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'Recovery' from chronic fatigue syndrome after treatments given in the PACE trial

Discussion in 'Latest ME/CFS Research' started by Sam Carter, Jan 31, 2013.

  1. Dolphin

    Dolphin Senior Member

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    It might be worthwhile if one or more people write to PDW. I think I might be about the last person he would reply to, although still might try myself.
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  2. ukxmrv

    ukxmrv Senior Member

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    I guess this is why the correspondence with Lady Mar was terminated this week as well.
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  3. Firestormm

    Firestormm Senior Member

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    I think this is very worrying. Also if 22% equates to 'moderately' effective it makes me wonder what on earth 'highly' effective might equate to.

    Will perhaps find a link for that Crawley statement of 40%. It does seem to fly in the face of all the pomp and sensationalist headlines we were subjected to, doesn't it? I mean 22%. Hardly worth writing home about.

    I am also very surprised that the DWP did not insist on an objective measure involving benefit withdrawal. Or some of the measures that we are subjected to in our work capability/disability assessments e.g. mobility components.

    As with the PACE trial itself I am left thinking - especially with White's comments above - that this did not live up to expectations and hardly offered value for money given the expense and time consumption involved.

    I still regard PACE as proving that whatever is responsible for this condition - generally - it can't be fixed by GET and CBT as some would have had us believe.

    Still like other options they are a 'suck it and see' approach that may or may not prove helpful but should definitely not be oversold or sold unrealistically.

    And what's with references to 'this episode of the illness'? I didn't get that one. It is suggestive of a 'recovery' being followed by a 'relapse'. But what recovery lasts 52 weeks? Or maybe when I read the paper it will show that I have misread this part of it.

    What would be interesting would be the possibility of all treatments esp. drug treatments being compared along similar lines to those used in this paper. I mean if it is acceptable to them for GET and CBT and SMT and APT - then why not also for some of the drugs/treatments that are also available?

    Have they unwittingly perhaps set a standard here? How might Ampligen for example stack up I wonder. Maybe the bar has been set now - too low perhaps - but set nonetheless. Beat PACE and you win.
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  4. user9876

    user9876 Senior Member

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    Recovery suggests a cure and hence would need a much longer follow up period to talk about in convincingly. I think for example that oncologists only ever talk about remission from cancer as they know that there is a high chance of it reoccuring at some point in the future - and they will do appropriate monitoring over 5+ years. I think they are actually making a sensible point that they cann't say that the recovery will last because they have only monitored patients for a year.

    If people have recovered then a remission could be due to a fluctuation where symptoms are less or it could be due to, say, the immune system getting back to a normal equilibria but disease could reoccur if people are genetically subseptable to viral triggers breaking affecting the immune system in bad ways. This argument seems irrelivant to PACE since I think a recovery there is to down play symptoms and play up activities.
  5. biophile

    biophile Places I'd rather be.

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    Indeed. We are such naughty misguided recalcitrants for not accepting the spin at face value.

    The PACE results do not warrant a widespread rolling out of CBT and GET. However, if the pending paper on predictors and mediators reveals clues into which patients are more likely to benefit, that may help their targeting, although I will not be holding my breath after seeing http://www.trialsjournal.com/content/12/S1/A144 .

    Also, good point about PACE lowering the standards for other treatments to compete. This would also include open-label Rituximab studies where patients taking it are told it is "powerful and safe"!
    Firestormm likes this.
  6. Firestormm

    Firestormm Senior Member

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    Well they don't target or offer anything - in PACE - for the severe/very severe patients of course. It would be interesting to see whether 'recovery' meshed with category e.g. did those in the 'mild' category benefit more from either or both therapies even using their own measures.

    Is this the sort of thing you mean they are hoping to achieve? A means of saying such and such a patient or group will potentially find these therapies more beneficial? Maybe a psyche evaluation would help pre-treatment. I mean if a patient was for example more physically able, but was, for example, concerned adversely about returning to work, say, then they might theoretically benefit more from CBT.

    I guess they will try to do this through statistical analysis but I am never solely convinced of this application in relation to therapies that cannot be subjected to more empirical measures. I am not able to understand that paper you link to, Bio. Above my abilities :)

    Edit:

    Given I have been writing about 'repeatedly, reliably and safely' in relation to benefit assessment; I wonder to what extent 'fluctuating' symptoms and debility was taken into account in PACE?
  7. snowathlete

    snowathlete

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    As they like Oxford definitions so much, let us take a look at how the Oxford Dictionary defines the word Recovery:

    1. "a return to a normal state of health, mind, or strength"

    Clearly, by using the word Recovery, but by redefining it to be below normal they are cheating and misleading their audience. The absolute shame of it.
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  8. Dolphin

    Dolphin Senior Member

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    from


    She was corresponding author
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  9. Research 1st

    Research 1st

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    Lets compare the medical therapy performance of the hugely expensive UK's Wessley School PACE trial vs a biomedical CFS drug trial:

    Result:

    PACE trial = 22% improvement.
    Chemotherapy drug trial for CFS = 67% improvement. *

    * Source:
    Fluge et al, 2011.
    Benefit from B-lymphocyte depletion using the anti-CD20 antibody rituximab in chronic fatigue syndrome. A double-blind and placebo-controlled study.
    PLoS One. 2011;6(10):e26358. doi: 10.1371/journal.pone.0026358. Epub 2011 Oct 19.


    Perhaps from the startling contrast in therapy outcome we can see the end of psychiatry and psychological chronic fatigue misrepresenting ME CFS is near? Finally there could be potentially effective and superior treatments on the near horizon to psychiatric accusations of 'faulty illness beliefs'. That's if if Rituximab research is to be permitted to continue without state interference (no funding).

    We need to spread the word that cancer drug therapy in CFS is around 3x more effective than psychotherapy
    in people without. Meanwhile, organic CFS patients like Robert Miller are so desperate for help that is denied by the CDC and FDA, they're on hunger strike as we speak! That is pretty shocking.

    First rule of medicine, do listen to your organically ill CFS ME patient. Don't listen to people who aren't studying your patients (psychological tiredness) whilst erroneously claiming they are i.e the PACE trial and allied psychiatric 'fatigue' research that has terrible treatment outcomes using CBT & GE and relapses ME patients, permanently in some cases.
    I should also add there is at least one case of an ME patient who died after engaging in an NHS graded exercise programme, a therapy which the Wessely school insist is safe. :mad:

    What an awful situation this all is, and unjustly caused by people who ignore biomedical CFS research spanning near decades. What will the CDC and Dr Unger do about this? Continue their five year chronic fatigue psychobehavioural approach and continue telling people with organic CFS to gently exercise themselves better to health?

    Think how stupid this all is and how costly in terms of human suffering.

    If altering thoughts and beliefs about the causes and maintainers of CFS was effective for treating CFS, then why does the Rituximab paper (which ignored thoughts and beliefs) have a three fold better outcome than psychotherapy?

    Answer: organic CFS and ME are not psychological disorders but contain a disease process that needs medical treatment with immunotherapy drugs.
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  10. Dolphin

    Dolphin Senior Member

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    The following paper that is referenced in the recovery paper is available for free at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3020067/

    I haven't read it yet but I suspect the points White et al. make that reference this paper are very questionable



    *I gave each sentence its own paragraph.
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  11. alex3619

    alex3619 Senior Member

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    Don't forget this was a preliminary result. I suspect its now over 70%, but we will find out when the final paper is released.
  12. Research 1st

    Research 1st

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    I hope you mean Doctor Fluge and colleagues Alex. :lol:

    Yes I would imagine that if they can use an immunological biomarker to select candidates who will be likely 'responders' (due to on-going experience in observing +/- outcomes from administering the drug) then the percentage rates of 'improvement' from CFS symptoms should indeed increase above 67%. Very good point.
  13. Dolphin

    Dolphin Senior Member

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    (Minor) good news:
    There doesn't seem to be any word or reference limit for Psychological Medicine: the guidelines don't mention them and I have gone through all the letters published in 2012 (excluding "research letters" i.e. which present new data) - all 2012 issues of the journal can be see for free for the next 5 weeks or so.
    I'll try to give some more information on the numbers when I read the letters (one or two may be more research-type letter when I read them).
    Probably still best to be under 500 words and, say, 13 references.
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  14. Research 1st

    Research 1st

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    Remember this old chestnut?

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  15. Dolphin

    Dolphin Senior Member

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    A more permanent home has now been found for this 12 MB file: http://evaluatingpace.phoenixrising.me/PACE_Protocol.pdf
  16. Nancy Blake

    Nancy Blake

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    ' Objective measures of physical activity have been found previously to correlate poorly with self-reported outcomes (Wiborg et al. 2010),' Hmmm - because self-reported outcomes were found to exaggerate increased activity as against objective measures (actometer) So the obvious thing was to drop the use of the actometer and rely only on self-reports. This apparently is an example of the commitment to 'science' for which a knighthood was recently conferred.
    Then there is the '33% depressed'. One day I will attempt a full analysis of the questionnaires used to diagnose depression, but it won't surprise anyone that on the Beck Inventory, for example, the 'physical' signs of 'depression' include fatigue, cognitive problems and disturbed sleep patterns..... Having worked in the field of mental health since 1971, I believe that I can reliably distinguish 'not feeling like doing anything' (apathy, low mood) - depression - from 'desperate to do things and when I try and find I can't, I get really upset' - ME. That's how hard it is to make a 'differential diagnosis'. But if you put ME symptoms on a list for diagnosing depression, it makes it a lot easier to claim that ME people are suffering from 'depression'. Mind you, being this sick for so long is a bit depressing, but there's nothing neurotic about that!
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  17. biophile

    biophile Places I'd rather be.

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    Depending on measures of improvement (lower is better for Number Needed to Treat) ...

    PACE Trial: 22% vs 8%. 40% vs 25%, ~75% vs ~60%. NNT = 7 (non-blinded).

    Rituximab: 67% vs 13%. 60% vs 7%. NNT = 2 (double-blinded).

    Do not forget that the Rituximab trial, while a small preliminary study with limited outcome measures, was also double-blind. PACE was non-blinded, and the mere act of admitting that blinding would have been impractical, does not make the complications of open-label trials magically disappear, particularly when the authors are focusing exclusively on self-reported symptoms of limited correlation while actively ignoring employment status, physical activity levels, walking distances, welfare receipts, etc, in their definitions of improvement and (*cough*) complete "recovery" (*cough*). Even worse, the PACE data on the latter measures looks very stark, and contradicts notions of recovery.

    NNT is dependent on the response size being measured. Furthermore, Leucht et al are reporting on placebo-controlled drug trials for medical and psychiatric conditions, some of which had much larger effect sizes than CBT and GET in PACE, where the net response rate required to get a NNT of 7 is also well within the range of a placebo response, being a non-blinded trial with different levels of encouragement and optimism between groups. That said, personally I doubt it would explain all improvement. However, it is a serious problem if therapies specifically aimed at changing patients' "unhelpful" beliefs and perceptions and behaviours are altering questionnaire-taking behaviour beyond what is actually happening.

    Interesting argument, there may be some overlap. Perhaps we could do a trial of all substances indicated to help CFS, and just add up all figures too for a hypothetical 200% success rate!
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  18. Nancy Blake

    Nancy Blake

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    And just to add to Dolphin's list of interesting sites, there is the King's College CFS information for patients and practitioners. (The one for practitioners urges people performing CBT to try to look beyond their protocols and at the patient's actual situation, or 'what some analysts refer to as 'The Real'. A truly radical proposal.)

    But even more exciting is the information contained in the advice to patients concerning 'The Physiology of CFS'. This begins with a list of the various physiological changes observed in people with CFS/ME, which leads the reader to think that, finally, they're acknowledging the physiological nature of this illness. But it turns out that every single one of these factors is caused by resting! (or may be, or probably is, or something very similar has been). It is particularly notable that when healthy subjects go to bed for three weeks, these symptoms appear, and when they get up again, these symptoms go away. The message is obvious: resting is a dangerous activity, while the curative potential of 'not resting' has yet to be fully explored. I don't know why this very important information, with its broad implications for both medical practice and everyday life, has been hidden away in an article about CFS.

    It states that the article is 'based on the work of Pauline Powell'. I looked her up, and she has, indeed, written a number of articles making these assertions, but I didn't see any research papers.
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  19. biophile

    biophile Places I'd rather be.

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    Firestormm.

    Re: severely affected. Obviously not covered by published evidence and the FINE Trial was a failure, but IIRC Wessely has claimed that his clinic get good results in the severely affected too, and the PACE manuals claim that the GET model should apply equally or even more in severely affected patients. Wessely has also said about bedridden patients: "In that kind of disability psychological factors are important and I don’t care how unpopular that statement makes me." So, severely affected patients are only sometimes spared having CBT/GET pushed on them because of the lack of published evidence, not because CBT/GET proponents do not want to treat them or do not actually treat them in practice.

    Re: targeting. CBT and GET only help a minority of Oxford criteria patients report modest improvements in some measures but not others. CBT/GET proponents admit to not knowing enough about what predicts and mediates the response, but there is still a wide application, all patients are encouraged to attempt it. Knowing more about what predicts and mediates the response may help to determine which patients need it and what aspects of therapy work best.
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  20. Esther12

    Esther12 Senior Member

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    Or maybe the SF36 PF or Chalder Fatigue Score meant that their criteria for Oxford did not apply, even if the patient still fulfilled the other parts of the criteria.


    I'm interested by the fact that this got so little press, as generally Science Media Centre stuff does. I wonder if journalists were scared of militant CFS patients? Or were they left wondering 'Didn't I report that this study showed a recovery rate of 1/3 two years ago?'

    There have been little bits on-line. I like the opening paragraph for this:

    http://psychcentral.com/news/2013/02/01/recovery-from-chronic-fatigue-syndrome-possible/51060.html

    This bit from Queen Mary is good too:

    If that is their definition of 'significant fatigue or physical difficulty', then we can say quite confidently that CBT and GET do not lead to significant reductions in fatigue or disability.

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