A general thread on the PACE trial!

Discussion in 'Psychosomatic research - ME/CFS and Long Covid' started by Esther12, Nov 7, 2017.

  1. Trish

    Trish Moderator Staff Member

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    The placebo response in the treatment of chronic fatigue syndrome: a systematic review and meta-analysis, 2005, Cho HJ1, Hotopf M, Wessely S.
    I haven't read all the preceding posts, but I am not surprised by low placebo response with CBT/GET because those patients who may start with hope of improvement and stick to the therapy may be made worse by it, over-riding any placebo response. Whereas with a blinded drug trial, the placebo group aren't made worse by the placebo, so placebo effect can still show up in the results.
    Or have I completely lost the plot?
     
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  2. Snow Leopard

    Snow Leopard Senior Member (Voting Rights)

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    The "placebo response" in patients is highly likely to be the same as it is in any other group of people. The problem is a variety of reporting biases are being bundled up as a "placebo effect" and then claiming that the placebo effect* is magically high in some cases and low in others. When the real reason is the reporting biases are better controlled in some contexts, compared to others.

    *placebo effect defined as: a beneficial effect produced by a placebo drug or treatment, which cannot be attributed to the properties of the placebo itself, and must therefore be due to the patient's belief in that treatment.
     
  3. Keela Too

    Keela Too Senior Member (Voting Rights)

    The “placebo effect” can also be nothing to do with expectations, but can show up because of the chance that some individuals out of both groups will make a spontaneous improvement. Ie Regression to the mean.
     
  4. Jonathan Edwards

    Jonathan Edwards Senior Member (Voting Rights)

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    This is to a large extent what my grand round presentation was about.

    I think there is a simple sense in which the placebo effect for healing of a broken bone is small and the placebo effect for anything where the ascertainment of outcome is subjective, as for pain, is likely to be larger. ME is bound to fall more in the second category at least in the wider context of a spurious positive result that gets bundled under placebo effect.
     
  5. Snow Leopard

    Snow Leopard Senior Member (Voting Rights)

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    Regression to the mean is not a placebo effect, it is a bias that is often falsely attributed to the placebo effect.
     
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  6. Keela Too

    Keela Too Senior Member (Voting Rights)

    Fair point. Unfortunately improvements in the placebo group are often all attributed to “the placebo effect” without any other acknowledgement of what can cause a placebo group to improve (or appear to improve)!
     
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  7. BruceInOz

    BruceInOz Senior Member (Voting Rights)

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    Is there a "real" placebo effect or is it just entirely due to hidden biases?
     
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  8. Snow Leopard

    Snow Leopard Senior Member (Voting Rights)

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    Yes, the real placebo effect is a transient reduction in pain due to conditioning of the bodies endorphin system. There is some biological evidence of this. This system has obvious evolutionary advantage, namely being able to temporarily suppress pain for the purpose of escaping danger.
     
  9. Jonathan Edwards

    Jonathan Edwards Senior Member (Voting Rights)

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    But @Keela Too did put it in quotes - "placebo effect" so she was absolutely correct. Just as one might say, and Noam Chomsky did, that the "mind-body problem" has in fact been a body-body problem since Newton's theory of gravitation.

    "Placebo effect" is all too often used to include regression to the mean by my colleagues.
     
  10. Cheshire

    Cheshire Moderator Staff Member

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    "Contextual effects" is sometimes used in French instead of placebo effect. I don't know if it's the case in English? It seems more accurate as it aknowledges that a lot of processes are at play and gets rid of the kind of esoteric mind body thinking that often accompanies the term placebo.
     
  11. Jonathan Edwards

    Jonathan Edwards Senior Member (Voting Rights)

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    What one might call semantic finesse, or finesse semantique?
     
  12. Hoopoe

    Hoopoe Senior Member (Voting Rights)

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    The endorphin release associated with placebos could be part of the body's behaviour control system. It could be seen as the reward for finding a solution a for health problem.

    It makes sense that it hurts until you find a solution to the pain. Then it no longer need to hurt as much and your efforts should be rewarded so that you continue to take care of yourself.

    Seeing a doctor and leaving with the feeling that you've done something useful seems to count as "finding a solution". Even if the treatment is actually ineffective.
     
    Last edited: Jun 5, 2019
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  13. Barry

    Barry Senior Member (Voting Rights)

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    Another thought on PACE, and probably other trials. Given it is often ethically unacceptable to include a control arm having no treatment, each arm therefore has one of the interventions plus SMC (standard medical care). But what about the case where SMC actually conflicts with the intervention, as would seem to have been the case with PACE. How does that work out?

    For example, SMC for pwME pre-GET, would have been much more inclined towards real pacing, and not pushing yourself beyond sensible limits, and to listen to your body; this is the sort of advice my wife received in 2006'ish. So how could you be having that treatment, whilst also having treatment encouraging you to ramp up your activity levels and to ignore your symptoms. That alone sounds bonkers.

    ETA: Just discussing this with my wife, and she reminded me that the ME specialist we saw in 2007, recommended pacing, and enquired at great length how my wife managed her days, and how she paced herself. He told her that although they could offer CBT they were not doing so for my wife because he felt it would provide no additional benefit to her. So I'm just clarifying the advice my wife was given at the time.
     
    Last edited: Jun 7, 2019
  14. Lucibee

    Lucibee Senior Member (Voting Rights)

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    This is from the SMC manual:
    But it also says:
    So I guess the SMC doctor would need to tailor the advice they gave depending on which group the participant was in.
     
  15. Unable

    Unable Senior Member (Voting Rights)

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    Now this is getting weird. The current NICE guidelines (CG53) recommending CBT & GET were put in place in 2007. I’m not sure of timescales, but is it possible that some PACE trial participants were getting CBT/GET as part of SMC?

    Or had the trial period ended before CG53 came into effect?
     
  16. Jonathan Edwards

    Jonathan Edwards Senior Member (Voting Rights)

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    My memory is that recruitment to PACE was 2005-2007? The SMC patients clearly did not get CBT or GET but it does all seem very muddled and I think Barry's point is basically valid. Adding CBT or GET to SMC is not necessarily a reality.
     
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  17. Unable

    Unable Senior Member (Voting Rights)

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    And as patient experiences of conventional care differ widely, it is likely there was nothing standard about SMC!

    On top of that many GPs use the less formal version of GET - it goes along the lines of “I’ve heard that exercise helps with ME, you should make sure to fit some exercise into your day if you want to improve.”

    If SMC had to be defined by PACE (eg don’t offer CBT/GET to any trial patients as part of the SMC you offer them) then it really wasn’t “standard” medical care, but yet another form of care.

    All very muddy indeed.
     
  18. Barry

    Barry Senior Member (Voting Rights)

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    In which case the SMC-only arm was useless as a control.
     
    Last edited: Jun 7, 2019
  19. Adrian

    Adrian Administrator Staff Member

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    This is one of the issues with treatment as usual controls. The treatment that patients get is very unclear and variable so a comparison is very difficult.
     
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  20. rvallee

    rvallee Senior Member (Voting Rights)

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    Pretty much a textbook apples to citruses control.
     
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