£5m GET/CBT trial Flops -No Objective Results

[Guest guest]

Tom Kindlon:

" £5m GET/CBT trial Flops when

one looks at Objective Results "

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Comment on the data we

have from the PACE Trial

Aug, 2012

by Tom Kindlon

PLOSone

http://bit.ly/NwKUZq

Title: All the cost-effectiveness

calculations involve self-report

measures (EQ-5D, CFQ, SF-36

PF)

The authors say(1):

" The study has limitations. First, we relied

on self-reported information on service use

and lost employment.

There may be issues of accuracy with this

approach but it was largely unavoidable

given the need for a comprehensive

perspective.

Other studies have shown this to be an

acceptable method [refs]. "

The paper does not mention that all the

cost-effectiveness calculations involve

self-reported information or measures.

That is to say QALYs were calculated using

the EQ-5D questionnaire, while the other

cost-effectiveness calculations involved the

Chalder fatigue questionnaire (CFQ) and the

physical function (PF) subscale of the

SF-36 questionnaire.

We have reason to believe self-report

measures with interventions that encourage

scheduling increasing exercise and activity

may have problems.

For example, a review of three studies of

CBT interventions found that changes in

physical activity (as measured by an

objective outcome measure, actometers)

were not related to the changes in fatigue

(2).

Also, although an improvement in fatigue

was reported over the control group, there

was no difference between the CBT and

control groups in terms of increases in

activity levels.

When one looks at the studies that made up

the review, one can also see that there

were other self-reported measures including

SF-36 physical functioning that had

reported improvements.

The actometer data from one of these three

studies wasn't published in the main paper

for the study(3), but was released in 2002

a long time (4) before the Wiborg et al.

review was published.

As I have highlighted before, Friedberg and

Sohl (5) have published results of a study

on an intervention involving Cognitive

Behavior Therapy (CBT) which included

encouraging patients to go for longer walks.

It found that on the SF-36 Physical

Functioning (PF) scale, patients improved

from a pre-treatment mean (SD) of 49.44

(25.19) to 58.18 (26.48) post-treatment,

equivalent to a Cohen's d value of 0.35.

On the Fatigue Severity Scale (FSS), the

improvement as measured by the cohen's d

value was even great (0.78) from an initial

pre-treatment mean (SD) of 5.93 (0.93) to

a 5.20 (0.95) post-treatment.

However on actigraphy there was actually a

numerical decrease from a pre-treatment

mean (SD) of 224696.90 (158389.64) to

203916.67 (122585.92) post-treatment

(cohen's d: -0.13).

So just because patients report lower

fatigue and better scores on the SF-36 PF

scale, doesn't mean th " It is not clear

whether subjective accounts of physical

activity level adequately reflect the actual

level of physical activity.

Therefore the primary aims of the present

study were to assess actual activity level in

patients with CFS to validate claims of

lower levels of physical activity and to

validate the reported relationship between

fatigue and activity level that was found on

self-report questionnaires.ey're doing more,

which is what GET and CBT based on GET

claim to bring about.

These results seem particularly pertinent for

this study given the primary outcome

measures are the SF-36 PF scale and a

fatigue scale.

Friedberg had also earlier released data

showing this effect of a graded activity

program not leading to increased total

activity levels (6).

In a case study paper on a single patient,

Friedberg found:

" using a 26-session graded activity

intervention involved gradual increases in

physical activity " that " from baseline to

treatment termination, the patient's

self-reported increase in walk time from 0

to 155 min a week contrasted with a

surprising 10.6% decrease in mean weekly

step counts. "

A CFS study published back in 1997 showed

the problem of using self-report data (7).

The authors' rationale for the study was:

" It is not clear whether subjective accounts

of physical activity level adequately reflect

the actual level of physical activity.

Therefore the primary aims of the present

study were to assess actual activity level in

patients with CFS to validate claims of

lower levels of physical activity and to

validate the reported relationship between

fatigue and activity level that was found on

self-report questionnaires.

In addition, we evaluated whether physical

activity level adequately can be assessed

by self-report measures. An Accelerometer

was used as a reference for actual level of

physical activity. "

The authors reported on the correlations on

7 outcome measures in relation to the

actometer readings:

" none of the self-report

questionnaires had strong

correlations with the Actometer.

Thus, self-report questionnaires

are no perfect parallel tests for

the Actometer. "

The authors of the 1997 study (7) pointed

out that:

" the subjective instruments do not measure

actual behaviour. Responses on these

instruments appear to be an expression of

the patients' views about activity and may

be biased by cognitions concerning illness

and disability " .

This was re-iterated in another paper (8):

" In earlier studies of our research group,

actual motor activity has been recorded

with an ankle-worn motion-sensing device

(actometer) in conjunction with self-report

measures of physical activity. The data of

these studies suggest that self-report

measures of activity reflect the patients'

view about their physical activity and may

have been biased by cognitions concerning

illness and disability. "

It seems easy to imagine that GET and

particularly CBT might alter such cognitions.

A systematic review of treatments for CFS

back in 2001 recommended the use of more

objective outcome measures (9) e.g.

" Outcomes such as " improvement, " in

which participants were asked to rate

themselves as better or worse than they

were before the intervention began, were

frequently reported.

However, the person may feel better able

to cope with daily activities because they

have reduced their expectations of what

they should achieve, rather than because

they have made any recovery as a result

of the intervention.

A more objective measure of the effect of

any intervention would be whether

participants have increased their working

hours, returned to work or school, or

increased their physical activities. "

As I mentioned above, the current authors

said the use of self-reported information on

service use and lost employment was

" largely unavoidable " , which may be true for

those measures (1).

But to get an idea of individuals' functioning,

actigraphy seems a good way of doing that.

The study investigators appear to agree as

the PACE Trial does use actometers to

measure baseline activity levels (10), which

also means they have this equipment.

They also said they planned initially to

use actometers as an outcome measure

but then changed their minds (11).

I think this is unfortunate they were not

used as an outcome measure.

I think in this study possibly the nearest

objective surrogate we have of actigraphy,

to help give us an idea of the levels of

activity participants are regularly

maintaining, is the 6 minute walking test

(MWT).

It found that despite various differences on

self-reported measures such as fatigue and

physical functioning between the CBT and

SMC and APT participants, there were no

differences between the three groups on

this outcome measure (12).

The GET participants did do a little better,

but a result of 379m is still not good for a

group with a mean age of 40 who do not

have a range of conditions (due to the

exclusions in the trial) and who were

adjudged well enough to attend outpatient

appointments.

Such individuals in the GET arm of the trial

would generally have had practice at

walking continuously for a few minutes so

might have been better able to know not to

go too fast or slow to get a better result ?

this is a bit like the training effect which

has shown to increase scores in the 6MWT.

GET participants might also have been more

motivated to push themselves and impress

their therapist than other therapists -

unfortunately the test doesn't involve

sufficient measurements to know if all

groups pushed themselves equally hard.

The CBT and GET groups had been told to

pay less attention to symptoms which might

have encouraged them to push themselves

harder.

M put the 6MWT results in context in

another comment:

" all of PACE's trial groups at 52 weeks after

baseline were still below those of patients

with various cardiopulmonary disorders and

patients with class III heart failure as well

as scores of 80-89 year olds, a result which

doesn't exactly scream good

health.(13-15) " .

The latest study shows neither CBT nor

GET led to an improved rate of days of

lost employment.

[Means (sds): APT: 148.6 (109.2); CBT:

151.0 (108.2); GET: 144.5 (109.4); SMC

(alone): 141.7 (107.5)] (Table 2).

Neither CBT nor GET led to improvements

in numbers receiving welfare benefits or

other financial payments (Table 4).

Combine those two sets of data with the

6MWT tests and the results for GET and

CBT really aren't good at all.

Incidentally, the authors previously said

(11):

" We have used several objective outcome

measures; the six minute walking test, a

test of physical fitness, as well as

occupational and health economic

outcomes. "

Thus far, the results of the test of

physical fitness have not been

released.

References:

1. McCrone P, Sharpe M, Chalder T, Knapp

M, AL, et al. (2012) Adaptive

Pacing, Cognitive Behaviour Therapy,

Graded Exercise, and Specialist Medical

Care for Chronic Fatigue Syndrome: A

Cost-Effectiveness Analysis.PLoS ONE

7(8):e40808.

doi:10.1371/journal.pone.0040808

2 Wiborg JF, Knoop H, Stulemeijer M, Prins

JB, Bleijenberg G. How does cognitive

behaviour therapy reduce fatigue in

patients with chronic fatigue syndrome?

The role of physical activity. Psychol Med.

2010 Aug;40(8):1281-7. Epub 2010 Jan 5.

3 Prins JB, Bleijenberg G, Bazelmans E, et al.

Cognitive behaviour therapy for chronic

fatigue syndrome: a multicentre randomised

controlled trial. Lancet 2001; 357: 841-47.

4. Van Essen, M and de Winter, LJM.

Cognitieve gedragstherapie by het

vermoeidheidssyndroom (cognitive

behaviour therapy for chronic fatigue

syndrome). Report from the College voor

Zorgverzekeringen. Amstelveen: Holland.

June 27th, 2002. Bijlage B. Table 2.

5 Friedberg F, Sohl S. Cognitive-behavior

therapy in chronic fatigue syndrome: is

improvement related to increased physical

activity? J Clin Psychol. 2009 Feb 11.

6 Friedberg, F. Does graded activity increase

activity? A case study of chronic fatigue

syndrome. Journal of Behavior Therapy and

Experimental Psychiatry, 2002, 33, 3-4,

203-215

7 Vercoulen JH, Bazelmans E, Swanink CM,

Fennis JF, Galama JM, Jongen PJ, Hommes

O, Van der Meer JW, Bleijenberg G. Physical

activity in chronic fatigue syndrome:

assessment and its role in fatigue. J

Psychiatr Res. 1997 Nov-Dec;31(6):661-73.

8 van der Werf SP, Prins JB, Vercoulen JH,

van der Meer JW, Bleijenberg G. Identifying

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9 Whiting P, Bagnall AM, Sowden AJ, Cornell

JE, Mulrow CD, Ramírez G. Interventions for

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JAMA. 2001 Sep 19;286(11):1360-8.

10 White PD, Sharpe MC, Chalder T,

DeCesare JC, Walwyn R; on behalf of the

PACE trial group. Protocol for the PACE trial:

a randomised controlled trial of adaptive

pacing, cognitive behaviour therapy, and

graded exercise, as supplements to

standardised specialist medical care versus

standardised specialist medical care alone

for patients with the chronic fatigue

syndrome/myalgic encephalomyelitis or

encephalopathy. BioMed Cent Neurol 2007;

7: 6. http://bit.ly/NwNtL4

11 White PD, Sharpe MC, Chalder T,

DeCesare JC, Walwyn R, for the PACE trial

management group. Response to comments

on " Protocol for the PACE trial " . BMC Neurol.

2007, 7:6doi:10.1186/1471-2377-7-6.

http://bit.ly/NwNFKb

12 White PD, Goldsmith KA, AL,

Potts L, Walwyn R, et al. (2011) Comparison

of adaptive pacing therapy, cognitive

behaviour therapy, graded exercise therapy,

and specialist medical care for chronic

fatigue syndrome (PACE): a randomised

trial. Lancet 377: 823?836.

13 Steffen et al. Age- and Gender-Related

Test Performance in Community-Dwelling

Elderly People: Six-Minute Walk Test, Berg

Balance Scale, Timed Up & Go Test, and

Gait Speeds Physical Therapy February

2002 vol. 82 no. 2 128-137

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14. Lipkin et al. Six minute walking test for

assessing exercise capacity in chronic heart

failure. Br Med J (Clin Res Ed) 1986; 292 :

653 doi: 10.1136/bmj.292.6521.653

http://bit.ly/NwO3Zp

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