PACE trial TSC and TMG minutes released

Trish said:
I think it's a shocking admission that they based their decision not to use actigraphy as an outcome measure on it not showing improvement in the Dutch study.
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I'd call it a smoking gun, unless otherwise proven.

Barry said:
Also for PwME, any supposedly-objective measures have to adequately account for cumulative energy drain effects. At least one PACE participant reported that in order to do the 6mwt they effectively "saved up" their energy in order to do it, and did less afterwards. So if their overall energy expenditure had been measured over one or more days, the result would probably have been significantly different.
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Which is precisely why compliance measures such as actigraphy are needed.

Without them the results are ambiguous.
 
Don't recall anything in the protocol at all about actigraphy. They had decided very early on to dump it as an outcome measure, possibly after early behind-the-scenes knowledge of the actigraphy results from the 3 studies eventually collated and reported by Wiborg.
 
Snow Leopard said:
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.
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But if some of that "smallest difference they could possibly report as statistically significant" was due to these patients they are still affecting the trial outcome. And the fact they included people with a different illness and palmed them off as ME, and paid GP to get these patients is important to show.
 
Sean said:
Don't recall anything in the protocol at all about actigraphy. They had decided very early on to dump it as an outcome measure, possibly after early behind-the-scenes knowledge of the actigraphy results from the 3 studies eventually collated and reported by Wiborg.
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In Feb 2007 they are still discussing the actigraphy analysis strategy. At this point, the protocol had already been submitted for publication.
 
Trish said:
I think it's a shocking admission that they based their decision not to use actigraphy as an outcome measure on it not showing improvement in the Dutch study.

It makes their approach to 'science' crystal clear - only use the outcome measures that show what we want them to show to 'prove' what we want to prove, not what is best for patients or good science.
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I wouldn't be surprised if they didn't even understand the enormity of this decision. For them the subjective reports are the proof they are right and the incongruity of actigraphy results are just seen as an anomaly, that they (more or less consciously) do not want to explore, to avoid facing a crude truth.

The more I read on this thread, the more shocked I am. With the number of flaws yet uncovered, I wouldn't have thought there was still so much to discover.

ETA: thanks to everyone who has dug into this.
 
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My hairs went up on reading the actigraphy stuff. Not only were they aware of the null results for actigraphy when they dropped it as a PACE outcome, but they were explicitly citing this data as part of their reason for dropping it. Wow.

I think it's important to avoid being too critical about some of the smaller things turning up in these minutes, but this seems like a big find to me.

Lucibee said:
More on actigraphy... (TMG #12)
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They really don't know what they're doing, do they.

Update: At subsequent meeting (TMG #14) they are considering reintroducing actigraphy at 52 weeks - but no decision yet...
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Lucibee said:
I found this on Actigraphy in TMG #11... View attachment 2407
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Maybe now would be a good time to draw attention to some old @Tom Kindlon comments on the PACE trial protocol? He got in there with pre-specified criticisms!: https://bmcneurol.biomedcentral.com/articles/10.1186/1471-2377-7-6/comments

Specifically:

Would it not be preferable if objective outcome measures were used?
23 May 2007

Another example as to why objective measures would be useful
30 August 2007

CFS intervention studies - lessons can be learned from a previous review
30 August 2007

If CBT for CFS is "to help patients improve activity levels and quality of life", would not actometers be useful for measuring outcomes?
13 November 2007

The relevant part of White's response:

Response to comments on “Protocol for the PACE trial”
28 July 2008

...

"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."

Then more from Kindlon:

The dropping of actometers as an outcome measure and other points relating to the outcome measures being used
22 October 2008

Further evidence showing why objective measures are preferable in CFS trials particularly where cognitions could be changed following the intervention
6 March 2009

Discrepancies between momentary fatigue and recalled fatigue can exist
1 July 2009

New paper lists 3 CFS studies where there was no improvement in the actometer readings but an improvement was reported in subjective outcome measures
12 May 2010
 
Can you imagine any other scientific study including patients with a different disease? Study MS and throw in some RA patients, study cancer and throw in some with dibetes to make the numbers up? This is horrifying and was not even declared. It really shows the utter contempt with which they hold pwme.

They refuse to even attempt to understand the disease, I suppose they think it doesn't matter as pwme and pwfm are all the same as both 'conditions' are all in the mind. But rather telling they didn't state the trial was studying both conditions.

Actigraphy won't indicate improvement, so we'd better drop that! My jaw is aching is has dropped so many times hearing all this.
 
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.

Chalder and Wessely have said:

"At the heart of CBT is a behavioural approach to the impairment of activity that is part of the definition of CFS."
http://www.amjmed.com/article/S0002-9343(99)80332-5/pdf
 
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Esther12 said:
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.
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Presumably just too much on top of all those marathons they were now running.
Not quite what it says in the minutes.
 
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.
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An instrument deliberately designed to be as unobtrusive as possible, weighing less than 50g (1.75oz), is claimed to be too much of a burden.

Just to put that in perspective, my short sleeved summer shirt comes in at 272g (9.5oz), more than 5 times the weight of the actometer.

Too much of a burden, my arse. :mad:

Add in

1. their explicit acknowledgement of the null results on previous studies using actometers, so they knew activity levels were not increasing (for CBT at least),

2. the statement from Wessely and Chalder that increase in activity levels "must ultimately be the aim of any treatment", and

3. the quote from Esther12 above,

and the case for scientific fraud is looking strong.

No wonder they didn't want these minutes to be released.
 
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Thanks for unearthing this actigraphy stuff @Lucibee.

A smoking gun indeed, @Sean.

I'm alarmed by their use of the word "useful". This hints at motivation. What was the purpose of the trial? To test whether CBT/GET are effective or to try to prove that they are? To suggest that an objective measure of activity which is likely to yield a null result is not "useful" is a shocking admission.

Rough translation of minutes on actigraphy:

Actigraphy is to be used at baseline as it's a good way of assessing how unwell someone is.
Actigraphy is not to be used as an outcome measure as it is a good way of assessing how unwell someone is (and this is not something we are interested in, unless it supports our hypothesis).

Barry said:
Feels to me it's not just the disease they don't understand, but the scientific process itself. Not claiming I do, but these folks really really should.
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Hard to know whether it is incompetence or a deliberate attempt to design a trial that will produce the result they want. Probably both.


This is starting to feel quite exciting. I’m getting a sense of how Bernstein and Woodward must have felt.
 
Cheshire said:
I wouldn't be surprised if they don't even understand the enormity of this decision.
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I think you're right.

This just gets weirder and weirder. The quote (linked below) shows that they actually knew that they would not be improving physical activity levels, only perceptions of fatigue, but apparently that didn't matter.

View attachment 2410
 
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So in 2005 they said they would discuss and decide later whether to do actigraphy at 12 month follow up as an outcome measure.

Trial Management Group Meeting # 14 - Thursday 28th April 2005 Page 3 8.

Actigraphy TMG12, A8: XX to ensure actigraphy at 52 weeks is added on to a future agenda.

The issue of using actigraphy as an outcome measure was raised. It was noted that the Dutch study by Bleijenberg and colleagues reported that actigraphy was not a good outcome measure since the majority of patients are reasonably active and there is no change in this in spite of improvement in fatigue. However, pervasively passive people at baseline may do worse on CBT and perhaps better on GET.

A final decision on using this as an outcome has been postponed until we see how much of a measurement load actigraphy is, and it was agreed that this may be changed later if desired. ACTION 5: XX to add actigraphy at 52 weeks to the September TMG agenda for discussion.
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As far as I can see the only discussion of Actigraphy included in @Lucibee's summary after that is whether they needed to buy more equipment, and how to analyse the data. No further mention of any discussion, let alone decision with reasons, on whether to use actigraphy as an outcome measure.

What are we missing here?

All we've been told is the totally crap excuse that it was considered too burdensome for patients.
 
Lucibee said:
More on actigraphy... (TMG #12)
View attachment 2408
They really don't know what they're doing, do they.

Update: At subsequent meeting (TMG #14) they are considering reintroducing actigraphy at 52 weeks - but no decision yet...
Click to expand...

Thanks for those replies Lucy.

This was their reason given in 'Response to comments on "Protocol for the PACE trial"' 28/07/2008.

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.
 
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