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PACE Trial and PACE Trial Protocol

Dolphin

Senior Member
Messages
17,567
However, the limitations of CBT noted above apply equally to somatization disorders - for example, only 30% of patients with CFS experience full recovery following conventional CBT [17].

17. White PD, Goldsmith KA, Johnson AL, Potts L, Walwyn R, et al. (2011) Comparison of adaptive pacing therapy, cognitive behaviour therapy, graded exercise therapy, and specialist medical care for chronic fatigue syndrome (PACE): a randomised trial. Lancet 377: 823–836. doi: 10.1016/s0140-6736(11)60096-2.


from

Mindfulness-Based Therapies in the Treatment of Somatization Disorders: A Systematic Review and Meta-Analysis

http://www.plosone.org/article/info:doi/10.1371/journal.pone.0071834
This refers to the "within normal range" data presented in the Lancet paper, in case some don't know what is being referred to.
 

biophile

Places I'd rather be.
Messages
8,977
Thanks Dolphin, another example to add to the collection (that is at least 5 so far from medical journals):

FWIW, I posted this comment on PLoS:

http://www.plosone.org/annotation/listThread.action?root=71123

-

Cited paper on conventional CBT for CFS did not report a 30% 'full recovery' rate

Posted by biophile on 31 Aug 2013 at 06:02 GMT

In their recent paper [1], Lakhan & Schofield state that: "However, the limitations of CBT noted above apply equally to somatization disorders - for example, only 30% of patients with CFS experience full recovery following conventional CBT." Without going into whether CFS is a "somatization disorder" per se, the cited paper for this statement (White et al, 2011) [2] did not report on a full recovery, which was made clear in a subsequent authors' reply. [3]

White et al had instead reported on the proportion of participants within 'normal range' at followup, defined as ≤ 18/33 points in fatigue score (CFQ, Likert scoring) and ≥ 60/100 points in physical function (SF-36 health survey). The proportion of participants meeting this threshold at followup was 15% for SMC (specialist medical care) and 30% for SMC+CBT, which translates to a Number Needed to Treat of about 7.

A similarly inaccurate comment about full recovery was made in the Lancet editorial [4] which accompanied the CFS study in question [2], which the Press Complaints Commission in the UK later ruled was misleading and raising a breach of Clause 1 (Accuracy) of the Code, because the authors of the editorial failed make it clear that their comment reflected their personal view rather than the paper being commented on.[5]

However, it should also be noted that even the authors of the Lancet editorial in question (Knoop & Bleijenberg) have previously co-authored papers on CFS in which 60-65/100 points in physical function was not only regarded as non-recovered [6], but even reflective of "severe" problems with physical functioning.[7][8][9]

Upon closer inspection, it becomes more obvious that the thresholds used do not indicate a full recovery. It was theoretically possible for a participant to be within 'normal range' at baseline, despite the same scores meeting trial eligibility criteria for "disabling fatigue". In practice, almost no participants reported normal fatigue at baseline, but 13% of participants had reported normal physical function at baseline, despite the same scores counting as "significant disability".[10][2]

These low thresholds were seemingly derived from the questionable use of normative population data.[11][12]

References:

1. Lakhan SE, Schofield KL (2013) Mindfulness-Based Therapies in the Treatment of Somatization Disorders: A Systematic Review and Meta-Analysis. PLoS ONE 8(8): e71834. doi:10.1371/journal.pone.0071834 http://www.plosone.org/article/info:doi/10.1371/journal.pone.0071834

2. White PD, Goldsmith KA, Johnson AL, Potts L, Walwyn R, et al. (2011) Comparison of adaptive pacing therapy, cognitive behaviour therapy, graded exercise therapy, and specialist medical care for chronic fatigue syndrome (PACE): a randomised trial. Lancet 377: 823–836. doi: 10.1016/s0140-6736(11)60096-2. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3065633

3. White PD, Goldsmith KA, Johnson AL, Walwyn R, Baber HL, Chalder T, Sharpe M, [on behalf of the coauthors]. The PACE trial in chronic fatigue syndrome — Authors' reply. The Lancet, Volume 377, Issue 9780, Pages 1834 - 1835, 28 May 2011 (Published Online: 17 May 2011). doi:10.1016/S0140-6736(11)60651-X http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(11)60651-X/fulltext

4. Bleijenberg G, Knoop H. Chronic fatigue syndrome: where to PACE from here? Lancet. 2011 Mar 5;377(9768):786-8. Epub 2011 Feb 18. DOI: 10.1016/S0140-6736(11)60172-4 http://www.ncbi.nlm.nih.gov/pubmed/21334060

5. http://www.pcc.org.uk/news/index.html?article=ODQwOQ==

6. Knoop H, Bleijenberg G, Gielissen MFM, van der Meer JWM, White PD. Is a full recovery possible after cognitive behavioural therapy for chronic fatigue syndrome? Psychother Psychosom 2007; 76: 171–76. PMID 17426416.

7. van't Leven M, Zielhuis GA, van der Meer JW, Verbeek AL, Bleijenberg G. Fatigue and chronic fatigue syndrome-like complaints in the general population. Eur J Public Health. 2010 Jun;20(3):251-7. Epub 2009 Aug 18. PMID 19689970 http://eurpub.oxfordjournals.org/content/20/3/251.long

8. Heins M, Knoop H, Nijs J, Feskens R, Meeus M, Moorkens G, Bleijenberg G. Influence of symptom expectancies on stair-climbing performance in chronic fatigue syndrome: effect of study context. Int J Behav Med. 2013 Jun;20(2):213-8. doi: 10.1007/s12529-012-9253-2. http://www.ncbi.nlm.nih.gov/pubmed/22865100

9. Tummers M, Knoop H, van Dam A, Bleijenberg G. Implementing a minimal intervention for chronic fatigue syndrome in a mental health centre: a randomized controlled trial. Psychol Med. 2012 Oct;42(10):2205-15. doi: 10.1017/S0033291712000232. Epub 2012 Feb 21. http://www.ncbi.nlm.nih.gov/pubmed/22354999

10. Queen Mary, University of London. FOI Request: 2013/F42. https://listserv.nodak.edu/cgi-bin/wa.exe?A2=ind1303c&L=co-cure&F=&S=&P=6559

11. Feehan SM; Liverpool ME Support Group. The PACE trial in chronic fatigue syndrome. Lancet. 2011 May 28;377(9780):1831-2. Epub 2011 May 16. doi: 10.1016/S0140-6736(11)60688-0 http://www.ncbi.nlm.nih.gov/pubmed/21592556

12. Kewley AJ. The PACE trial in chronic fatigue syndrome. Lancet. 2011 May 28;377(9780):1832. Epub 2011 May 16. doi:10.1016/S0140-6736(11)60681-8 http://www.ncbi.nlm.nih.gov/pubmed/21592552
 

Dolphin

Senior Member
Messages
17,567
For what it's worth (see from the 3rd sentence on):


5. Conclusion

In summary, these findings provide initial support for the notion that CFS patients having more confidence in their stress management skills may show less emotional distress and fatigue and that these associations are most pronounced in a subgroup of CFS patients presenting with indicators of neuroimmune dysfunction. This raises the possibility that teaching stress management skills to individuals with CFS may help them to reduce emotional distress, and reduce fatigue. While cognitive-behavioral therapy (CBT) interventions have long been used in the treatment of CFS and have been seen to reduce fatigue, they have generally been aimed at modifying illness beliefs in order to increase levels of physical activity among participants. However, a recent meta-analysis by Wibourg and colleagues (2010) demonstrated that physical activity does not mediate the effect of cognitive-behavioral therapy (CBT) on reductions in fatigue in CFS patients. Moreover, recent critiques of graded exercise interventions for CFS patients (White et al., 2011) have noted that using overly inclusive diagnostic criteria for CFS studies has created confusion in the literature concerning the efficacy of physical activity-based interventions for symptom management (Lancet, 2011). This lack of physical activity mediation found in Wibourg’s meta-analysis, and the ongoing controversy concerning diagnostic criteria in the CFS literature, together with the results from the present study, suggest that emotional distress reduction, rather than modification of beliefs surrounding physical activity, may mediate the relationship between CBT and fatigue reductions in certain subgroups of CFS patients.

[Aside: It should be Wiborg not Wibourg]


From
Stress management skills, neuroimmune processes and fatigue levels in persons with chronic fatigue syndrome.

Lattie EG, Antoni MH, Fletcher MA, Penedo F, Czaja S, Lopez C, Perdomo D, Sala A, Nair S, Fu SH, Klimas N.


Brain Behav Immun. 2012 Aug;26(6):849-58. doi: 10.1016/j.bbi.2012.02.008. Epub 2012 Mar 6.
 

Bob

Senior Member
Messages
16,455
Location
England (south coast)
Stress management skills, neuroimmune processes and fatigue levels in persons with chronic fatigue syndrome.
Lattie EG, Antoni MH, Fletcher MA, Penedo F, Czaja S, Lopez C, Perdomo D, Sala A, Nair S, Fu SH, Klimas N.
Brain Behav Immun. 2012 Aug;26(6):849-58.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3572196/#R94

Moreover, recent critiques of graded exercise interventions for CFS patients (White et al., 2011) have noted that using overly inclusive diagnostic criteria for CFS studies has created confusion in the literature concerning the efficacy of physical activity-based interventions for symptom management (Lancet, 2011).

I've just looked at the first reference in this quote (White et al. 2011), and it's for the PACE trial.
The details for the second reference (Lancet, 2011) are as follows:
Lancet. Patients’ power and PACE. The Lancet. 2011;377:1808.
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(11)60696-X/fulltext

It's the ridiculous Lancet editorial that attacks detractors of the PACE trial.
The editorial certainly does not critique the use of an overly inclusive diagnostic criteria for CFS studies.
The most it says (discussing the correspondence in response to the PACE trial) is "Many of the letters critique the definitions of secondary outcomes, question protocol changes, and express concern over generalisability."
So perhaps the Lattie et al. paper is making a reference to the public letters published in response to the PACE trial.
The letters are all listed together with the Lancet editorial as 'linked articles', on the right-hand side of the editorial webpage.

It's a shame that Lattie et al. didn't give references to the specific letters that they are referring to.
 

Bob

Senior Member
Messages
16,455
Location
England (south coast)
Just for interest...
Re the Wiborg 2010 study cited in the Lattie 2012 paper...

The Wiborg study was a re-analysis of three randomised controlled trials previously conducted to evaluate the efficacy of CBT for CFS. In all the samples re-analysed, actigraphy was used in the trials to assess the level of physical activity prior and subsequent to treatment or a control group.

The Wiborg abstract says:

"Results: Although CBT effectively reduced fatigue, it did not change the level of physical activity. Furthermore, changes in physical activity were not related to changes in fatigue. Across the samples, the mean mediation effect of physical activity averaged about 1% of the total treatment effect. This effect did not yield significance in any of the samples."


How does cognitive behaviour therapy reduce fatigue in patients with chronic fatigue syndrome? The role of physical activity.
Wiborg JF, Knoop H, Stulemeijer M, Prins JB, Bleijenberg G.
August 2010
Psychol Med. 2010 Aug;40(8):1281-7.
doi: 10.1017/S0033291709992212.
http://www.ncbi.nlm.nih.gov/pubmed/20047707
 

Tom Kindlon

Senior Member
Messages
1,734
I've just looked at the first reference in this quote (White et al. 2011), and it's for the PACE trial.
The details for the second reference (Lancet, 2011) are as follows:
Lancet. Patients’ power and PACE. The Lancet. 2011;377:1808.
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(11)60696-X/fulltext

It's the ridiculous Lancet editorial that attacks detractors of the PACE trial.
The editorial certainly does not critique the use of an overly inclusive diagnostic criteria for CFS studies.
The most it says is "Many of the letters critique the definitions of secondary outcomes, question protocol changes, and express concern over generalisability."
So perhaps the Lattie et al. paper is making a reference to the public letters published in response to the PACE trial..
Yes, you could be right.

The letters are all listed together with the Lancet editorial as 'linked articles', on the right-hand side of the editorial webpage. (Including a letter by someone called Tom Kindlon
Never heard of him. ;)


Just for interest...
Re the Wiborg 2010 study cited in the Lattie 2012 paper...

The Wiborg study was a re-analysis of three randomised controlled trials previously conducted to evaluate the efficacy of CBT for CFS. In all the samples re-analysed, actigraphy was used in the trials to assess the level of physical activity prior and subsequent to treatment or a control group.

The Wiborg abstract says:

"Results: Although CBT effectively reduced fatigue, it did not change the level of physical activity. Furthermore, changes in physical activity were not related to changes in fatigue. Across the samples, the mean mediation effect of physical activity averaged about 1% of the total treatment effect. This effect did not yield significance in any of the samples."


How does cognitive behaviour therapy reduce fatigue in patients with chronic fatigue syndrome? The role of physical activity.
Wiborg JF, Knoop H, Stulemeijer M, Prins JB, Bleijenberg G.
August 2010
Psychol Med. 2010 Aug;40(8):1281-7.
doi: 10.1017/S0033291709992212.
http://www.ncbi.nlm.nih.gov/pubmed/20047707
FWIW, Wiborg et al. was referenced in two of the Lancet letters:
Andrew Kewley:
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(11)60681-8/fulltext
and my one:
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(11)60684-3/fulltext
 

ukxmrv

Senior Member
Messages
4,413
Location
London
The press conference is important as some of the reporters went on to write newspaper or TV reports on PACE. At the press conference they were given the spin on the results and also given printed material to use in their work.
 

Dolphin

Senior Member
Messages
17,567
Finally, and most importantly, clinicians and patients should complain to trialists and publishers if trials are published with inadequate descriptions of their interventions. Clinicians and patients are the last line of defence against poor reporting.


From:
Descriptions of non-pharmacological interventions in clinical trials.BMJ. 2013 Sep 11;347:f5212. doi: 10.1136/bmj.f5212.

Cook A, Douet L, Boutron I.
Source

Wessex Institute, University of Southampton, Southampton SO16 7NS, UK.
----
This is a recognition of the potential value of patients' input.

[With the issue of descriptions of non-pharmacological interventions, the PACE Trial is probably better than most, with the release of the manuals; but the point I think would also apply to other times patients give input.]
 
Messages
13,774
I couldn't access that page, or find any Dr larun by google. Any chance we'll get the protocol defined outcomes from this?
 
Messages
13,774
Oops. Found her with a new Google search.

'Identity and coping experiences' abstract from her didn't look terrible considering the nature of that sort of work. Some hope?

Just found one of her papers on exercise therapy, arguing that while the evidence for efficacy was not currently great, the "empirically based hypotheses about disease mechanisms" it was likely that future studies would show GET to be a good 'un.
 

Dolphin

Senior Member
Messages
17,567
I couldn't access that page, or find any Dr larun by google. Any chance we'll get the protocol defined outcomes from this?

Dr. Larun wrote these three PubMed-listed pieces:
http://www.ncbi.nlm.nih.gov/pubmed/?term=larun+chronic+fatigue+syndrome
As I recall, she is a physiotherapist (=physical therapist) by training.

My impression is she is more into GET/exercise than I'd like - sample quote:

While the avoidance of exercise maybe caused by beliefs that exercise is damaging or could exacerbate illness [17], appropriate physical activity may help breaking the vicious circle maintaining symptoms of sustained arousal and adjust stimulus and expectation responses in CFS patients [26].


This contradicts the arguments from patient organisations that physical activity is contraproductive for this patient group [12,13].

[12] Shepherd C. Pacing and exercise in chornic fatigue syndrome. Physiotherapy 2001;87:395–6.

[13] Bjorkum T, Wang CE, Waterloo K. Pasienterfaringer med ulike tiltak ved kronisk utmattelsessyndrom.[Patients’ experience with treatment of chronic fatigue syndrome].Tidsskr Nor Laegeforen 2009;129:1214–6.
 

Dolphin

Senior Member
Messages
17,567
Somebody just posted this on another forum. I don't think they post here so thought I'd post it:

PD White took 9 months off to "complete" PACE Trial


http://www.linkedin.com/pub/norman-poole/50/906/101

Norman Poole

Consultant Psychiatrist at Royal London Hospital

London, Greater London, United Kingdom Mental Health Care

Current

East London NHS Foundation Trust,
Institute of Psychiatry

Previous

East London NHS Foundation Trust,
Frenchay Hosipital

Education

Kings College London

Locum Consultant in Liaison Psychiatry

East London NHS Foundation Trust





February 2010 – October 2010 (9 months) St Bartholomew's Hospital

Locum Consultant cover for Professor Peter White at St Bartholomew's Hospital, London while he completed the PACE trial in Chronic Fatigue Syndrome
 

Dolphin

Senior Member
Messages
17,567
Not sure I ever read this before. And don't think it was ever highlighted:
http://www.healthcentral.com/chronic-pain/c/5949/137621/background
PACE Trial Results Misleading: Part I – Background

By Karen Lee Richards, Health Guide Saturday, April 30, 2011
She seems to be summarising the big document "Magical Medicine" by Malcolm Hooper that was written before the results were out. I have only read a small part of Magical Medicine.

This piece by Karen is quite cynical of individuals and bodies, probably over cynical for my liking. However, perhaps for some people who are not sceptical of all, it might have a value.
 

Dolphin

Senior Member
Messages
17,567
Not sure I ever read this before. And don't think it was ever highlighted:

http://www.healthcentral.com/chronic-pain/c/5949/137621/background
PACE Trial Results Misleading: Part I – Background

By Karen Lee Richards, Health Guide Saturday, April 30, 2011

She seems to be summarising the big document "Magical Medicine" by Malcolm Hooper that was written before the results were out. I have only read a small part of Magical Medicine.

This piece by Karen is quite cynical of individuals and bodies, probably over cynical for my liking. However, perhaps for some people who are not sceptical of all, it might have a value.
I read read part 2:

PACE Trial Results Misleading: Part II – Flaws in the Study

Karen Lee Richards


By Karen Lee Richards, Health Guide Saturday, April 30, 2011
http://www.healthcentral.com/chronic-pain/c/5949/137641/misleading-ii/
I preferred this to part 1. It dealt more with issues rather that speculating about motivation and the like.

For the old hands here, nothing new I think. But perhaps it might be a useful summary of some critiques of the trial for somebody new.
 

aimossy

Senior Member
Messages
1,106
I was trained in cbt and pacing as an occupational therapist. I do not read anything about it as a matter of my own principle because this being advocated as a cure really makes me sooo MAD!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!
I use cbt and pacing in order to help myself cope with being this sick yes. but I stress the word HELP. has it improved my illness or physical and mental fatigue or any of the weird crap that happens to me and is affecting my activities of daily living NO NO NO. it just helps me to adjust my thinking to feel less stressed about it happening,oh for gods sake. cbt and pacing are a constant thing,its something you are always working on in our cases.
im so glad people are pulling it to threads because I get to spiting level about it and so mad its advocated as a fix for me/cfs in this way! I can barely cope with thinking about it.
some people find mindfulness better or just going to or being involved with a support group.if this is off thread or topic I apologise I had a maddening need to vent.