PACE Trial and PACE Trial Protocol

[Esther12]

Related to that, I always felt a bit unsure about this, and how much it may affect things (do not tend to give them the benefit of the doubt anymore):

Although it seemed that slightly smaller proportions had recovered from the illness as a whole, when the criterion ‘not meeting the London criteria for ME’ was applied, we found that the differences were due to missing data rather than to change in recovery status.For this reason, we made a post-hoc decision to model the more complete data set of those meeting the trial definition of recovery rather than the illness definition of recovery.

 

[worldbackwards]

Wow that DWP FOI response is just astonishing.

Quite. It's remarkable that the DWP's enormous vested interest hasn't been explored more. This is surely an example of policy based evidence in action if I ever saw one.

I suspect the fact that their 'interest' wasn't born out is unlikely to stop them using this against patients at some point, especially since Monday's speech indicates that, twelve years after PACE was funded and with a hell of a lot of water (and blood) under the bridge, they still appear to be singing from precisely the same hymn sheet.

It's amazing how little a change in government has affected the rationale at the DWP. I've always wondered how much the Whitehall machinery has influence over the policy debate and how fashionable ideas get ingrained in a department without there being the slightest evidence that they work, particularly when the lives of the vulnerable are at stake. I suspect that 'advisors' embed themselves to some degree and frame the debate in their own inimitable fashion.

 

[Sasha]

Just been looking at this and thought I would park it here:

CHRONIC FATIGUE TREATMENT TRIAL

People want to learn as much as possible from the PACE trial for chronic fatigue syndrome

Tom Kindlon assistant chairperson
Irish ME/CFS Association, PO Box 3075, Dublin 2, Republic of Ireland

One reason that the minutes are sought for the PACE (Pacing, Graded Activity, and Cognitive Behaviour Therapy—a Randomised Evaluation) trial, which looked at the effectiveness of treatments for chronic fatigue syndrome, is to find out why outcome measures were changed.1 None of the three primary outcomes were reported as in the protocol. 2 The recovery criteria in the protocol were very different from what were reported on. 2 3

Non-pharmacological therapies are less well regulated than pharmacological ones. For example, there is no equivalent to the yellow card system for adverse events seen with these therapies, so trial reporting becomes more important. Reporting of harms in trials of cognitive behavioural therapy and graded exercise therapy for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) has generally been poor. 4 Harms reporting in the PACE trial was improved but problems still remain. 4 5

Outside of trials, people with ME/CFS have reported being made more ill by such interventions, but this has largely been ignored, 4 which can make people frustrated. This was an important trial: £5m (€6m; $8m) of taxpayers’ money was invested in it, and it was meant to be the definitive trial. It’s understandable that people want to get as much information from the trial as possible.

Competing interests: TK works in a voluntary capacity for the Irish ME/CFS Association.

1 Dyer C. College was right not to disclose deliberations about chronic fatigue treatment trial, tribunal rules. BMJ 2013;347:f5355. (30 August.)

2 White PD, Sharpe MC, Chalder T, DeCesare JC, Walwyn R; PACE trial group. Protocol for the PACE trial: a randomised controlled trial of adaptive pacing, cognitive behaviour therapy, and graded exercise, as supplements to standardised specialist medical care versus standardised specialist medical care alone for patients with the chronic fatigue syndrome/myalgic encephalomyelitis or encephalopathy. BMC Neurol 2007;7:6.

3 White PD, Goldsmith K, Johnson AL, Chalder T, Sharpe M; PACE Trial Management Group. Recovery from chronic fatigue syndrome after treatments given in the PACE trial. Psychol Med 2013; published online 31 Jan.

4 Kindlon T. Reporting of harms associated with graded exercise therapy and cognitive behavioural therapy in myalgic encephalomyelitis/chronic fatigue syndrome. Bulletin of the IACFS/ME 2011;19:59-111.

5 Kindlon T. The PACE trial in chronic fatigue syndrome. Lancet 2011;377:1833. Cite this as: BMJ 2013;347:f5731

http://www.bmj.com/content/347/bmj.f5963

 

[Dolphin]

I found this on the WhatDoTheyKnow.com website for UK Freedom of Information requests:
https://www.whatdotheyknow.com/request/fitness_data_for_pace_trial

A request for the fitness data was turned down as vexatious even though they've already published the data in graph form.

One can see that CBT and GET had the lowest (i.e. worst) fitness at 52 weeks (the last measurement).

View attachment 12007

I've started a thread on this at: http://forums.phoenixrising.me/inde...-theyve-already-published-in-graph-form.38978

Graham asked for an internal review. They again refused to release the data:
http://forums.phoenixrising.me/inde...lished-in-graph-form.38978/page-3#post-634494

 

[Tom Kindlon]

One person mentioned the PACE Trial in the ME Association Survey published this year:
http://www.meassociation.org.uk/2015/05/23959/

#986:
ME moderate before course, remained moderate after course. Symptoms were the same after. Course not appropriate to needs. Part only attended. Reason given – it was not working.

“The course of CBT I was given was part of the Pace Trial. At the time I had no idea of the politics involved and was so desperate for help with CFS that I would just about have accepted any treatment.

However, it soon became apparent to me that the CBT therapist was biased and his only concern was to elicit the desired results pertinent to his research. He could not answer questions I asked him regarding the efficacy of CBT and made false claims about its efficacy (stating it had a 99% success rate in helping people with CFS/ME), he got angry and caused me immense stress whenever I took issue with anything in the pace trial folder by Chalder et al, and he would promise to discuss issues in my life that were affecting my CFS and then refuse to do so etc. etc.

Worst of all, when I told him I was leaving the trial since the CBT was not helping me, he phoned me twice to put pressure on me to stay in the trial – thus confirming that his only concern was for his research results rather than genuinely helping me with my CFS.”

 

[Dolphin]

"CBT & exercise in Chronic Fatigue Syndrome have no evidence" (Translation of Swedish pretty good)
http://forums.phoenixrising.me/inde...nce-translation-of-swedish-pretty-good.39601/

The PACE Trial is discussed among other things.

 

[Dolphin]

I just posted this on thread on the Cochrane Review http://forums.phoenixrising.me/inde...cochrane-report-says.35474/page-5#post-637809 and thought it might also be of interest to some following this thread:

For what it's worth (some might not agree with about the PACE Trial for example but they don't cover the recovery criteria which is where the biggest problem was I think it's fair to say):

Selective reporting
Two studies (Wearden 2010; White 2011) referenced published protocols, and when we checked these against the published results, we found that reporting was adequate. In one study (Wearden 1998), trial investigators reported numerical data for only one subscale (health perception) of the Medical Outcomes Survey (MOS) scale (Ware 1992), for which data favour the intervention group; no numerical data were given for the five other subscales, nor for another scale (anxiety), as data were “similar in trial completers.” It was not possible to check the other studies for selective reporting bias; therefore their risk of bias is considered unclear.

@biophile has drawn my attention to the "Criteria for judging risk of bias in the ‘Risk of bias’ assessment tool (8.5 The Cochrane Collaboration's tool for assessing risk of bias)"
http://handbook.cochrane.org/chapte...a_for_judging_risk_of_bias_in_the_risk_of.htm

I found:

SELECTIVE REPORTING

Reporting bias due to selective outcome reporting.

Criteria for a judgement of ‘Low risk’ of bias.

Any of the following:

• The study protocol is available and all of the study’s pre-specified (primary and secondary) outcomes that are of interest in the review have been reported in the pre-specified way;
  
  
• The study protocol is not available but it is clear that the published reports include all expected outcomes, including those that were pre-specified (convincing text of this nature may be uncommon).

Criteria for the judgement of ‘High risk’ of bias.

Any one of the following:

• Not all of the study’s pre-specified primary outcomes have been reported;
  
  
• One or more primary outcomes is reported using measurements, analysis methods or subsets of the data (e.g. subscales) that were not pre-specified;
  
  
• One or more reported primary outcomes were not pre-specified (unless clear justification for their reporting is provided, such as an unexpected adverse effect);
  
  
• One or more outcomes of interest in the review are reported incompletely so that they cannot be entered in a meta-analysis;
  
  
• The study report fails to include results for a key outcome that would be expected to have been reported for such a study.

Criteria for the judgement of ‘Unclear risk’ of bias.

Insufficient information to permit judgement of ‘Low risk’ or ‘High risk’. It is likely that the majority of studies will fall into this category.

The Cochrane review gave the PACE Trial, White et al. a low risk of bias grade for "Selective reporting (outcome bias)" (see Figure 2, page 15).

This doesn't seem like the right allocation given none of the 3 primary outcome measures in the PACE Trial were analysed as promised:

Primary outcome measures – Primary efficacy measures
Since we are interested in changes in both symptoms and disability we have chosen to designate both the symptoms of fatigue and physical function as primary outcomes. This is because it is possible that a specific treatment may relieve symptoms without reducing disability, or vice versa. Both these measures will be self-rated.

The 11 item Chalder Fatigue Questionnaire measures the severity of symptomatic fatigue 27], and has been the most frequently used measure of fatigue in most previous trials of these interventions. We will use the 0,0,1,1 item scores to allow a possible score of between 0 and 11. A positive outcome will be a 50% reduction in fatigue score, or a score of 3 or less, this threshold having been previously shown to indicate normal fatigue 27].

The SF-36 physical function sub-scale 29] measures physical function, and has often been used as a primary outcome measure in trials of CBT and GET. We will count a score of 75 (out of a maximum of 100) or more, or a 50% increase from baseline in SF-36 sub-scale score as a positive outcome. A score of 70 is about one standard deviation below the mean score (about 85, depending on the study) for the UK adult population 51,52].

Those participants who improve in both primary outcome measures will be regarded as overall improvers.

Also:

Adverse outcomes
Adverse outcomes (score of 5–7 of the self-rated CGI) will be monitored by examining the CGI at all follow-up assessment interviews 49]. An adverse outcome will be considered to have occurred if the physical function score of the SF-36 28] has dropped by 20 points from the previous measurement. This deterioration score has been chosen since it represents approximately one standard deviation from the mean baseline scores (between 18 and 27) from previous trials using this measure 23,25]. Furthermore, the RN will enquire regarding specific adverse events at all follow-up assessment interviews.

Data was never published on those who scored a CGI of 5. Nor do I believe was data ever published on people who dropped by 20 points from the previous measurement (they did scores of 20 or more at two consecutive measurements and also an extra paper on decreases of 8 or more).

I think it would be good if one or more people submitted comments highlighting the problem with the outcome reporting particularly for the efficacy measures.

 

[Dolphin]

Epistemically Challenged: Julie Rehmeyer
by sasusa | Sep 8, 2015

What problem of knowledge really interests you and why? How might it be solved? Epistemically Challenged puts those questions to award-winning math and science writer Julie Rehmeyer.

http://www.senseaboutscienceusa.org/epistemically-challenged-julie-rehmeyer/

Criticises the PACE Trial among other things.

Thread on this at:

http://forums.phoenixrising.me/inde...een-affected-by-my-experience-with-cfs.39786/

 

[Dolphin]

Did we know this? I know the official paper hasn't been published but I can't remember whether it was ever said at a presentation somewhere:

Support Groups.
Membership in support groups was associated with a worse outcome in the PACE trial.

From:

Fibromyalgia and chronic fatigue syndrome: management issues.
Bourke J.
Adv Psychosom Med. 2015;34:78-91. doi: 10.1159/000369087. Epub 2015 Mar 30. Review.

Some possible reasons I've heard that could partly or fully explain such a finding:
(i) Patients who are members of support groups have already learned a lot of what can be learned about management strategies so are closer to their ceiling already (I think @Graham was the first person I recall saying it).

(ii) Patients might be less concerned about feeling pressure to report they're doing well (the results are usually self-report measures).

(iii) Patients may be different on average e.g. a higher percentage with a more physical rather than psychological reason for their chronic fatigue who might then be less likely to respond to therapies like CBT and GET.

 

[Esther12]

I mentioned some of that paper you just read, parts of which were available on google books: http://forums.phoenixrising.me/inde...pace-trial-protocol.3928/page-127#post-586931

 

[Jonathan Edwards]

Did we know this? I know the official paper hasn't been published but I can't remember whether it was ever said at a presentation somewhere:



From:


Some possible reasons I've heard that could partly or fully explain such a finding:
(i) Patients who are members of support groups have already learned a lot of what can be learned about management strategies so are closer to their ceiling already (I think @Graham was the first person I recall saying it).

(ii) Patients might be less concerned about feeling pressure to report they're doing well (the results are usually self-report measures).

(iii) Patients may be different on average e.g. a higher percentage with a more physical rather than psychological reason for their chronic fatigue who might then be less likely to respond to therapies like CBT and GET.

The journal is not one of the several hundred on the UCL electronic resource, so presumably not very mainstream. It is not clear to me whether this is less good outcome in terms of absolute score or change of score during the trial. It would also be interesting to know if the effect was seen for all 4 arms.

 

[Dolphin]

The journal is not one of the several hundred on the UCL electronic resource, so presumably not very mainstream. It is not clear to me whether this is less good outcome in terms of absolute score or change of score during the trial. It would also be interesting to know if the effect was seen for all 4 arms.

I'm pretty sure there will be a full paper on predictors in the PACE Trial (one has been promised).

 

[Dolphin]

@maxwhd on Twitter drew my attention to the following:

http://www.aepc.es/psclinica_web/CV/CVChalder_en.html

8th INTERNATIONAL CONGRESS and 13th NATIONAL of CLINICAL PSYCHOLOGY
19-22 NOVEMBER 2015, GRANADA (SPAIN)

Trudie ChalderPresident of British Association for Behavioural & Cognitive Psychotherapies (BABCP)UNITED KINGDOM

English
Trudie Chalder is Professor of Cognitive Behavioural Psychotherapy at King’s College London.

She has worked as a clinician and a researcher in the area of long term conditions such as chronic fatigue syndrome and irritable bowel syndrome for about 25 years.

She develops specific cognitive behavioural models for understanding and treating these conditions and evaluates the approaches within the context of randomised controlled trials in primary and secondary care.

Her recent research involves investigating not only whether treatment works but how it works using mediational analyses.

Trudie has published approximately 200 articles. She is currently the Past President of the British Association of Behavioural and Cognitive Psychotherapy and is an Editor of the Journal of Mental Health.

CONFERENCE ABSTRACT

Chronic Fatigue Syndrome: a cognitive behavioural approach

Chronic Fatigue Syndrome (CFS) otherwise known as Myalgic Encephalomyelitis is characterised by severe physical and mental fatigue of at least six months duration and is associated with significant disability.

It is a controversial condition which has been associated with polarised debates about whether the condition is physical or psychological in nature.

In order to transcend this dualistic bio-medical approach a cognitive behavioural model is used to understand the condition, which makes a distinction between precipitating and perpetuating factors.

During treatment, a range of techniques such as a graded approach to activity and cognitive restructuring are used with the aim of improving disability and reducing symptoms.

If appropriate, once the client has broadened his/her view of health and illness, more sophisticated cognitive techniques are introduced to address perfectionism or beliefs about showing emotions publically.

There are several randomised controlled trials providing evidence for cognitive behaviour therapy or graded exercise therapy including the large PACE trial.

Recent studies suggest that fear avoidance beliefs mediate change in social adjustment and fatigue in the context of CBT and graded exercise therapy.

White, P. D., Goldsmith, K. A., Johnson, A. L., Potts, L., Walwyn, R., DeCesare, J. C., 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(9768), 823-836.

 

[Denise]

@maxwhd on Twitter drew my attention to the following:

http://www.aepc.es/psclinica_web/CV/CVChalder_en.html

Argh!

 

[Cheshire]

It is a controversial condition which has been associated with polarised debates about whether the condition is physical or psychological in nature.

In order to transcend this dualistic bio-medical approach a cognitive behavioural model is used to understand the condition, which makes a distinction between precipitating and perpetuating factors.

What a joke!!

 

[A.B.]

In order to transcend this dualistic bio-medical approach a cognitive behavioural model is used to understand the condition

That's all this branch of psychoquackery can do: endlessly create self serving hypotheses and surround them with a lot of psychobabble to give the impression that there is more than the personal belief of the therapist behind it.

 

[Snowdrop]

But even perpetuating factors rely on a physical system to do the work. It's not as if the amorphous mind continues to create pain (for example) out of thin air. The physical system must in fact continue to fire signals.

This is so disingenuous. How do you prove or disprove something that cannot be measured or even seen ie the effect of the 'mind' on the physical system.

To me this comes straight out of the 70's when people were discovering outliers or unusual people who could control their body systems.
But this is not the case for just anyone. These people spent years and virtually all their time training to be able to do this. One doesn't simply get sick and then have the capacity to do this because they are a little anxious.

How this nonsense is not called out is beyond me.

 

[Sean]

It is a controversial condition which has been associated with polarised debates about whether the condition is physical or psychological in nature.

Gee, I wonder how that situation came about?

 

[Chrisb]

Be fair, guys. CBT and GET clearly work. Some of us may be housebound but just look at the locations to which people may be transported by these therapies.

And if you wish to establish a quasi religious cult to enable your name to pass down through millennia best follow precedent. I understand that "take up your bed and walk" is a tried and tested formula.

 

[Esther12]

Not v interesting, but White wrote a chapter in 2001 titled 'Solutions to stigma: sharing knowledge with the patient' in:

http://www.amazon.com/Every-Family-Land-Understanding-discrimination/dp/185315573X

There was one page I couldn't access, but I thought I'd post the (imo) most relevant two bits. The intro, and then when he says: "At its least effective, it cannot be harmful to reduce the sense of secrecy, which sometime surrounds doctors' communications and their medical records. After all, the illness belongs to our patients, not oursleves."

...