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PACE Trial and PACE Trial Protocol

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

  1. Dolphin

    Dolphin Senior Member

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    For what it's worth:
    I've found post-ME but if doubt suddenly enters my mind about a memory, I'm not so good at remembering it into the future. So I could have known something well for 10+ years; then one day for some reason I have difficulty recalling it or I doubt it. Then after that, I tend not to be sure about it again. (At least I think it is an ME phenomenon - I became ill at 16 so hard to remember exactly how things were before that, over two decades ago).
  2. MeSci

    MeSci ME/CFS since 1995; activity level 6

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    I get that too to some extent, maybe when I am tired and/or have PEM. Passwords and usernames, for example. I often find that if I try too hard to remember them, it gets even harder, in the same way as remembering how to perform a common physical task has become more instinctive than intellectual so is a type of procedural memory. I have to relax and gently coax it back to the front of my brain. Or just try the most likely combinations I can think of!

    After a spell in hospital with hyponatraemia I couldn't even remember how to make a cup of tea at first!
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  3. Tom Kindlon

    Tom Kindlon Senior Member

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    My new 1000-word BMJ rapid response (i.e. e-letter) on the £5m PACE Trial, "PACE Trial: Simply giving a reason why an outcome measure was changed is not necessarily sufficient".

    It lists all sorts of reasons why I'm unhappy with the changes made to the PACE Trial outcome measures.

    I'm afraid I knew it would be too long to get published, so didn't spend as much time on the wording as other letters where I'm hoping they might be published in the print edition.

    http://www.bmj.com/content/347/bmj.f5963?tab=responses
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  4. Tom Kindlon

    Tom Kindlon Senior Member

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    Sean Lynch, a psychiatrist, has now responded, approx. 24 hours after my comment went up. Authors get automatic alerts for responses - I wonder whether there might be a connection?

    His defence of the changes to the PACE Trial protocol largely seem to depend people trusting him as some sort of expert, perhaps an unbiased expert. There is little substance in them. It's like an appeal to authority.

    Sean Lynch was one of the co-authors of the Royal Colleges of Report on CFS (1996) (Word file of this is available here:
    http://bit.ly/HFQeOM ). As well as recommending CBT and GET, and little else, it gave very few suggestions for biological research.

    He calls for more trials like the PACE Trial:
    [..]
    so that'd be CBT and GET trials and the like.
    Last edited: Nov 8, 2013
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  5. Dolphin

    Dolphin Senior Member

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    Here's Sean Lynch's own letter that he references:

  6. Dolphin

    Dolphin Senior Member

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    James C. Coyne PhD in a recent blog said people who write commentaries on papers are often the reviewers (he suggested they volunteer; it would make sense also as they would have an indepth knowledge of the paper which is what one would want from a commentator). This suggests one of PACE Trial reviewers were Knoop or Bleijenberg. Peter White suggested a reviewer suggested the normal range data; they used it in their full recovery paper (Knoop et al., 2007). It was also mentioned in their commentary on the PACE Trial.
  7. biophile

    biophile Places I'd rather be.

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    I am still not 100% clear whether this means the peer reviewer requested the normal range be added or just that it should be described as post-hoc. I am leaning towards Dolphin's interpretation because normal range is not mentioned in the Statistical Analysis Plan. Neither is recovery mentioned, so maybe that wasn't changed yet, although no mention at all is odd. Perhaps PACE liked how the normal range gave an inflated sense of success and decided to adopt it for their redefining of recovery?

    If either Knoop or Bleijenberg were peer reviewers of the Lancet paper and suggested the normal range, that just makes their associated blunders even worse and possibly more incestuous, since White was a co-author of Knoop et al 2007. Knoop and Bleijenberg claimed that the Lancet paper had a "strict" criteria for "recovery" based on a "healthy" population. All aspects of their claim were utterly and irrefutably false. Hooper said the Lancet promised a proper correction, but this never happened.

    It was later revealed that White even approved the editorial in question, making his later impartially-sounding non-apologetic "correction" (i.e. we did not report on recovery) about in the authors' reply a tad disingenuous.

    Furthermore, both Knoop and Bleijenberg have previously published papers in which 60/100 points in physical function was clearly regarded as major disability. Perhaps a simple mistake, albeit bizarre one? Nope. After being called out for it, they fully stood by their comment. After initially defending them in the "strongest terms possible", the PCC later conceded that this statement in the editorial by Knoop and Bleijenberg was misleading.

    White was a co-author of Knoop et al 2007, yet he claims in the recovery paper that PACE used the more conservative mean minus 1SD to derive their threshold rather than the less conservative mean minus 2SD used in Knoop et al. Their comparison was also wrong. Knoop et al used the same mean minus 1SD that PACE used and came up with 80 points. Describing their method as "conservative" was already questionable, but White seems to have trouble interpreting papers he has co-authored himself. To err is human, but such a series of blunders is baffling until you realize that every single one of them just happens to make their pet therapies look better than they otherwise would have. Coincidence?
    Last edited: Nov 26, 2013
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  8. ukxmrv

    ukxmrv Senior Member

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    Sorry, this is off topic a little but shows how things changed from the original plan of the PAC study. Was looking through my old emails and found this one from Chris Clark - ex-AFME CEO in 2004.

    From: Chris Clark
    Subject: action for m.e. statement - PACE criteria


    ACTION FOR M.E. STATEMENT

    I note that there has been some comment on the e-groups
    regarding the criteria for the PACE study. Some time ago the
    researchers agreed at our request to also record all those in
    the study against BOTH the Fukuda criteria and the
    operationalised criteria for myalgic encephalomyelitis.

    It is intended that this should provide information on whether
    any of the treatments being compared are more helpful or more
    harmful than the others for different definitions of CFS / M.E.

    Chris Clark
    Chief Executive
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  9. Valentijn

    Valentijn Activity Level: 3

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    It's always nice to see AfME standing up to represent the interests of everyone except ME/CFS patients. :rolleyes:
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  10. Bob

    Bob

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    @ukxmrv, they did assess the therapies for patients diagnosed using the London ME criteria and the CDC's Reeves criteria, in the main (Lancet) PACE paper. However, these criteria were used only after patients had been selected to the study using Oxford. This isn't good practise. I suppose it could be compared to selecting patients with progressive MS to a study, and then re-assessing these patients for relapsing-remitting MS. It just isn't appropriate.
    Last edited: Nov 26, 2013
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  11. Valentijn

    Valentijn Activity Level: 3

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    And it doesn't matter who they're studying, when the outcome measurements are all subjective and the recovery thresholds are meaningless.
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  12. Bob

    Bob

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    And the self-reported results were no better than would be expected for placebo or homeopathy, etc. etc. etc. etc.
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  13. Dolphin

    Dolphin Senior Member

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  14. Dolphin

    Dolphin Senior Member

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    I was thinking about this a little more and remembered that the PACE Trial peer review was fast-tracked (I think only started in January 2011? - it was published on Feb 18, 2011). This would seem to make it even more likely Knoop and/or Bleijenberg were a reviewer.

    Also, it would seem that it was even more likely they might already have been thinking about their editorial, if they were the reviewer who asked the PACE Trial investigators for a normal range analysis.

    It also seems a bit odd for a reviewer to ask this of investigators given how much the investigators were already trying to squash into the 4,000-word limit for the Lancet incl. some secondary outcome measures that weren't reported on, etc. Also seems a bit odd given this was a fast-track review.

    ETA: Given all the things I mention in the last paragraph, I think the PACE Trial investigators could probably have resisted it if they'd wanted.
    Last edited: Dec 1, 2013
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  15. Dolphin

    Dolphin Senior Member

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    FWIW:
    I'm just reading:
    It uses the Holmes CDC criteria for CFS (1988) which are generally seen as more strict than the Fukuda criteria.

    They didn't find many (just 3) with CFS.
    Anyway, the average SF-36 PF score of these 3 was 75 i.e. they would on average have been "back to normal".

    In total, they found 74 with chronic fatigue alone i.e. 71 of whom didn't satisfy the CFS criteria for one reason or another but who did say yes to:
    "Have you felt unusual fatigue or loss of energy, either constantly or repeatedly, for at least the past 6 months"
    and
    "Does this state of fatigue interfere with your work or responsibilities at home such that you have had to reduce your level of activity by at least one half?"
    This group with chronic fatigue had an average SF-36 physical functioning score of 81.3.
    (The average for the matched controls was 93.6).
    The point is that people can have scores in the 70s or 80s and still answer yes to both those questions.
    [These questions are a bit like the Oxford criteria questions, although the Oxford criteria also does have exclusions].
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  16. Tom Kindlon

    Tom Kindlon Senior Member

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    Queen Mary FOI Request 2014/F6

    I didn't get any new data directly but they have promised me it will be in a subsequent paper


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  17. biophile

    biophile Places I'd rather be.

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    LOL @ all the talk about analytical vigour and a rigorous peer-review process and similar scrutinies for commentaries.

    How did the misleading claims and frankly schoolboy errors pass through then?

    The "rigorous peer-review process" (or as chief editor Richard Horton put it, "endless rounds of peer review") of the Lancet spawned the so-called normal range in fatigue and physical function, you know, the one which overlaps with the trial eligibility criteria for disabling fatigue. It also failed to spot the mislabeling of the dataset for the normative population.

    White personally waved through an editorial comment in the Lancet written by sympathetic peers, you know, the one which the Press Complaints Commission later ruled to be misleading about the issue of "recovery". White et al acted innocent when called on the 2011 recovery fiasco by David Tuller as to why reporters commonly confused normal for recovery.

    The "rigorous peer-review process" of Psychological Medicine allowed the normal range absurdity to continue, and failed to spot that the PACE reasoning for abandoning the original definition of recovery was completely bogus and based on an error which even high-school students should have been able to spot easily. It also allowed more false claims to be made in the form of a misleading and erroneous comparison to a previous CBT trial on recovery in which White was even a co-author of, so there should be less excuse for just another blunder.

    It is difficult to have confidence and respect for peer-reviewers who collectively display incompetence.

    Not to mention all the other problems elucidated in the 2000+ posts on this current thread.
    Last edited: Feb 5, 2014
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  18. MeSci

    MeSci ME/CFS since 1995; activity level 6

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    Anyone know a good medium? :lol:
  19. alex3619

    alex3619 Senior Member

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  20. biophile

    biophile Places I'd rather be.

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    Technically, PACE did not use either the Fukuda criteria or what ended up being known as the Reeves 2005 criteria, as the latter is slightly different than the Reeves 2003 paper, although I do not recall what those differences were. And whatever CDC criteria they used, PACE later admitted to not using it properly at some stage i.e. not requiring symptoms for 6 months.
    Last edited: Feb 21, 2014
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