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PACE Trial and PACE Trial Protocol

Discussion in 'Latest ME/CFS Research' started by Dolphin, May 12, 2010.

  1. oceanblue

    oceanblue Senior Member

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    I read a lot of papers trying to back up exactly that point, mainly for MS and Rheumatoid Arthritis. The problem is that the evidence is all over the place with some studies showing great results and some little gain from CBT/GET - and mostly the research is of poor quality*. That recent MS study is a perfect example: only 26 patients and no control group (results are for pre/post treatment). So while I suspect the point is true, I couldn't find robust evidence one way or another for the effectiveness of CBT/GET in such illnesses. If anyone knows different, please let me know.

    *it was quite an eye-opener to see just how much rubbish research is out there across a range of illnesses: CFS is by no means unique.
    ukxmrv, urbantravels and WillowJ like this.
  2. Esther12

    Esther12 Senior Member

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    Yeah... but... the charities had to prepare responses without having the paper. It did allow others to act as if the response was 'anti-science', and maybe no immediate response at all would have been preferable, but they were in a difficult situation.

    They were right not to trust the interpretation of results presented by Chalder and White, but were poorly placed to respond full to it.
  3. Marco

    Marco Old blackguard

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    I agree Esther but it isn't too late to add this interpretation to any mention they make of PACE specifically or CBT/GET generally or when commenting on government provided information etc.
  4. Esther12

    Esther12 Senior Member

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    Yeah - sorry. I took 'response' to mean 'initial response'. Really though, it's only the initial response that got reported in the media.
  5. Dolphin

    Dolphin Senior Member

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  6. Marco

    Marco Old blackguard

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    Excellent

    I wonder would Fiona Godlee (BMJ editor) care to comment given that she has made her position so clear on adhering to published protocols?
  7. Bob

    Bob

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    Here's a new critique of the PACE Trial, by Prof Malcolm Hooper, which highlights and explains a few of the statistical flaws in the published Lancet paper...

    It also includes some interesting background info about how Hooper's critique was rejected for publication in the magazine of the Royal Statistical Society, Significance.

    It's quite dense reading, but I think it throws some devastating punches, esp re the 'normal range', use of the term 'moderate improvements', and the 'six minute walking distance test' results.

    It's published on Invest in ME's website...

    Webpage:
    http://www.investinme.org/Article435 Statistics and ME.htm?forumid=331851

    PDF version:
    http://www.investinme.org/Documents/PACE Trial/Statistics and ME.pdf
    Dolphin likes this.
  8. Dolphin

    Dolphin Senior Member

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    Pity it wasn't published. Interesting that they got a request.
  9. Sean

    Sean Senior Member

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    Thank you Tate Mitchell. :thumbsup:



    This graph seems to be missing the critical definition of the green and purple colouring.

    Purple = baseline
    Green = therapeutic gain



    If I may be so bold and suggest a handful of small clarifications in a passage from Section VI, so it reads:

    In the PACE Trial, actometers were used at baseline, but were not used outcome. The only objective outcome measure reported was the six-minute walk test (6MWT), which only increased for CBT participants by 21m to 354m, a change that was actually slightly smaller than that of the (SMC) control group.



    Additional issues that add to the PACE problems include:

    1) not using a test - retest protocol, especially for any objective measure(s)

    2) the reliability of the way they used the 6MWT (did they account properly for the learning effect?)

    3) what exactly was "specialist" about the Standard Specialist Medical Care they used, beyond the standard general practitioner (primary care physician) level of medical care?

    4) why any supposed therapeutic gains tapered off by about the 12th week of the 52 week trial, with no further gains being made for the remainder of the trial?
  10. biophile

    biophile Places I'd rather be.

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    Good suggestion and questions, Sean.

    Have only skim read the new documents from Hooper and Mitchell respectively, but so far so good.

    Judging from the invitation that Hooper received, the editor seemed aware of Hooper's critical views and knew what to expect. Hooper's introduction was clever:

  11. Purple

    Purple Bundle of purpliness

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    My understanding is (please correct me if I am wrong) that the SMC group is not a control group - a control group would be a 'no intervention' group, i.e. no treatment at all. So this is not a controlled trial, just a randomised trial. (Comparison of adaptive pacing therapy, cognitive behaviour therapy, graded exercise therapy, and specialist medical care for chronic fatigue syndrome (PACE): a randomised trial.)

    This is what Prof Hooper says about this in the second last paragraph of the document linked by Bob:
    ...the international ME community wonders why the PACE Trial is being hailed as a gold standard study which demonstrated the efficacy of CBT and GET for ME/CFS patients (although the Protocol refers to it as an RCT, The Lancet paper at no point describes PACE as a controlled trial, yet it was described in the press release as the highest grade of clinical evidence and as extremely rigorous (and) carefully conducted).

    also from the document:
    In a radio interview, one of the Investigators stated candidly: What this trial isnt able to answer is how better are these treatments than really not having very much treatment at all

  12. biophile

    biophile Places I'd rather be.

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    The 2007 PACE trial protocol refers to itself as a randomized controlled trial. Dropping of the word "controlled" in the 2011 Lancet paper may have been to save space in the title, although it is interesting that they do not refer to it elsewhere as a controlled trial. Perhaps because the SMC-alone group received more sessions of SMC than the adjunctive therapy groups and therefore was not adequately controlled? A trial does not have to blinded or placebo-controlled to be regarded as a RCT, but obviously response bias can be a problem too in an unblinded trial aimed at altering patients perceptions and behaviours then asking them to fill out subjective questionnaires. I tentatively view the SMC-alone group as a de facto control group, but yes there should have been a 5th group that received nothing at all just like in the real world.
  13. oceanblue

    oceanblue Senior Member

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    This, from Statistics on ME, was new to me:
    Nice.

    Though of course the PACE authors would fall back on their guff about continuous outcome measures being more appropriate (even though they add in the categorical post-hoc normal measure, while claining there was "insufficient space" to report on the categorical recovery item specified in the protocol).
    Dolphin likes this.
  14. oceanblue

    oceanblue Senior Member

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    Control group or not?

    I've long been puzzled by this. The authors studiously avoid refererring to a control group, yet I agree with Biophile that the SMC group is a control of sorts - it's what the study compares treatments against, which is exactly the way any other trial would use a control group.

    Ideally, I think they should have used an attention-placebo control eg relaxation therapy, as other trials have done. This would also have helped to control for any self-report bias resulting from a strong relationship between therapist and patient.
  15. Bob

    Bob

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    My thoughts about this are that the authors wish to downplay and obscure the significance of the SMC being a control group, as they have done persistently in their media work by only quoting the "30%" figure (The "30%" improvement was as a result of GET+SMC or CBT+SMC, not GET or CBT alone, which was only about 15%.)

    In the protocol(s), they clearly set out that the SMC was to be used as a control group, and also that each of the groups was to be used as a control group for all the other groups to be compared with. So the authors also used the SMC+CBT and SMC+GET groups as control groups to compare the SMC+APT group against (i.e. they have compared the APT group to the CBT group to highlight how ineffective their form of 'pacing' is.)

    Here are some helpful quotes from the protocol(s):

    "SSMC is also the trial comparison intervention against
    which the three supplementary therapies will be judged."

    "This trial compares the efficacy of the additional therapies when added to
    specialist medical care against specialist medical care alone."

    "There is therefore an urgent need to: (a) compare the supplementary
    therapies of both CBT and GET with both APT and SSMC alone, seeking evidence of both
    benefit and harm (b) compare supplementary APT against SSMC alone and (c) compare
    the supplementary therapies of APT, CBT and GET in order to clarify differential predictors
    and mechanisms of change."


    This shows that the intention was for it to be an RCT:

    "Long title of trial:
    A randomised controlled trial of adaptive pacing, cognitive behaviour therapy, and graded
    exercise, as supplements to standardised specialist medical care versus standardised
    specialist medical care alone for patients with the chronic fatigue syndrome / myalgic
    encephalomyelitis or encephalopathy"




    One very interesting, and telling, section from the protocol is this:

    "4.4.2 Differential outcomes
    Because CBT and GET are based on a graded exposure to activity or exercise, they may
    preferentially reduce disability
    , whilst APT, being based on the theory that one must stay
    within the limits of a finite amount of "energy", may reduce symptoms, but at the expense
    of not reducing disability. By measuring both symptoms and disability as our primary
    outcomes, we will be able to test this secondary hypothesis."


    Notice that their hypothesis was demonstrated to not carry any weight because while CBT minimally improved subjective fatigue, it failed to improve physical function or disability. This clearly took them by surprise, and went against all their expectations, and they conveniently failed to highlight this failure of CBT in the final paper.
    WillowJ likes this.
  16. Esther12

    Esther12 Senior Member

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    This looks really good.

    lol at how long this nicely condensed summary is though. No wonder it's hard to explain the problems to anyone.

    Including quotes with the references is a really good idea too - it makes it a lot easier to casually look in to references, especially for those who struggle to access academic papers. I'm going to start doing this.
  17. urbantravels

    urbantravels disjecta membra

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    I wonder if the Hooper paper could be submitted for PLosOne. I'm not clear on whether it would be considered "primary research" or a "systematic review" by their standards, but it seems like something worth looking into...?

    http://www.plosone.org/static/guidelines.action
  18. biophile

    biophile Places I'd rather be.

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    Good idea. One wonders if the 2011 Lancet paper on the PACE Trial itself would meet PLoS ONE standards? (emphasis added): ...

  19. Mark

    Mark Acting CEO

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    Doesn't seem to fit the first requirement though:

    "1. The study presents the results of primary scientific research."
  20. Dolphin

    Dolphin Senior Member

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