PACE trial TSC and TMG minutes released

[JohnTheJack]

Who cares?

They used the most non-specific criteria possible (Oxford) and still had zero change on the step test and trivial changes on the 6 minute walking distance test (albeit which wasn't conducted in a high quality manner - has been criticised that making people walk up and down a short corridor is a poor choice for this test). The changes on the self-report questionnaires were minimal, basically the smallest difference they could possibly report as statistically significant and such small changes could easily be influenced by other biases, such as difference in encouragement between groups etc. leading to a difference in questionnaire results.

Yes, I think that's important. They essentially did everything they could to get a positive result and even with everything rigged in their favour, they didn't find anything more than a small, subjective, temporary effect which can be explained by other factors.

 

[JohnTheJack]

I've put together a PDF with all the Actigraphy mentions in the minutes.

Thanks.

 

[Esther12]

I've put together a PDF with all the Actigraphy mentions in the minutes.

Thanks Lucibee. It's also odd how in this they were talking about the rush to get baseline actimeter data ready for publication... nearly a decade later and it has still not been published.

 

[Daisybell]

So essentially PACE was a trial of how to stop those pesky patients from complaining?
Obviously actual activity didn’t need to be measured - because the patients could be active if they wanted...
This seems to prove that GET is just physical CBT in their minds.
Fatigue is only subjective and behaviour change as a result is just maladaptive.....
So no need to waste time on objective measures - especially if they are going to muddy the waters by not backing up the subjective improvements gained by trying to brainwash participants into behaving ‘properly’ again.

 

[Adrian]

Thanks Lucibee. It's also odd how in this they were talking about the rush to get baseline actimeter data ready for publication... nearly a decade later and it has still not been published.

I get the impression that the necessary analytics was too complex for them.

 

[Barry]

paid GP to get these patients

Is that true?

 

[Invisible Woman]

I get the impression that the necessary analytics was too complex for them.

Hmmmm... or was it?

 

[Adrian]

Hmmmm... or was it?

Given it was just baseline data I suspect it was. But it could be it exposed something uncomfortable for them.

 

[Barry]

So essentially PACE was a trial of how to stop those pesky patients from complaining?
Obviously actual activity didn’t need to be measured - because the patients could be active if they wanted...
This seems to prove that GET is just physical CBT in their minds.
Fatigue is only subjective and behaviour change as a result is just maladaptive.....
So no need to waste time on objective measures - especially if they are going to muddy the waters by not backing up the subjective improvements gained by trying to brainwash participants into behaving ‘properly’ again.

It's really amazing (except nothing amazes me with this lot now) how their very own extreme expectation bias, fed through into everything else they touched, right from the outset.

 

[Sbag]

From Magical Medicine again:

Initially, the Trial Investigators planned to use objective measures of physical ability at the conclusion of the Trial (the cost of the Actiwatch sensors was included in the funding application), but Peter White decided that any actigraphy measurements should not be taken at the end of the Trial. As Tom Kindlon from Ireland points out, this is notable, since Professor White is aware that self‐reported (ie. subjective) improvements may not match real (ie. objective) improvements and equally that there are discrepancies between subjective and objective measures of activity (http://www.biomedcentral.com/1471‐2377/7/6/comments#333618).

Not to use objective measures of improvement (such as actigraphy; physiological measurements; return to employment) is deemed by many to be scientifically inexcusable in an MRC trial that specifically sets out to assess the efficacy of the interventions employed in the trial.

Then:

Participants are told that they will be lent a heart rate monitor so that they can measure how hard they are working during their exercises and are instructed on how to use it (it is to be strapped under the shirt and it transmits a signal to a receiver on a strap like a watch strap).

This makes all the more incomprehensible Professor Peter White’s decision to abandon the use of actigraphy monitors that are strapped round an ankle and which provide an objective measure of improvement (or otherwise); compared with using a heart rate monitor and the need to keep daily activity diaries, RPE scores, goal sheets, exercise diaries, GET plans, progress sheets and other records, the wearing of an
actigraphy monitor for a week at the end of the PACE Trial would not be at all onerous.

:

(10) The Investigators originally intended to obtain a non‐invasive objective measure of outcome using post‐treatment actigraphy but abandoned this on the grounds that wearing such a monitor would be too great a burden at the end of the trial (http://www.biomedcentral.com/1471‐2377/7/6/comments). Therefore, after
spending millions of pounds of public money and involving hundreds of people in an intensive regime, they completely fail to obtain objective measurements that would reveal whether or not the interventions are successful.

:

Furthermore, a study on (ME)CFS patients in the US by Friedberg et al that used CBT and which also encouraged activity found on actigraphy measurements that there was in fact a numerical decrease from the pre‐treatment baseline (Cognitive‐behaviour therapy in chronic fatigue syndrome: is improvement related to increased physical activity? J Clin Psychol 2009, Feburary 1).

 

[Daisymay]

Is that true?

http://www.margaretwilliams.me/2010/magical-medicine_hooper_feb2010.pdf

p58

"That FM patients were to be included in the PACE Trial was further confirmed on 12th May 2004 by Parliamentary Under Secretary of State at the Department of Health, Dr Stephen Ladyman, at an All Party Parliamentary Group on Fibromyalgia, who announced that doctors were being offered financial inducements to persuade patients with FM to attend a “CFS” Clinic to aid recruitment to the PACE Trial (EIF: Spring/Summer 2004, page 19).

This caused written representations to be made to the MRC, because FM is classified as a distinct entity in ICD‐10 at section M79.0 under Soft Tissue Disorders and it is not permitted for the same condition to be classified to more than one rubric, so concern was expressed as to how the intentional inclusion of disparate disorders could yield meaningful results, especially as FM was expressly excluded from the Systematic Review of the literature on CBT/GET carried out by the Centre for Reviews and Dissemination at York, whose authors were categoric: “Studies including patients with fibromyalgia were not selected for review” (JAMA 2001:286:11:1360‐1368)."

 

[Esther12]

I thought I'd post some slightly OT notes I have relating to PACE dropping actometers:

Discussion on the need for more objective outcomes (following on from the previous meeting where they also discussed the impossibility of blinding) - from PACE Trial Joint meeting of the Trial Steering Committee and Data Monitoring and Ethics Committee

2pm to 5pm, Monday 27th September. 2004

ACTION 8: Professor White to re-write section 8 as per TSC recommendation.

m) Professor White led discussion on the outcomes, and the TMGs struggle to find an objective outcome measure as requested by the TSC at their last meeting, particularly as CFS/ME is a subjective condition. It is proposed that the protocol does not alter from the three primary objectives already set.

How PACE explained using actometers at baseline only, after the failure to use them as an outcome measure led to critical comments on the trial's protocol in 2007: https://bmcneurol.biomedcentral.com/articles/10.1186/1471-2377-7-6/comments

"Objective outcome measures

We have used several objective outcome measures; the six minute walking test [1], a test of physical fitness [2], as well as occupational and health economic outcomes [3]. Although we originally planned to use actigraphy as an outcome measure, as well as a baseline measure, we decided that a test that required participants to wear an actometer around their ankle for a week was too great a burden at the end of the trial. We will however test baseline actigraphy as a moderator of outcome. No biological measures were sufficiently well established to justify their use as outcomes in the trial."

This is how PACE justified dropping actimeters after this attracted criticism, from FAQ 2 (appx 2011?2012?): https://www.qmul.ac.uk/wolfson/media/wolfson/current-projects/faq2.pdf

25. Why did you omit actigraphy as an outcome measure?

Actigraphy is a measure of physical activity, measured by a wrist
watch sized accelerometer, worn around the ankle continuously for a
week. Before we started the trial, we were advised that the number
and scope of the outcome measures were too great and that it might
reduce the proportion of participants making it through to the end of
the trial. Actigraphy was the obvious measure to reject because of its
burden in time and effort required by participants. The patient charity
advising us agreed that this would be sensible

No mention in the above of their decision having been based on news of results from Wiborg/Bleijenberg showing CBT failed to lead to an improvement in objectively measured activity levels: https://www.ncbi.nlm.nih.gov/pubmed/20047707?dopt=Abstract

Now we have these new excerpts from their TSC minutes from 2005:

They were circulating these null results before deciding what to do... and they have completely failed to admit publicly to the role this played in their decision making.

I'm sure that they've also been called out on the dropping of actometers in letters to journals, and that they've responded their too, but I cannot remember exactly which one.

PS Bonus from FAQ3!:

Q: Most of the measures used were self - rep ort ed (participants ’ response to questionnaires). Are these as relevant as objective measures such as the walking test? A: Yes they are. In fact they are arguably more important as they are measures of the ultimate aims of treatment; for patients to feel better while getting on with their lives.

https://www.qmul.ac.uk/wolfson/media/wolfson/current-projects/faq3.pdf

And from Knoop on objectively measured activity:

"Recovery of CFS was possible, even if the physical activity level of the patient remained low."

From p 104 here: https://www.academia.edu/3382407/Is...avioural_therapy_for_chronic_fatigue_syndrome

 

[Woolie]

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Good Grief! They hardly needed to do the trial, being as they were so confident of what outcome measures they could safely gloss over!

"but not useful for outcome" ... not useful to who, we might wonder.

Wow, they admitted they left out actigraphy because they knew that GET doesn't genuinely increase activity.

Most here suspected this was the reason. But there it is, in black and white.

 

[Woolie]

Also - it's a bit odd to suggest that actometers aren't suitable outcome measures because patients' activity is already so high at baseline, when CBT and GET both aim to improve activity levels.

Yes, and the whole behavioural-deconditioning model kind makes explicit the deconditioning thing.

 

[Trish]

It looks like deliberate deception to me.

1. Agree privately it's not a good outcome measure because the Dutch studies showed it didn't show improvement and that's not the outcome wanted from the trial.
2. Then tell everyone publicly the reason it's not being used as an outcome measure is because it's too much of a burden for patients.

 

[Jonathan Edwards]

I thought I'd post some slightly OT notes I have relating to PACE dropping actometers:

Thanks @Esther12, I have logged it in my notebook too.

 

[Jonathan Edwards]

Of course way back in 1989 Wessely pointed out that ME muscles are not actually low on function, in the same paragraph that he warned about the dangers of getting low muscle function in ME.

But if people put on red noses and baggy pants that is only circumstantial evidence. If they actually push custard pies in each others' faces you have objective outcome measures.

 

[Sean]

Wow, they admitted they left out actigraphy because they knew it GET doesn't genuinely increase activity.

Most here suspected this was the reason. But there it is, in black and white.

Looks that way, doesn't it.

 

[Sly Saint]

too much of a burden for patients.

Didn't White use a similar excuse for not doing tilt-table testing? (not for PACE).

 

[Adrian]

Of course way back in 1989 Wessely pointed out that ME muscles are not actually low on function, in the same paragraph that he warned about the dangers of getting low muscle function in ME.

But if people put on red noses and baggy pants that is only circumstantial evidence. If they actually push custard pies in each others' faces you have objective outcome measures.

I seem to remember that Wessely was claiming that one small study on one aspect of muscle function meant that there couldn't possibly be anything wrong with muscle function.