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'Recovery' from chronic fatigue syndrome after treatments given in the PACE trial

Dolphin

Senior Member
Messages
17,567
The only 5 year followup study I'm aware of is this one: http://ajp.psychiatryonline.org/article.aspx?articleid=175215 . It has quite a few issues, such as being a chronic fatigue study (oxford definition), not an ME/CFS study. Plus the CBT included pacing, and the "relaxation" was of the sort using muscle tensing - something I've crashed from when guided to do it by a really stupid "relaxation" therapist.

It's also a very small study (53 patients total), and showed improvement in only certain areas: the GET group was working more hours, but had the same amount of unemployed patients as the "control" group (about 50%). In addition, three of the CBT group had been misdiagnosed (1 with cancer, 2 with celiac), which also likely skews the results, as those 3 account for 12% of the CBT group.

Something I find very interesting, if looking at Table 1, is that the CBT patients reported a huge improvement at 6 months on some questionnaires, which completely disappeared at 5 years. Brainwashing, anyone? :p In fact, the only questionnaire outcome measurement where the was a (barely) statistical signficance at 5 years was self-rating of improvement. And if you take into account the 12% of known misdiagnosed CBT patients (who probably had a full recovery due to getting appropriate treatment), there's probably no statistical significance in any of the 5 year results.

That study is worthless.

Lots of good points, thanks.
 

biophile

Places I'd rather be.
Messages
8,977
Re: Occupational Aspects of the Management of Chronic Fatigue Syndrome: a National Guideline.

Ross et al (2004) review mentioned on page 14:

Employment outcomes

A preliminary literature search showed that, although there is a considerable body of research on CFS, few studies have looked at employment outcomes. During the first GDG meeting, a paper specifically focussing on work outcomes was identified: “Disability and chronic fatigue syndrome – a focus on function” by SD Ross et al. [48]. This paper summarises a systematic review of studies published in English from 1 January 1988 to 15 November 2001. Interventional and observational studies of adults with CFS were eligible for inclusion in the Guideline Development Group’s evidence review if they reported measures of disability and employment. This identified 3,840 studies, of which 37 reported employment status and some measure of mental or physical impairment associated with disability. Most patients with CFS in these studies were unemployed. In 22 studies, the employment status of controls was also available. Only depression seemed to be associated with unemployment in patients with CFS. No other measurable impairment seemed to be consistently associated with disability or work outcomes. Only CBT, rehabilitation, and exercise therapy interventions were associated with restoring the ability to work. No specific patient characteristics were identified as best predictors of positive employment outcomes. The Ross paper concluded that for questions of disability and employment in CFS, the limitations inherent in the current literature are extensive.

Last year I wrote harshly about using this to support CBT/GET. "Associated" with restoring the ability to work does not mean actually restoring said ability. Basically, three of the four studies had uncontrolled comparisons, and the employment data on the remaining study was based on only 2 people.

Then the national guidelines explores the evidence for itself. Page 19 has the method for selection of papers for critical appraisal. Page 21 has the grading of reviewed evidence. Page 22 has the limitations of the literature review.

Grade A: At least one meta-analysis, systematic review or RCT rated as 1++, and directly applicable to the target population; or A systematic review of RCTs or a body of evidence consisting principally of studies rated as 1+, directly applicable to the target population, and demonstrating overall consistency of results.

Grade B: A body of evidence including studies rated as 2++, directly applicable to the target population, and demonstrating overall consistency of results; or Extrapolated evidence from studies rated as 1++ or 1+.

[etc C and D]

Page 25 has "4. Treatments for CFS that have been shown to improve work outcomes."

Evidence for CBT ("A Grade")

Butler et al. 1991 [40], Deale et al. 1997 [22], Deale et al. 2001 [23].

22. Deale A, Chalder T, Marks I, Wessely S. Cognitive behavior therapy for Chronic Fatigue Syndrome: a randomized controlled trial. American Journal of Psychiatry 1997, 154(3)408–414.
http://ajp.psychiatryonline.org/data/Journals/AJP/3674/408.pdf

Deal et al 1997: Oxford or CDC was used. Table 1 seems to suggest similar levels of unemployment between groups. On quick glance I cannot find mention of employment outcomes. According to the national guidelines:

The study looked at 10 different outcome measures, one of which was the Work and Social Adjustment Scale (WASAS). This scale measures impairment in work, home management, social activities and private leisure. Impairments are measured on a scale of 0–8. 8 represents maximum impairment. Pre-treatment mean WASAS was 6.0 for the 30 CBT patients and 6.1 for the 30 relaxation patients. At 6 months after treatment, mean WASAS was 3.3 for the CBT group and 5.4 for the relaxation group. At six months follow-up, 70% of those who had completed CBT achieved substantial improvement in physical functioning compared with 19% of the relaxation group.

In other words it appears that the WASAS is being confused with employment outcomes.

23. Deale A, Husain K, Chalder T, Wessely S. Long-term outcome of cognitive behavior therapy versus relaxation therapy for Chronic Fatigue Syndrome: a 5-year follow-up study. American Journal of Psychiatry 2001, 158(12)2038–2042. http://psychiatryonline.org/data/Journals/AJP/3731/2038.pdf

Deale et al 2001: Similar proportions of patients were employed, but patients in the cognitive behavior therapy group worked significantly more mean hours per week : 35.57(8.11) hours vs 24.00 (4.97) hours, p<0.04.

I do not recall all the criticisms for this study but I remember being somewhat surprised when first hearing about them because I did not realize it was that bad. FWIW, this is the only study in the national guidelines which actually has relevant evidence for employment outcomes, and the much larger and better conducted PACE Trial (which showed no improvements in employment outcomes) trumps it anyway.

Interesting quote: "Predetermined criteria for 'complete recovery' required that patients no longer met chronic fatigue syndrome criteria, were employed full-time, and scored less than 4 on the Fatigue Questionnaire and more than 83 on the Medical Outcomes Study Short-Form General Health Survey physical functioning scale."

40. Butler S, Chalder T, Ron M, Wessely S. Cognitive behavioral therapy in chronic fatigue syndrome. Journal of Neurology, Neurosurgery and Psychiatry 1991, 54:153–158. http://jnnp.bmj.com/content/54/2/153.full.pdf

Butler et al 1991: Was an uncontrolled pilot study, (it was rated 2+ which is "Well-conducted case-control or cohort studies with a low risk of confounding, bias, or chance and a moderate probability that the relationship is causal.")

Evidence for GET ("B Grade")

"Prins and couper 1998 [27], and White 1997 Fulcher [32]"

The citation here is somewhat confusing. There is no "Prins and couper 1998". The only mention of Couper is a Cochrane review on CBT not GET. Reference 27 is a CBT study too:

27. Prins JB, Bleijenberg G, Bazelmans E, Elving LD, De Boo TM, Severens JL, Van Der Wilt GJ, Spinhoven P, Van Der Meer JWM. Cognitive behaviour therapy for chronic fatigue syndrome: a multicentre randomised controlled trial. Lancet 2001, 357:841–847. http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(00)04198-2/abstract

"Patients were eligible for the study if they met the US Centers for Disease Control and Prevention criteria for CFS,[1] with the exception of the criterion requiring four of eight additional symptoms to be present."

In other words, not a study about CFS.

32. Fulcher KY, White PD. Randomised controlled trial of graded exercise in patients with the chronic fatigue syndrome. British Medical Journal 1997, 314:1647–1652. www.ncbi.nlm.nih.gov/pmc/articles/pmid/9180065/

Fulcher & White 1997: The guidelines graded this as "1+ Well-conducted meta-analyses, systematic reviews of RCTs or RCTs with a low risk of bias." and stated that "Patients were followed up by questionnaire approximately one year after supervised treatment stopped. 66% of patients who completed exercise treatment were working or studying at least part-time, compared with 39% of all 66 patients before treatment (95% confidence interval of difference 9% to 44%)."

However, AFAIK the comparison of improved occupational status was uncontrolled at 12 month follow-up because it was a crossover study which did not account for dropouts or compare with the controls that only did the flexibility program instead of the exercise program The authors acknowledge this weakness but then dismiss it by claiming that spontaneous improvement was an unlikely explanation because it didn't occur in a "similar sample" in another study. The sparse details are on p1651. Table 6 of Ross et el points out that follow-up figures are "based on the number of patients enrolled" and at 15 month follow-up from baseline the rate of employment went from 39% to 47% (no control group).

The evidence has never been strong and is now clearly overshadowed by the PACE Trial.
 

Legendrew

Senior Member
Messages
541
Location
UK
Is the general consensus that CBT/GET are of little to no use then? I've been suffering for a year and living with pacing as i'm a little skeptical of CBT/GET since they seem a little silly when they serve to make me feel more ill.
 
Messages
15,786
23. Deale A, Husain K, Chalder T, Wessely S. Long-term outcome of cognitive behavior therapy versus relaxation therapy for Chronic Fatigue Syndrome: a 5-year follow-up study. American Journal of Psychiatry 2001, 158(12)2038–2042. http://psychiatryonline.org/data/Journals/AJP/3731/2038.pdf

Similar proportions of patients were employed, but patients in the cognitive behavior therapy group worked significantly more mean hours per week : 35.57(8.11) hours vs 24.00 (4.97) hours, p<0.04.

I do not recall all the criticisms for this study but I remember being somewhat surprised when first hearing about them because I did not realize it was that bad. FWIW, this is the only study in the national guidelines which actually has relevant evidence for employment outcomes, and the much larger and better conducted PACE Trial (which showed no improvements in employment outcomes) trumps it anyway.
I probably made my post on the subject at http://forums.phoenixrising.me/inde...n-in-the-pace-trial.21628/page-18#post-373446 while you were writing your novel post :D

Basically 12% of the CBT group was misdiagnosed (1 cancer, 2 celiac) yet were included in the followup data anyhow. That was more than enough to seriously alter the results and remove any statistical significance. And even if we take those results seriously, they're cherry picking outcome measures, as there's no difference in many of them.

Also, Oxford was used.
 
Messages
15,786
Is the general consensus that CBT/GET are of little to no use then? I've been suffering for a year and living with pacing as i'm a little skeptical of CBT/GET since they seem a little silly when they serve to make me feel more ill.
It's the consensus among most CCC/ICC defined ME/CFS patients and medical researchers. The BPS (psychological) groups are really the only holdout, though they make up for it by being prolific in their views. Governments also tend to prefer the BPS views because they offer the cheaper solution.
 
Messages
13,774
Is the general consensus that CBT/GET are of little to no use then? I've been suffering for a year and living with pacing as i'm a little skeptical of CBT/GET since they seem a little silly when they serve to make me feel more ill.

It's possible that some people may find them helpful, but if you've found them unhelpful, and the models which underpin them don't seem to apply to you, then there's a good chance that they'll do more harm than good.

There are a lot of misleadingly positive claims made about CBT/GET for CFS from those who make money from/build careers on them.

Sorry to hear about your ill-health. I'm wary to give any advice to anyone with CFS, as the evidence about how best to respond seems so poor, and it's likely that lots of people with different problems end up with the diagnosis. If I was in your position, I would try to just do what I felt like, and do what made me feel best in the short-term (partly because this is the opposite of what I was told to do!). Hopefully you will start to improve soon, and it does seem that those who have been ill less long are more likely to improve. Best of luck.
 

Simon

Senior Member
Messages
3,789
Location
Monmouth, UK
I had a quick look into the effect of corridor length on the 6MWD score.

One of the sources cited by White et al states that, "The walking course must be 30 m in length. [...] A shorter corridor requires patients to take more time to reverse directions more often, reducing the 6MWD. Most studies have used a 30-m corridor, but some have used 20- or 50-m corridors (52–55). A recent multicenter study found no significant effect of the length of straight courses ranging from 50 to 164 ft, but patients walked farther on continuous (oval) tracks (mean 92 ft farther) (54)." http://www.thoracic.org/statements/resources/pfet/sixminute.pdf

"Recent study suggests that there is no significant difference on the distance walked in courses between 15 and 50 meters, although oval tracks can increase the results (Weiss et al. 2000)." http://kennisbank.hva.nl/document/219224

These above statements are referring to the following (unpublished?) paper:
Weiss RA, et al. Six minute walk test in severe COPD: reliability and effect of walking course layout and length. Paper presented at ACCP Conference; September 2000; San Francisco.

However I did find another very similar paper (Sciurba et al 2003), possibly the same study, which consisted of 761 COPD patients with severe emphysema: "Among the 14 clinics with straight walking courses, the mean length of the course ranged from 50 to 164 feet (mean 99.9 ± 34.1 feet). [...] Among the 14 clinics with straight course layout, there was no statistically significant effect of track length on 6-minute walk distance in bivariate as well as multivariate analyses."
http://www.atsjournals.org/doi/full/10.1164/rccm.200203-166OC

This small study (Veloso-Guedes et al 2011) of 10 patients on the waiting list for liver transplantation, mentions the American Thoracic Society's recommendations of 30m but found no significant difference between 30m and 20m. Perhaps a larger sample size would find a statistically significant difference, but it probability would not be a large effect? http://www.ncbi.nlm.nih.gov/pubmed/21620120

This small study (Ng et al 2011) on 26 patients with chronic stroke tested the 6MWT with 10m, 20m, 30m. It did find a statistically significant difference, but I have not seen the full text. http://www.ncbi.nlm.nih.gov/pubmed/21530729
Full text here

As far as I can tell (based on fig 1) the distance walked with a 30m course was 17% higher than when the same people walked over a 10m course. Though those other studies suggest the effect generally might be less than this.
 

Bob

Senior Member
Messages
16,455
Location
England (south coast)
Re the 6MWDT...
...the same process occurred for SMC and SMC+CBT, so we can still say that CBT led to no additional improvement in their chosen objective measure of physical fitness.

Good point. White's response to the criticisms of the 'recovery' definition was something along the lines of the CBT group performing better than the SMC group, however they measured the improvements. That answer fails to respond to the criticisms and, of course, it ignores all the objective measures, none of which showed better outcomes in the CBT group.

White et al said:
"The findings from the PACE trial are clear; however we measured recovery, CBT and graded exercise therapy (GET) were more likely to lead to recovery, when added to specialist medical care (SMC), compared to either adding APT or SMC alone."
 

Graham

Senior Moment
Messages
5,188
Location
Sussex, UK
And just a reminder in case anyone missed it, that they still paid for the actometers, and used them at the start of the trial. It was just at the end of the trial, at the time one measures whether treatments/therapies worked or not, that they dropped using them.
But they only costed for 12 actometers to be shared amongst all 640 patients. How on earth did they expect that to work out without hitches?
 

Dolphin

Senior Member
Messages
17,567
But they only costed for 12 actometers to be shared amongst all 640 patients. How on earth did they expect that to work out without hitches?

Don't know. But not sure we know yet that they ran out of them/had any problems?
 

user9876

Senior Member
Messages
4,556
Full text here

As far as I can tell (based on fig 1) the distance walked with a 30m course was 17% higher than when the same people walked over a 10m course. Though those other studies suggest the effect might be less than this.


I was wondering if the faster people are able to walk then the greatest difference turning would make. I'm assuming that people will accelerate to their natural walking speed over a few meters and then have to slow abit to turn.

I was also thinking that the reason for the differences in stroke cases may be because people can loose co-ordination after a stroke hence turning may take more time.
 

Graham

Senior Moment
Messages
5,188
Location
Sussex, UK
Don't know. But not sure we know yet that they ran out of them/had any problems?

Well the form for their use suggests that patients would be expected to wear them for 1 week. 640 patients, one week at start, one at end, allow 1 week changeover, 12 actometers: 640 x 3 / 12 = 160 weeks. That would assume utter efficiency. Allowing for holidays (like Christmas) and occasional difficulties in maximising efficient use, then I guess that would fill 4 years pretty solid. I think they had 3 centres, so say 4 actometers each. If just one actometer broke down then that could slow the results of that centre down by a good six months (or by however long it took to get another one, and rejig the schedule).

So either their maths wasn't up to it and they planned it badly, or they were never really serious about using them in the first place.
 

Graham

Senior Moment
Messages
5,188
Location
Sussex, UK
I was wondering if the faster people are able to walk then the greatest difference turning would make. I'm assuming that people will accelerate to their natural walking speed over a few meters and then have to slow abit to turn.

I was also thinking that the reason for the differences in stroke cases may be because people can loose co-ordination after a stroke hence turning may take more time.

In defence of the possibility that the short distance did reduce the results, it is true that many people with ME, like those with strokes, have poor balance.

But here's the big question as far as I am concerned: if they didn't work out how many actometers they would really need, and didn't work out how to conduct the 6 minute walk test properly so that the results could be compared with healthy folk, was it because of incompetence, or was it that they were just going through the motions of having some objective data to obtain funding, whilst really only wanting to concentrate on the subjective assessments? It isn't scientific to speculate on their motivation, but it is appropriate to draw attention to the fact that neither of these objective tests were properly researched or prepared.
 

Sean

Senior Member
Messages
7,378
So either their maths wasn't up to it and they planned it badly, or they were never really serious about using them in the first place.

But here's the big question as far as I am concerned: if they didn't work out how many actometers they would really need, and didn't work out how to conduct the 6 minute walk test properly so that the results could be compared with healthy folk, was it because of incompetence, or was it that they were just going through the motions of having some objective data to obtain funding, whilst really only wanting to concentrate on the subjective assessments? It isn't scientific to speculate on their motivation, but it is appropriate to draw attention to the fact that neither of these objective tests were properly researched or prepared.

Completely justified questions.
 

taniaaust1

Senior Member
Messages
13,054
Location
Sth Australia
Is the general consensus that CBT/GET are of little to no use then? I've been suffering for a year and living with pacing as i'm a little skeptical of CBT/GET since they seem a little silly when they serve to make me feel more ill.

It may well depend on what subgroup you fit and what your illness is caused by.. generally the ME subgroup, its general consensus things like GET can do more harm then good so best for many to be avoiding. Only you youself probably will know whether CBT/GET is likely to help you or not, if it doesnt seem like good idea for you, it probably isnt.

I dont think everyone can be lumped in one basket, CBT/GET it does help a "few" "CFS" people but it harms more ME people
 

taniaaust1

Senior Member
Messages
13,054
Location
Sth Australia
But they only costed for 12 actometers to be shared amongst all 640 patients. How on earth did they expect that to work out without hitches?

Maybe they planned from the start and knew it wouldnt be wise to use them, hence what I'd call a "token purchase" (how could it be called anything else).. maybe they were used just so they could "say" they used them during their trial. The word "acrometers" helped make their study sound better didnt it to everyone.

(or maybe it was also a word used to help get patients to agree to be in this study? .. "hey we are doing a study and are going to use acrometers to study the real effects if this therapy, will you partake?" who knows.. I bet there is a very good reason why they said they were using those!! but werent really serious about them. ("token purchase" as ME/CFS patients had complained they werent used in previous studies???). Whatever the reason for them were, I think it was done as part of a deception. They set out wanting to show these therapies were good and didnt care about much else.. well not in getting the truth out anyway.

Most medical professions do not dig deep into studies to realise how poor they are (they wouldnt expect studies as poor as the PACE trial to be being published).. so to most, this is a study in which "actometers" were used. Its all part of the misleading deception which Im sure is purposely put out there (who'secret pay books are people like Wessely on). My CFS specialist who hasnt read the fully study and doesnt know all the details, thinks the PACE trial was a great one.
 

Dolphin

Senior Member
Messages
17,567
Maybe they planned from the start and knew it wouldnt be wise to use them, hence what I'd call a "token purchase".. maybe they were used just so they could "say" they used them during their trial. The word "acrometers" helped make their trial sound better.

Most medical professions do not dig deep into studies to realise how poor they are (they wouldnt expect studies as poor as the PACE trial to be being published).. so to most, this is a study in which actometers were used.

It is interesting if their trial was funded, after going through peer review, based on using actometers as outcome measures, and then they go and drop them. I am not sure I know exactly when they did so.
 

taniaaust1

Senior Member
Messages
13,054
Location
Sth Australia
It is interesting if their trial was funded, after going through peer review, based on using actometers as outcome measures, and then they go and drop them. I am not sure I know exactly when they did so.

Ive been wondering that too dolphin..if they said it just to make sure they were given a funding grant, either way if it was that.. that's deception too thou more along a criminal line I would think.
 

biophile

Places I'd rather be.
Messages
8,977
Re how PACE managed to share 12 actometers between 640 patients. Remember that the trial recruitment process alone occurred over a period of about 44 months:

"We recruited 641 participants from consecutive new out patients attending six specialist chronic fatigue syndrome clinics in the UK National Health Service between March 18, 2005, and Nov 28, 2008, and completed outcome data collection in January, 2010."

That statement is from the 2011 Lancet paper, but most of the recruitment progress (up to July 2008) is graphed in a patient newsletter: http://www.pacetrial.org/docs/participantsnewsletter3.pdf

#25. Why did you omit actigraphy as an outcome measure?

Actigraphy is a measure of physical activity, measured by a wrist watch sized accelerometer, worn around the ankle continuously for a week. Before we started the trial, we were advised that the number and scope of the outcome measures were too great and that it might reduce the proportion of participants making it through to the end of the trial. Actigraphy was the obvious measure to reject because of its burden in time and effort required by participants. The patient charity advising us agreed that this would be sensible.

http://www.pacetrial.org/faq/faq2.html

So, Action for ME, at the time, agreed it was "sensible" to drop actigraphy. Oh, the herculean burden of wearing a "wrist watch sized accelerometer" for one week to gather crucial data! As others haver already noted, this decision coincided with emerging data from other trials which demonstrated no significant increases in objectively measured activity on average. This would have challenged the ongoing claims about CBT and GET effectively increasing physical function, a rather inconvenient fact for those promoting it for CFS. Which reason is more likely the real one?
 

biophile

Places I'd rather be.
Messages
8,977
Full text here. As far as I can tell (based on fig 1) the distance walked with a 30m course was 17% higher than when the same people walked over a 10m course. Though those other studies suggest the effect might be less than this.

Thanks! When first looking at the paper, I wondered how much of that was the learning effect, but all the tests were done in random sequence:

Condition 1: Turning to the affected side, with a 10-m walkway.
Condition 2: Turning to the affected side, with a 20-m walkway.
Condition 3: Turning to the affected side, with a 30-m walkway.
Condition 4: Turning to the unaffected side, with a 10-m walkway.
Condition 5: Turning to the unaffected side, with a 20-m walkway.
Condition 6: Turning to the unaffected side, with a 30-m walkway.

The subjects performed the 6MWT under the 6 conditions in a random sequence determined by drawing lots. Each subject completed 6 conditions over 3 separate days, with 2 conditions conducted on each day. A 20-minute rest was allowed between conditions. Each subject performed only 1 trial in each condition.