Establishing research cohorts of 'Canadian' criteria patients: an urgent need

[Dolphin]

1. Obviously Hooper et al's 'Magical Medicine' contains a LOT of information. I found their section 4 to contain the newest information I would say, but using the left hand contents column on the pdf has been useful for me to find other key points:

http://www.meactionuk.org.uk/magical-medicine.htm

Thanks for the tip. I am interested in it but have so far been put off by the length (and have been doing other things).

 

[Gerwyn]

@ Gerwyn:

Yes this is a pretty concise list of most of the methodological problems that became evident. Looking at the manuals and Hooper et al's analysis, more issues have come to light, for example the risk of confirmatory bias (am I right on that?) AGAINST 'APT', as well as the discrepancy between pacing as PACE authors construct it, and anyone else might understand it (i.e. banal and understandable autonomonous managing of activity). Other issues around ideology and bias- which can and should be discussed in scientific discourse, and ethics, seem to be coming up as well. The retrospective application of the 'London' and Fukuda is going to be 'interesting' also.

But otherwise you've encapsulate most of it I'd say.

They are only going to use Oxford and not Feduka at all .fine print I,m sure that one of the tests was parametric .spot on on bias.

 

[Dolphin]

They are only going to use Oxford and not Feduka at all

Completion of baseline assessment
The following baseline assessments will be completed at visit 2:

[..]

2. The CDC criteria for CFS [1]

 

[Gerwyn]

At the bottom of the methodology section they clearly state that the weeded out patients will fit the oxford criterea

 

[Gerwyn]

Sorry Tomk This is what is getting me hot under the collar.In 25 years it is the worst study I,ve ever seen. Not ONE criterea for an RCT has been met! They can even adjust a patients self reports to adjust for" completeness "according to predetermined criterea.You cant even tell whether ant treatment is better than a cup of tea and a chat - oh and by the way patients have been allocated into groups based on the severity of their DEPRESSION Let me guess the milder depressed ones got CBT and or standard treatment and the pacing group were so depressed that they could barely cross a room!
nclusion criteria

1. Both participant and clinician agree that randomisation is acceptable.

2. The participant has given written informed consent.

3. The participant meets operationalised Oxford research diagnostic criteria for CFS [2].

4. The participant's Chalder Fatigue Questionnaire score is 6 or more [27].

5. The participant's SF-36 physical function sub-scale score [28] is 65 or less.

6. The participant is aged at least 18 years old.
Exclusion criteria

1. All potential participants will be screened for medical exclusions, by history and physical examination [1,2,4,29]. Appropriate investigations [4,29] will be undertaken by either the referring doctor or the centre doctors (checked by the research nurse) in the six months before baseline screening. Patients with a relevant alternative medical diagnosis will be excluded [2]. Investigations will be those recommended by the Royal Colleges' Report on CFS/ME and the CMO's working group report [4,29].

2. The research nurse (RN) will use a standardised psychiatric interview (the Structured Clinical Interview for DSM-IV – SCID) [30], under supervision by a participating centre PI or nominated deputy, to exclude those who are at significant risk of self-harm and those with psychiatric exclusions listed in the Oxford diagnostic criteria for CFS [2].

3. Patients who are considered by the RN, in discussion with their centre leader, to be unable to do one or more of the trial therapies or to complete all trial measures or for whom participation in the PACE trial would be inappropriate to their clinical needs (e.g. someone with significant post-traumatic stress disorder or borderline personality disorder).

4. Patients who have previously attended a PACE centre specialist fatigue clinic and received a course of treatment, from a specialist, considered to be similar to SSMC or any of the supplementary therapies of APT, CBT, or GET as delivered in the trial will be excluded from taking part in the trial.
Screening/Baseline Procedures

 

[starryeyes]

Thanks for answering my questions. It's inspiring to see all the well-researched comments you all are making on these studies.

 

[Dolphin]

Thanks for answering my questions. It's inspiring to see all the well-researched comments you all are making on these studies.

Thanks very much teejkay. :Retro smile:

 

[Dolphin]

At the bottom of the methodology section they clearly state that the weeded out patients will fit the oxford criterea

Yes, that is right (all will satisfy the Oxford criteria) but they will note who satisfy the Fukuda definition (but not note who satisfies the Canadian criteria) which I believe is what Angela was alluding to.

 

[Dolphin]

Sorry Tomk This is what is getting me hot under the collar.In 25 years it is the worst study I,ve ever seen. Not ONE criterea for an RCT has been met!!

Are you sure? What explicitly are you saying? I imagine they see the SSMC as the control group. And they do seem to do some sort of randomisation.

My guess is that in terms of the points system for trials, it will has been designed to do well.

They can even adjust a patients self reports to adjust for" completeness "according to predetermined criterea.

This is the only reference to "completeness" I can find.

Data will be recorded on Case Report Forms (CRFs). These
will be completed by the patient for the self-report measures,
and all other data will be collected and completed by
the RN. The CRFs will be checked for completeness and
legibility by the RN before being entered onto the trial
database by a local data manager (DM). Once data has
been entered onto the local database, the data will be
transferred to the senior data manager on the trial who
will compare the hard copy CRFs with the database to
check accuracy. S/he will check all the primary outcome
variables and a randomly chosen 20 percent of the other
variables. All CRFs for the first ten patients randomised
per centre will be double checked. If there are any errors
on primary outcomes, or greater than 1% errors of other
variables, 100% data checks will be completed until the
error rate ceases or drops. The database will not include
the assigned treatments – these will be recorded in a separate
database, in order for the statistician analysing the
data to remain blind to treatment allocation

What are you saying is bad about this (i.e. quote about this line)?

You cant even tell whether ant treatment is better than a cup of tea and a chat - oh and by the way patients have been allocated into groups based on the severity of their DEPRESSION Let me guess the milder depressed ones got CBT and or standard treatment and the pacing group were so depressed that they could barely cross a room!

They claim that people will be divided up in equal amounts. Although not everyone might trust them.

Participants will be allocated to one of the four trial arms
(ratio 1:1:1:1) by the Mental Health & Neuroscience Clinical
Trials Unit (MH&N CTU) based at the Institute of Psychiatry.
Allocation will be stratified by centre, CDC Criteria
(met or unmet), London Criteria (met or unmet) and
depressive disorder (major, minor depressive episode and
dysthymia being present or absent) using minimisation
with a random component [45]. The stratification on
these criteria is to ensure equal proportions in each treatment
arm.

 

[Gerwyn]

Are you sure? What explicitly are you saying? I imagine they see the SSMC as the control group. And they do seem to do some sort of randomisation.

My guess is that in terms of the points system for trials, it will has been designed to do well.



This is the only reference to "completeness" I can find.



What are you saying is bad about this (i.e. quote about this line)?


They claim that people will be divided up in equal amounts. Although not everyone might trust them.

There is no such thing as standard therapy it is just a term they have coined.you can see that complete has two meanings here they are free to amend the forms since when has this being science.The final inclusion criterea are those that conform to oxford only only the prelim is "CDC".If you look you will see that pts were stratified according to severity of depression-patients with depression should be actively excluded! how can you allocate patients to a study with the label CDC criterea of unmet you can alter a patients self report according to PREDETERMINED criterea. a RCT uses the Null hypothesis does not go looking to get support for theories uses objective measureable end points internationally agreed diagnostic criterea and is blinded and the measurements once made cannot be unblinded.Every thing is a subjective interpretation.

 

[Dolphin]

The final inclusion criterea are those that conform to oxford only only the prelim is "CDC".

I am not sure what you are saying? My impresion is that all will satisfy the Oxford criteria but they will note who satisfy the Fukuda definition (but not note who satisfies the Canadian criteria) - are you saying that is wrong? I suppose one aspect is that excludes Fukuda-but-not-Oxford patients - but is that many? I'm not sure how they do the exclusions e.g. is a positive Romberg sign an exclusion from Oxford? Reeves actually uses it as an exclusion from the CDC research (even before the empiric definition).

If you look you will see that pts were stratified according to severity of depression-patients with depression should be actively excluded!"

Some of this depression won't be particularly serious

depressive disorder (major, minor depressive episode and dysthymia being present or absent

They might argue that, like with conditions like MS, some of the people with "CFS" will also have some form of depression in a real practice. Although given the possible lack of certainty as to the correct diagnosis of some people, it might be better to try to have a pure sample.
My fear is we may be selectively be given figures which suggest the depression issue isn't an issue as there will be so many figures they could give but they can choose what they want to show us.

Also it is interesting that they tend to exclude people from CFS research if you have another physical condition, but not if you have some psychiatric conditions.

how can you allocate patients to a study with the label CDC criterea of unmet!"

Yes, I agree, like previous studies you really have to wonder what a lot of these Oxford-criteria-but-not-Fukuda-criteria patients have. But again, I worry they will twist the figures and claim the results are the same for all groups and so we they will claim we shouldn't criticise the earlier studies which used the Oxford criteria.
Also, not sure if you know but initially the FINE Trial was just going to be on the Fukuda criteria. Then quite late in the day, it was altered to match the PACE Trial in a few ways e.g. it uses the Oxford criteria as the main criteria but will check for the Fukuda criteria.

a RCT uses the Null hypothesis does not go looking to get support for theories uses objective measureable end points internationally agreed diagnostic criterea and is blinded and the measurements once made cannot be unblinded.Every thing is a subjective interpretation.

I agree.

 

[Gerwyn]

I am not sure what you are saying? My impresion is that all will satisfy the Oxford criteria but they will note who satisfy the Fukuda definition (but not note who satisfies the Canadian criteria) - are you saying that is wrong? I suppose one aspect is that excludes Fukuda-but-not-Oxford patients - but is that many? I'm not sure how they do the exclusions e.g. is a positive Romberg sign an exclusion from Oxford? Reeves actually uses it as an exclusion from the CDC research (even before the empiric definition).

Some of this depression won't be particularly serious
They might argue that, like with conditions like MS, some of the people with "CFS" will also have some form of depression in a real practice. Although given the possible lack of certainty as to the correct diagnosis of some people, it might be better to try to have a pure sample.
My fear is we may be selectively be given figures which suggest the depression issue isn't an issue as there will be so many figures they could give but they can choose what they want to show us.

Also it is interesting that they tend to exclude people from CFS research if you have another physical condition, but not if you have some psychiatric conditions.

Yes, I agree, like previous studies you really have to wonder what a lot of these Oxford-criteria-but-not-Fukuda-criteria patients have. But again, I worry they will twist the figures and claim the results are the same for all groups and so we they will claim we shouldn't criticise the earlier studies which used the Oxford criteria.
Also, not sure if you know but initially the FINE Trial was just going to be on the Fukuda criteria. Then quite late in the day, it was altered to match the PACE Trial in a few ways e.g. it uses the Oxford criteria as the main criteria but will check for the Fukuda criteria.

I agree.

minor depression would be serious to you and me --these guys are clever with wording that is not english but has a very precise meaning in psycho land.Major depression as a comorbidity is ex rare.Oxford is final inclusion criterea ones who dont fit are weeded out..Thanks about FINE very interesting.I really appreciate your input I will get back to you regarding other points got to take kids to school