PACE Trial and PACE Trial Protocol

[Sean]

BTW, does anyone know whether there is any way to download such files? I like to store things in my PACE Trial folder but didn't see any easy way of storing this.

I would just take a screen snap. The article is only two pages, and they can be displayed as one image (on the site).

Kinda crude, but does the job.

 

[Dolphin]

I would just take a screen snap. The article is only two pages, and they can be displayed as one image (on the site).

Kinda crude, but does the job.

Thanks. I hadn't tried it. I tried Awesome Screenshot but could only get it to work when the piece was outside the magazine and then the text was just indecipherable. I tried printing to a pdf when looking at it but made a 1KB file. I'm no expert at using such tools so they may do the trick. If anyone manages it, let me know - thanks.

 

[Graham]

Thanks Dolphin for the tables - I have saved them to study this weekend. Thanks Alex for the comments. Now to put it all together.

If I can earn my keep - I did a delayed time screen grab of the full screen display, and it is in TIFF format (although I can convert it to other formats if you like). It isn't the best quality, but it is better than the smaller display. So if it is of any use to anyone, I don't know how to make it available to you, but if you send me a pm with your email address, I can email it (or tell me how to send it otherwise).

 

[Graham]

Bob has just sent me a better quality one! So either of us can let you have that. It'

 

[Dolphin]

Thanks Graham. Bob took the initiative and sent me one. Thanks.

 

[Sean]

Thanks Bob & Graham.

Apologies Dolphin, I could have just as easily emailed you my screen snap. I plead it was after midnight and the ol' brain was operating on reflex.

 

[Dolphin]

Thanks Bob & Graham.

Apologies Dolphin, I could have just as easily emailed you my screen snap. I plead it was after midnight and the ol' brain was operating on reflex.

No problem - I asked partly as I wanted to know how to do it in the future - I'm come across the odd thing on issuu in the last while and have wondered how to save stuff.

 

[oceanblue]

CFQ problems

I am just putting together an argument as to how it is possible that it was quite difficult for some patients to record worsening score. It isn't quite ready yet, but basically, if you have ME and, on the Chalder scale, rate 6 things as really bad (score 3 each), two as bad (score 2 each) and the remaining 3 items (like muscle weakness) not affected by the ME (score 1 each), you would score 25. But unless the treatment affected the things that hadn't been part of the problem, you can only drop your score to 27, even if it nearly kills you. Trying to put together the data on the 26 patients in the recent Goudsmit study suggests that it didn't quiet work like that for those 26 patients - there was a cluster of 5 scoring 11 (bimodal) which transferred to 32 or 33 on the Likert scale, so they couldn't get much worse: 5 of the remaining 8 on a score of 11 transposed to 30, so they could deteriorate by 3 points. The other three on 11 converted to 27, 28 and 29. Those on lower bimodal scores of 8,9 or 10 seem to have put half in the score 3 category and half in the score 2, so they could drop by 4 or 5 points if things got bad.

I'd agree that the oddest thing about CFQ is that scoring max depends as much on the nature of your symptoms as the severity of fatigue - so that you can max out with a score well below 33.

As an extreme example, many years ago I was admitted to hospital as an emergency case because my ME was so severe - I could only talk for literally 2-3 minutes before needing an hour or so to recover. Yet I would have scored maybe 27 on the CFQ as I didn't have problems with memory, finding words or slips of the tongue. Even though mental fatigue was my worst problem - and I was the worst case any of the medics had seen, I scored only 6 out of a possible 12 points on mental fatigue.

I also suspect that the 'difficulty starting things' question may relate more to motivation than fatigue, particularly for those well enough to be part of a clinical trial.

Apart from the fact that so many CFS patients have hit a CFQ ceiling - even those with a score less than 33, the scalel sufers from effectively having just 3 levels at heart: no fatigue, some or a lot.

Finally, going back to the original paper, the scale was developed using new registrants to a general practic, and attenders, ie not a specifically fatigued population, and 'validated' not even against another fatigue scale but using the fatigue questions on the psychological CIS-R questionnaire. Unfortunately I can't now remember where I saw it, but I recently came across CFQ compared with another fatigue scale and the correlation between the two was under 0.2, which is pretty weak. there's no guarantee the other scale was much good either, but it is not a good sign.

I don't know if the other fatigue scales are so hot either, but the CFQ is definitely not.

 

[Dolphin]

I'd agree that the oddest thing about CFQ is that scoring max depends as much on the nature of your symptoms as the severity of fatigue - so that you can max out with a score well below 33.

As an extreme example, many years ago I was admitted to hospital as an emergency case because my ME was so severe - I could only talk for literally 2-3 minutes before needing an hour or so to recover. Yet I would have scored maybe 27 on the CFQ as I didn't have problems with memory, finding words or slips of the tongue. Even though mental fatigue was my worst problem - and I was the worst case any of the medics had seen, I scored only 6 out of a possible 12 points on mental fatigue.

I also suspect that the 'difficulty starting things' question may relate more to motivation than fatigue, particularly for those well enough to be part of a clinical trial.

Apart from the fact that so many CFS patients have hit a CFQ ceiling - even those with a score less than 33, the scalel sufers from effectively having just 3 levels at heart: no fatigue, some or a lot.

Finally, going back to the original paper, the scale was developed using new registrants to a general practic, and attenders, ie not a specifically fatigued population, and 'validated' not even against another fatigue scale but using the fatigue questions on the psychological CIS-R questionnaire. Unfortunately I can't now remember where I saw it, but I recently came across CFQ compared with another fatigue scale and the correlation between the two was under 0.2, which is pretty weak. there's no guarantee the other scale was much good either, but it is not a good sign.

I don't know if the other fatigue scales are so hot either, but the CFQ is definitely not.

You might be thinking of this study (Chalder score categories are on left hand side):

Table 1 Correlations of Two Fatigue Rating Scales


______________________________________________________________________
Fatigue Severity Scale (Krupp et al., 1989)

Overall Sample CFS-like Group Control Group
(N = 213) (N = 166) (N = 47)
___________________________________________________________

Fatigue Scale (Chalder et al., 1993)

Total Scale Score 0.28** 0.10 0.38*

Physical Fatigue Score0.24** 0.07 0.30

Mental Fatigue Score 0.23** 0.10 0.37*

_____________________________________________________________________________________________
* Indicates significance at p < 0.05 level
** Indicates significance at p < 0.01 level

from

Fatigue rating scales: an empirical comparison.

Psychol Med 2000 Jul;30(4):849-56

Taylor RR, Jason LA, Torres A

Department of Psychology, DePaul University, Chicago,
IL 60614, USA.

PMID: 11037093, UI: 20488564

BACKGROUND: There has been limited research comparing
the efficacy of different fatigue rating scales for
use with individuals with chronic fatigue syndrome
(CFS). This investigation explored relationships
between two commonly-used fatigue rating scales in CFS
research, the Fatigue Scale and the Fatigue Severity
Scale.

Theoretically, these scales have been described as
measuring different aspects of the fatigue construct.
The Fatigue Scale was developed as a measure of the
severity of specific fatigue-related symptoms, while
the Fatigue Severity Scale was designed to assess
functional outcomes related to fatigue.

METHODS: Associations of these scales with the eight
definitional symptoms of CFS and with eight domains of
functional disability were examined separately in: (1)
an overall sample of individuals with a wide range of
fatigue severity and symptomatology; (2) a subsample
of individuals with CFS-like symptomatology, and, (3)
a subsample of healthy controls.

RESULTS: Findings revealed that both scales are
appropriate and useful measures of fatigue-related
symptomatology and disability within a general
population of individuals with varying levels of
fatigue. However, the Fatigue Severity Scale appears
to represent a more accurate and comprehensive measure
of fatigue-related severity, symptomatology, and
functional disability for individuals with CFS-like
symptomatology.

 

[Dolphin]

In: Jason, L.A. & Choi, M. (2008). Dimensions and assessment of fatigue. In Y. Yatanabe, B. Evengard, B.H. Natelson, L.A. Jason, & H. Kuratsune (2008). Fatigue Science for Human Health. (pp 1-16). Tokyo: Springer.

See last sentence:

The Fatigue Scale: The Fatigue Scale40 is a 14-item verbal rating instrument with a 4-choice format that measures fatigue intensity. This scale was originally used in a hospital-based case control study41 and in a study designed to measure response to treatment42. David and associates43 found a continuous distribution of fatigue scores on this scale in a sample in Great Britain. The Fatigue Scale produces a total score, a score reflecting mental fatigue, and a score reflecting physical fatigue. The Fatigue Scale was further refined by Chalder and associates40. Despite its brevity, the scale was found to be reliable and valid, and it has good face validity and reasonable discriminant validity. The 11-item scale is commonly scored in one of two ways. Continuous scoring codes responses according to a four-option continuum, with codes ranging from 0 to 3 and total scores ranging from 0-33 (with higher scores signifying greater fatigue). Dichotomous scoring codes responses according to a two-option dichotomy, where responses normally coded as 0 or 1 are represented by a score of 0, and responses normally coded as 2 or 3 are represented by a score of 1. The total dichotomous scores of four or more items coded as 1, characterize cases of significant fatigue40. The Fatigue Scale is commonly used in community-based studies of fatigue, chronic fatigue, and CFS44,45. Jason and associates46 used a Receiver Operating Characteristic curve analysis to differentiate those with CFS from healthy controls, although those with SLE were most similar to those with CFS. Factor analysis has uncovered, two dimensions, physical and mental fatigue, although one study questioned the stability of this factor structure47. One limitation in this scale is its inability to distinguish between CFS and primary depression patients.

40. Chalder, T., Berelowitz, G., Pawlikowsy, J., Watts, L. & Wessely, D. (1993).
Development of a fatigue scale. Journal of Psychosomatic Research, 37, 147-153.
41. Wessely, S., & Powell, R. (1989). Fatigue syndromes: A comparison of chronic 'postviral' fatigue with neuromuscular and affective disorders. Journal of Neurology, Neurosurgery and Psychiatry, 52, 940-948.
42. Butler, S., Chalder, T., Ron, M., & Wessely, S. (1991). Cognitive behavior therapy in chronic fatigue syndrome. Journal of Neurology. Neurosurgery and Psychiatry, 54, 153-158.
43. David, A.S., Pelosi, A., McDonald, E., Stephens, D., Ledger, D., Rathbone, R., & Mann,.(1990).Tired, weak, or in need of rest: fatigue among general practice
attenders. British Medical Journal, 301, 1199-1202.
44. Pawlikowska, T., Chalder, T., Hirsch, S. R., Wallace, P., Wright, D. J. M., & Wessely, S. C. (1994). Population based study of fatigue and psychological distress. British Medical Journal, 308, 763-766.
45. Loge, J. H., Ekeberg, O, & Kaasa, S. (1998). Fatigue in the general Norwegian population: Normative data and associations. Journal of Psychosomatic Research, 45 (1), 53-65.
46. Jason, L.A., Ropacki, M.T., Santoro, N.B., Richman, J.A., Heatherly, W., Taylor, R.R., Ferrari, J.R., Haney-Davis, T.M., Rademaker, A., Dupuis, J., Golding, J.,
Plioplys, A.V., & Plioplys, S. (1997). A screening scale for Chronic Fatigue
Syndrome: Reliability and validity. Journal of Chronic Fatigue Syndrome, 3, 39-59.
47. Morriss, R. K., Wearden, A. J. & Mullis, R. (1998). Exploring the validity of the Chalder fatigue scale in chronic fatigue syndrome. Journal of Psychosomatic Research, 45, 411-417.

 

[oceanblue]

Thanks, Dolphin, for going to so much trouble with this. The Jason/Krupp data wasn't what I was thinking of but says the same thing ie the correlation of CFQ with other fatigue scales among CFS (-like) patients is minimal: 0.10 for Krupps, (0.11 for the Fatigue Visual Analogue Scale - I remembered, it's here, table 2).

CFQ seems to be OK at telling people with Chronic Fatigue Syndrome from healthy individuals but whoopee doo. A 12 year-old science student could probably design a questionnaire that would do that too.

The real test is: can it usefully measure fatigue amongst fatigued patients? In particular, it needs to be able to:
- distinguish between levels of fatigue severity amongst patients
- measure changes in patients over time (both improvements and any deterioration)
both are needed for it to be useful in clinical trials like PACE. The Jason research you helpfully posted suggests CFQ doesn't do too well.

In fact, I haven't seen any evidence that CFQ is appropriate for such use in clinical trials. The very weak correlation with other fatigue scales in CFS (like) population raises further concerns.

Maybe CFQ is a perfectly good way of measuring fatigue in PACE. But I have my doubts. I guess the real question is: would the PACE results have been any different using using an 'ideal' fatigue scale?

 

[Dolphin]

Link to Goudsmit et al. (2008) on CFQ

A paper on the Chalder Fatigue Questionnaire (CFQ) that probably is fairly easy to understand (or it should be fairly easy to understand the Figure(s) anyway) is http://www.iacfsme.org/LinkClick.aspx?link=292&tabid=290

 

[Dolphin]

Thanks, Dolphin, for going to so much trouble with this. The Jason/Krupp data wasn't what I was thinking of but says the same thing ie the correlation of CFQ with other fatigue scales among CFS (-like) patients is minimal: 0.10 for Krupps, (0.11 for the Fatigue Visual Analogue Scale - I remembered, it's here, table 2).

CFQ seems to be OK at telling people with Chronic Fatigue Syndrome from healthy individuals but whoopee doo. A 12 year-old science student could probably design a questionnaire that would do that too.

The real test is: can it usefully measure fatigue amongst fatigued patients? In particular, it needs to be able to:
- distinguish between levels of fatigue severity amongst patients
- measure changes in patients over time (both improvements and any deterioration)
both are needed for it to be useful in clinical trials like PACE. The Jason research you helpfully posted suggests CFQ doesn't do too well.

In fact, I haven't seen any evidence that CFQ is appropriate for such use in clinical trials. The very weak correlation with other fatigue scales in CFS (like) population raises further concerns.

Maybe CFQ is a perfectly good way of measuring fatigue in PACE. But I have my doubts. I guess the real question is: would the PACE results have been any different using using an 'ideal' fatigue scale?

Well spotted on that correlation. A VAS (Visual Analog Scale) might be considered the purest sort of fatigue scale so that's a low correlation. Technically that's the bimodal while in the end they used the Likert (0-33) scale in the PACE Trial.

It would be interesting to know if another scale would have made a difference. A general question I have is about the 0 scoring ("Less than usual"); as we saw with the CBT for MS trial, people were clearly giving some 0s for some symptoms and if that was more common with some interventions e.g. CBT and GET for CFS, it could cause problems. As I said in a recent message, I am suspicious of these 0 scores rather than 1s ("No more than usual") where usual is before one got CFS.

 

[oceanblue]

Well spotted on that correlation. A VAS (Visual Analog Scale) might be considered the purest sort of fatigue scale so that's a low correlation. Technically that's the bimodal while in the end they used the Likert (0-33) scale in the PACE Trial.

It would be interesting to know if another scale would have made a difference. A general question I have is about the 0 scoring ("Less than usual"); as we saw with the CBT for MS trial, people were clearly giving some 0s for some symptoms and if that was more common with some interventions e.g. CBT and GET for CFS, it could cause problems. As I said in a recent message, I am suspicious of these 0 scores rather than 1s ("No more than usual") where usual is before one got CFS.

Yes, and a VAS would not have the CFQ problem of requiring a particular set of symptoms to get the maximum score. Thanks for the Ellen Goudsmit paper; more evidence of ceiling effect (and at least some of those with sub-maximal scores have probably hit a ceiling given their particular symptoms).

The use of 'less fatigue than normal' is odd and confusing. In a clinical trial, some patients may wrongly rate themselves to how they were earlier in the trial (as opposed to before they were ill). I think there was just the one MS trial with sub-11 CFQ scores and these occurred in both the Relaxation Therapy and the CBT group; I suspect a therapist effect here (same therapist carried out both treatments).

 

[Dolphin]

Just to point out that just because scores in the PACE Trial weren't under 11 doesn't mean there were few 0s on individual items.

 

[Dolphin]

From another general paper I was reading:

CMAJ. 2004 Sep 28;171(7):735-40.
Outcome reporting bias in randomized trials funded by the Canadian Institutes of Health Research.
Chan AW, Krleza-Jeri? K, Schmid I, Altman DG.
Free full text at: http://www.cmaj.ca/content/171/7/735.long

Major discrepancies in primary outcomes were identified between protocols and publications in 40% of the trials in our cohort. Possible explanations for the observed discrepancies include the following: a preference for primary outcomes that demonstrate particular results; logistical barriers to measuring the original primary outcome; low event rates for binary primary outcomes; new evidence that invalidated the original primary outcome, or supported the use of a more appropriate outcome; formal amendments made to the original protocol before trial initiation that were not submitted to CIHR/MRC; and researchers' lack of awareness that retrospective revisions to prespecified outcomes and analyses can be methodologically unsound.

Not sure how many apply for the PACE Trial.

 

[Dolphin]

Study which found self-report measures of activity in trials are problematic

I and others (IIRC) had hypothesised that self-report measures might cause problems in trials such as PACE which test GET and GAT-based/GET-based CBT. So it was interesting to see this study:

The effect of a physical activity intervention on bias in self-reported activity.

Ann Epidemiol. 2009 May;19(5):316-22. Epub 2009 Feb 20.

Taber DR, Stevens J, Murray DM, Elder JP, Webber LS, Jobe JB, Lytle LA.

http://forums.phoenixrising.me/show...ention-on-bias-in-self-reported-activity-(gen)

 

[Bob]

I don't have an 'edit' button on my posts before post #1000 in this thread.
Could someone have a look to see if it is the same for them please?

 

[Sean]

I don't have one either. But this is pretty standard on forum software, I think. There is usually an edit window, the length of which can be set by the admin (x minutes, days, months, etc).

 

[Dolphin]

I don't have an 'edit' button on my posts before post #1000 in this thread.
Could someone have a look to see if it is the same for them please?

I can't edit my posts thru' June 3. I can edit my June 5th post. I imagine the forum must have been set that one can only edit posts from the last two months - I've seen forums/fora with shorter periods. Unfortunately, the meanies won't let me edit other people's posts at all.