The 12th Invest in ME Research Conference June, 2017, Part 2
MEMum presents the second article in a series of three about the recent 12th Invest In ME International Conference (IIMEC12) in London.
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PACE trial re-analysis and the 2007 NICE guideline on ME/CFS

Discussion in 'General ME/CFS Discussion' started by charles shepherd, Sep 21, 2016.

  1. charles shepherd

    charles shepherd Senior Member

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    PACE trial re-analysis and the 2007 NICE guideline on ME/CFS

    For the benefit of people who are now querying what effect this paper will have on the calls to immediately revise the NICE guideline on ME/CFS - the answer at the moment is probably 'very little'

    This is a preliminary report

    If a further more detailed re-analysis and report confirms these findings, AND this gains the endorsement of yet more reputable members of the research community, then NICE will have to take serious note of the findings

    Remember - the 2007 NICE guideline recommendations on CBT and GET were based on results from ALL the clinical trials prior to 2007 involving these interventions

    The PACE trial results had not been published in 2007

    When the results did appear in 2011 in The Lancet:
    http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(11)60096-2/abstract

    …..NICE just took the view that they added further support to what the NICE guideline was already recommending about the use of CBT and GET in mild and moderate cases of ME/CFS

    In the meantime, the pressure on NICE is continuing and they are being informed about these developments

    And this is the latest position (September 2016) that we have from NICE:

    Re NICE clinical guideline chronic fatigue syndrome/myalgic encephalomyelitis (or encephalopathy): diagnosis and management (CG53).

    With regards to a potential review and update of the guideline, we currently expect to publish the review decision at the end of 2017. The review decision, once published, will outline whether NICE intends to update the guidance. We are committed to reviewing the guidance earlier than the original anticipated review date of 2019 and have brought this review date forward following information provided to NICE since the previous review took place. In accordance with our current schedule, it is unlikely that the review could take place any earlier than the end of 2017.

    Details from the last formal (Forward ME Group) meeting with Professor Mark Baker from NICE and follow up with NHS England:

    http://www.meassociation.org.uk/201...statement-by-the-me-association-10-july-2014/

    http://www.meassociation.org.uk/201...heir-classification-of-mecfs-18-october-2014/

    Dr Charles Shepherd
    Hon Medical Adviser, MEA
     
    Last edited: Sep 21, 2016
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  2. flybro

    flybro Senior Member

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    pluto
    Thank you,

    What is the MEA recommending that PWME, PWCFS carers and advocates tell their GP's or consultants, now?

    Thank you in advance.

    fly
     
  3. BurnA

    BurnA Senior Member

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    That may be the case but if the results from those trials were so good then PACE wouldn't have been required.

    I am sure we can dig up some quotes from the archives from those heavily invested in the PACE trial about how important it was and how it was such a big piece of the jigsaw.

    Either PACE served a purpose or it didn't - they can't dismiss the results all of a sudden because they don't like them.

    Has anyone even begun to look at the flaws in those other trials? If necessaary i am sure it be done but if PACE was the 'gold standand' and that produced a null result the other trials are meaningless.
     
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  4. A.B.

    A.B. Senior Member

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    I don't remember seeing anthing of the sort. They probably have the same or even worse flaws as PACE. At least some of them claim to show even larger effects.

    @Simon may have something to say about clinical trials tending to show smaller and smaller results as time passes.
     
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  5. charles shepherd

    charles shepherd Senior Member

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    At the moment I would suggest (where/if necessary) that they take a copy of the re-analysis paper to show their GP if they are being encouraged to have a course of GET but are reluctant to do so!

    A copy of the summary of the MEA report on CBT, GET and Pacing (free to download on MEA website home page) would help to reinforce the message!

    MEA report summary:

    http://www.meassociation.org.uk/how-you-can-help/introduction-to-our-cbt-get-and-pacing-report/
     
  6. charles shepherd

    charles shepherd Senior Member

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    Short summary re CBT trials from the MEA purple booklet.

    Other more detailed critiques of these trials are available…


    7.6.4 Cognitive behaviour therapy
    CBT is an aspect of management that causes considerable controversy – largely because of the various ways it is administered in the case of ME/CFS. At the one end of the spectrum, CBT is used – as it is with many other chronic medical conditions – to help people develop better ways of coping with symptoms such as fatigue, pain, or sleep disturbance, with a clear acceptance that these have a genuine physical basis. This type of approach may, therefore, be helpful to patients who are not managing their lifestyle adjustment in an appropriate manner or where there is depression or psychosocial distress complicating the clinical picture. At the other end of the spectrum, CBT is a therapy based on the idea that ME/CFS is essentially a psychological illness that may well be triggered by an infection but is then perpetuated by a vicious circle of abnormal illness beliefs and abnormal illness behaviour – both of which need to be addressed and challenged if recovery is going to occur. Not surprisingly, this is an approach that many patients find both inappropriate and offensive.

    A number of clinical trials involving the use of CBT, including the PACE trial, have shown that this approach can sometimes be of some help to some people with research-defined CFS (Deale et al 1997, 2001; Prins et al 2001; Sharpe et al 1996; Stulemeijer et al 2004). However, in other trials, CBT has produced little or no benefit overall (Friedberg and Krupp 1994; Huibers et al 2004; Lloyd et al 1993; O’Dowd et al 2006; Whitehead and Campion 2002) or has not benefitted a significant proportion of patients (Akagi et al 2001). CBT has also been reported to have an effect on heart-rate variability (Hansen et al 2013). For some people with ME/CFS who require this sort of help, straightforward counselling is an option that has been reported as being a cost-effective alternative to CBT (Ridsdale et al 2001).

    In patient feedback obtained by The MEA and other ME/CFS charities for the Chief Medical Officer’s report, only 7% of patients found CBT to be “helpful”; 26% said it made their condition “worse”, and 67% reported “no change”. In the survey done for the MEA Management Report, 25.9% reported that CBT had “improved” or “greatly improved” their symptoms; 54.6% reported “no change”, and 19.5% reported that CBT had made their condition “slightly worse” or “much worse”.
     
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  7. BurnA

    BurnA Senior Member

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    Thanks for this - I was thinking more along the lines of deep dive into the methodological flaws such as patient selection, subjective outcomes, protocol changes, undeclared conflicts of interest....you know - the kind of things that we are accustomed to :)
     
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  8. Jonathan Edwards

    Jonathan Edwards "Gibberish"

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    A number of physicians have done this and have Power Point slides that show the various quality indices for the trials. If my memory is correct Luis Nacul presented such an analysis at the RSM meeting a year or so ago. It may be that they are all referring to the same analysis made some time back. The real problem is that psychiatrists appear to accept a level of evidence that would not normally be considered adequate by physicians. Everything will hinge on who undertakes the NICE review.
     
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  9. A.B.

    A.B. Senior Member

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    Re. flaws in older CBT/GET studies, I'm no expert but maybe (hopefully) not completely ignorant either at this point. I looked at the Stulemeijer paper http://repository.ubn.ru.nl/bitstream/handle/2066/48827/48827.pdf?sequence=1 and it seems to show a decent effect.

    However the CBT group had quite a few more patients withdrawing from treatment, and the authors dealt with missing data with the "last observation carried forward" method which can create bias.

    They also used actometers but the results are not shown, which probably tells us something already. Is this one of the trials which found no actometer measured increase in activity?

    School attendance did increase more in the CBT group than in the wait list control group which is definitely a plus. There didn't seem to be a followup which I think is important and would help distinguish a temporary motivational effect from CBT from actual improvement.

    Edit: they also wrote that
    Which I find egregious spin. Recovery means recovery from the illness, not "some degree of reduced symptoms".
     
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  10. Jonathan Edwards

    Jonathan Edwards "Gibberish"

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    Dear Charles (@charles shepherd),

    I think I disagree, Charles. These recent findings - the 2015 follow-up paper, the QMUL re-analysis and Matthees et al. re-analysis - leave no real need for more detail. They show pretty clearly that CBT and GET are unlikely to have any useful role in treatment, at least in the form used in the UK. They provide significant evidence against the prior assumption of some efficacy. And PACE is incapable of giving a reliable positive result anyway.

    I am also not quite sure what you mean by 'reputable'. I have endorsed these findings and consider myself reputable. But that may not help! I think you may be referring to people with bigger reputations, and that may well be an issue. However, one of the aspects of all this is that it shows that a big reputation in this context means nothing in scientific terms. The PACE authors have made it clear from their recent memorandum that they still do not understand the necessary issues of methodology. Nor do certain eminent supporters.

    I agree that the outcome of a NICE review at this stage is hard to rely on. But at least we have an independent opinion from the Information Officer that the claim the criticism is unreasonable and malicious is nonsense.
     
  11. Valentijn

    Valentijn WE ARE KINA

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    Yes, it's one of the three studies where the Wiborg review of actometer data showed that there was no increase in actual activity levels, despite self-report claims of improvement.

    The Wiborg review is available at http://sci-hub.cc/10.1017/s0033291709992212
     
    Last edited: Sep 23, 2016
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  12. A.B.

    A.B. Senior Member

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    Is anyone surprised that the data they preferred not to show contradicts their conclusions? :rolleyes: And actually makes one doubt the validity of the treatment entirely.

    Also, how would the results change if they removed patients that withdrew from the study from the statistical analysis rather than applying a "last observation carried forward" method? The CBT group had a 19% withdrawal rate. That could affect the results quite a bit.
     
  13. Glycon

    Glycon World's Most Dangerous Hand Puppet

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    This is actually false. Given the terminological and methodological mess that is ME research, a large, standardized study such as PACE is precisely what is called for. In fact, this is exactly why PACE's failure to support CBT/GET is such a big deal for the future of ME research. Regardless of what policymakers do, medical scientists will have to take notice.
     
  14. BurnA

    BurnA Senior Member

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    Not sure I follow you.
     
  15. Glycon

    Glycon World's Most Dangerous Hand Puppet

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    Basically, this:
    PACE is indeed a watershed moment, but not quite in the way its authors intended. :)
     
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  16. Jonathan Edwards

    Jonathan Edwards "Gibberish"

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    I agree but I think you misread what BurnA's sentence said - that PACE would not have been needed if a good enough study already existed.
     
  17. charles shepherd

    charles shepherd Senior Member

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    Thanks Jonathan

    I agree that this is a robust re-appraisal with a very clear conclusion - but I think I'm right in saying that further work on the data is still going to be done, which should add additional weight to what has been said today

    I've rephrased the sentence you refer to because the meaning could be misunderstood. I know we have some very reputable scientists in agreement already - including yourself!

    So it now says: …... yet more reputable members of the research community

    It would be helpful to have some more high quality research people from the UK expressing their concerns - we might then be able to start changing minds at The Lancet, NICE, NHS England and the Dept of Health

    My gut feeling is that this re-analysis will now lead to questions being asked at NICE and NHS England - but no immediate action as far as a revision of the NICE guideline. Part of the problem here is that NICE is overloaded with new guideline work and there is big reluctance to start fiddling with existing guidelines as well…….
     
  18. Glycon

    Glycon World's Most Dangerous Hand Puppet

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    Not sure why you think that, but we are certainly in agreement about it! Indeed, that's precisely why I said:
     
  19. BurnA

    BurnA Senior Member

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    Because you disagreed with me claiming what i said was false and then you said something that was in agreement with what I was saying.
    Let's not get sidetracked but maybe reread my post. Tks.
     
  20. Glycon

    Glycon World's Most Dangerous Hand Puppet

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    If that is the case, then I'm not sure what you meant by "required". Or "good". :)
     

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