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An open letter to Psychological Medicine, again! by D Tuller et al

A.B.

Senior Member
Messages
3,780
There seems to be no standardized plan for a clinical trial, which I find surprising because it would make it easier to compare different interventions as well as preventing mistakes by inexperienced investigators.

Of course there has to be some flexibility to account for the different characteristics of diseases and interventions but a lot could be standardized, and the "moving parts" could be designed according to an algorithm rather than allowing researchers to do whatever they like.
 
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Messages
2,391
Location
UK
I am the first person to be cautious of over-zealous regimentation of leading edge research. Excessive regulation and process can completely stifle innovation - human creativity is not something to be commanded at will, where every inventive thought gets interrupted by some inane bureaucratic intervention.

But where human safety is involved there has to be a sound process involved, and the process has to be designed to accommodate the needs of all parts of that process; the need to foster and support highly innovative research endeavours, together with the overarching requirement for human safety and welfare. Such a process has to be feasible, but it is not going to happen unless people recognise the need for it, and apply themselves to designing and peer reviewing such a process. But "doing it like we've always done it" just does not cut it any more. PACE has really brought that to the fore.

Clinical research is going to have to change its ways. It is unfortunate for those who have always done it with integrity and professionalism, but one day medical history may teach that PACE proved to be the turning point, after which nothing could be the same again.
 
Messages
2,158
I would think that as a start any trial which is unblinded and only has questionnaire based outcome measures should have to be run and analysed by people with no financial or career advantage at stake.

They should also not use statistical tests designed for linear measures to analyse data which is not linear. (eg number of steps, time taken for a task, weight etc are objective linear numerical measures, whereas Chalder fatigue scale and SF-36 physical function are not.)

In any trial of ME/CFS, subjective measures should only be secondary outcomes, whereas actometer readings can give a good measure of how much activity a patient actually does, and should be primary outcomes along with things like 2 day CPET and, hopefully soon, blood tests etc.

And protocols should be pre-published and stuck to. And open peer review, and raw data publication and and and....

We all know this. Why don't so called researchers, especially in psychology. (With honourable exceptions).
 
Messages
2,391
Location
UK
I would think that as a start any trial which is unblinded and only has questionnaire based outcome measures should have to be run and analysed by people with no financial or career advantage at stake.

They should also not use statistical tests designed for linear measures to analyse data which is not linear. (eg number of steps, time taken for a task, weight etc are objective linear numerical measures, whereas Chalder fatigue scale and SF-36 physical function are not.)

In any trial of ME/CFS, subjective measures should only be secondary outcomes, whereas actometer readings can give a good measure of how much activity a patient actually does, and should be primary outcomes along with things like 2 day CPET and, hopefully soon, blood tests etc.

And protocols should be pre-published and stuck to. And open peer review, and raw data publication and and and....

We all know this. Why don't so called researchers, especially in psychology. (With honourable exceptions).
An awful lot of why's regarding researchers distinctly lacking in wisdom.
 

BruceInOz

Senior Member
Messages
172
Location
Tasmania
Just for fun, I plotted the baseline Chalder Fatigue scores for all PACE participants versus the baseline 6 minute walk distances (being the only somewhat objective measure available). Can anyone spot a correlation? Surely something like this should have been part of validating the CFQ?
CFQvs6MWT.jpg
 

TiredSam

The wise nematode hibernates
Messages
2,677
Location
Germany
I think its use is not that wide spread outside a small group in the UK and possibly the netherlands.
I've had to fill it in twice in Germany - once at the university hospital in Berlin and once at my local clinic before having a tilt-table test.

EDIT: Second one was actually SF-36, which I regarded as an offensive piece of crap. I seriously considered leaving the clinic without doing the tilt-table test when I was presented with the questionnaire. Trouble was it was the only tilt-table in my whole area, for historical reasons it was hidden in the depths of a psychosomatic clinic, and they weren't letting anyone else have it.

So I just sniffed haughtily and flung my cape over my shoulder in a contemptuous manner to register my disapproval, not that I think anyone noticed. I was in a corridor on my own so it was a bit of a waste of time actually, but I felt better.
 
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Messages
2,125
From the original research paper for the CFQ:
"
Comparing the Fatigue Scale with the fatigue question in the CIS-R, ROC analysis was used to define the
best Fatigue Scale cut-off score on the 100 consecutive attenders.
The results (Table IV) suggest that the optimum cut-off is 3/4 with the area under the ROC curve being 0.85.
This is of course a conservative estimate as it assumes that the answer to the CIS question is the ‘Gold Standard’,and that the CIS is error free.
Both of these assumptions are open to question."

"
It is recommended, however, that the scale is not used alone to detect cases, but should be used as an adjunct
to a thorough clinical assessment.
The scale has good face validity, and reasonable discriminant validity.
Although evidence of validity as an estimator of change has been established in an open-treatment
trial further evidence could be obtained by using the scale before and after treatment in a con-trolled trial."

Interesting split of the word controlled........an omen?

eta: a scale based on assumptions 'open to question' does not sound very reliable to me.
 
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user9876

Senior Member
Messages
4,556
The scale has good face validity, and reasonable discriminant validity.
Although evidence of validity as an estimator of change has been established in an open-treatment
trial further evidence could be obtained by using the scale before and after treatment in a con-trolled trial."

I assume discriminant validity simply means testing ill or not ill.

The big question is whether it is a good estimator of change as they put it. To me that means if we have a perfect fatigue estimator which is linear then the CFQ would need to approximate this. Important properties being:
If patient A at position Xa on the scale improves on our perfect fatigue estimator by a quantity of I to a new value of Ya and patient B at position Xb improves by the same amount I to Ya then For all I, (Ya-Xa)~=(Yb-Xb).

I'm not sure how you would ever prove such a thing. But thing that can be done is to substitute an alternative fatigue scale for the perfect fatigue estimator. Hence you at least test the consistency of the two scales together (where I is scaled). But this involves more than drawing ROC curves and saying they are equally good at dealing with ill|not ill comparisons.

With the CFQ they have two marking schemes so we could look at the consistency across the two different schemes. I think given the two schemes it is clear that they are not consistent. As we even get the case where one patient can improve and get worse - This can be because there are improvements on some questions that count in the Likert scoring but not in the binomial scoring and a worsening of 1 question where the Binomial scoring counts. Comparing patients has a similar issue.

There will be edge effects as well but I think even in the area of interest at the middle of the scale things are dodgy.

One reason for wanting the property I have stated is that if you want to look at the mean differences over a set of patients (P). Basically the mean = sum(i member P, (Yi-Xi))/|P| so if the improvements are not equal due to the starting position then the mean difference does not have a good meaning.

A further complexity is introduced in that the CFQ acknowledges that mental and physical fatigue can change independently. It also has a different number of questions for mental and physical fatigue.
 

adreno

PR activist
Messages
4,841
Just for fun, I plotted the baseline Chalder Fatigue scores for all PACE participants versus the baseline 6 minute walk distances (being the only somewhat objective measure available). Can anyone spot a correlation? Surely something like this should have been part of validating the CFQ?
View attachment 20154
It looks like no matter their fatigue scores, they all center around 3-400 meter walking distance = no correlation at all.
 

Keela Too

Sally Burch
Messages
900
Location
N.Ireland
Just for fun, I plotted the baseline Chalder Fatigue scores for all PACE participants versus the baseline 6 minute walk distances (being the only somewhat objective measure available). Can anyone spot a correlation? Surely something like this should have been part of validating the CFQ?
View attachment 20154
Saw this on Twitter and my comment was that people who can walk almost no metres can score the same on the Chalder scale as someone able to walk 100s metres. So really no correlation to physical ability at all.
 

user9876

Senior Member
Messages
4,556
Saw this on Twitter and my comment was that people who can walk almost no metres can score the same on the Chalder scale as someone able to walk 100s metres. So really no correlation to physical ability at all.

By having self reported physical function and fatigue as 2 primary outcomes in PACE they are saying that they are different things. So they may be happy with a lack of correlation. The question from the PACE perspective is whether the sf36 physical function values correlate with the 6 minute walking test.

Then there is a separate question around expected correlations between fatigue and physical function.
 

Jan

Senior Member
Messages
458
Location
Devon UK
We know from research that exercise harms pwme, it's a biological fact. How, then, can this still be legal? How can they keep ignoring all the recent studies? As we have said a million times, if these treatments were drugs they would have been withdrawn long ago. NICE and the NHS are far too complacent that they will not face legal consequences. They should, they are dangerously harming people, this poor person may never recover from this. It breaks my heart over and over to keep hearing these stories, we've got to get these guidelines stopped!
 
Messages
2,125
I'm only reposting this because I would like @Jonathan Edwards opinion.

I can't understand how the Chalder Fatigue Scale (which I've only just twigged is co-incidentally abbreviated to CFS:cautious:)
has been so widely accepted and used as a reliable means of measuring fatigue? (It makes me think of the current adverts for smart meters).
this was the actual study 1993:
http://simonwessely.com/Downloads/Publications/CFS/32.pdf
also used the fatigue questions from clinical interview schedule (cis r, regarded as the 'gold standard')

eta: I should say 'sometimes' abbreviated to CFS (see the chinese study).
just found thisfrom 1998 but can only view the abstract:
https://www.ncbi.nlm.nih.gov/pubmed/9835234
Exploring the validity of the Chalder Fatigue scale in chronic fatigue syndrome
 
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