Phoenix Rising tells QMUL: release the PACE trial data
Mark Berry, Acting CEO of Phoenix Rising, presents the Board of Directors’ open letter to Queen Mary University of London (QMUL) urging them to release the PACE trial data, and hopes that other non-UK organisations will join British charities in the same request...
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Rehabilitative therapies for chronic fatigue syndrome: a secondary mediation analysis of PACE trial

Discussion in 'Latest ME/CFS Research' started by Dolphin, Jan 13, 2015.

  1. Dolphin

    Dolphin Senior Member

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    This thread is for discussion of the paper itself

    There's a separate thread for discussion of the media coverage, etc. here: http://forums.phoenixrising.me/index.php?threads/new-pace-paper-more-smc-spin.34924/

    If you want to write a letter, here are the details:
    http://www.thelancet.com/lanpsy/information-for-authors/article-types-manuscript-requirements

     
    Last edited: Jan 13, 2015
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  2. Dolphin

    Dolphin Senior Member

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    This paper is open access (requires free registration)

    Note there's also a supplemental file which is free:

     
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  3. Dolphin

    Dolphin Senior Member

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    It should be noted that what is discussed is the mediators of two subjective outcomes.

    Here's one of them:

     
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  4. Dolphin

    Dolphin Senior Member

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    Here's the other subjective outcome measure that was used:

    Scoring is basically:
    Yes, Limited A Lot: 0 points each
    Yes, Limited A Little: 5 points each
    No, Not Limited At All: 10 points each
     
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  5. charles shepherd

    charles shepherd Senior Member

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    Statement from The ME Association - issued to health journalists and editors on 12 January 2014

    The ME Association believes that energy management, which involves both physical and mental activity, is the most important aspect of managing ME/CFS.

    Consequently, we welcome research which aims to improve our knowledge of how this can best be achieved.

    Energy management programmes should be individually tailored. And they must take account of the wide range of clinical presentations and disease pathways that come under the ME/CFS umbrella.

    We are therefore very critical of over-simplistic exercise regimes which are based on deconditioning, fear of activity and the assumption that people just need to 'try harder' in order to get better.

    This approach does not acknowledge the muscle, brain and immune system abnormalities in ME/CFS, which help to provide a physical explanation for the debilitating central (brain) and peripheral (muscle) fatigue that occurs in this illness.

    Feedback from patients, who are not normally treated as part of research studies, consistently indicates that around 25% find exercise programmes to be of no value. Around 50% report that their condition worsens as a result.

    So the real reason why cognitive behaviour therapy and graded exercise therapy are not producing significant benefits across the whole ME/CFS population is that they are based on a flawed model of illness causation. They are are not taking account of the medical complexities involved.

    In our experience, patients with ME/CFS are highly motivated to get better.

    They are very willing to take part in energy management programmes that establish a safe baseline of activity, take account of the stage and severity of their illness, involve increases in physical and mental activity that are gradual, flexible and do not result in the person going beyond their limitations and causing symptom exacerbation.

    We fear that the results of this study will be interpreted to reinforce the over-simplistic view that rest is bad and exercise is good for people with ME/CFS.

    And without discussing the medical complexities involved, they also infer that any reluctance to progressively increase activity levels is far more related to fear or avoidance behaviour than any underlying disease process.

    What we desperately need are high quality research studies that are aimed at producing a range of individual energy management programmes based on clinical presentation, stage, and severity of illness.

    Dr Charles ShepherdHon Medical Adviser, MEA

    Background information:
    The MEA submission to NICE, regarding their recommendations relating to the use CBT and GET in their current (2007) guideline on ME/CFS:

    CBT, GET and Pacing

    Our principal reason for requesting a fundamental review of the NICE guideline on ME/CFS relates to the recommendation that CBT and GET should be automatically offered to everyone with mild or moderate ME/CFS.

    This is coupled with the continuing failure of NICE to take note of highly consistent patient evidence, dating back to evidence that was published in the 2002 Chief Medical Officer’s report on ME/CFS, regarding the efficacy and safety of these two behavioural treatments.

    The largest ever survey of patient evidence relating to all aspects of the management of ME/CFS was carried out by The ME Association and published in 2010 (ME Association). The report provided important evidence regarding concerns over the efficacy of CBT and the safety of GET.

    For CBT (997 responses)
Greatly improved: 2.8%
Improved: 23.1%
No change: 54.6%
Slightly worse: 11.6%
Much worse: 7.9%

    For GET (906 responses)
Greatly improved: 3.4%
Improved: 18.7%
No change: 21.4%
Slightly worse: 23.4%
Much worse: 33.1%

    For Pacing (2137 responses)
Greatly improved: 11.6%
Improved: 59.6%
No change: 24.1%
Slightly worse: 3.5%
Much worse: 1.2%

    The MEA is currently in the final stages of preparing a further report covering the use of CBT, GET and Pacing – but this time in much greater depth. The report will be based on the answers to questions on the above three treatments that were provided through 3142 responses given by 1429 respondents during 2012.

    Overall, the patient evidence contained in this new MEA report is very similar to the evidence contained in the 2010 report. The two MEA surveys show a total of 6599 responses about the effect of treatments on symptoms, and a total of 6838 responses about appropriateness of courses, effectiveness of self management and helpfulness of consultations and general satisfaction.

    However, to date NICE has failed to consider any of this patient evidence and both MEA reports support the findings from patient surveys referred to in the Chief Medical Officer’s Working Group report into ME/CFS.

    We are therefore looking at a consistent picture from patients with regard to all three approaches to management going back over at least a decade and the picture has not improved.

    As a result of growing concern amongst people with ME/CFS about the efficacy and safety of CBT and GET, we will be making a number of radical recommendations regarding the future use of CBT and GET in ME/CFS in this report.

    This is clearly important new evidence that cannot be ignored by NICE.

    The PACE trial and the March 2011 surveillance review

    Finally, in relation to CBT and GET and Pacing, we assume that the NICE guideline surveillance review that took place in March 2011, and which followed publication of the PACE trial results in February 2011, simply ‘rubber stamped’ the 2007 NICE guideline recommendations on the basis that the PACE trial had supported the recommendations relating to CBT and GET.

    However, there has been widespread and valid criticism about the way in which the PACE trial was carried out, as well as the way in which the results were presented and reported.

    In addition, it should be noted that the cost effectiveness paper by McCrone et al reported that take up of state sickness benefits had increased during the PACE trial for all four treatments (ie CBT, GET, Pacing and Standard Medical Care). The MEA report will also contain similar information on benefit status.
     
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  6. Dolphin

    Dolphin Senior Member

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    Note that buried in the paper they report that CBT & GET didn't result in improvements on fitness/step test

    This can be seen in Figure 3.
     
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  7. lansbergen

    lansbergen Senior Member

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    I think this is a good statement. Even journalist must be able to understand it.
     
  8. Bob

    Bob

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    Well spotted, Dolphin.

    There's an interesting passage about "fitness" (step test) vs "physical activity" (6MWDT)...
    I'm not certain but they seem to be rebutting/trashing their own deconditioning hypothesis (while propping up their fear/avoidance hypothesis), as also suggested by these extracts...
     
    Last edited: Jan 13, 2015
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  9. Bob

    Bob

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    They've carried out an analysis of the 6MWDT for the first time, and they've managed to portray GET as having a significant effect in the 6MWDT:
     
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  10. Bob

    Bob

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    Interesting to note:
     
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  11. Sean

    Sean Senior Member

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    Is this the first time they have reported on the step test outcomes?

    The increase was barely statistically significant, and didn't reach the much more important and relevant measure of clinical significance. PACE patients (average age 40 years old at trial end) still ended up only scoring the same as people twice their age, and scored worse than almost every category of serious cardio-pulmonary disease, including terminal ones.

    BFD. :meh:
     
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  12. Dolphin

    Dolphin Senior Member

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    We have new 6-minute walking test data in the supplement. These are the scores at 24 weeks.

    Here are the results at 52 weeks:
    So doesn't look like one can conclude that they are gradually getting better after an initial slight improvement all around

    They have data at baseline and 52 weeks for:
    The 5% drop off (8 people) for GET makes me wonder whether people in GET were more likely to overpush themselves at 24 weeks and then have payback and so decide not to do the test at 52 weeks.

    Knoop and Wiborg themselves speculated this might be happening:
     
    Last edited: Jan 13, 2015
  13. Bob

    Bob

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    Yes, I think it is...

    So, as @Dolphin said on the other thread, it can now be said that: "Most objective measures showed no difference in the PACE Trial."
     
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  14. Dolphin

    Dolphin Senior Member

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    I believe so. (I think it might have been mentioned at a lecture (Bristol?) but not published)
     
  15. Bob

    Bob

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    Yes, like you say, it was a barely significant result and I'm pretty certain that it did not reach a moderate effect size.
    I'm not yet sure what their newly published outcomes indicate e.g. GET vs SMC 0·46, 0·28–0·63
    I wonder if "0.46" is supposed to be an effect size, or what? It looks far too large to be a cohen's d effect size.
     
  16. Sean

    Sean Senior Member

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    "Most objective measures showed no difference in the PACE Trial."

    I think we can safely say something much more definitive and punchy:

    No objective measure showed any clinically significant improvement.

    I don't know if that dropout rate is normal, let alone acceptable, for clinical studies. But given the very meagre 6MWT 'gains', presumably it could easily confound that result.
     
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  17. Dolphin

    Dolphin Senior Member

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    I edited the following into the post above at some stage around when you posted.

     
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  18. Bob

    Bob

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    Just noting that they do say something about the drop-out rates (and dismiss its importance, naturally)...
     
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  19. Sean

    Sean Senior Member

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    So, on the 6MWT, the GET arm results are:

    1. A barely statistically significant improvement, (a gain of just 35.3 metres, as mean difference from SMC),

    2. no clinically significant improvement,

    3. patients still scoring worse than almost all of one of the sickest disease groups in medicine, (with any ambulatory function left – the cardio-pulmonary disorders, including terminal end-stage forms),

    4. the outcome data for the (objective) 6MWT is only available for 69-74% of patients, compared to the range for (subjective) self-report measures of 89-97%, and

    5. the highest drop out rate of all arms.

    Correct?
     
  20. anciendaze

    anciendaze Senior Member

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    I'd say it wouldn't have made much difference if patients had supplied no data at all. This bunch is used to ignoring what patients say or do. Perhaps the next paper in this series will analyze the patterns of tea leaves left in cups patients used to show that there will be great improvements for these patients at some unspecified time in the future.
     

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