It's clear as mud. They need to be much clearer about what they are referring to.

The key is the timeframe - the claim that one third improve by one year most likely is based on time of acute onset - a third improve somewhat until their illness plateaus.

But the PACE trial did not involve capturing acute onset and diagnosis in a community/population sample and subsequent treatment, so the two improvement claims are not comparable.

Fair enough.

However, their actual results (per protocol) fell a long way short of the assumptions for the trial:
At one year we assume that 60% will improve with CBT, 50% with GET, 25% with APT and 10% with SSMC. The existing evidence suggests that at one year follow up, 50 to 63% of participants with CFS/ME had a positive outcome, by intention to treat, in the three RCTs of rehabilitative CBT, [18, 25, 26] with 69% improved after an educational rehabilitation that closely resembled CBT.[43] This compares to 18 to 63% improved in the two RCTs of GET, [23, 24] and 47% improvement in a clinical audit of GET.[54] Having usual medical care allowed 6% to 17% to improve by one year in two RCTs.[18, 25] There are no previous RCTs of APT to guide us,[11, 12] but we estimate that APT will be at least as effective as the control treatments of relaxation and flexibility used in previous RCTs, with 26% to 27% improved on primary outcomes.[23, 26] We propose that a clinically important difference would be between 2 and 3 times the improvement rate of SSMC.
 
On a slightly different note, would anyone be able to link me to the Research Ethics Committee responsible for the PACE trial, please?

This was in the Protocol:
Research Ethics Approval (MREC)
Ethical approval for the PACE trial was given by the West Midlands MREC (reference number MREC/02/7/89). Local REC approvals have been sought and obtained as required.

ETA: Date of approval was 31 Mar 2003 according to http://www.isrctn.com/ISRCTN54285094
 
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Just to add, the research ethics committee doesn't provide "ethical approval" (despite what the Protocol says). They provide assurance to the sponsor (QMUL) that their researchers broadly seem to be following ethical guidelines, as far as they can tell.

ETA: I guess what I'm trying to say is that they hold no responsibility as such over the trials they provide with a "favourable opinion".
 
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Just to add, the research ethics committee doesn't provide "ethical approval" (despite what the Protocol says). They provide assurance to the sponsor (QMUL) that their researchers broadly seem to be following ethical guidelines, as far as they can tell.

ETA: I guess what I'm trying to say is that they hold no responsibility as such over the trials they provide with a "favourable opinion".
Who does take responsibility then, and formally provide such approval?
 
I’m quite new to this. I postponed reading the actual PACE trial documents until recently. What struck me is how bad the results are even if you were to take everything the PACE-authors said for granted.

Take for example CBT: null results for the 6 min walking test, the step-fitness test, levels of disability benefits, insurance payments and days of employment. There was only a significant result on subject measures such as fatigue and physical function (if you were to believe the PACE authors) but those disappeared at long term follow-up.

Following the PACE-saga by reading blogs and news articles I very much got the impression that PACE proved that GET and CBT worked, but that there were so many flaws in the trial that these results cannot be trusted. Therefore we needed to get rid of it: a full retraction of PACE papers and its misleading message.

By reading the actual results, I’ve got a very different impression. Now I see that PACE actually proved that CBT and GET do not work in ME/CFS. There were a couple of smaller and poorly designed RCT’s that came before it, finding that these treatments could improve subjective outcomes. But PACE, being the larger and better designed study - conclusively showed that these do not represent clinical meaningful changes: subjective improvements after GET/CBT are not only very small (virtually nonexistent in the analysis according the original protocol), they disappear at follow-up, patients remain very sick and there is no improvement on multiple objective outcomes. The questionable outcomes switching by the PACE authors doesn’t actually change much to that conclusion.

As I see it, the fiercest proponents of GET and CBT received the ultimate opportunity to prove their favored therapies are effective. They had millions of pounds to do it. They’ve got to select patients according to their bogus criteria, they didn’t have to provide an adequate control arm, they could choose the outcomes measures they want and they even were allowed to send participants a letter claiming GET and CBT are effective. And despite all of that, there were no results for both these treatments.

So now I see PACE differently; as the definite proof that GET and CBT do not work. And I think I’m going to use it in advocacy more (especially regarding CBT as some psychologists in Belgium seem willing to dump GET to save CBT at the moment), without waiting for The Lancet and the other journals to correct the unacceptable outcome switching and other flaws.

Just to be clear: I do not wish to minimize the amazing work by the patients/scientists who exposed the many flaws of the PACE-trial (you guys are my heroes). In fact I think the exposure of these flaws very much changed the field of ME/CFS in the last couple of years. It showed the outside world how unscientific and irresponsible BPS proponents are and it drew many 'outsiders' (Tuller, Coyne, Hughes etc.) into the field getting ME/CFS attention in the news and scientific community and so much more.

I just wanted to suggest that maybe we could already use PACE more in advocacy as the definite proof GET and CBT do not work, even as things stand for the moment. I would love to hear what the more experienced forum members think of this.

Cheers,
 
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I’m quite new to this. I postponed reading the actual PACE trial documents until recently. What struck me is how bad the results are even if you were to take everything the PACE-authors said for granted.

Take for example CBT: null results for the 6 min walking test, the step-fitness test, levels of disability benefits, insurance payments and days of employment. There was only a significant result on subject measures such as fatigue and physical function (if you were to believe the PACE authors) but those disappeared at long term follow-up.

Following the PACE-saga by reading blogs and news articles I very much got the impression that PACE proved that GET and CBT worked, but that there were so many flaws in the trial that these results cannot be trusted. Therefore we needed to get rid of it: a full retraction of PACE papers and its misleading message.

By reading the actual results, I’ve got a very different impression. Now I see that PACE actually proved that CBT and GET do not work in ME/CFS. There were a couple of smaller and poorly designed RCT’s that came before it, finding that these treatments could improve subjective outcomes. But PACE, being the larger and better designed study - conclusively showed that these do not represent clinical meaningful changes: subjective improvements after GET/CBT are not only very small (virtually nonexistent in the analysis according the original protocol), they disappear at follow-up, patients remain very sick and there is no improvement on multiple objective outcomes. The questionable outcomes switching by the PACE authors doesn’t actually change much to that conclusion.

As I see it, the fiercest proponents of GET and CBT received the ultimate opportunity to prove their favored therapies are effective. They had millions of pounds to do it. They’ve got to select patients according to their bogus criteria, they didn’t have to provide an adequate control arm, they could choose the outcomes measures they want and they even were allowed to send participants a letter claiming GET and CBT are effective. And despite all of that, there were no results for both these treatments.

So now I see PACE differently; as the definite proof that GET and CBT do not work. And I think I’m going to use it in advocacy more (especially regarding CBT as some psychologist in Belgium seem willing to dump GET to save CBT at the moment), without waiting for The Lancet and the other journals to correct the unacceptable outcome switching and other flaws.

Just to be clear: I do not wish to minimize the amazing work by the patients/scientists who exposed the many flaws of the PACE-trial (you guys are my heroes). In fact I think the exposure of these flaws very much changed the field of ME/CFS in the last couple of years. It showed the outside world how unscientific and irresponsible BPS proponents are and it drew many 'outsiders' (Tuller, Coyne, Hughes etc.) into the field getting ME/CFS attention in the news and scientific community and so much more.

I just wanted to suggest that maybe we could already use PACE more in advocacy as the definite proof GET and CBT do not work, even as things stand for the moment. I would love to hear what the more experienced forum members think of this.

Cheers,

I think you're right, Michiel. In fact, that was pretty much my view when I first started learning about the trial. They loaded all the dice in their favour and still all they found was a small, temporary, subjective improvement in a small number of patients taken from those well enough to attend clinics.

Put that alongside the null finding in FINE and really it's case closed.
 
I’m quite new to this. I postponed reading the actual PACE trial documents until recently. What struck me is how bad the results are even if you were to take everything the PACE-authors said for granted.

I agree with you. I remember reading the original PACE paper published back in 2011 and thinking the conclusions of efficacy were not justified by the outcomes even then. I was completely ignorant of the story behind it, the changes in outcome measures and all the other things I've learned about since, but as an ME sufferer, I could see the results were so slight as to be meaningless. And I looked up the Chalder fatigue questionnaire and couldn't believe it was taken seriously by anybody, let alone used in a multi million pound clinical trial.

Then when the long term follow up paper came out and showed no between group differences, I was astonished that the authors managed to spin a null result into a 'success' for GET/CBT. That was when I started joining groups, and finding out the back story. I was and still am deeply shocked that doctors who are supposed to be helping patients could be so unscientific and unprincipled.
 
I just wanted to suggest that maybe we could already use PACE more in advocacy as the definite proof GET and CBT do not work, even as things stand for the moment. I would love to hear what the more experienced forum members think of this.

I think most of the 'old timers' would agree, especially Tom.

The only Catch22 is that if they frightened off all the people with real ME and only studied people without ME then they did't even prove the treatments did not work in ME because they did not study it. It takes quite a stretch to see why they should work in real ME but there is a hint of cherry-picking about saying they nailed the disproof when the methodology was so bad it could not disprove anything much!
 
Didn't they just sort of disprove their methods work for anything that could have been included by the selection criteria (whatever that may have been) and now the onus would be on whoever still wants to find out if their 'treatments' are ever of any use whatsoever to find exceptions to that rule?
 
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