PACE trial TSC and TMG minutes released

Jonathan Edwards said:
It seems to me we now have enough information to propose that there is a formal independent enquiry into the trial. Since the concern relates to what is supposed to be the highest arbiter within science, the MRC, the enquiry would presumably have to be parliamentary. It looks as if there is at least one MP, Carol Monaghan, who is interested in exploring the problem. But the level of discussion has to rise above what we have seen so far. Independent experts in trial design, probably from abroad, should be brought in to give evidence. The issue is not simply one of the PACE trial. It is how the MRC trials staff oversaw such incompetence in a publicly funded trial.
Click to expand...

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.
 
Adrian said:
I think someone had done some analysis and the drug companies had cleaned up their act quite well but universities were less likely to follow good methodology. The last thing drug companies want is for a drug not to be approved because they have not followed the rules. They probably think more about the measures up front now.
Click to expand...

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.
 
Sasha said:
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.
Click to expand...
They didn't but there was someone accusing Goldacre's team of being misleading by including lots of old stuff and pointing to others papers who were finding different things.
 
Sasha said:
One might argue that NICE is already aware of the faults of PACE and that such an inquiry might be redundant,
Click to expand...

I think there are other needs for an inquiry. Its not necessarily about PACE but about the standards of governance that the MRC apply to trials they fund and whether it is robust. They seem to just hand out money and then say put a few independent people on a trial committee and it will all be ok.
 
Adrian said:
I think there are other needs for an inquiry. Its not necessarily about PACE but about the standards of governance that the MRC apply to trials they fund and whether it is robust. They seem to just hand out money and then say put a few independent people on a trial committee and it will all be ok.
Click to expand...

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).
 
I hope an enquiry would also scupper all ofCrawleys trials too. In fact from .David Tuller's work on Crawley, I'd say there is plenty of evidence for an enquiry into MAGENTA, SMILE, FITNET and her smaller studies, and the poor quality of both ethics and funding approvals for these.

I think psychology and psychiatry have become so accustomed to working within their own bubble, researching psychological treatments for mental health conditions that can only have subjective outcome measures, so sloppy science with open label trials with subjective measures became accepted as the norm on the grounds that nothing else was possible.

They are now trying to pass that off as good science for testing psychological treatments for physical conditions, deliberately ignoring and dismissing objective measures as primary outcome measures, knowing full well from past experience that it won't work. I keep being reminded of the asthma study of a psychological therapy which showed the patients in the therapy group reported improvements that weren't borne out by objective spirometry measurement.
 
Sasha said:
Is this true, though? What about all that work by Ben Goldacre's team (irony, irony) on outcome switching? It seems to be being done on a huge scale (and they're looking specifically at trials published in the top five medical journals):
Click to expand...

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.
 
Sasha said:
But we do know something about that. We know what was in the manuals.
Click to expand...

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.
 
Sasha said:
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.
Click to expand...

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.
 
Jonathan Edwards said:
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.
Click to expand...

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.

Jo said:
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.
Click to expand...

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?
 
Woolie said:
Would it be a digression to ask you about the airline safety example, @Lucibee? Afraid I'm ignorant about it.
Click to expand...

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.
 
Jonathan Edwards said:
It seems to me we now have enough information to propose that there is a formal independent enquiry into the trial. Since the concern relates to what is supposed to be the highest arbiter within science, the MRC, the enquiry would presumably have to be parliamentary. It looks as if there is at least one MP, Carol Monaghan, who is interested in exploring the problem. But the level of discussion has to rise above what we have seen so far. Independent experts in trial design, probably from abroad, should be brought in to give evidence. The issue is not simply one of the PACE trial. It is how the MRC trials staff oversaw such incompetence in a publicly funded trial.
Click to expand...

I have been thinking for some time that we need to do something similar, but I think it would be worth waiting a little while yet.

I think it will be interesting, for example, to see how the MRC respond to my complaint. The more we get, the better the case.

My view is that before the end of the year we would be in a stronger position. I think then there should be a comprehensive report written and sent to all the public authorities, essentially saying that there are grave concerns about possible misconduct and that a proper investigation needs to be conducted.
 
Esther12 said:
I remember some on-line comment from someone who said that they were a PACE participant, and that they had stopped conducting the step test towards the end of the trial as they were getting too many bad reactions. It's always worth being cautious about what one reads on the internet, but these minutes indicate that there was concern about the step test. I wonder if there was a sharp decline in participation rates towards the end of the trial.... guess we'd need access to the secret data to check.
Click to expand...

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.
 
Sasha said:
Is it likely that all the therapists and assessors would have been unaware of what was in the protocol?
Click to expand...

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.
 
JohnTheJack said:
I think then there should be a comprehensive report written and sent to all the public authorities, essentially saying that there are grave concerns about possible misconduct and that a proper investigation needs to be conducted.
Click to expand...

Which ones do you have in mind?
 
Sasha said:
Which ones do you have in mind?
Click to expand...

I don't know if it's possible, but if we could get proper report written and signed by eg the kind of people who wrote open letter to Lancet (ie renowned and respected, not just patients), then I'd go nuclear: send it to Dept of Health copied to all the relevant depts, all the HoC overseeing committees, universities involved etc
 
Robert 1973 said:
Not only an unblinded trial which primed participants on the effectiveness of CBT and relied on subjective outcomes measures, but also one in which patients volunteered to join because they were already convinced of the potential effectiveness of CBT and GET and became depresssed if they did not get these treatments. This really is a textbook example of how not to conduct a clinical trial – or how to ensure a positive result for an ineffective treatment.


Click to expand...

"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.
 
You must log in or register to reply here.
Back
Top Bottom