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All the cost-effectiveness calculations involve self-report measures (EQ-5D, CFQ, SF-36 PF)

Posted by tkindlon on 05 Aug 2012 at 01:29 GMT

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 they'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. JohnM 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, Johnson 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 physical activity patterns in chronic fatigue syndrome using actigraphic assessment. J Psychosom Res. 2000 Nov;49(5):373-9.

9 Whiting P, Bagnall AM, Sowden AJ, Cornell JE, Mulrow CD, Ramírez G. Interventions for the treatment and management of chronic fatigue syndrome: a systematic review. 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://www.biomedcentral....

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://www.biomedcentral....

12 White PD, Goldsmith KA, Johnson 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 http://physicaltherapyjou... <http://physicaltherapyjou...>

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://www.bmj.com/conten... <http://www.bmj.com/conten...>

15. Kadikar A, Maurer J, Kesten S. The six-minute walk test: a guide to assessment for lung transplantation. J Heart Lung Transplant. 1997 Mar;16(3):313-9.

Competing interests declared: I work in a voluntary (i.e. unpaid) capacity for the Irish ME/CFS Association