PACE Trial and PACE Trial Protocol

[Snowdrop]

Perhaps if this issue received a lot of press there might be some decent human being with a conscience willing to leak the info to the public.

 

[Dolphin]

Just got the following e-mail:

New updates for the request 'Timing of changes to PACE Trial recovery criteria'

===============================================================================


Mr Matthees added an annotation (10 April 2015)

"In response to QMUL's refusal to grant this FOI request after an internal review, I submitted a complaint to the ICO. I sent the correspondence from th..."

https://www.whatdotheyknow.com/request/timing_of_changes_to_pace_trial#comment-59096

I started a specific thread to highlight and discuss this:
http://forums.phoenixrising.me/inde...hanges-to-pace-trial-recovery-criteria.36800/

 

[Esther12]

I've just been reading little publicly available bits of:

Fibromyalgia and chronic fatigue syndrome: management issues.
Bourke J1.

http://www.ncbi.nlm.nih.gov/pubmed/25832515

He's from Barts, and it seems pretty crap.

He does say:

Membership in support groups was associated with a worse outcome in the PACE trial. This is surprising and conflicts with reports from other disorder, although the reasons for this association are unclear.

I don't think that we've had any data for this released, have we? As he's at Barts I wonder if he's referring to unpublished data. [edit: Also, he was a co-author of the PACE pain paper that didn't get a lot of attention here].

When describing 'one of the most important findings' he chooses to ignore that PACE are refusing to release results for the recovery criteria laid out in their protocol, and are instead fighting nihlism with a 'recovery' criteria so loose that on both of the trial's primary outcomes it overlaps with the trial's entry criteria which required "severe and disabling fatigue".

What a loathsome quack.

[edit 2: It is he and White who are running the pain research for Action for ME. I look forward to their inspiringly spun results].

 

[MeSci]

I've just been reading little publicly available bits of:

Fibromyalgia and chronic fatigue syndrome: management issues.
Bourke J1.

http://www.ncbi.nlm.nih.gov/pubmed/25832515

He's from Barts, and it seems pretty crap.

Bourke does concede that NHS services do not perform well in improving physical function, and doesn't appear to rule out the possibility that the 'content' of the treatment is to blame, and says that 'effect sizes' are moderate and complete resolution is rare.

He also refers to 'recovery' in a qualified way: "as defined in the Chalder Fatigue Questionnaire", and doesn't draw conclusions as to causation re the 'predictors of a poorer response'.

 

[Esther12]

He also refers to 'recovery' in a qualified way: "as defined in the Chalder Fatigue Questionnaire", and doesn't draw conclusions as to causation re the 'predictors of a poorer response'.

I think that makes it more irritating to me. It indicates that he's aware what a BS version of 'recovery' he's promoting, and wants to be suitably evasive about it, but he doesn't provide the context and information needed for anyone who has not looked closely at PACE to be able to really understand how seriously devalued 'recovery' has been by White et al.

It seems totally lacking in integrity to me.

 

[user9876]

Bourke does concede that NHS services do not perform well in improving physical function, and doesn't appear to rule out the possibility that the 'content' of the treatment is to blame, and says that 'effect sizes' are moderate and complete resolution is rare.

He also refers to 'recovery' in a qualified way: "as defined in the Chalder Fatigue Questionnaire", and doesn't draw conclusions as to causation re the 'predictors of a poorer response'.

Recovery isn't defined in a questionnaire but White chose thresholds to apply to both the CFQ and the SF36 physical function scale in the protocol and then after the trial finished he chose new ones which were much more easier to meet and with the SF36 measure below the trial entry conditions.

 

[Dolphin]

Is withholding your data simply bad science, or should it fall under scientific misconduct?
July 3
http://blogs.lse.ac.uk/impactofsoci...secrecy-bad-science-or-scientific-misconduct/

Thread on this:
http://forums.phoenixrising.me/inde...fall-under-scientific-misconduct-july3.38531/

 

[Dolphin]

This comment was submitted on the AHRQ treatment review. They are aiming for it to get published (<=400 words and <=5 references). To be considered for publication in the print, letters have to be sent within 30 days (so aim for on or before July 15) though comments will still be accepted after that.

http://annals.org/article.aspx?articleid=2322801#tab9

Treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Posted on
June 30, 2015

PD White, MD,1 DJ Clauw, MD,2 JWM van der Meer, MD,3 R Moss-Morris, PhD,4 RR
Taylor, PhD,5

1. Wolfson Institute of Preventive Medicine, Barts and the London
School of Medicine, Queen Mary University, London, UK 2. Department of
Anesthesiology, Medicine and Psychiatry, University of Michigan

Conflict of Interest: PDW, JWMvdM and RMM were principal investigators or
co-investigators in some of the trials reviewed. PDW does consultancy work
for the UK government and a re-insurance company.

In their systematic review, Smith and colleagues concluded that "trials of .
counseling therapies, and graded exercise therapy suggest benefit for some
patients meeting case definitions for CFS, whereas evidence for .. harms is
insufficient."(1)

While we support the general conclusion of benefit with these treatments, we
suggest that some aspects of this review may be misinterpreted. Firstly, the
most frequently tested behavioural intervention has been cognitive behaviour
therapy (CBT), which aims to reduce symptoms and improve functioning, and it
would be unusual to consider this as "counseling", which has different
objectives and content. One would not combine different types of medicines
in a review; why do this with therapies? A review that combines counselling
and CBT simply dilutes the efficacy of CBT, which has been amply
demonstrated in several previous meta-analyses (2).

Secondly, there is little evidence of harm caused by graded exercise therapy
(GET); a Cochrane systematic review of eight trials of exercise therapy for
chronic fatigue syndrome (CFS), published this year, concluded that "..no
evidence suggests that exercise therapy may worsen outcomes." (3) Suggesting
evidence of harm by stating that "one trial reported significantly more
serious adverse events ..and more nonserious adverse events . in the GET
versus comparison groups,." without mentioning that serious adverse events
were independently judged to be unrelated to the intervention, and that the
differences between non-serious adverse events was not statistically
significant, is a potentially misleading representation of the evidence.
Adding that "..in a trial of GET, 20% of patients declined to repeat
exercise testing because of perceived harm of testing" encourages further
misunderstanding by failing to mention that the exercise testing was not
part of the therapy and that the proportion of patients in the control
intervention who also declined exercise testing was 50% (4). (Incidentally
the proportion declining testing in the GET arm was 44%, not 20%.4) There is
a world of difference between the effects of maximum exercise testing and
graded exercise therapy. It is important not to overemphasise the harms
associated with an effective treatment when there are so few others
available.

Finally, the authors concluded that we need trials with analyses of patients
meeting different case definitions; we agree and this has already happened.
White and colleagues found no statistically significant differences in the
efficacy of CBT and GET in sub-groups of those patients meeting Oxford
criteria for CFS who also met either CDC defined CFS or myalgic
encephalomyelitis (ME)(5).

Note: Seven other CFS clinical scientists supported and approved this
letter.

References
1. Smith MEB, Haney E, McDonagh M, Pappas M, Daeges M, Wasson N, et al.
Treatment of myalgic encephalomyelitis/chronic fatigue syndrome: A
systematic review for a national Institutes of Health pathways to prevention
workshop. Ann Intern Med 2015; 162: 841-50.
2. Castell BD, Kazantzis N, Moss-Morris RE. Cognitive behavioral
therapy and graded exercise for chronic fatigue syndrome: A meta-analysis
Clin Psychol Sci Prac 2011; 18: 311-24.
3. Larun L, Brurberg KG, Odgaard-Jensen J, Price JR. Exercise therapy
for chronic fatigue syndrome. Cochrane Database of Systematic Reviews 2015,
Issue 2. Art. No.: CD003200.
4. Moss-Morris R, Sharon C, Tobin R, Baldi JC. A randomized controlled
graded exercise trial for chronic fatigue syndrome: outcomes and mechanisms
of change. J Health Psychol 2005; 10: 245-59.
5. White PD, Goldsmith KA, Johnson AL, Potts L, Walwyn R, DeCesare JC,
et al. Comparison of adaptive pacing therapy, cognitive behaviour therapy,
graded exercise therapy, and specialist medical care for chronic fatigue
syndrome (PACE): a randomised trial. The Lancet 2011;377:823-36.

 

[Snow Leopard]

If GET isn't supposed to increase fitness or exercise capacity, then what the hell is it supposed to do?

 

[Dolphin]

If GET isn't supposed to increase fitness or exercise capacity, then what the hell is it supposed to do?

I think the Annals paper gives an opportunity to post a comment on the rubbish results found in the PACE Trial.

 

[Graham]

If GET isn't supposed to increase fitness or exercise capacity, then what the hell is it supposed to do?

Change the grade that you give your physical activity level on the questionnaires. It isn't even very good at that.

 

[jimells]

This comment was submitted on the AHRQ treatment review.

The psychobabblers seem to be a tad defensive about their "treatments". Which rat will desert the seriously listing S.S. PsychoSomatic first???

 

[Graham]

I'm sure you will find, jimells, that none of them were ever actually on the S.S. PsychoSomatic: that any written or photographic evidence to that effect will have been taken out of context, and that they have always worked for the Cruise Ship "Further Research", which sadly was kept in dock for 35 years because of a serious lack of experienced biomedical researchers.

 

[Dolphin]

Perhaps there might be somebody who is interested in this:

The Chalder Fatigue Questionnaire is a valid and reliable measure of perceived fatigue severity in multiple sclerosis
http://forums.phoenixrising.me/inde...re-of-perceived-fatigue-severity-in-ms.38622/

Free full text at: https://kclpure.kcl.ac.uk/portal/fi...gue_CFA_final_submitted_MS_JUNE_2015_v4_.docx

 

[Dolphin]

(This was posted on a mailing list I'm on with regard to Dr Miller. The person said I could re-post it. I asked her and she said her comments related to the PACE Trial rather than the GETSET trial)

"He (DrM) reviewed all the adverse events for the PACE trial and is on the steering committee for the GETSET trial.”

What he actually did was ignore adverse events by declaring they had nothing to do with taking part in the trial/CFS – in his opinion.

I’m aware of patients made extremely ill who are still housebound / bedbound and one who was hospitalised and very nearly died. The laters GP was furious that these extreme adverse events were dismissed.

It’s easy to dismiss things if you can get an expert medical advisor to sweep things under the carpet that you don’t like to hear.

Eminence based medicine not evidenced based medicine.

 

[Scarecrow]

(This was posted on a mailing list I'm on with regard to Dr Miller. The person said I could re-post it. I asked her and she said her comments related to the PACE Trial rather than the GETSET trial)

I've been wondering about adverse events and PACE for some time and now seems like as good a time as any to ask the question.

Why were the investigators allowed to dismiss serious adverse events that were not considered to be serious adverse effects? Is it normal to do this when investigating behavioural therapies? I can't imagine it being allowed when trialling pharmaceutical therapies but perhaps someone can set me straight.

 

[Esther12]

There wasn't much evidence of harms either (compared to what we see reported in the real world, when GET is being provided without the sort of oversight seen in PACE), but I wonder if they were committed to being able to say 'no harm', rather than needing to have any discussion about potential harms.

 

[Sean]

but I wonder if they were committed to being able to say 'no harm', rather than needing to have any discussion about potential harms.

Or needing to deliver any actual meaningful objective gains.

 

[Dolphin]

(This was posted on a mailing list I'm on with regard to Dr Miller. The person said I could re-post it. I asked her and she said her comments related to the PACE Trial rather than the GETSET trial)

"He (DrM) reviewed all the adverse events for the PACE trial and is on the steering committee for the GETSET trial.”

What he actually did was ignore adverse events by declaring they had nothing to do with taking part in the trial/CFS – in his opinion.

I’m aware of patients made extremely ill who are still housebound / bedbound and one who was hospitalised and very nearly died. The laters GP was furious that these extreme adverse events were dismissed.

It’s easy to dismiss things if you can get an expert medical advisor to sweep things under the carpet that you don’t like to hear.

Eminence based medicine not evidenced based medicine.

Just a reminder of one of the issues. The Appendix of the PACE Trial paper in the Lancet listed
"Web Appendix Table C: Description of Serious Adverse Reactions"
However, it didn't mention which arm of the trial each adverse reaction took place (it could have been done by having a superscript (little letter) for example.

This does not seem very satisfactory (though isn't Dr Miller's fault).

 

[MeSci]

"Web Appendix Table Cescription of Serious Adverse Reactions"

Looks like you have a problem of an uninvited emoticon as I have had - maybe due to using something like 'c:' (see if that does it). No - maybe it was 'c:-' Nope. C-?

Well - whatever you wrote.