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PACE Trial - letters that were not accepted by the Lancet

Discussion in 'Latest ME/CFS Research' started by Dolphin, Apr 18, 2011.

  1. Dolphin

    Dolphin Senior Member

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    I thought I would start a thread for letters in reply to the PACE Trial that were not accepted by the Lancet.

    It might act as a sort of summary of some observations people made.

    People can PM their letters if they prefer (I can include it either with or without their name - it doesn't matter to me).

    Best to keep comments on letters to another thread (you can link to the posts) I think.

    ETA: There are now 30 letters from 25 people/groups in this thread.
     
  2. Dolphin

    Dolphin Senior Member

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    This was posted on Co-Cure http://listserv.nodak.edu/cgi-bin/wa.exe?A2=ind1104C&L=CO-CURE&P=R1953&I=-3 which has a public archive:

    Also:
     
  3. Dolphin

    Dolphin Senior Member

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    Dr. Charles Shepherd (MEA)

    Dr. Charles Shepherd (ME Association):
    http://www.meassociation.org.uk/?p=4900
     
  4. Dolphin

    Dolphin Senior Member

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    Invest in M.E.

    Invest in M.E.
    http://www.investinme.org/IIME Statement 2011-03-01.htm
     
  5. Dolphin

    Dolphin Senior Member

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    One person sent me theirs and asked that it being posted without their name:

     
  6. Marco

    Marco Old blackguard

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    Near Cognac, France
    Here's my attempt :


    Are the PACE trial results 'well anchored'?


    A common consideration in clinical trials is determining the degree to which any objectively measured changes may be considered to be clinically significant, particularly when such changes are small.

    A widely used concept is to 'anchor' such changes with participants' subjective assessment of the degree to which measured changes have impacted more generally on their perceived sense of well being and functioning.1 The PACE authors define 'clinically useful differences' in relation to the Chalder Fatigue questionnaire and the SF 36 physical function sub-scale, both of which rely on participants' self-rated responses.2 It would seem reasonable to conclude from the results that, while the improvements seen in the only objective measure reported (the six minute walking test) were modest, they were considered clinically useful by a proportion of participants.

    Such conclusions are however problematic in trials such as PACE where the therapy arms under investigation actively target participants' subjective experience and reporting of symptoms and understanding of prognosis. In the case of CBT and GET, participants are encouraged to believe that recovery is possible and that symptoms are not clinically meaningful, while in the APT arm they are encouraged to believe that the illness is not reversible and that they must operate within a 'energy envelope'.

    I would submit that, contrary to usual practice, subjective responses are not a reliable indicator of a clinically useful difference where therapies aim to change subjective experiences and that further objective measures of functioning would be a more appropriate 'anchor'.


    1. Guyatt GH, Osoba D, Wu, AW, Wyrwich KW, Norman GR, and the clinical significance consensus meeting. Methods to Explain the Clinical Significance of Health Status Measures Mayo Clin Proc. 2002;77:371-383

    2. White PD, Goldsmith KA, Johnson AL, et al, on behalf of the PACE trial management group. Comparison of adaptive pacing therapy, cognitive behaviour therapy, graded exercise therapy, and specialist medical care for chronic fatigue syndrome (PACE): a randomised trial. Lancet 2011; published online Feb 18. DOI:10.1016/S0140-6736(11)60096-2.
     
  7. Snow Leopard

    Snow Leopard Senior Member

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    Australia
    Some good points that weren't published. :(

    Peter Kemp in particular..
     
  8. Dolphin

    Dolphin Senior Member

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    Somebody asked me to post this for them:



     
  9. Dolphin

    Dolphin Senior Member

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    This seems to be the standard message from the Lancet:
     
  10. Dolphin

    Dolphin Senior Member

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    I've now heard of 16 people whose letters were not accepted.
    Hopefully more of these letters will be added here in time.
     
  11. Sean

    Sean Senior Member

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    Was asked to post this up:

     
  12. Dolphin

    Dolphin Senior Member

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    Here's another person's letter:

     
  13. Dolphin

    Dolphin Senior Member

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    Here's another person's letter. Thanks for everyone who took the time to write.

     
  14. Dolphin

    Dolphin Senior Member

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    Joan Crawford's letter: Effect size overstated

    Joan Crawford's letter

     
  15. oceanblue

    oceanblue Senior Member

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    Trial's definition of 'within the normal range' is flawed

    It is notable that the PACE Trial did not report recovery as defined by the original protocol,1,2 instead conducting a post-hoc analysis [note 1] of the proportion of participants within the normal range on both primary outcomes after therapy. Crucially, these post-hoc thresholds were much lower than those defined for recovery, with up to 30% of participants being classed as normal. The rates for normality were referred to as recovery rates both in the media and in the accompanying Lancet editorial.3

    However, the post-hoc thresholds a short form-36 Physical Function (SF-36) score of 60 and a Chalder Fatigue questionnaire (CFQ) score of 18 in no way represent normal health. The PACE trial defined the severe and disabling fatigue that characterises Chronic Fatigue Syndrome as a SF-36 score of 65 (i.e. above that required for normality) or less, and a bimodal CFQ score of 6 or more (which could meet the Likert-scored normal threshold of 18). The trial thus may nonsensically define a participant as having severe and disabling fatigue yet simultaneously as being within the normal range.

    The normal range was defined as one standard deviation from the mean, (despite the data being highly skewed),4 setting the threshold at around the 16th percentile [note 2], which is very low when 22% of the general population report a long-standing illness.5

    As the Trial definition of within the normal range does not seem to accurately define normal health, it would be helpful if the authors now published recovery rates according to the original protocol.

    Notes (not in the original letter)
    Note 1. Post-hoc means after the researchers got their hands of the data. Good practice is to define in a protocol how the research will be analysed before seeing the data (as was the case for the original definition of recovery). Post-hoc analyses are always seen as slightly suspect since researchers have been able to torture the data until it tells them what they want to hear.
    Note 2. Setting the threshold at the 16th percentile means that 16% of the normal population have this score or less (so 84% score higher than this, which makes it a very low definition of normal).

    1. White PD, Goldsmith K, Johnson A, Potts L, Walwyn R, DeCesare J, et al. Comparison of adaptive pacing therapy, cognitive behaviour therapy, graded exercise therapy, and specialist medical care for chronic fatigue syndrome (PACE): a randomised trial [Internet]. Lancet 2011; published online Feb 18. DOI:10.1016/S0140-6736(11)60096-2.
    2. White P, Sharpe M, Chalder T, DeCesare J, Walwyn R, the PACE trial group. 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 Cent Neurol 2007;7:6.
    3. Bleijenberg G, Knoop H. Chronic Fatigue Syndrome: where to PACE from here? Lancet 2011; published online Feb 18. doi:10.1016/S0140-6736(11)60172-4
    4. Prieto L, Alonso J, Ant JM. Estimating sample sizes for studies using the SF-36 health survey. J Epidemiol Commun H 1996; 50 (4): 473474.
    5. Jenkinson C, Coulter A, Wright L. Short form 36 (SF36) health survey questionnaire: normative data for adults of working age. BMJ 1993; 306(6890): 14371440.
     
  16. oceanblue

    oceanblue Senior Member

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    Another unpublished letter someone asked me to post:

     
  17. Dolphin

    Dolphin Senior Member

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    "Graded exercise not safe for individuals with post-exertional malaise"

    Somebody asked me to post this for them:

     
  18. Dolphin

    Dolphin Senior Member

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    "CBT/GET is not an effective treatment for ME/CFS"

    Another letter I was asked to post. This had more than one author I think:

     
  19. Dolphin

    Dolphin Senior Member

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    Susanna Agardy's letter

    Susanna Agardy said I could post her letter with her name on it

     
  20. Dolphin

    Dolphin Senior Member

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    "Disclosure may aid interpretation of PACE Trial Results"

    Another one I've been asked to post:

     

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