Great work - thanks to all who were involved. That was a tour-de-force.
I've got one main question, and then just a few notes I pulled out as I went through.
No method of correction was specified
in the trial protocol,...
Does this mean that we can/can't say "using the prespecified analysis for the trial's primary outcome there was no significant treatment effect for [CBT and/or GET]"?
Or do we once again have to deal with niggling complexities which prevent a nice simple statement (ideally one suited to those of us not used to discussing Bonferroni correction)?
Using this definition, 11% of Control participants
improved, compared to 22% and 21% of CBT and
GET participants respectively.
That is right on the edge of what they define as a clinically important difference in the full trial protocol:
"We propose that a clinically important
difference would be between 2 and 3 times the improvement rate of SSMC."
However, in May 2010, several months after data
collection was complete, this primary outcome
measure was replaced with two continuous
measures: fatigue and physical function ratings on
the two scales described above (see [13,14] for
details).
I didn't know/had forgotten that there was a date available for that. Where was that from?
The PACE investigators have not
specified when the decision to change the
definition of recovery was made, except to say it
was "before the analysis occurred" [19]; the change
does not appear in any documentation prior to the
final publication, and there is no published
evidence that it was approved by the trial steering
committee.
I'd have liked a mention of the fact that after the 2011 Lancet paper was released, they claimed that the results for the recovery criteria laid out in their protocol were due for publication in an academic journal. [
http://www.meassociation.org.uk/2011/05/6171/ http://www.meassociation.org.uk/wp-content/uploads/2011/06/FOI+from+Queen+Mary.pdf ] I know that there are too many problems to detail in just one paper though.
There's also this quote from Sharpe from 2011:
Michael Sharpe :
16 Apr 2011 6:12:59pm
I would just like to respond to the comment about data from measures listed in the protocol not being reported in the Lancet paper. This is simply because there is too much data to adequately report it in a single paper (the Lancet like most other journals has a strict word limit of 4000 words). There is a publication plan for this, so far unpublished, data which includes papers on: 'recovery'(careful reading will make it clear that recovery is not reported in the Lancet paper, longer term outcome, mediators and moderators of response, and economic aspects including employment. I hope this is helpful.
Michael Sharpe
Co-PI PACE trial
http://www.abc.net.au/radionational...son-of-treatments-for-chronic-fatigue/2993296
I don't really understand this sentence in the paper about this:
Again, the timing of the change to the recovery
definition – over a year after the trial was
completed - is highly problematic.
Are you saying that the recovery definition was changed before the Lancet paper was released? Do you have access to some info on this that has not been made public, or am I misunderstanding you?
There seem to be missing italics here:
"The main finding of this long-term follow-up
study of the PACE trial participants is that the
beneficial effects of the rehabilitative CBT and
GET therapies on fatigue and physical functioning
observed at the final 1 year outcome of the trial
were maintained at long-term follow-up 2,5 years
from randomisation." ([7] p. 1072, Italics added).
Is this 'good' justified? How good was SMC?: "Patients do just as well with some good basic medical care."
Typo: "Amore plausible explanation"
"It is
concerning that these negative findings were not
even published until years after the primary results
had been reported, so these inconsistencies are not
immediately apparent to the reader."
This reminded me that we're still waiting for some LTFU data, eg employment.
The behavioural-deconditioning model, on
which the treatments were based, assumes that
there is no underlying disease process in CFS, and
that patients' concerns about exercise are merely
"fearful cognitions" that need addressing ([41], p.
47-8).
Was the decision to keep that 'merely' in there at least partly for the fun of pushing this peer reviewer to follow through on their promise to slag you off for it?
https://jcoynester.wordpress.com/20...bused-by-a-peer-reviewer-and-silenced-by-bmj/
There were so many parts I wanted to pull out and praise that I'm having to restrain myself. Although it's not a killer bit to quote, and there were other bits I enjoyed even more, I really appreciated the careful phrasing of this section, so will highlight that to remind me to steal it in future:
Self-rated physical function scores
showed greater improvement in the GET group
than in the Control group - but not self-rated fatigue
scores - which suggests GET had a modest effect
on patients' perceptions of their physical function,
but did not do much to alter symptom perceptions.
Conversely, self-rated fatigue showed greater
improvement in the CBT group than in Controls -
but not physical function - which suggests CBT
elicits modest reductions in symptom-focusing, but
does not do much to improve patients' confidence
in their physical capacities
It made me 'heh' a few times during reading.
