC and other medical education sources must change their ME treatment recommendations and NIH must fund treatment trials.
The fact that AHRQ declined to reanalyze the PACE trial is shocking.
Do you believe that AHRQ will reconsider their decision to reanalyze the PACE trial based on the Tribunal order yesterday to release the PACE data and the anticipated independent analysis of the released raw data?
Based on your recent meeting with Dr. Karen DeSalvo at HHS, would she be willing to advocate for these issues?
Mary, when you revise your book on the history of ME, I hope you will add this action of yours and Jennie’s into the book as a significant factor in the fight to get the government to properly define this disease. It is major, imo. Thank you both for your commitment, diligence, and just plain hard work!
Ditto to what everyone said.
Thank you to Mary and Jen for all of your hard work advocating for those of us with ME/CFS. And maybe this accomplishment is the beginning of real changes within the government about our disease.
Therapy helps with support and advice and knowing someone is in your corner. But it does not alleviate the symptoms of this disease nor cause physical improvements. It just doesn’t. It doesn’t help us get stronger or more physically able to accomplish tasks or go out of the house, travel, etc. Nor does it ease physical pain or cognitive problems.
Nor does exercise. I say this as I can only do three leg lifts today when I try to do 12, once hit 18. Very rare. The stamina doesn’t build up; it vacillates due to other factors–exertion, tiredness, lack of sleep, too much use of the computer. Also, aging.
My doctor, who is uptodate on this disease, just told me that it’s a slowly progressive disease. Did I need to hear that? Nope. But he said it and I know it.
Congratulations on bringing one important breakthrough for us.
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But we won’t be done until they say not only, ‘Insufficient evidence’ – a weasel statement if I ever saw one – but ‘Actively bad for ME/CFS patients’ (especially GET).
Neutral isn’t good enough. Many people have been harmed by attempting to do what their doctors ordered based on this. Big crashes, PEM, and long aftereffects – there are plenty of stories!
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Great work. I also think they are getting ahead of the curve because they see the crazy train coming with a bunch of crazy data.
Also, can you believe those questioning and wanting the data were presented by QMUL lawyers to the Tribunal as sociopaths and psychotics? Rebuked you were bad, bad lawyer.
Congratulations and a heartfelt thank you!
What’s puzzled me is how GET can be even neutral? I know if I was in a GET program I’d either quit very soon or become extremely ill – well both actually did happen when a physio put me on a similar walking program many years ago. Seems strange that the drop-out rates look similar in the various groups in the PACE study but I guess that can be explained by the Oxford criteria being used. I look forward to the day when it’s general medical knowledge that rest is so important in the early days of M.E.
I was diagnosed in January 2014 with Fibromyalgia/ME.
Since then I’ve been given ‘medication’; physio x 1; 6 sessions ‘exercise’, and honestly very little helps. I do take some medication to help me sleep; they are not ‘sleeping pills’ per se. I do sleep better, and my sleep is not so ‘disturbed’ as before. Of course it’s hard to get out of bed most days; I just want to stay there. The chronic pain of Fibro, and the debilitating exhaustion of ME, make doing anything very difficult. It’s a chore in itself, not to fall into depression with it all.
Just the thought of doing exercise to ‘help’ my ME/Fibro is laughable to me. I could do light exercise but it doesn’t make me any less ‘exhausted’. In fact, when I am ‘active’ my Fibro usually immediately flares up afterwards, and I’m quite ill for days afterwards.
I’m having an ‘exhausting’ day today, as I went out yesterday for 5 hours, and now I’m suffering the consequences. I am too ‘fatigued’ to even read this article properly; I just skimmed over it, saving it for a ‘better’ day.
IMO the medical profession, led by Government, don’t want to recognise ME or Fibro as the ‘floodgates’ might open in terms of claims for financial assistance. So we have to suffer in silence. I am told that Fibro is recognised as a ‘Disability’ but not recognised enough to be able to claim any Benefits for having it; I’m still deemed ‘fit for work’, even though I had to retire 2 years ago as I could no longer do by job.
I thank you all for ‘fighting’ for me and others like me.
Thank you for this hard work you have ACCOMPLISHED!! Things can change! and you made it change; but it requires such hard work. Very appreciated. Just read David Tuller’s useful detailed articles. I have to remember how, sometimes, so much effort is needed to break through.
Bobbi
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Thank you so much for all your hard work! Great accomplishment!
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