PACE trial TSC and TMG minutes released

I think the proper downfall of PACE will take such an inquiry, since the authors and the host journals and the MRC will never admit fault and, as you say, there's no one else to abritrate. One might argue that NICE is already aware of the faults of PACE and that such an inquiry might be redundant, as far as patients are concerned, but if PACE falls, and falls properly, so do all the other CBT/GET CFS studies - and it could bring a lot of the MUS and more general BPS edifice down with it, as well as potentially scuppering a lot of the open-label/subjective measures stuff that goes on in psychiatry.

 

I don't know how Goldacre's team broke down their analyses - I wonder if they looked at drug vs non-drug and academia vs pharma.

 

This is true - it goes well beyond PACE (just as what's going on at the BMJ at the moment goes well beyond Esther Crawley's school absence study).

 

Unpublishable might be too strong a word. In rheumatology when I was involved I think it would be fair. However, I guess that there may be other branches of medicine where things have been murky - anti-diabetic agents, cardiovascular drugs maybe.

 

Useful to see that @Sasha.
I guess my point relates to what we can reasonably expect the body language to be when the assessor hands the patient the self-report form on APT - which would be crucial to bias.

Whatever the manuals say the therapists and assessors might have viewed the trial as trying to see if any of the three treatments were associated with improvement. If APT provided the right conditions for natural recovery then maybe there would be quite a bit of recovery. If the 'philosophy' was that nobody knew and that this was a good opportunity to test both the therapies in use and a pacing regimen - as it was sold to patient organisations as far as I understand, (And presumably deliberately implied in the use of the PACE acronym to satisfy the patient organisations.) then body language would be of one sort. If the 'philosophy' was as Horton said to counter one approach against the other then the body language would be quite different.

 

I tend to agree. On the other hand enquiries are sometimes epiphenomena that run alongside a shift in thinking that they then rubber stamp.

At some point someone important at the MRC needs to say 'we got this wrong'. I am not naming names but someone has already implied this about a minor event in the story. When it comes to Fellows of the Royal Society, being perceived as important still comes secondary to being perceived as having a razor sharp intellect. At some point it will not be tenable to defend both PACE and ones razor sharp intellect. That point will be reached when all the critical evidence reaches a level of visibility such that nobody can pretend not to have been aware of it. At the moment people like Mark Walport can pretend not to have been briefed on the details.

 

I think that the manuals that the patients received already built in considerable bias and that the kind of face-to-face pressure that you're talking about would be unnecessary icing on the cake, as far as needing to show that bias could account for the results.

It was clear from the original protocol that CBT and GET were expected to outperform APT - the hypotheses are unidirectional, asking whether CBT/GET were more effective than APT.

Primary objectives

1. Is APT and SSMC more effective than SSMC alone in reducing (i) fatigue, (ii) disability, or (iii) both?
2. Is CBT and SSMC more effective than APT and SSMC in reducing (i) fatigue, (ii) disability or (iii) both?
3. Is GET and SSMC more effective than APT and SSMC in reducing (i) fatigue, (ii) disability, or (iii) both?
4. Are the active rehabilitation therapies (of either CBT or GET) more effective than the adaptive approach of APT when each is added to SSMC, in reducing (i) fatigue and/or (ii) disability?

​

Is it likely that all the therapists and assessors would have been unaware of what was in the protocol?

 

Sure. It's a bit of a long read, but very well explained here: https://www.newstatesman.com/2014/05/how-mistakes-can-save-lives

In summary, those running the show can often get fixated on the wrong things, leading to mistakes that just get bigger and bigger. Involving all members of the team, particularly the most junior members, can help prevent things getting out of control - resets the focus.

The PACE team are so bound up with their ideology that they have completely forgotten what they are supposed to be doing: - helping patients.

 

Well that would certainly explain why they are so reluctant to release the data on the step test, because the missing data will show this.

But it says so much about their whole approach, and the red flags they have kept missing all the way through. At every point over the decades where they have noted that the objective data does not confirm their theory, they have discarded the objective measures, rather than reassessing their theory. Instead, they have sought subjective measures that back up their theory. That is bad science. All it does is preserve the myths. It's how religions get started.

 

Indeed not. But it is easy enough for someone like me, and so any other member of the establishment who might be useful, not to have read through this. And even if you are involved in a trial what is in a protocol comes second to the body language of the co-ordinator at the initial clinicians' briefing. And in the clinic body language overrides anything written on a piece of paper. Horton is relaying the body language of whoever had primed him about how s***-hot this trial was going to be, and why. The comparisons in the list just categorise by type of method (active) - dispassionately. But Horton is telling us that this was a deliberate tussle of philosophies. OK we know that, but some people might try to deny it - including Horton.

 

Thanks. That figures.

 

Which ones do you have in mind?

 

"... design and management ... directed by Professor Simon Wessely ..." doesn't sound very hands-off to me.

 

"Participants appear to be developing depression as result of being randomised only to receive SSMC."

This surely is an example of how unblinding could have negative bias on the outcomes of one arm, and not just positive bias on other arms.