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PACE Trial and PACE Trial Protocol

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

  1. Snow Leopard

    Snow Leopard Senior Member

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    And more importantly, could they repeat that distance over the next few days...

    I'm not a big believer in conspiracies, but!?!

    By the way, I hope someone else discusses the problems of the cohort definitions in depth in their letter, because I won't be. Damn 250 word limit.
    Dr Jason has many good articles to read and reference. http://condor.depaul.edu/ljason/leonard.html#pubs
  2. Esther12

    Esther12 Senior Member

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    Instinctively, I'd assume that this would be a test which many CFS patients could be shown to be 'normal' on, even if they were not at all healthy. I walk at normal speed... six minutes would be pushing it but I could possibly get within the normal range, I'd just be destroyed afterwards. I'm not sure what level of cynicism is appropriate here either... it could be that CBT and GET do have some real but limited benefits for patients, and help them walk in a more natural manner. It does seem a very strange test to use though, especially considering that patients with serious mobility problems were excluded by the nature of the trial. (CBT improvement were pretty limited too)

    re withdrawals: One problem with the strange and restrictive approach to pacing ... those who were recovering as part of the natural course of their illness could see pacing as a burden, and withdraw. For CBT and GET, those whose condition worsened could see treatment as more of a burden, and withdraw. I don't think this is a significant point, and withdrawels weren't that big a problem (11% from CBT though), but thought I'd mention it. It could be these slight biases would affect the data collected from a randomly fluctuating patient population.

    The Work and Social adjustment scale is just another questionnaire: http://bjp.rcpsych.org/cgi/content/full/180/5/461
    I was hoping for some more objective data on hours worked etc... but given the lack of sub-dividing, I'm not sure how interesting it would have been.

    I'm really disappointed by the appendix. I thought we would see a serious attempt to assess all these patients as individuals, and try to understand who would be most/least likely to benefit from different treatment approaches. Devoting yourself to GET for limited/no improvement has a really high cost for patients, and even accepting the most positive of spins to their work, this is what happens for nearly half their patients. They seem to have no interest in recognising the innate burden of engaging with these sorts of therapies when they're ineffective. Or with CBT... teaching patients who do not have control over their symptoms that they do is a terrible thing, even if this is not picked up in worsening scores on the Chalder fatigue scale.

    Overall: I've only given it a quick look. To me, the worst thing about the paper is that so much was spent on a study that presented so little worthwhile data. Because some of the results have clearly been dishonestly presented, it means that we really can't trust the rest of it. I didn't really find much to pick apart, other than what others have already mentioned, and the innate limitations of using these sorts of RCTs to assess psychosocial approaches to CFS. I'm tempted to agree with Cort's appraisal... it's conclusions are so weak it might even be good for us. But given how the study has been promoted and reported, and how similarly weak studies have been used misleadingly in the past, I'm afraid that's probably a rather panglossian view of things.
  3. Dolphin

    Dolphin Senior Member

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    Thanks. But data might show they were still walking slower.

    Here are the numerical results again on this:
    APT: increased by 20 steps (314 to 334)
    CBT: increased by 21 steps (333 to 354)
    Control group: increased by 22 steps (326 to 348)

    Only difference is with the GET group:
    GET: increased by 67 steps (312 to 379).

    But not the best as you say. Exercise testing often involves measuring gases etc to see the biological demands the exercise is putting on somebody.
  4. Dolphin

    Dolphin Senior Member

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    In case you missed it, they did measure it - it was one of their secondary outcome measures, they just didn't report it.
    This is what they had said themselves in the trial protocol:
    http://www.biomedcentral.com/1471-2377/7/6
  5. Dolphin

    Dolphin Senior Member

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    I think the point in bold is worth mentioning in a letter. At the moment, that's what I'm thinking of using but they might not like my wording but might like how somebody else said it.

    We need quite a few people writing in, either making the same or different points so that they at least publish one or two letters. Although there are disadvantages in more than one person making the same point, at the same time, a few people may turn the editor around to the point while maybe if only one person said it, they might not have been convinced. It's a pain that the journal doesn't allow e-letters - trials in the BMJ for example can get a bashing from lots of people. Complaining about the outcome measures wouldn't require many references or knowledge of the literature - they can be "self-evident".
  6. Cort

    Cort Phoenix Rising Founder

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    You are good Dolphin- you navigate these waters with ease :). That's $8,000 US dollars that were spent. ?
  7. Cort

    Cort Phoenix Rising Founder

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    This is what I have on this so far....

  8. Esther12

    Esther12 Senior Member

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    Does their 'normal range' include seriously ill people?

    "In another post-hoc
    analysis, we compared the proportions of participants
    who had scores of both primary outcomes within the
    normal range at 52 weeks. This range was defi ned as
    less than the mean plus 1 SD scores of adult attendees
    to UK general practice of 142 (+46) for fatigue (score
    of 18 or less) and equal to or above the mean minus 1 SD
    scores of the UK working age population of 84 (–24) for
    physical function (score of 60 or more).32,33"


    32 Cella M, Chalder T. Measuring fatigue in clinical and community
    settings. J Psychosom Res 2010; 69: 17–22.
    33 Bowling A, Bond M, Jenkinson C, Lamping DL. Short form 36
    (SF-36) health survey questionnaire: which normative data should
    be used? Comparisons between the norms provided by the
    Omnibus Survey in Britain, The Health Survey for England and
    the Oxford Healthy Life Survey. J Publ Health Med 1999, 21: 255–70.

    I'm afraid my partner's just come down with a migraine, so I'm probably not going to be able to spend much time on this for the next few days (I'm a poorly carer!), but will be happy to look in to little things like that when we're back to normal here. I might try and write a letter then too - I won't be able to come up with anything that solid, but in 250 words, I'm not sure many will.
  9. Cort

    Cort Phoenix Rising Founder

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    I'm going to put my paper up on the Forums today. We can move it to the WIKI and work on it more to produce a more detailed response if anyone wants to do that.
  10. oceanblue

    oceanblue Senior Member

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    Sorry to hear your partner is not well, we'll miss your contribution.

    Clearly using adult attenders to GPs is no way to measure fatigue levels in the healthy population! It is self-evident nonsense and it's hard to see how this got through the reviewers (ok, we know how it did that...)

    For the SF-36 data surely the relevant measure for measuring 'recovery' is that for healthy people, not the whole population which will inevitably include everyone who is ill too. And I'm not too sure that SF-36 PF scores are normally distributed on the 0-100 scoring (athletes don't score higher than moderately fit people so the scores are bunched up at 80+) and if that's the case using mean minus one SD might not be appropriate.

    But I think getting to the bottom of these numbers is crucial. Exposing them as flawed would be a huge blow against the way the results have been spun.
  11. oceanblue

    oceanblue Senior Member

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    6 minute walking test

    I was also a bit sceptical about walking tests as a measure of physical activity, perhaps because I walk at a normal pace (but not for very far).

    But those figures from Cort about puttering around the house are interesting: what was the source?

    That said, the walking test was done in hospital corridors (so lots of walking up and down a short stretch) rather than outdoors, so that may have affected speed/total steps.
  12. Dolphin

    Dolphin Senior Member

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    :D
    US$8,000,000 (although better to put it as US$8m as it's not like it's exactly US$8,000,000.
  13. Esther12

    Esther12 Senior Member

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    Thanks OB.

    The editorial from Bleijenberg & Knoop came close to openly promoting deception as treatment. I think there's a good case for tying the way the Pace results were produced and promoted to the notion that patients need to be positively deluded for their own good. It would be difficult to make it in 250 words though.

    "Both graded exercise therapy and cognitive behaviour therapy assume that recovery from chronic fatigue syndrome is possible and convey this hope more or less explicitly to patients. Adaptive pacing therapy emphasises that chronic fatigue syndrome is a chronic condition, to which the patient has to adapt. Although PACE was not intended to compare cognitive behaviour therapy and graded exercise therapy with each other, there was actually no difference between the two. Both were more effective than adaptive pacing.

    Graded exercise therapy and cognitive behaviour therapy might assume that recovery from chronic fatigue syndrome is possible, but have patients recovered after treatment? The answer depends on one’s definition of recovery.3 PACE used a strict criterion for recovery: a score on both fatigue and physical function within the range of the mean plus (or minus) one standard deviation of a healthy person’s score. In accordance with this criterion, the recovery rate of cognitive behaviour therapy and graded exercise therapy was about 30%—although not very high, the rate is significantly higher than that with both other interventions."
  14. Dolphin

    Dolphin Senior Member

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    PACE Trial: Participant newsletter February 2011 Issue 4

    Funny definition of "normal levels of fatigue and physical function" they use given having a SF-36 physical functioning score of 60 and Chalder Fatigue Scale of 18 would also mean one was eligible to take part in the trial!

    http://www.pacetrial.org/docs/participantsnewsletter4.pdf


  15. Dolphin

    Dolphin Senior Member

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    I recall something vague in my head that 25% of GP attendees present with fatigue. I'm not going to swear on that figure but sometimes high figures are thrown around when justifying fatigue papers.
  16. Dolphin

    Dolphin Senior Member

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    Agreed.

    Here are some population norms for South Australia: http://www.health.sa.gov.au/PROS/portals/0/sa-pop-norm-SF-36.pdf . It's the PF (Physical Functioning) scale.

    So if one looks at 35-44 year olds, the 25th percentile is 90 with 45% scoring 100/100.
    And they want to tell us 60 is a normal score!
    ----
    At http://www.sf-36.org/nbscalc/index.shtml , one can see the population norms for Sweden: (Mean, SD) Physical Function(ing) (87.9, 19.6), Role-Physical (83.2, 31.8), Bodily Pain (74.8, 26.1), General Health (75.8, 22.2) Vitality (68.8, 22.8), Social functioning (88.6, 20.3), Role-Emotional (85.7, 29.2), Mental Health (80.9, 18.9), Physical Composite Score (PCS) (50.0, 10) and Mental Composite Score (MCS) (50.0, 10).

    Also the US, Norway and Canada (I had copied the Swedish ones before which is why I did them).

    Note population norms for healthy people and/or working age adults would be more interesting - including people in their 80s (say) shouldn't count. I think I've seen them before for the SF-36.
  17. Dolphin

    Dolphin Senior Member

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  18. Snow Leopard

    Snow Leopard Senior Member

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    Thanks Dolphin. Are you going to cite one of those?

    Five reference limit. :(

    Actually, you could substitute the reference of the trial protocol for one of those. Hmm..
  19. Dolphin

    Dolphin Senior Member

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    My first draft letter doesn't cite any of them. Would be nice but ran out of words. Others can feel free to use them.
  20. oceanblue

    oceanblue Senior Member

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    Comments of thresholds for 'recovery'

    Not much time to do this but i see Dolphin has been doing some great digging - here are a few comments from me

    Using GP attenders as a sample of a healthy population is patently ridiculous, but it's worse than that: PACE set the threshold as one Standard Deviation below the mean, which statistically is equal to the 15th percentile. This means they took 15% most fatigued patients attending GP surgeries and said any fatigue less than that counts as 'recovered'.

    The Oxford criteria require that "c) The fatigue is severe and disabling". However, the PACE trial went futher than this, requiring that the disability (activity) element of a SF-36 PF subscale score of 65 or less. Thus the PACE trial recruitment criteria sets a disability threshold of 65 or less.

    Using this threshold, 12% (251 ex 2,080 diagnosed as meeting the Oxford Criteria, from Figure 1) were excluded from the trial due to a PF score of 70 or more (let's assume it was 70 exactly). Yet these excluded patients had already been diagnosed by trial clinicians as suffering from 'severe & disabling fatigue'.

    So we know that, according to PACE clinicians, a PF score of 70 counts as disabling fatigue.
    Yet, when it comes to assessing recovery, a PF score of 60, ie 10 points lower , counts as 'normal'.

    Black is white, the moon's a balloon and we're a bunch of malingerers.

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