1. Patients launch $1.27 million crowdfunding campaign for ME/CFS gut microbiome study.
    Check out the website, Facebook and Twitter. Join in donate and spread the word!
The ePatient Revolution
Ryan Prior shares his experience and his thoughts from attending the Stanford Medicine X Conference as he contemplates the rising of the ePatient Revolution ...
Discuss the article on the Forums.

PACE Trial and PACE Trial Protocol

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

  1. Bob

    Bob

    Messages:
    8,851
    Likes:
    12,406
    South of England
    Does anyone have any links to any informal or off-the-cuff comments or discussion by White (or even Wessely) about the PACE Trial?
    Thank you for any info.
     
  2. Esther12

    Esther12 Senior Member

    Messages:
    5,383
    Likes:
    5,882
    Michael Sharpe: "Chronic fatigue syndrome: Neurological, mental or both" incl. PACE

    http://forums.phoenixrising.me/show...tal-or-both-quot-incl.-PACE&highlight=wessely

    ABC radio interview:

    http://forums.phoenixrising.me/show...eatments-for-CFS-PACE-trial&highlight=wessely

    There was that recent Wessely presentation where he mentioned Pace... but I can't find it now. A collection of slides, and audio of him speaking. He describes it as 'beautiful and elegant', or something like that.
     
  3. oceanblue

    oceanblue Senior Member

    Messages:
    1,174
    Likes:
    343
    UK
    try this Wessely talk:
     
  4. Angela Kennedy

    Angela Kennedy *****

    Messages:
    1,026
    Likes:
    154
    Essex, UK
    But people need also to be aware that Warlow has a conflict of interest in that he is a co-author with Sharpe, and promotes psychogenic explanations for difficult to diagnose somatic (meaning bodily) illnesses.
     
  5. Enid

    Enid Senior Member

    Messages:
    3,309
    Likes:
    841
    UK
    What a tangled web it all is Angela. One feels bound to ask this lot about the basis of their "difficult to diagnose" patients for which the psychogenic "model" is deemed the treatment. I hear we have very basic blood tests here and yet all the likely viruses etc. (or combinations of) are found widely with accurate testing - as all on PR. What may be difficult to them is apparently not for Docs outside the UK. Perhaps they should update their diagnostic "tools" first - and find a lot less difficult to diagnose !.
     
  6. Bob

    Bob

    Messages:
    8,851
    Likes:
    12,406
    South of England
    *sigh*

    Is there no escape from these people?!?

    I did wonder about the word 'independent'!

    I'm guessing that the Lancet have to pay them to be their 'independent' ombudsman (that's a guess), in which case, they are not entirely independent.
     
  7. Bob

    Bob

    Messages:
    8,851
    Likes:
    12,406
    South of England
    Thanks for the links Esther and ocean.
    Much appreciated.
     
  8. Jenny

    Jenny Senior Member

    Messages:
    1,233
    Likes:
    200
    London
    The letter on PACE that Ocean Blue and I wrote for The Psychologist has been published in the June edition (both on-line and print editions).

    It was unedited, but oddly it was under the heading 'In defence of PACE' and coupled with another letter that was somewhat positive about the trial.

    Here is the text of our letter:

    Your summary of the findings of the PACE trial (White et al., 2011), which evaluated the effectiveness of CBT and graded exercise therapy as treatments for ME/CFS (Fatigue evidence gathers PACE, April 2011), gave a somewhat misleading impression of the outcomes of this study. You said that self-reports on measures of fatigue and physical function showed that 30% of CBT patients and 28% of exercise patients had returned to normal function. This suggests that nearly one-third had recovered with these treatments. Unfortunately this is far from the case.

    First, the thresholds for normal were set so low they could include those with considerable disability. The authors defined within the normal range as a Short Form-36 Physical Function (SF-36) score of 60 or more (0-100 scale), yet the problems with physical functioning that characterise CFS were defined by a SF-36 score of up to 65 - which overlaps with normality. The situation with fatigue scores is similar, so that a participant may have met the trial fatigue criteria for CFS yet simultaneously have met the criteria for normal. Consequently the figures you quoted tell us little meaningful about the PACE trials effectiveness.

    Secondly, it is of some concern that the authors inexplicably changed the criteria for positive primary outcomes originally proposed by them in the protocol for the study
    (White et al., 2007). On the Chalder Fatigue Scale, for example, they stated that a positive outcome would be a 50% reduction in self-reported fatigue, or a score of 3 or less. And on the SF-36 scale of physical function a score of 75 or more, or a 50% increase from baseline would be required. So the figures you reported are misleading.

    Thirdly, you omitted to mention the disappointing outcomes on more objective measures of functioning. For example, after a year of treatment, patients receiving graded exercise therapy had on average increased the distance they were able to walk in 6 minutes from 312 to 379 metres. Even patients suffering from serious chronic cardiopulmonary diseases can manage more than this (in a sample of over 1,000 such patients the mean distance walked was 393 metres [Ross, Murthy, Wollak, & Jackson, 2010]), and at normal walking speed people typically cover around 500 metres. CBT treatment had no significant effect on walking distance.

    Perhaps these results are unsurprising, given that the treatments focused on reducing patients assumed fear of engaging in activity, and completely failed to acknowledge the complexity of this illness. We are much concerned that exaggerated claims for these treatments will create a false impression of the effectiveness of PACE amongst psychologists, and will continue to divert scarce resources away from effective medical treatments for this devastating condition.

    References
    Ross, R.M., Murthy, J.N., Wollak, I.D., & Jackson, A.J. (2010). The six-minute walk test accurately estimates mean peak oxygen uptake. BMC Pulmonary Medicine, 10.31. http://www.biomedcentral.com/1471-2466/10/31

    White P.D., Sharpe M.C., Chalder T., DeCesare J.C., Walwyn R., and the PACE Trial Group (2007). Protocol for the PACE 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. BioMed Central Neurology, 2007;7:6. http://www.biomedcentralcom/1471-2377/71/6

    White, P.D., Goldsmith, K.A., Johnson, A.L, Potts, L., Walwyn, R., DeCesare, J.C, Baber, H.L., Burgess, M., Clark, L.V., Cox, D.L., Bavinton, J., Angus, B.J., Murphy, G., Murphy, M., ODowd, H., Wilks, D., McCrone, P., Chalder, T., Sharpe, M.C., on behalf of the PACE trial management group (2011). Comparison of adaptive pacing therapy, cognitive behaviour therapy, graded exercise therapy, and specialist medical care for chronic fatigue syndrome (PACE). The Lancet, published online February 2011. DOI:10.1016/So140-6736(11)60006-2.
    Edit Report .Results 1 to 1 of 1
     
  9. ukxmrv

    ukxmrv Senior Member

    Messages:
    3,530
    Likes:
    2,081
    London
    Congratulations Jenny and Oceanblue, for writing such a fine letter, getting through their exhausting process and having it printed

    Thank you!

    :balloons::victory::D
     
  10. Dolphin

    Dolphin Senior Member

    Messages:
    6,870
    Likes:
    6,155
    Yes well done, Jenny & Oceanblue. Good you were on the ball that there are/were other places to post criticisms.
     
  11. Dolphin

    Dolphin Senior Member

    Messages:
    6,870
    Likes:
    6,155
  12. Bob

    Bob

    Messages:
    8,851
    Likes:
    12,406
    South of England
    Congratulations Jenny and oceanblue. And thank you. :D

    And a big thank you to everyone else who has been working so hard on this issue over the past few months, for representing our community so brilliantly.
     
  13. Bob

    Bob

    Messages:
    8,851
    Likes:
    12,406
    South of England
    From the Action for ME website:

    The comment about pacing is interesting... I hadn't thought of that angle before.

    Pacing is an extension of what people do naturally when they are tired or exhausted... They slow down and rest.
    It's a natural, inbuilt, human survival mechanism.
    It's very natural, and not at all contrived, and so it is very easy for patients to understand.
    (But according to Horton on the abc radio interview, scientists are 'sceptical' about it!)

    So, yes, participants in all groups in the PACE Trial would have been employing a form of pacing, whether they knew it or not.
    When we feel exhausted, we slow down or stop. It's as simple as that.
     
  14. Dolphin

    Dolphin Senior Member

    Messages:
    6,870
    Likes:
    6,155
    PACE press conference audio and transcript

    PACE press conference audio and transcript

    This might be better discussed on the thread specifically for it:
    http://forums.phoenixrising.me/showthread.php?12043-PACE-press-conference-audio-and-transcript

     
  15. Andrew

    Andrew Senior Member

    Messages:
    1,977
    Likes:
    1,267
    Los Angeles, USA
    I've been reading the comments here and I have questions, so I hope someone can help me out.

    Would it be reasonable for me to say to a doctor:

    The study was not CFS as we know it in the U.S, but rather a group of unexplained fatigue causes, some of which might have been what we call CFS in the U.S. and elsewhere. Most subjects had no improvement. The minority that did improve had increase that was so slight they did not reach a normal range. As for the question of no harm, the study included inadequate information about people who could not complete the study. This is the group that is most likely to contain people who had bad reactions and could not continue. So we don't have a clear picture of safety. Also, the protocol mentions the use of actimeters, but the data was not reported. In a previous study where mild improvement was reported, the actimeters showed no increase in activity. Because the current researchers withheld this data from their report, this leaves a big hole in the analysis. And because we don't know the outcome of subjects would fit the Fukuda or Canadian Consensus diagnosis for CFS. no conclusions about CFS can be drawn.

    If any of this is wrong or overstated, please let me know.
     
  16. Esther12

    Esther12 Senior Member

    Messages:
    5,383
    Likes:
    5,882
    Hi Andrew. I'm not sure about all this, but will add my comments in bold, and see if anyone corrects me.

    A lot depends, imo, on how your doctor raises it.

    Hopefully that will get the ball rolling.
     
  17. Snow Leopard

    Snow Leopard Senior Member

    Messages:
    2,412
    Likes:
    2,066
    Australia
    I posted a reply to Andrew's post about 30 minutes ago, but it doesn't seem to have turned up. (it might have been due to connection problems on my end)

    I think you need to use different language for medical practitioners..

    The issue with the Oxford criteria is because it only requires unexplained fatigue for 6 months, it has much lower specificity than Fukuda or CCC and is much more likely to produce a heterogeneous group, including many with mild depression related fatigue and these cases are much more common than moderate-severe CCC CFS.

    Secondly, the authors previously published a fairly rigorous protocol with thresholds for 'clinical significance' and 'recovery'. But in the Lancet paper, they did not report outcomes according to the protocol. No data was published on how many subjects reached these thresholds. So the clinical significance is uncertain and likely to be small since these thresholds were not reached in most subjects.

    Secondly, no objective data on activity levels were reported (as you suggest), such as hours spent employed (paid/volunteer) or in study/training. In a review of the outcomes of the Belgian rehabilitation programme (combined GET, CBT, physiotherapy, referrals to employment assistance etc), with a total of 593 adults, they found that paid employment decreased and activity levels did not change (volunteer work/study increased while paid employment decreased).
     
  18. Graham

    Graham Senior Moment

    Messages:
    846
    Likes:
    2,233
    Sussex, UK
    I'd like to think of the PACE report in a different way. The problem to me with there being so many faults with the study, that we can miss the big picture.

    Everything was set up in such a way that the bias was towards success with GET and CBT. Despite all the many dissatisfactions that we have with it and its lack of scientific rigour, it is pretty conclusive in showing that the absolute best we can expect from CBT and GET is that perhaps 2 in 15 people, after a whole year, will show some progress, but not good progress (if I am wrong and some do show good progress, then the proportion drops to much less than 1 in 15). The rest, at the very best, will make minimal progress or get worse. (Bob and I set up a little blog to illustrate that - meanalysis ) That is the most that GET or CBT can achieve for a very large group of patients, and this is a trial that was set up by GET and CBT "experts" and proponents. Of course the truth is likely to be much worse than that, due to the errors in the trial, and there may well be people who, to my intense frustration, are harmed, but in a scientific sense, that is irrelevant because there is now strong evidence that there is no justification for expecting GET or CBT to help with CFS under any set of criteria. The small number of individuals that may be helped clearly fill some other criteria, yet to be determined, but not relevant to CFS (it may, for example, turn out to be a subset of people with depression).

    I think that, viewed dispassionately, the study provides a very strong case for abolishing CBT or GET for CFS of any form, and in doing that, it totally undermines the psychological assumptions about CFS that underpin it. It will just take a long time for the logic to sink in.
     
  19. Bob

    Bob

    Messages:
    8,851
    Likes:
    12,406
    South of England
    Could somebody help me with something that's been puzzling me please...
    When Sharpe says the following in the abc radio interview:

    Michael Sharpe: We have a number needed to treat; I think it's about seven to get a clinically important treatment benefit with CBT and GET. What this trial isn't able to answer is how much better are these treatments than really not having very much treatment at all.

    Is he basing that 'one in seven' figure (to get a clinically important treatment benefit) on the results for the 'normal range'?

    Normal Range at 52 weeks:
    SMC 22 of 152 participants (15%)
    GET 43 of 154 participants (28%) (This is 13% more than the SMC group)
    CBT 44 of 148 participants (30%) (This is 15% more than the SMC group)


    'One in seven' is 14.3%, which is nearly 13% and 15%, as per the net values for GET and CBT.



    By the way, I think that's a very useful quote to remember:

    Michael Sharpe: "What this trial isn't able to answer is how much better are these treatments than really not having very much treatment at all." http://www.abc.net.au/rn/healthreport/stories/2011/3192571.htm#transcript

    What an admission! Doesn't this make our case for us?!? (or am i missing something?)
     
  20. Dolphin

    Dolphin Senior Member

    Messages:
    6,870
    Likes:
    6,155
    I think it's more likely "clinically important treatment benefit" refers to the following:

    So 61% (GET) - 45% (SMC) = 16%

    59% (CBT) - 45% (SMC) = 14%.
     

See more popular forum discussions.

Share This Page