PACE Trial and PACE Trial Protocol

[Sam Carter]

...

Specific to the Oxford Criteria

1. Fatigue present for the last 6 months for more than half the time.
2. Illness affects both physical ability and mental functioning
3. Fatigue is the principal symptom
4. Fatigue out of proportion 'to what you would expect as normal for this level of exertion'
5. As judged by the Research Nurse: can the fatigue be distinguished from low mood, sleepiness and low motivation?

Actually, I was surprised by 5, in that it makes some effort to exclude fatigue purely as a result of mood factors.

...

This is one of the many grey areas and ambiguities in the Oxford Criteria, oceanblue.

For instance, they also state:

"psychiatric disorders (including depressive illness, anxiety disorders, and hyperventilation syndrome) are not reasons for exclusion" [emphasis added]

Therefore, a participant with fatigue and depression can be included, but a participant with fatigue and low mood / low motivation can, apparently, be excluded.

Also of note is the wording of the first question in the operationalised OC:

"Is your fatigue (or a synonym), the principal (main, primary) symptom (e.g. tiredness, lack of energy, weariness, exhaustion)?"

Fatigue or a synonym.

Basically, everyone is welcome except those with demonstrable organic pathology.

 

[oceanblue]

Therefore, a participant with fatigue and depression can be included, but a participant with fatigue and low mood / low motivation can, apparently, be excluded.

Actually, my reading of that was that only someone with fatigue that was the result of low mood could be excluded, while someone with low mood as a results of fatigue would not be excluded. I thought that generally the criticism of the Oxford Criteria is that it includes people whose fatigue is by-product of a mood disorder rather than the result of an organic disorder.

The London criteria (haven't posted on that yet) does exclude anyone with depression or anxiety, even if it is as a result of their illness.

Also of note is the wording of the first question in the operationalised OC:
"Is your fatigue (or a synonym), the principal (main, primary) symptom (e.g. tiredness, lack of energy, weariness, exhaustion)?"

Worrying - I'm not clear what 'operationalised OC' is - is this something from the PACE protocol?

 

[Sam Carter]

Actually, my reading of that was that only someone with fatigue that was the result of low mood could be excluded, while someone with low mood as a results of fatigue would not be excluded. I thought that generally the criticism of the Oxford Criteria is that it includes people whose fatigue is by-product of a mood disorder rather than the result of an organic disorder.

The London criteria (haven't posted on that yet) does exclude anyone with depression or anxiety, even if it is as a result of their illness.



Worrying - I'm not clear what 'operationalised OC' is - is this something from the PACE protocol?

Hi oceanblue,

The OC are, I would argue, unclear on this point.

These are the exact quotes:

""""""
For the Research Nurse to judge: Can the fatigue be
distinguished from low mood, sleepiness and lack of
motivation?
""""""

and

""""""
Other psychiatric disorders (including depressive illness, anxiety disorders, and
hyperventilation syndrome) are not reasons for exclusion.
""""""

The first requirement suggests that fatigue secondary to depression would preclude entry to the trial; the second requirement, to me at least, does not seem consistent with the first, and, therefore, entry to the trial becomes contingent on the RN's subjective assessment of the participant.

If one reads the CBT Therapist's Manual it is very clear that they expect to be treating people whose symptoms result not from physical disease -- this is one of the assumptions on which the intervention is predicated -- but from physical deconditioning secondary to depression.

Sam

 

[oceanblue]

'London' Criteria - as applied by PACE trial

Now for the near-mythical 'London' M.E. criteria, as applied in the PACE trial. Again, starting with patients meeting the Oxford Criteria, there are 4 mandatory symptoms for inclusion and one exclusion:

1. Exercise induced fatigue precipitated by trivial mental or physical exertion relative to the patient's previous exercise tolerance
2. Impairment of short-term memory and loss of powers of concentration
3. Fluctuations of symptoms ('the usual precipitation by mental/physical exercise should be recorded but is not necessary to meet criteria')
4. Symptoms should have been present for at least 6 months and should be ongoing [nb unlike Oxford & CDC criteria that allow intermittent symptoms]
5. There is no primary depressive illness and no anxiety disorder/neurosis

The PACE protocol Case Report form also adds the symptoms are:
'usually coupled with other disturbances (which it says should be recorded but are not necessary for diagnosis) including:

• emotional lability (easily upset but upset is brief and does not persist)
• problems finding the right word
• distrubed sleep
• disequilibrium (feeling of imbalance)
• tinnitus

So that's the London Criteria - as defined by the PACE trial.

 

[oceanblue]

The first requirement suggests that fatigue secondary to depression would preclude entry to the trial; the second requirement, to me at least, does not seem consistent with the first, and, therefore, entry to the trial becomes contingent on the RN's subjective assessment of the participant.

If one reads the CBT Therapist's Manual it is very clear that they expect to be treating people whose symptoms result not from physical disease -- this is one of the assumptions on which the intervention is predicated -- but from physical deconditioning secondary to depression.
Sam

Hi Sam

I'd agree with your first point about inconsistency but I'm inclined to think that in practice fatigue secondary to depressioin won't be an exclusion a) because it never has been in practice with the Oxford Criteria before and b) because of your second point - they'd be spoiling their own trial!

 

[Sam Carter]

Hi Sam

I'd agree with your first point about inconsistency but I'm inclined to think that in practice fatigue secondary to depressioin won't be an exclusion a) because it never has been in practice with the Oxford Criteria before and b) because of your second point - they'd be spoiling their own trial!

Hi oceanblue,

I think we're actually in agreement here! The OC are sufficiently obtuse to be clinically meaningless and have no place in the empirical(*) study of disease.

Sam

* empirical in the classical sense; not the Bill Reeves-ian sense .

 

[oceanblue]

These are the exact quotes:

""""""
For the Research Nurse to judge: Can the fatigue be
distinguished from low mood, sleepiness and lack of
motivation?
""""""

and

""""""
Other psychiatric disorders (including depressive illness, anxiety disorders, and
hyperventilation syndrome) are not reasons for exclusion.
""""""

The first requirement suggests that fatigue secondary to depression would preclude entry to the trial; the second requirement, to me at least, does not seem consistent with the first, and, therefore, entry to the trial becomes contingent on the RN's subjective assessment of the participant.

Reading that again, the second point would cover people who have a fatguing illness and secondary depression, anxiety etc, which isn't inconsistent with the first point. But I am surprised that it's left to the Research Nurse to make the call on whether or not "fatigue be distinguished from low mood, sleepiness and lack of motivation".

 

[oceanblue]

PACE trial using modified Oxford Criteria

Another of the wildly popular posts on case definitions used in the PACE trial...

The PACE trial has made two additons to the published Oxfrod Criteria and I'd be interested to know how significant people think these modifications are (points 4 and 5):

1. Fatigue present for the last 6 months for more than half the time.
2. Illness affects both physical ability and mental functioning
3. Fatigue is the principal symptom
   [*]Fatigue out of proportion 'to what you would expect as normal for this level of exertion'
   [*]As judged by the Research Nurse: can the fatigue be distinguished from low mood, sleepiness and low motivation?

Both of these changes address the criticism of the Oxford Criteria, that they pull in people who have mood disorders first and fatigue second. Interestingly, they also tie in with Peter White's published views that mood disorders do not explain CFS and also that post-exertional fatigue is a key symptom (both findings based on his glandular fever prospective studies; I only recently discoverd the post-exertional fatigue one).

Both changes also look a bit vague to me in how they are phrased and I wonder how much difference they will make in practice. For comparison, this is the phrase used in the London Criteria to capture post-exertional fatigue:
"Exercise induced fatigue precipitated by trivial mental or physical exertion relative to the patient's previous exercise tolerance".

The purpose of this post is to clarify the criteria used by the PACE trial, to help people interpret the findings. I make no judgement on the validity or appropriateness of the criteria.

 

[ukxmrv]

1.Fatigue out of proportion 'to what you would expect as normal for this level of exertion'


I hate the use of the word "expect". It is either is or it isn't. "expect" makes it sound as if it is patients perception of their fatigue so that perception can be worked on.

 

[Snow Leopard]

I agree. It is far too subjective.

 

[Jenny]

MAY BE REPOSTED

From media calls just started to coming in, it looks as though the results of
the PACE study will be announced this evening.

Broadcasters and journos are being invited to an embargoed news conference at
the Science Media Centre in London this evening where the results of "an
evaluation of various forms of treatment for ME" will be announced. The
place.... the subject.... both seem to fit into PACE!

I'm looking for volunteers prepared to be interviewed in their own homes by TV,
radio and press at the moment only in the London, Bristol and Edinburgh areas.
But the net will widen, I'm sure, so offers from anywhere in the UK will be
welcome.

You know where to find me:

tony_mea @btinternet.com
Tel: 01406 370-294 begin_of_the_skype_highlighting 01406 370-294 end_of_the_skype_highlighting
Mob: 07880 502923 begin_of_the_skype_highlighting 07880 502923 end_of_the_skype_highlighting

 

[Esther12]

I wonder if any of the ME/CFS charities will have someone at the SMC conference.

 

[Angela Kennedy]

MAY BE REPOSTED

From media calls just started to coming in, it looks as though the results of
the PACE study will be announced this evening.

Broadcasters and journos are being invited to an embargoed news conference at
the Science Media Centre in London this evening where the results of "an
evaluation of various forms of treatment for ME" will be announced. The
place.... the subject.... both seem to fit into PACE!

I'm looking for volunteers prepared to be interviewed in their own homes by TV,
radio and press at the moment only in the London, Bristol and Edinburgh areas.
But the net will widen, I'm sure, so offers from anywhere in the UK will be
welcome.

You know where to find me:

tony_mea @btinternet.com
Tel: 01406 370-294 begin_of_the_skype_highlighting 01406 370-294 end_of_the_skype_highlighting
Mob: 07880 502923 begin_of_the_skype_highlighting 07880 502923 end_of_the_skype_highlighting

thanks for this Jenny.

And why aren't they looking for people capable of rebutting any untenable claims likely to come out of this?

 

[Angela Kennedy]

I wonder if any of the ME/CFS charities will have someone at the SMC conference.

Do you mean AfME, who've supported the trial?

 

[Jenny]

thanks for this Jenny.

And why aren't they looking for people capable of rebutting any untenable claims likely to come out of this?

Perhaps they are - perhaps that's the point of the interviews.....

Jenny

 

[Angela Kennedy]

Perhaps they are - perhaps that's the point of the interviews.....

Jenny

but it looks like 'volunteer' patients in own homes- usually that means 'the human side' which to be frank we really don't need. This trial - whatever the results- is likely to be 'spun' positively, so some effective rebuttal responses are needed.

 

[Esther12]

Do you mean AfME, who've supported the trial?

I was wondering if those critical would get in? Maybe they wouldn't be welcome?.. Or not interested in attending?

 

[Esther12]

but it looks like 'volunteer' patients in own homes- usually that means 'the human side' which to be frank we really don't need. This trial - whatever the results- is likely to be 'spun' positively, so some effective rebuttal responses are needed.

I think I agree with this. If the results ar being spun it will be difficult for any patient to respond of the cuff without coming across as unreasonable.

 

[Angela Kennedy]

I think I agree with this. If the results ar being spun it will be difficult for any patient to respond of the cuff without coming across as unreasonable.

Yes. This will need a careful, rigourous response. People have been working on 'PACE watching' for years, and a good rigourous critique can be made if people pull together.

 

[Angela Kennedy]

I was wondering if those critical would get in? Maybe they wouldn't be welcome?.. Or not interested in attending?

If it's a press conference- I doubt others will be allowed in?