PACE Trial and the criteria for M.E. used

[Dolphin]

I know that people like Angela Kennedy have been complaining about the use of the London criteria in the PACE Trial for many years so I don't claim I am saying anything novel; however, I just thought I'd post my thoughts/observations for what they are worth.
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PACE Trial - 97% of the participants who didn't have a psychiatric disorder satisfied the definition of M.E. used

In the Lancet paper on the PACE Trial (by White et al (2011)), it said:
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"Participants were also assessed by international criteria for chronic fatigue syndrome,12 requiring four or more accompanying symptoms, and the London criteria13 for myalgic encephalomyelitis (version 2), requiring postexertional fatigue, poor memory and concentration, symptoms that fluctuate, and no primary depressive or anxiety disorder (interpreted as an absence of any such disorder)."

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I was not 100% sure what "no primary depressive or anxiety disorder (interpreted as an absence of any such disorder)" meant in relation to the percentage we were given for "any psychiatric disorder" i.e. could there be an overlap.

The following is an extract of a letter that clarifies it (see underlined bit in bold) - the letter was written by PD White, KA Goldsmith, AL Johnson, R Walwyn, HL Baber, T Chalder, M Sharpe, on behalf of all the co-authors (of the PACE Trial)

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The trial did not study ME/CFS (pages 12-18)

The selection of patients was for CFS operationalised using the broadest criteria (the Oxford criteria). No sensible neurologist would apply the diagnosis of CFS (or indeed ME) to patients who had "proven organic brain disease", such as Parkinson's disease. For the purposes of this trial ME was not regarded as a "proven organic brain disease". In order to ensure balance between the trial arms in those participants who met alternative criteria for CFS and ME, randomisation was stratified by the International (Centers for Disease Control) criteria (which require additional symptoms) and by the London ME criteria (based on Melvin Ramsay's original description, and which excludes co-existing "primary" psychiatric disorders [which we interpreted as any psychiatric disorder] and emphasises post-exertional fatigue). We were provided with the second revised version of the London ME criteria; we did not invent our own. We considered use of the Canadian criteria for ME but we found it impossible to operationalise them adequately for research purposes; to our knowledge they have not been used in a major research trial. We studied the results for differently defined subgroups and they were similar to those in the entire group.

(source: http://www.meactionuk.org.uk/whitereply.htm )

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The figures from the paper (Table 1) show that, of the 640 participants, 300
(46.9%) had "any psychiatric disorder" and 51.4% (329) satisfied the London criteria*.

This means that of the 340 patients in the trial (i.e. who satisfied the Oxford criteria**, with a principal symptom of fatigue, who did not have a psychiatric disorder), 329 (96.8%) satisfied the London criteria for M.E., the definition of M.E. used in the trial!

This is an amazingly high figure for a definition of M.E. given the "looseness" of the Oxford criteria e.g. unlike the Fukuda CFS criteria or Carruthers ME/CFS criteria, it doesn't require other symptoms apart from fatigue.

It seems to me the definition for M.E., at least as it was used in this trial, is very suspect. And hence it is questionable what can read into how people with M.E. responded in the trial.

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*One can how the London Criteria were used here:

**
One can how the Oxford Criteria were used here:

Annex 1:
We already cannot be sure if the participants are representative of patients in the community based on who refused to take part, were excluded, etc.

 

[wdb]

It seem a bit sneaky that they state

London criteria13 for myalgic encephalomyelitis (version 2), requiring postexertional fatigue, poor memory and concentration, symptoms that fluctuate, and no primary depressive or anxiety disorder (interpreted as an absence of any such disorder)."

But then if you look at the London ME criteria the instructions are that only criteria 1 to 4 must be met, ie 5) primary depressive or anxiety disorder - can be present

 

[oceanblue]

This is an amazingly high figure for a definition of M.E. given the "looseness" of the Oxford criteria e.g. unlike the Fukuda CFS criteria or Carruthers ME/CFS criteria, it doesn't require other symptoms apart from fatigue.

It seems to me the definition for M.E., at least as it was used in this trial, is very suspect. And hence it is questionable what can read from into how people with M.E. responded in the trial.

Agreed, and I also find the fact that 67% of Oxford Criteria patients met International criteria very surprising too. something doesn't quite add up here.

 

[Dolphin]

But then if you look at the London ME criteria the instructions are that only criteria 1 to 4 must be met, ie 5) primary depressive or anxiety disorder - can be present

That made me less confident about what was said initially. But it appears that if a person had any psychiatric disorder presumably assessed using the SCID (separately) they weren't included.

 

[Dolphin]

Agreed, and I also find the fact that 67% of Oxford Criteria patients met International criteria very surprising too. something doesn't quite add up here.

Yes, I'm guessing if somebody clicked "present a little" that it was counted as having the symptom:

 

[Angela Kennedy]

Yes, thanks for this Dolphin.

There are certainly some discrepancies in White's account in his letter to Hooper, and the actual 'London criteria' used in the PACE trial protocol, which seems to have been mangled. and their relationship to the first wave of exclusions rendered by the Oxford Criteria. I haven't had a chance to look at the letter in full yet, but isn't White claiming something like 'someone else' gave him a version of the 'London' to use?

This gets more and more discrepant the deeper I'm looking, certainly.

 

[Angela Kennedy]

This constitutes another thread of course, and a lot of the work I was doing previously on the cohorts are on theose other threads. I tried to keep threads to a minimum but you all know how it gets sometimes with different people starting up new threads- it's an occupational hazard we all face!

But related to this thread, there's another thread here:

http://forums.aboutmecfs.org/showthread.php?10219-PACE-study-and-oxford-criteria/page3

in which I made some comments on post #28 which I think may be relevant to this thread specifically:

White et al's 'London criteria', contained in the PACE trial protocol - appears different to the 'London' criteria recently put out on the MEA website by Charles Shepherd (we already know the London criteria are controversial). I'm still analysing this- and it appears to be a game of semantics, but neurological signs and symptoms are not necessary (and patients with these will have been already been excluded by Oxford). So at present, one cannot even say 'the London criteria' were used (though what the London criteria actually are is unstable in itself!!!!)

...There is uncertainty over how 'Reeves' were used. On one table they place them as a sub-group of the cohort (which might lead one to believe they were inclusionary criteria performed after Oxford). But the text on page 2 shows that Reeves were used for exclusionary purposes (to "exclude alternative diagnoses") along with NICE (those are the two references given here). There is no literature on the PACE protocol that I can see that sets out standardisation of Fukuda (or Reeves) inclusion or exclusion requirements. But it looks like that 'sub-group' might have been only EXCLUSIONS, not INCLUSIONS. It is possible this is the case. It does need clarifying.

So far- there is overlap between the (actually) three 'embedded sub-groups' on the table provided (if you count the third group as SCID psychiatric disorders). So - the cohorts on sight appear very similar as groups (especially in the lack of neurological dysfunction). I'm trying to get someone to help me carry out a 't-test' to help establish if my hypothesis is correct there.

47% of the cohort had a psychiatric disorder. Now - there is some strange comment on the Pace Trial protocol about the "grey box ineligible for trial" because even on the pdf- there are three shades of grey (and two textures of 'hashed' and 'smooth'!) But it looks like all sorts of people were eligible for inclusion, including agoraphobics, any phobics, OCD, PTSD, and lifelong psychosis, and there appears some confusion between the SCID form and the 'Oxford form about inclusion/exclusion of bipolars, and schizophrenics! Funnily enough- considering the frequent claims about 'personality disorder' in CFS - these are not included as exclusions (so mean all sorts of personality disorders could be included).