CORRESPONDENCE The PACE trial of treatments for chronic fatigue syndrome: a response to WILSHIRE et al (2019) Sharpe, Goldsmith & Chalder

strategist said:
As far as I know, they did this because it was planned in the original protocol. The PACE authors appear to consider this "excessive" because it doesn't give the results they were expecting (the original protocol is very optimistic about finding large treatment effects that would easily withstand such corrections).
Click to expand...

I'm not sure if they planned it but it is the correct handling of having the multiple things they were testing for. I suspect they hadn't understood or thought through the implications when they wrote the protocol.
 
MSEsperanza said:
https://static-content.springer.com...288-x/40359_2019_288_ReviewerReport_V0_R1.pdf
Click to expand...

I think this is revealing:
I am aware of the importance of this debate, in the general field of psychology, and I believe that, rather than facing as a reviewer the content itself, the paper deserves publication as a part of the ongoing discussion. Therefore, I will not enter into the merit of the discussion (who I think is right on a certain raised point), as it seems that, from a certain perspective, a sort of post-publication peer review process is ongoing.

It appears that this letter (it is under correspondence so I don't think it counts as an article) was only subject to one referee's report and this referee made a point of not commenting on the quality of the arguments.

The initial justification for this is fair. However, the reality is that no referee is going to make this strange disclaimer if he or she thinks the arguments provided, even on a cursory reading, are reasonably sound. There would no need to opt out if the letter's content was fairly argued.

The reviewer's second justification (note that there is a redundancy of explanations here) looks weak and probably illegitimate. The impression is given that the reviewer does not like the idea of post-publication peer review - perhaps because he would not like people to pick holes in his published papers.

So the unconscious message here seems to be that the reviewer felt distinctly uncomfortable about giving the letter a straightforward OK - as in 'well argued reply, but one or two bits of text need some tidying'. And so he is saying 'between the lines' that he does not see why he should get stick from the authors and their friends for being critical so is going to opt out of any comment.

That is about as damning a review of a letter as you can get in the circumstances.
 
Nothing spells being silenced like getting a PR puff piece promoted by international news organisations while also publishing yet another research paper on the field he alleges to have "quit".

I'd love to one day be as silenced as Michael Sharpe, what with his multimillion dollar research funding and his research being enacted in national clinical guidelines, or dear old Simon, whose career is basically non-existent, only being in charge of a full review of mental health, a knight and commingling with the royals.

That's some awful silence. The poor dears. Can't someone harm millions of people without being criticized for it? Oh, the humanity.
 
pteropus said:
Monty Python's "Dead Parrot Sketch" ???
Click to expand...
I'm thinking more of another Monty Python:

tumblr_mj88inc4aw1rnzcl1o1_500.gif
 
Trish said:
So they admit that they think their recovery rates are better because they 'prefer' their definition.
Click to expand...
While also admitting that they do not know what recovery means or how to define it. But this changes nothing to their assertions that participants met a "strict criterion" for recovery. Also no bias in responses because. Just that, because.

And if you don't like that explanation, they have a dozen more if you prefer. One of those involves smoke bombs while another, somehow, requires someone to make horsey-gallopey noises with a coconut while delivering it or it just doesn't quite have the same impact.

Excuses, excuses for saaale!
 
Some people say ME is the same as CFS. Those "some people" being themselves and bona fide members of their mutual admiration society. Hmmm...

How to invent a controversy 101: make stuff up, point to made-up stuff as contrarian opinion justifying its controversial nature, spin it all around.

Yeah, well, some people say I deserve $1M in my bank account. It may be controversial but payment is nonetheless expected promptly.
 
Barry said:
[my bold]

Only!? So the scoring method is of no consequence then. Maybe we could modify all manner of scoring systems so that 13% of people are deemed improved at something even when they have not.
Click to expand...
Now that is a technique penis enlargement treatments would love to be able to get away with.

"Our trial has reported that 93% of our participants now self-report as having a gigantic penis that feels so much more heavy and powerful. Post-hoc changes to size categorization were deemed sensible because we prefered the results they gave us. We don't really know what gigantic means but we like it so we consider it a strict criterion for penile gigantization. By the way, did you know we are top researchers in the field? Top. Researchers."
 
Last edited:
Jonathan Edwards said:
I think this is revealing:
I am aware of the importance of this debate, in the general field of psychology, and I believe that, rather than facing as a reviewer the content itself, the paper deserves publication as a part of the ongoing discussion. Therefore, I will not enter into the merit of the discussion (who I think is right on a certain raised point), as it seems that, from a certain perspective, a sort of post-publication peer review process is ongoing.

It appears that this letter (it is under correspondence so I don't think it counts as an article) was only subject to one referee's report and this referee made a point of not commenting on the quality of the arguments.

The initial justification for this is fair. However, the reality is that no referee is going to make this strange disclaimer if he or she thinks the arguments provided, even on a cursory reading, are reasonably sound. There would no need to opt out if the letter's content was fairly argued.

The reviewer's second justification (note that there is a redundancy of explanations here) looks weak and probably illegitimate. The impression is given that the reviewer does not like the idea of post-publication peer review - perhaps because he would not like people to pick holes in his published papers.

So the unconscious message here seems to be that the reviewer felt distinctly uncomfortable about giving the letter a straightforward OK - as in 'well argued reply, but one or two bits of text need some tidying'. And so he is saying 'between the lines' that he does not see why he should get stick from the authors and their friends for being critical so is going to opt out of any comment.

That is about as damning a review of a letter as you can get in the circumstances.
Click to expand...
Sounds like it should be a response to the reanalysis paper itself, not an entirely new paper. Especially if the reviewer deems it to be an opinion and doesn't even want to attempt to review it.

Must be nice to be able to publish an op-ed as a research paper that looks like it's been peer-reviewed but actually hasn't. It's very bad for science and medicine but whatever, apparently the rules don't matter to those guys.
 
rvallee said:
Some people say ME is the same as CFS.
Click to expand...

I find it interesting that they seem to be doubling down on trying to "disappear" ME again. I note that in their citing of the Reuters article (Special Report) they refer to CFS and not ME (although the article itself uses the term CFS/ME throughout), and Sharpe has already made it clear that he thinks CFS and ME are different things, although he's never properly explained what he means by that.

In this letter too, that theme seems strong:
Myalgic Encephalomyelitis (ME) is thought by some to be the same disorder (then referred to as CFS/ME) and by others to be different. There is an urgent need to find effective treatments for CFS.
Click to expand...

The emphasis here seems to be that it is important to find effective treatments for CFS (and not ME or even CFS/ME), as far as they are concerned.
 
Lucibee said:
I find it interesting that they seem to be doubling down on trying to "disappear" ME again. I note that in their citing of the Reuters article (Special Report) they refer to CFS and not ME (although the article itself uses the term CFS/ME throughout), and Sharpe has already made it clear that he thinks CFS and ME are different things, although he's never properly explained what he means by that.

In this letter too, that theme seems strong:


The emphasis here seems to be that it is important to find effective treatments for CFS (and not ME or even CFS/ME), as far as they are concerned.
Click to expand...




 
According to the PACE authors, bias in subjective outcomes was not really a problem.

Wilshire et al. suggest that, as the primary outcomes in PACE were participant-rated (CFS is defined by self-report as there are no reliable objective measures)and the participants inevitably knew what treatment they were given (the therapies tested could not be blinded asthey were collaborative between therapist and partici-pant), the trial findings can be dismissed as simply due to participant bias when rating outcomes. We disagree with this proposition. Whilst participant rated outcomes do potentially pose a risk of bias for all trials testing the effect of unblindable treatments, we do not agree that this is a convincing alternative explanation for the PACE trial findings. This is because: First, participants did not just give global ratings at the end of treatment, they answered specific questions about fatigue and function, as long as six months after therapy was completed, making a transient ‘placebo’ type effect very unlikely. Second, the majority of the trial secondary measures showed a similar pattern as the primary outcomes. Third, and most importantly, the trial design controlled for a non-specific effect of treatment by comparing three therapies (CBT, GET and APT) that wereall attention and credibility matched. Credibility matching was determined by asking participants how logical they found the treatment they were allocated to and how confident they were it would help them before they received it; the credibility rating of APT was higher than CBT, and similar to GET. Despite this control the biggest difference in outcomes was between APT and both CBT and GET. Indeed, one could argue that if the participant rated outcomes had been biased by the non-specific factors, such as perceived credibility, APT should have performed best, when in fact it performed worst.
Click to expand...


First, participants did not just give global ratings at the end of treatment, they answered specific questions about fatigue and function, as long as six months after therapy was completed, making a transient ‘placebo’ type effect very unlikely.
Click to expand...

Presumably they are referring to the scales used, the Clinical Global Impression Scale, the SF-36 physical function scale, the Chalder Fatigue Scale and some others.

They appear to be suggesting that scales like the SF-36 with specific questions (as opposed to the CGI with vague ratings) are unaffected by bias, which is obviously complete nonsense.

They also suggest that any bias had likely disappeared at the time the patients filled out the questionnaires. This is news to me, I was not aware that there was a delay. They say the delay was up to six months, but that raises the question of how long the average delay was, and whether there was a relationship between worse outcomes and greater delay. Anyway, the claim is essentially that in ME/CFS, biased self-reporting is only a short term problem. While it's true that placebo effects wear off (see long term follow up), I don't think one can reasonably be sure that whatever delay there ultimately was would eliminate bias.

It is interesting to contrast the open-label with the double blinded Rituximab trial. We have been told there was no difference between the groups in the double-blinded trial. Yet in the open label trial one can see what looks like long sustained responses. That's most likely entirely or almost entirely due to biased reporting. There is no real effect.

journal.pone.0129898.g002.PNG

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0129898
 
Last edited:
strategist said:
It is interesting to contrast the open-label with the double blinded Rituximab trial. We have been told there was no difference between the groups in the double-blinded trial. Yet in the open label trial one can see what looks like long sustained responses. That's most likely entirely or almost entirely due to biased reporting. There is no real effect.
Click to expand...

This is a really useful comparison. I had forgotten that there was an open label rituximab study. The phase 2 blinded study gives very wobbly curves and its 'positive' result was post hoc anyway so it does not help comparing the two blinded studies. But comparing the unblinded results with the phase 3 gives a very nice indication of the potential for a long term 'placebo' (in the broad sense) effect.
 
Second, the majority of the trial secondary measures showed a similar pattern as the primary outcomes.
Click to expand...

I'm not sure what to say about this argument, except I can't believe they are writing this.

Third, and most importantly, the trial design controlled for a non-specific effect of treatment by comparing three therapies (CBT, GET and APT) that wereall attention and credibility matched.
Click to expand...

To their credit, they did try to control for some non-specific effects related to the presence of a therapist by turning pacing into a therapist assisted treatment (APT). Contact time was also matched I believe except for the control group that had much less contact time and was therefore inadequate. Where it all went wrong is that CBT and GET were presented as highly effective and that recovery was possible. There's also the issue that CBT and GET intentionally try to change how patients see their symptoms. Therapists were likely to be people with professional investment in CBT and GET. So in the end the comparison is not fair and I don't see what the authors could have done to make it fair. The right thing would have been not to do this sort of trial, or use objective outcomes measures.
 
Jonathan Edwards said:
I will not enter into the merit of the discussion (who I think is right on a certain raised point), as it seems that, from a certain perspective, a sort of post-publication peer review process is ongoing.

The reviewer's second justification (note that there is a redundancy of explanations here) looks weak and probably illegitimate. The impression is given that the reviewer does not like the idea of post-publication peer review - perhaps because he would not like people to pick holes in his published papers.
Click to expand...

You would understand reviewer code better than I would, but I read that differently. I read it as an endorsement of the discussion, that he is saying the debate about the trial is providing a necessary and interesting review of the PACE papers and there's really no need for him to say anything more.
 
"[Use of CBT/GET] they imply that CFS or ME is psychiatric or psychological in nature"

I know others have pointed out the many reasons why this is not the argument, but while doing a transcript of Trudie Chalders recent lecture (long way off finished), right at the beginning she says
chronic fatigue syndrome is where people have a primary complaint of fatigue. It’s associated with substantial disability and associated disabilities. …handicap. And its associated with sleeping problems, memory problems, and concentration problems and muscle pain. And symptoms are made worse by activity, at least that’s what the patients experience is.

So half these patients are unemployed, they have ten times the amount of sick leave than other general medical outpatients. The prognosis is very poor if left untreated. And in primary care only one third improve by one year. And of those referred to secondary care less than 10% return to premorbid functioning.
Click to expand...
Back in the summer of '89.....The mainstay of treatment was rest and it was based on the idea that the illness was a physical one.
Click to expand...

as opposed to 'based on the idea' that it is a psychological one?

(nothing we didn't know already I know but again shows how they twist things to obscure the truth).
 
You must log in or register to reply here.
Back
Top Bottom