PACE study and oxford criteria

[Angela Kennedy]

I said in last post: "We've also already seen that the way London was used could allow people to be designated 'London ME' even if they were very similar to Oxford, and neurological symptoms and signs are not necessary to get a London designation (remember London were also supposed to be 'research' and not 'clinical' criteria). If you put London against Ramsay or CC, for example, this becomes obvious."

And to demonstrate that, here is Malcolm Hooper's response to David Jameson on this issue:

You state that the trial compared subsets using “the London criteria for ME (requiring postexertional malaise…”). The original intention of the PIs was to use the Ramsay definition of ME, and you will see from page 417 of “Magical Medicine” these were date-stamped by the MREC as received on 21st March 2003 (http://www.meactionuk.org.uk/magical-medicine.htm). Once again, however, Professor White amended the Protocol and he substituted what appears to be his own version of the “London Criteria” for the Ramsay definition. You will see from page 417 of Magical Medicine that the Ramsay definition required the following: fluctuation of symptoms from day to day or within the day; headaches; giddiness; muscle pain; muscle cramps; muscle twitchings; muscle tenderness; muscle weakness; pins and needles; frequency of passing water; blurred vision; double vision; increased sensitivity of hearing; increased sensitivity to noise; feeling generally awful, and muscle weakness after exercise.

In contrast, Professor White’s version of the “London Criteria” specifically states on page 188 of the Full Protocol that neurological disturbances “are not necessary to make the diagnosis” and they further state that “the usual precipitation by ‘physical or mental exercise’ should be recorded but is not necessary to meet criteria”. Notwithstanding this clear statement in the Full Protocol that postexertional malaise is not necessary to meet the London Criteria, the text of the Lancet article states that participants were also assessed by “the London criteria for myalgic encephalomyelitis (version 2) requiring postexertional fatigue” so there is a significant discrepancy that requires explanation by Professor White, since two such divergent criteria cannot both have been used in the PACE Trial (note that Professor White’s “version 2” is dated 26.11.2004).

According to Professor White’s version of the “London Criteria”, there is no requirement for impairment of short-term memory and loss of concentration, nor is there any requirement for primary depression or anxiety disorder to be present (indeed, if depression or anxiety disorder are present, the Full Protocol states “This means if any depressive or anxiety disorder is present, the London criteria are not met”). This makes the fact that the PIs reported a 47% prevalence of mood and anxiety disorder at baseline particularly notable, because the PIs state that of the 641 participants, 329 (ie. 51.3%) met Professor White’s version of the “London Criteria”; in other words, virtually everyone who did not have anxiety or depression met the “London Criteria” used in the PACE Trial, but Professor White’s “London Criteria” in the Full Protocol (to which the PIs were obliged to adhere) do not require precipitation of symptoms by physical or mental exercise. Put another way, of the 53% who did NOT have anxiety or depression at baseline, 96.8% met Professor White’s “London Criteria”, but those criteria do not require the cardinal feature of ME to be present. This begs the question as to what disorder was being studied under the title of ME/CFS, because the clear distinction between Ramsay-defined ME and somatisation disorder has been significantly lessened by the PIs.

Whilst the Ramsay definition does exist (Postgrad Med J 1990:66:526-530), I would remind you that the “London Criteria” do not in fact exist and that the reference cited in the Lancet is to the 2004 Westcare Report, which simply said that they were “proposed” criteria. The “London Criteria” have no known authors; they have never been published; there is no methods paper which specifically describes them as a “case definition”; they have never been approved nor have they even been finally defined (there are various versions); they have never been validated and they are not on PubMed thus are not available for scrutiny so they cannot be accessed for comparison. This means that Professor White was essentially able to create his own version of the “London Criteria” as evidenced on page 188 of the Full Protocol. Your assertion that the London Criteria required postexertional malaise is thus incorrect despite the PIs having said in their Lancet paper that it was required, and this is an issue for Professor White to address ie. he needs to clarify whether or not he adhered to his own Protocol.

 

[Angela Kennedy]

Another little gem from the PACE article (page 13)

Although more than 3000 patients attending
clinics had to be screened to identify the 641 recruited,
the commonest reason for exclusion at screening was
not having chronic fatigue syndrome.

Now they've already told us (page 2) that:

We recruited 641 participants from consecutive
new out patients attending six specialist chronic fatigue
syndrome clinics in the UK National Health Service...

So, all those patients (more than 2300), who had to be excluded from the research because they didn't have Oxford defined Chronic Fatigue Syndrome, came from the Chronic Fatigue Syndrome clinics!!!!!

 

[Angela Kennedy]

To further discuss the facilitation of exclusion of actual ME sufferers from the PACE trial:

Information from the MS society about symptoms that present in MS. Note how they acknowledge these aren't unique to MS- but are serious enough to indicate a severe neurological condition:

http://www.mssociety.org.uk/about_ms/symptoms/index.html

MS can cause a wide variety of symptoms. Many people experience only a few symptoms and it is unlikely that anyone will develop them all.

People can have different symptoms at different times and, although some are very common, there is no typical pattern that applies to everyone.

The symptoms listed below can also have other causes, so even if someone has a diagnosis, it should not always be assumed they are all due to the MS. If they have another cause, the treatment might also need to be different.

This list is for information only – it isn’t a comprehensive checklist of symptoms that people with MS experience. Some are more common than others.

If these symptoms occur, tell your doctor or health care team so they can help find the cause and best way to manage them. Drug treatments as well as help from specialists, like physiotherapists and occupational therapists, can help people manage many MS symptoms very effectively.


Difficulties with balance and dizziness

Fatigue - an overwhelming sense of tiredness

Visual problems such as blurred or double vision

Numbness, tingling or pins and needles - sometimes these sensory changes can feel painful

Bladder problems

Cognitive problems (problems with memory and thinking)

Stiffness or spasms in muscles - sometimes called 'spasticity'

Emotional and mood changes

Tremor

Bowel problems

Sexual problems

Speech difficulties

Swallowing difficulties

Now let's look at some of the symptoms (which may also engender clinical neurological signs) in ME, as described by Ramsay (this is from page 417 of the pdf 'Magical Medicine':

Headaches
Giddiness
muscle pain
muscle cramps
muscle twitchings
muscle tenderness
muscle weakness
pins and needles
frequency of passing water
blurred vision
double vision
increased sensitivity of hearing
increased sensitivity to noise
tinnitus
feeling awful
muscle weakness after exercise

Then we can look at Canadian defined ME/CFS, summarised here:

http://www.cfids-cab.org/MESA/ccpc.html

1. POST-EXERTIONAL MALAISE AND FATIGUE: There is a loss of physical and mental stamina, rapid muscular and cognitive fatigability, post-exertional fatigue, malaise and/or pain, and a tendency for other symptoms to worsen. A pathologically slow recovery period (it takes more than 24 hours to recover). Symptoms exacerbated by stress of any kind. Patient must have a marked degree of new onset, unexplained, persistent, or recurrent physical and mental fatigue that substantially reduces activity level. [Editor’s note: The M.E. Society prefers to use “delayed recovery of muscle function,” weakness, and faintness rather than “fatigue.” Further, we disagree that the muscle dysfunction and post-exertional sickness is “unexplained.”

2. SLEEP DISORDER: Unrefreshing sleep or poor sleep quality; rhythm disturbance.

3. PAIN: Arthralgia and/or myalgia without clinical evidence of inflammatory responses of joint swelling or redness. Pain can be experienced in the muscles, joints, or neck and is sometimes migratory in nature. Often, there are significant headaches of new type, pattern, or severity. [Editor’s note: neuropathic pain is a common symptom and should be added here as well.]

4. NEUROLOGICAL/COGNITIVE MANIFESTATIONS: Two or more of the following difficulties should be present: confusion, impairment of concentration and short-term memory consolidation, difficulty with information processing, categorizing, and word retrieval, intermittent dyslexia, perceptual/sensory disturbances, disorientation, and ataxia. There may be overload phenomena: informational, cognitive, and sensory overload -- e.g., photophobia and hypersensitivity to noise -- and/or emotional overload which may lead to relapses and/or anxiety.

5. . AT LEAST ONE SYMPTOM OUT OF TWO OF THE FOLLOWING CATEGORIES:

(a) AUTONOMIC MANIFESTATIONS: Orthostatic Intolerance: e.g., neurally mediated hypotension (NMH), postural orthostatic tachycardia syndrome (POTS), delayed postural hypotension, vertigo, light-headedness, extreme pallor, intestinal or bladder disturbances with or without irritable bowel syndrome (IBS) or bladder dysfunction, palpitations with or without cardiac arrhythmia, vasomotor instability, and respiratory irregularities. [Editor’s note: low plasma and/or erythrocyte volume should be added as another explanation for orthostatic intolerance in this disease. More cardiac symptoms should be listed such as left-side chest aches and resting tachycardias, which, in addition to low blood volume, have also been documented in the research. The full text of the case definition does suggest 24-hour Holter monitoring, and when tachycardias with T-wave inversions or flattenings are present that they not be labeled as nonspecific since they aid in the diagnosis of ME/CFS. The frequent tachycardias seen in ME/CFS have been shown by Dr. Paul Cheney to be a compensatory mechanism that serves to increase cardiac output in the presence of low stroke volume due to diastolic dysfunction in the heart. Orthostatic problems may also be related to diastolic dysfunction as recently shown by Dr. Paul Cheney. See our Cardiac Insufficiency Hypothesis page.]

(b) NEUROENDOCRINE MANIFESTATIONS: loss of thermostatic stability, heat/cold intolerance, anorexia or abnormal appetite, marked weight change, hypoglycemia, loss of adaptability and tolerance for stress, worsening of symptoms with stress and slow recovery, and emotional lability.

(c ) IMMUNE MANIFESTATIONS: tender lymph nodes, sore throat, flu-like symptoms, general malaise, development of new allergies or changes in status of old ones, and hypersensitivity to medications and/or chemicals.

Forgetting the Editors caveats with the CC (which I agree with) - the issue here is what are ME sufferers (even if they are given a CFS diagnosis) presenting with? Unless my daughter is very rare, and I've been engaging with the completely wrong community for many years, MOST of you will have a constellation of symptoms (and, if looked for, signs) of the above neurological manifestations, even if some of you did not realise these were neurological in origin, and many of them overlap with presentations of MS.

Now, over 2300 people SENT TO ONE OF SIX CHRONIC FATIGUE CLINICS BY THEIR GPS were deemed unsuitable for the trial because they allegedly did NOT have 'chronic fatigue syndrome'- whatever that means! Whatever happened to them (likely many sent back to the chronic fatigue clinic for non researched cbt/get and some psychogenic dismissal of their symptoms and signs), while they were being considered for selection into the cohort, by the rubric of Oxford and Fukuda, Reeves and NICE (but let's focus Oxford as that very specific first application of exclusion), a person turning up with the neurological manifestations (as signs and/or symptoms) might be at risk of having, let's argue, just for the moment, not even ME, but Multiple Sclerosis. The last thing White, Wessely, Sharpe etc. want is MS sufferers in their cohorts, and they would actually be required to select these out.

Because ME has been so downplayed, so trivialised and the sufferers demonised, it's often very hard for people, even sufferers themselves, to understand how neurological the condition is. It is this very neurological presentation that allows them to be selected out of RESEARCH cohorts, even while their neurological and other impairments are, in clinical practice, downplayed and overlooked by their GPs and at the 'chronic fatigue' clinics, and subject to psychogenic explanations and dismissal.

I also think it has been very hard for people (and I include myself here) to get their heads around the fact that they could be actively excluded from the psych research. The psychs do appear to have heterogenous cohorts (looking at the Webappendix serious adverse events record demonstrates that, for example) - so all sorts of people might be herded into the fatigue clinics, for example. BUT - despite this heterogeneity, the mechanisms for active exclusion of neurological ME sufferers for RESEARCH are there in Oxford, Fukuda, NICE, Reeves 2003 and 2005 etc. so that the one group who really SHOULD be the key components of the research cohorts, can be neatly excluded.

 

[alex3619]

So, all those patients (more than 2300), who had to be excluded from the research because they didn't have Oxford defined Chronic Fatigue Syndrome, came from the Chronic Fatigue Syndrome clinics!!!!!

Hi Angela, this inference is not valid. It could be true, but it could also be false. At the other extreme, it is also possible they only accepted patients from chronic fatigue syndrome clinics as having real CFS. In between, it could be that they had, for example, 2000 patients who were not from chronic fatigue syndrome clinics and so were rejected.

I suspect you are correct Angela, but this conclusion requires more evidence than you cite.

Bye,
Alex

 

[alex3619]

Hi Angela, with respect to post 23, I worry even more that only quite healthy and mobile CFS patients are treated and researched, as large numbers of us could not even get to clinics for treatment. How many studies are they going to keep doing on the moderately and barely sick? When are they going to start studying housebound patients? What about bedbound patients? How are severe bedbound patients going to even listen to a CBT therapist, or remember any of it? How can a severe bedbound patient do more than twitch their fingers for exercise? Its a travesty to claim the things the biopsychosocial "researchers" claim. Bye, Alex

 

[Angela Kennedy]

Hi Angela, this inference is not valid. It could be true, but it could also be false. At the other extreme, it is also possible they only accepted patients from chronic fatigue syndrome clinics as having real CFS. In between, it could be that they had, for example, 2000 patients who were not from chronic fatigue syndrome clinics and so were rejected.

I suspect you are correct Angela, but this conclusion requires more evidence than you cite.

Bye,
Alex

Alex, firstly, what's real CFS?

Secondly, The PACE article itself says (page 2):

We recruited 641 from consecutive new outpatients attending six specialist chronic fatigue syndrome clinics in the UK National Health Service

All patients screened and assessed were from the above.

But actually, you are right about the 2300 figure not being a total reflecting people 'not having chronic fatigue syndrome'. Looking at the article demonstrates that.

From the CONSORT trial profile (page 4 of the pdf), out of 3158 screened and 'assessed' for eligibility, if my calculations are correct, 2517 people were excluded, at two levels.

Now the PACE authors at this stage say NOTHING about EXCLUSION criteria, funnily enough. They don't give figures for exclusions. But:

1011 had 'no' current Oxford diagnosis of CFS at 'screening', while 67 did not meet Oxford diagnosis of CFS at 'assessment'

That's an awful lot of people being farmed off to a chronic fatigue unit by their GPs, who are not actually eligible for the chronic fatigue/chronic fatigue syndrome criteria!

That's even before we look at some of the other vague reasons for exclusion:

"unable to comply with protocol" (139 at 'screening', 52 at 'assessment')
"contraindication to treatment" (71 at 'screening', 13 at 'assessment')

I think the fact that exclusion figures (whether using Oxford, Reeves 2003, or NICE) are not quantified is significant, and that it is reasonable of to infer that this is related to the objections people made about Oxford criteria throughout the trial, and to the evidence available demonstrating that they could (and I believe did) exclude 'neurological' ME sufferers from the research cohort.

 

[Angela Kennedy]

Hi Angela, with respect to post 23, I worry even more that only quite healthy and mobile CFS patients are treated and researched, as large numbers of us could not even get to clinics for treatment. How many studies are they going to keep doing on the moderately and barely sick? When are they going to start studying housebound patients? What about bedbound patients? How are severe bedbound patients going to even listen to a CBT therapist, or remember any of it? How can a severe bedbound patient do more than twitch their fingers for exercise? Its a travesty to claim the things the biopsychosocial "researchers" claim. Bye, Alex

Yes, I agree totally Alex. This is another important issue that people will have to push as an objection to the claims of the PACE authors.

 

[Angela Kennedy]

From other threads, some further comments of relevance:

Lacklustre results notwithstanding, this trial has been spun, both in the Lancet and in the press, as substantiating the safety of CBT/GET for ME sufferers (even if they use their term 'CFS/ME'). These results are generally no more impressive than any CBT/GET trials done in the past, but that wasn't necessarily their primary aim. This appears to have been to dismiss the claim that CBT/GET is unsafe for ME sufferers, because this is an extremely serious allegation.

They've managed to pooh-pooh concerns about safety, and THIS will be the serious issue people will be faced with in the future.

Showing how poor the results of this trial are is one thing (in important one). But it will still be business as usual unless we can show that CBT/GET is still potentially unsafe. The reasons we know CBT/GET has not been established as 'safe' for ME sufferers are:

1. The PACE cohorts have potentially eliminated all ME sufferers from the trial. AT BEST, very few will have got in. Maybe none at all were in there. If this happened, it will have been achieved at the doctor examination/history taking stage, which WAS ad hoc (the only standardised form was a sign off by the research nurse after the doctors had 'screened' the patients). It would be highly problematic for the doctors to include any people with neurological deficit in the trial- because those deficits may have represented other neurological illnesses, like MS etc. I believe it is significant that so many people attending the 'specialist clinics' (over 1000) were deemed not to have met Oxford. Previous 'CFS' research cohorts in the UK have been worked so that people with organic dysfunction seen in ME (say Canada, even the historical ME case descriptions etc.) are excluded from these.

2. 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.

3. As someone has already said, 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).

4. The PACE version of the London criteria used actually a diagnosis of 'ME' based on: Exercise induced fatigue (who doesn't get tired after exercise?!) but the 'exercise'/'exertion' has to be 'trivial' in self report; impaiment of short term memory and loss of concentration; fluctuation of symptoms (ubuquitous in all health states and difficult to quantify); 6 months plus duration; no primary depressive illness or anxiety/'neurosis'. That is all that is necessary to meet the criteria for ME (though don't get me started on the instability of the terms anxiety and neurosis!)

5. They have not addressed the issue of abnormal physiological response to exertion, either within the biomedical literature or the reports from patients. This is a major omission. They have NOT considered the differential cohort that would have been established by applying say the Canadian Criteria either, even though this was brought to their attention a good few times. This should have been a limitation of study item (I note there was no such section in the article).

6. Obviously seriously affected/ bedbound etc. weren't included. But they are likely to try and claim slightly and moderately affected are still 'safe' with CBT/GET (and pacing is useless).

And this:

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!!!!)

Secondly, as I said above, 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.

Oh - and even IF they were INCLUSIONARY criteria, they weren't Reeves 2005, but Reeves 2003, which may, or may not, be the same as 'Fukuda'! (i have to go back to that article to check.)

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.

 

[Angela Kennedy]

Tom Kindlon has posted some very interesting information on Co-cure about the PACE trial's apparent use of -mm- Reeves? Fukuda? Having seen that case report form, this throws up some more questions (of course!):

If one assumes the forms in the long PACE Trial document are correct (they
look very genuine to me!), for the CDC/International criteria - they only
asked about symptoms in the last week!!

=======================================

Appendix 6: Case Report Forms

A6.4 CDC

CDC

Please score whether you have had any of the following symptoms in the last
week:

Score each symptom by putting a circle round the number that most closely
resembles the frequency and intensity of that particular symptom.

Symptoms

not present at all
present a little
presence more often than not
present most of the time
present all of the time

------------

Impaired memory or Concentration

Sore throat

Tender lymph node (glands) in your neck or under your arms

Muscle pain

Joint pain in several joints without swelling or redness

New headache

Unrefreshing sleep

Feeling ill after exertion

====================================

The CDC criteria asks for symptoms over the last 6 months. People can have
temporary symptoms for all sorts of reasons e.g. Pre-Menstrual
Syndrome/similar - this would allow them satisfy these criteria.

And I'm guessing that "present a little" may have counted as having it.

Also, the "post-treatment" data for symptoms in Table 6 and in sentences
like "Postexertional malaise was lower after CBT and GET than it was after
APT and SMC" would also be based on this wording (i.e. 1 week duration).

Tom

The second post from Tom:

Somebody asked could those questions asking about CDC symptoms over the last
week have been asked weekly.

According to p.53 of the full PACE Trial protocol, they were just used at
baselines and 52 weeks (or treatment discontinuation if that occurred).

http://bit.ly/fD23GY i.e.
http://rapidshare.com/files/453102201/PACE_Trial_Protocol_searchable.pdf

 

[Dolphin]

No, you're right, they don't mention this. But, by them referencing the 2003 paper, you've assumed they've used Fukuda- but that might not be the case at all. I think what may have happened is that they used Reeves 2005, but erroneously referenced Reeves 2003.

I'm not convinced of that. For one thing, White is one of the authors of the 2003 paper so I think he wouldn't get the two mixed up.

 

[biophile]

Angela Kennedy wrote: No, you're right, they don't mention this. But, by them referencing the 2003 paper, you've assumed they've used Fukuda- but that might not be the case at all. I think what may have happened is that they used Reeves 2005, but erroneously referenced Reeves 2003.

Dolphin wrote: I'm not convinced of that. For one thing, White is one of the authors of the 2003 paper so I think he wouldn't get the two mixed up.

Ah, just like how they "didn't mix up" the normative data for a working age population despite showing familiarity with the figures? ;-)

 

[Angela Kennedy]

I'm not convinced of that. For one thing, White is one of the authors of the 2003 paper so I think he wouldn't get the two mixed up.

Thanks Dolphin for mentioning this on this thread. I had forgot to put my recent findings about this issue (which we've discussed on the other thread) here.

They DID use Reeves et al 2003. Reeves et al 2003 are even more exclusionary than Fukuda (and more resembling Oxford!) in that any clinical SIGN associated with Fukuda symptoms (for example, actual swelling or redness of joints, inflamed throat and tonsils, palpable lymph nodes!) are to be in effect EXCLUSIONARY for CFS. Reeves et al actually say 'alternative diagnoses should be sought' for these signs!

In a research setting, this means such patients will be excluded from research where Reeves et al, 2003, are the selection criteria.

Taking these, the NICE exclusions and the first line Oxford exclusion, into account demonstrates that there was a determined effort to try and ensure no patients with physical signs were included in the PACE trial. Indeed, to deny this would contradict their own methodology, both in the PACE trial and in other projects!

 

[oceanblue]

They DID use Reeves et al 2003. Reeves et al 2003 are even more exclusionary than Fukuda (and more resembling Oxford!) in that any clinical SIGN associated with Fukuda symptoms (for example, actual swelling or redness of joints, inflamed throat and tonsils, palpable lymph nodes!) are to be in effect EXCLUSIONARY for CFS. Reeves et al actually say 'alternative diagnoses should be sought' for these signs!
In a research setting, this means such patients will be excluded from research where Reeves et al, 2003, are the selection criteria.

That's possible, but 'alternative diagnoses should be sought' presumably means just that; such signs are not listed under the exclusionary criteria, though presumably would lead to exclusion if an alternative diagnosis was found - but not if no such diagnosis was made. It would be very helpful, though, to know how many prospective PACE particpants had signs rather than symptoms.

 

[Angela Kennedy]

That's possible, but 'alternative diagnoses should be sought' presumably means just that; such signs are not listed under the exclusionary criteria, though presumably would lead to exclusion if an alternative diagnosis was found - but not if no such diagnosis was made. It would be very helpful, though, to know how many prospective PACE particpants had signs rather than symptoms.

But this was an 'identification of ambiguities' in Fukuda: the whole article was an attempt to make less ambiguous FOR RESEARCH, NOT CLINICAL PURPOSES.

Now, you could argue that they didn't do a very good job of this, because you have read into it what you have- but I need to make clear, that was not what they've argued (that if alternative diagnoses are not found for clinical signs, that means the patients has CFS).

The point is, the mechanism is there to exclude patients with clinical SIGNS. Indeed, this mechanism is consistent with CFS as a diagnosis of exclusion, and Wessely and others focus on patients allegedly only having 'symptoms', not 'signs' (which is highly unsafe as a claim- but is nevertheless made).

I really cannot see the notes being released publicly to see how many of the PACE cohort (or those excluded) had signs! Can anyone?

 

[Dolphin]

Ah, just like how they "didn't mix up" the normative data for a working age population despite showing familiarity with the figures? ;-)

Well, to be serious, I don't think Peter White would have criticiued the Reeves et al. 2005 criteria as a peer reviewer in late 2006 (here: http://www.biomedcentral.com/imedia/1083914155124266_comment.pdf ) if they had used it.