JIM: Van der Meer and Lloyd Critique International Consensus Criteria ME

[Firestormm]

I will be honest Ember and say that I was also (still am) confused about this one. When the criteria were first published and following all the discourse it prompted, I am still left wondering if some people think it is intended to replace CFS with ME entirely, or only those who meet the criteria leaving X number of people with CFS. I had thought that ICCME would simply tighten up on CCC ME/CFS, but if it 'creates' a distinct disease entity then what of the CCC for ME/CFS I wonder?

Broderick also - in his letter - was not exactly confident with the name Myalgic Encephalomyelitis if I recall correctly. It would seem that had they been another option, another name, that perhaps better reflected the condition as he and the others view it and which was similarly recognised by WHO; it might have been chosen instead. It appears almost the case that CFS as a name is crap and ME as a name is a bit better.

I think the nomenclature will remain a key weakness in any continuing debate and critique. Until and unless research is properly geared to examining patients and confirms the presence of inflammation but even then the terms themselves are not wholly exclusive. Maybe the problem lies with the WHO? Radical perhaps but what if WHO put CFS alongside or linked to ME?

I will read both letters in full myself as soon as I can. I have though read your exchanges. And 'liked' your comments too. Thanks.

 

[Ember]

I will be honest Ember and say that I was also (still am) confused about this one....
I will read both letters in full myself as soon as I can.

The difference is that you aren't the CEO of the CAA and spokesperson for Research1st, Firestormm. You're allowed not to have read the letters yet.

Why hasn't Kim McCleary contacted the authors of the ICC if she needs clarification? I peppered Dr. Carruthers with my questions both before and after his presentation at the MEFM Society of BC's AGM. And I'm not paid to understand and communicate these things.
'
By the way, if you're referring in your post to the names given our disease, you're right in assuming that the terms are not wholly exclusive as they're being used. Dr. Carruthers called ME a form of CFS (and he was happy for me to quote him}.

 

[Firestormm]

Thanks. You are quite right. I don't think - as I have said before - many (anyone?) in positions of 'authority' have really given much time to analysing and understanding the ICCME or critiquing it - or to accepting that it is 'real'.

Hopefully, this might prompt them to do so. Now the Norwegian's appear to have adopted these criteria in preference to anything else - and presumably the name too - surely others will 'wake up and smell the coffee'? Not that I can understand the Norwegian decision though...

 

[Dolphin]

I think the nomenclature will remain a key weakness in any continuing debate and critique. Until and unless research is properly geared to examining patients and confirms the presence of inflammation but even then the terms themselves are not wholly exclusive. Maybe the problem lies with the WHO? Radical perhaps but what if WHO put CFS alongside or linked to ME?

In the main ICD-10 from the early 90s, CFS is linked to G93;3. The more recent debate was about the US version of ICD-10 - they are a bit behind!

 

[Firestormm]

I wonder if (having read Cort's latest) that the NIH recognising ME/CFS i.e. synonymously is seen as helping the situation or confusing it even more?

As I said in my reply to Cort - there was a time when this recognition would have been welcomed warmly I would have thought but am now not so sure.

Still, I shall look forward to following the debates on ICCME and CCC and how they will all fit together with the other criteria (or replace them) for research and/or clinical diagnoses.

 

[oceanblue]

Apparently, Gordon Broderick's suggestion that we only use the name ME for those who meet the more restrictive ICC criteria for this very serious disease, which is consistent with the WHO ICD neurological classification surprises Kim McCleary (see comments: http://www.research1st.com/2012/01/...&utm_campaign=Feed:+Research1st+(Research1st)). Having read the first sentence of the ICC, Kim seems to have understood it to mean that everyone diagnosed with CFS should instead be said to have ME. Now, faced with her obvious misinterpretation, the best she can come up with is this:

To interpret this statement to mean that 'ME' should be used...simply [as] a replacement for existing CFS criteria seems to me a stretch, but if Kim is genuinely confused, shouldn't she be seeking competent clarification, especially given her expressed concern about medical-legal issues for those who (she somehow acknowledges) might meet the 1994 Fukuda criteria for CFS but do not fully meet the new criteria for M.E?

This may or may not be relevant, but the CAA's Suzanne Vernon co-authored a 2009 paper that concluded

the core dimensions specified in the 1994 [Fukuda] definition have construct validity and do not need to be revised.

so perhaps the CAA thinks there is nothing but "CFS" out there.

I hope this will be put to the test with research.

 

[Firestormm]

Perhaps the NIH recognising ME as being synonymous with CFS will be deemed sufficient? Appears to be the case over here at any rate.

 

[Ember]

I wonder if (having read Cort's latest) that the NIH recognising ME/CFS i.e. synonymously is seen as helping the situation or confusing it even more?

I'm not sure that's what is implied, Firestormm, i.e., that the NIH is necessarily "recognizing ME as being synonymous with CFS." I've responded to you and to Cort on his thread (see posts #25 and #26 http://forums.phoenixrising.me/show...-The-NIH-on-ME-CFS-in-201&p=236882#post236882).

 

[oceanblue]

The editorial claims that:

we previously demonstrated that chronic
fatigue states regardless of exactly how they are defined,
share a common and relatively stereotyped set
of symptom domains which can be readily identified
in the community, at all levels of health care, and
across cultures [24].

The sampe paper [24] also concludes:

"We also suggest thatthere is little to be gained by further reorganization of
the diagnostic criteria, or the related diagnostic entities."

24 Hickie I, Davenport T, Vernon SD et al. Are chronic fatigue and
chronic fatigue syndrome valid clinical entities across countries
andhealthcare settings?AustNZ JPsychiatry2009;43:2535.

However, it turns out that this paper doesn't include the relevant analysis to support these claims. Actually, it seems this analysis was done and included in an earlier draft of the paper, but the analysis contradicts the authors claims, which might explain why it was omitted from the final version.

 

[Ember]

However, it turns out that this paper doesn't include the relevant analysis to support these claims. Actually, it seems this analysis was done and included in an earlier draft of the paper, but the analysis contradicts the authors claims, which might explain why it was omitted from the final version.

Thanks for unearthing this apparent deception.

As far as I can see, the van der Meer and Lloyd critique misrepresents the ICC in claiming that its authors seek to 'abolish' CFS (!) and discard the findings in published studies that have applied the existing international criteria, if the results do not fit with their notions of causation. CBT is the example they use: If a study shows that CBT is effective, these authors suggest that the study actually included patients with psychiatric disorders, and not ME; hence, the positive results can be ignored.

It's true that the ICC criticizes the Oxford criteria for being broadly inclusive and that it ignores the PACE trial results (their being outside the scope of its discussion). But wasn't it the PACE trial authors themselves who admitted to not studying ME?

In their letter, Peter White et al state: The PACE trial paper refers to chronic fatigue syndrome (CFS) which is operationally defined; it does not purport to be studying CFS/ME.

The sentence continues by stating that the PACE Trial studied: CFS defined simply as a principal complaint of fatigue that is disabling, having lasted six months, with no alternative medical explanation (Oxford criteria) (http://www.meactionuk.org.uk/Hoopers-initial-response-to-PDW-letter.htm).

Are the Oxford criteria considered international? (I hadn't assumed that its participants comprised an international body.) In an editorial on diagnostic criteria, slipping between so-called existing international criteria as if they were equal seems disingenuous.

Earlier in the editorial, Van der Meer and Lloyd refer to an approach that has already been proposed and applied [25], in relation to the existing international criteria [26]. The approach they cite involves the validation of the Multidimensional Fatigue Inventory (MFI-20), a 20-item self-report questionnaire produced in the Netherlands. Its application to Fukuda (also cited) isn't explained.

Van der Meer and Lloyd's claim that their concern is for scientific credibility: We fear that with the publication of this report, that both the clinical and research agendas in relation to CFS will lose their credible scientific base, via introduction of yet another diagnostic criteria set. Yet both letters allude to selective ignorance. Van der Meer and Lloyd accuse the ICC authors of ignoring the fact that inflammation (-itis) has not convincingly been demonstrated in any organ [28]. Broderick counters that there is simply too much evidence of pathophysiologic neurological and immune dysregulation, immune activation and an imbalance between inflammatory and anti-inflammatory mediators to be ignored [3256].

Without being an answer in itself, perhaps the ICC will prove to be a means of finding one.

 

[Dolphin]

Earlier in the editorial, Van der Meer and Lloyd refer to an approach that has already been proposed and applied [25], in relation to the existing international criteria [26]. The approach they cite involves the validation of the Multidimensional Fatigue Inventory (MFI-20), a 20-item self-report questionnaire produced in the Netherlands. Its application to Fukuda (also cited) isn't explained.

What they're talking about is the (so-called) empirical criteria (Reeves et al., 2005) which are a (badly) operationalized version of the Fukuda criteria.

The Fukuda criteria for Chronic Fatigue Syndrome require somebody to have fatigue.

The (so-called) empirical criteria (Reeves et al., 2005) "operationalize" this as:

We defined severe fatigue as ? medians of the MFI general fatigue (? 13) or reduced activity (? 10) scales.
(ref: http://www.biomedcentral.com/1741-7015/3/19)

 

[Ember]

What they're talking about is the (so-called) empirical criteria (Reeves et al., 2005) which are a (badly) operationalized version of the Fukuda criteria.

Thanks, Dolphin. I would have expected them to cite Reeves. The original MFI-20 article (rather than the validation paper) is cited by Reeves et al., 2005, so that must explain their reference to the validation paper here, as you suggest.

 

[oceanblue]

Without being an answer in itself, perhaps the ICC will prove to be a means of finding one.

That's well put.

 

[Andrew]

Interesting how this worked out. The critique of the ICC allowed committee to respond. And in so doing they were able to make their position even stronger. With what is there now, I think I can do a follow up on some activism I was doing elsewhere.

 

[Esther12]

Sorry for bumping this... but the hilarity of this paragraph keeps catching me, especially for those of us who know the background.

It cannot be denied CFS⁄ME is a controversial
condition. The controversy – sometimes deteriorating
into overt dispute – is between those that believe
that it is a nonexistent illness (‘maladie imaginaire’);
those that feel it is a psychiatric disorder;
and the activists (comprising patients, doctors and
even some scientists) who are convinced of a somatic
disease – all are unfortunately simplistic
perspectives on a complex disorder. Separately,
there are clinicians and scientists with an open
mind, who recognize the disability associated with
this enigmatic clinical illness, and who seek to engage
scientifically in the challenge of defining the
pathophysiology, and are therefore motivated to
elucidate the biological basis of CFS in a systematic
and unbiased fashion. This dispute between
the various protagonists recently surfaced with the
PACE trial published in the Lancet [2], which provided
evidence for effectiveness of elements of cognitive-
behavioural therapy (CBT) and graded exercise
therapy (GET) for patients with CFS. This
publication triggered unscientific and sometimes
personal attacks on the researchers in both the
scientific literature [3–10] and via the Internet
[11].

(Drat - I just had a long post deleted! Not sure how or why. Will stop this now.)

PS: Any news on if any of the authors of the PACE letters have got in contact about their legitimate concerns being classed as unscientific or personal attacks?

 

[alex3619]

I think the nomenclature will remain a key weakness in any continuing debate and critique. Until and unless research is properly geared to examining patients and confirms the presence of inflammation but even then the terms themselves are not wholly exclusive. Maybe the problem lies with the WHO? Radical perhaps but what if WHO put CFS alongside or linked to ME?

I think nomeclature is a problem and will continue to be. Without clearly validated biomarkers we have few options. When we have such markers, and a clear pathophysiological mechanism is implicated, there will be a definitive name change. Any label we use at present is only temporary ... but temporary could be a long time.

Bye, Alex

 

[Esther12]

That reminds me, Tom Kindlon said that he had sent a letter to both the authors, but never received a reply:

Dear Dr. Van der Meer,

I find your comments (copied below) in:

Van der Meer J, Lloyd A. A controversial consensus. J Intern Med
2011; Oct 11. DOI: 10.1111/j.1365-2796.2011.02468.x. [Epub ahead of print].

on my letter in the Lancet, and indeed the other letters in the Lancet (all copied below), bizarre: in particular, the comments on “personal attacks” - what are the things that you think I or others shouldn't be saying?

Regards,

Tom Kindlon



"It cannot be denied CFS⁄ME is a controversial
condition. The controversy – sometimes deteriorating
into overt dispute – is between those that believe
that it is a nonexistent illness (‘maladie imaginaire’);
those that feel it is a psychiatric disorder;
and the activists (comprising patients, doctors and
even some scientists) who are convinced of a somatic
disease – all are unfortunately simplistic
perspectives on a complex disorder. Separately,
there are clinicians and scientists with an open
mind, who recognize the disability associated with
this enigmatic clinical illness, and who seek to engage
scientifically in the challenge of defining the
pathophysiology, and are therefore motivated to
elucidate the biological basis of CFS in a systematic
and unbiased fashion. This dispute between
the various protagonists recently surfaced with the
PACE trial published in the Lancet [2], which provided
evidence for effectiveness of elements of cognitive-
behavioural therapy (CBT) and graded exercise
therapy (GET) for patients with CFS. This
publication triggered unscientific and sometimes
personal attacks on the researchers in both the
scientific literature [3–10] and via the Internet
[11]. Similarly, the recent controversy on the role
of the retrovirus, XMRV, in CFS [12] is a good
example of how science and emotion (in this case
mostly fear of contagion) commonly collide with regard
to CFS [13–20]. Ultimately, only high-quality
science will prevail."

References:

2 White PD, Goldsmith KA, Johnson AL et al. Comparison of adaptive
pacing therapy, cognitive behaviour therapy, graded exercise
therapy,and specialist medical care for chronic fatigue syndrome
(PACE): arandomisedtrial.Lancet2011;377:823–36.
3 Feehan SM. The PACE trial in chronic fatigue syndrome. Lancet
2011;377:1831–2.
4 Giakoumakis J. The PACE trial in chronic fatigue syndrome.
Lancet2011;377:1831; author reply 4–5.
5 Kewley AJ. The PACE trial in chronic fatigue syndrome. Lancet
2011;377:1832; author reply 4–5.
6 Kindlon T. The PACE trial in chronic fatigue syndrome. Lancet
2011;377:1833; author reply 4–5.
7 Mitchell JT Jr. The PACE trial in chronic fatigue syndrome.
Lancet2011;377:1831; author reply 4–5.
8 ShinoharaM. The PACE trial in chronic fatigue syndrome. Lancet
2011;377:1833–4; author reply 4–5.
9 Stouten B, GoudsmitEM, Riley N. The PACE trial in chronic fatigue
syndrome.Lancet2011;377:1832–3; author reply 4–5.
10 Vlaeyen JW, Karsdorp P, Gatzounis R, Ranson S, Schrooten M.
The PACE trial in chronic fatigue syndrome. Lancet 2011; 377:
1834; author reply -5.
11 Prins JB, van der MeerJWM, BleijenbergG.Chronic fatigue syndrome.
Lancet2006;367:346–55.

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The Lancet, Early Online Publication, 17 May 2011
doi:10.1016/S0140-6736(11)60689-2

The PACE trial in chronic fatigue syndrome
Jane Giakoumakis a

In their randomised trial of treatments for patients with chonic fatigue syndrome, Peter White and colleagues (March 5, p 823)1 define a clinically useful difference between the means of the primary outcomes as “0·5 of the SD of these measures at baseline, equating to 2 points for Chalder fatigue questionnaire and 8 points for short form-36”. They cite achieving a mean clinically useful difference in the graded exercise therapy or cognitive behaviour therapy groups, compared with specialist medical care alone, as evidence that these interventions are “moderately effective treatments”.

The source for this definition of clinically useful difference states that such a method has a “fundamental limitation”: “estimates of variability will differ from study to study…if one chooses the between-patient standard deviation, one has to confront its dependence on the heterogeneity of the population under study”.2 In White and colleagues' study, we do not have heterogeneous samples on the Chalder fatigue questionnaire and short-form 36 physical function subscale, since both are used as entry criteria.1

Patients had to have scores of 65 or less on short-form 36 to be eligible for the study.1 However, most, in practice, would probably need to have scores of 30 or more to be able to participate in this clinic-based study. Indeed, only four of 43 participants in a previous trial of graded exercise therapy scored less than 30.3, 4 Guyatt and colleagues2 suggest that “an alternative is to choose the standard deviation for a sample of the general population”, which White and colleagues have given as 24.1 An SD of 24 gives a clinically useful difference of 12; both graded exercise therapy and cognitive behaviour therapy fail to reach this threshold. Whether they “moderately improve outcomes”, as claimed,1 is therefore questionable.


I am chair of a myalgic encephalomyelitis support and advice group—an unpaid voluntary position.

References

1 White PD, Goldsmith KA, Johnson AL, et alon behalf of the PACE trial management group. Comparison of adaptive pacing therapy, cognitive behaviour therapy, graded exercise therapy, and specialist medical care for chronic fatigue syndrome (PACE): a randomised trial. Lancet 2011; 377: 823-836. Summary | Full Text | PDF(309KB) | CrossRef | PubMed

2 Guyatt GH, Osaba D, Wu AW, et al. Methods to explain the clinical significance of health status measures. Mayo Clinic Proc 2002; 77: 371-383. PubMed

3 Fulcher KY. Physiological and psychological responses of patients with chronic fatigue syndrome to regular physical activity. Loughborough: Loughborough University of Technology, 1997. http://hdl.handle.net/2134/6777. (accessed March 4, 2011).

4 Fulcher KY, White PD. Randomised controlled trial of graded exercise in patients with the chronic fatigue syndrome. BMJ 1997; 314: 1647-1652. PubMed

a Barr Grove, Glasgow G71 6TL, UK

------

John T Mitchell's letter

The Lancet, Early Online Publication, 17 May 2011

doi:10.1016/S0140-6736(11)60683-1

The PACE trial in chronic fatigue syndrome

John T Mitchell a

Much has been made of the “recovery” achieved by some participants in Peter White and colleagues' PACE trial,1 one of the authors having stated to the media that “twice as many people on graded exercise therapy and cognitive behaviour therapy got back to normal”2 and the accompanying Comment stating that, by use of a “strict criterion” for recovery, “the recovery rate of cognitive behaviour therapy and graded exercise therapy was about 30%”.3

Although the trial protocol4 does give a strict definition for recovery, this information is omitted from the published paper, which instead refers to physical function and fatigue in the “normal range”. Whether the values given are indicative of normal function is open to question, however. For instance, although a score of 60 or more on the short-form 36 (SF-36) physical function subscale and of 18 or less on the Chalder fatigue questionnaire are characterised as being in the “normal range” by White and colleagues, and as “recovery” in the accompanying Comment, an SF-36 physical function score of 65 was low enough for a patient to be included in the trial to begin with. Additionally, the above definitions for recovery and normal range would not even have qualified as being a positive outcome (75 or more on SF-36, bimodal fatigue scale score 3 or less) as published in the original protocol. Data on increases in baseline scores, the other positive outcome measure, are not given.

Also in question is how White and colleagues arrived at their reduced thresholds, since the trial protocol states that an SF-36 score of 70 is one SD below the mean of the UK adult population, but in the published paper this figure drops to 60 without explanation.

I am a CFS patient.

References

1 White PD, Goldsmith KA, Johnson AL, et alon behalf of the PACE trial management group. Comparison of adaptive pacing therapy, cognitive behaviour therapy, graded exercise therapy, and specialist medical care for chronic fatigue syndrome (PACE): a randomised trial. Lancet 2011; 377: 611-690. Full Text | PDF(70KB) | CrossRef | PubMed

2 Boseley S. Study finds therapy and exercise best for ME. The Guardian Feb 18, 2011. PubMed

3 Knoop H, Bleijenberg G. Chronic fatigue syndrome: where to PACE from here?. Lancet 2011; 377: 786-788. Full Text | PDF(378KB) | CrossRef | PubMed

4 White PD, Sharpe MC, Chalder T, et al. 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. BMC Neurol 2007; 7: 6. CrossRef | PubMed

a 14109 College Road, Lincoln, AR 72744, USA

---------

Sarah M Feehan's letter

The Lancet, Early Online Publication, 17 May 2011

doi:10.1016/S0140-6736(11)60688-0

The PACE trial in chronic fatigue syndrome

Sarah M Feehan a, on behalf of the Liverpool ME Support Group

Peter White and colleagues1 say that normal fatigue is represented by a figure of 18 or less on the Chalder fatigue questionnaire (Likert scoring), rather than the validated definition of fatigue caseness (4 or more, bimodal scoring) used in the trial's protocol.2, 3 A score of 18 represented the mean plus 1 SD (14·2 + 4·6) for a control group who had attended their general practitioner in the previous 12 months.4 This figure almost certainly would have been lower if those who had not attended their general practitioner had also been included when deriving population data. Indeed, normative data from a Norwegian study gave a mean of 12·2 (SD 4·0).5 Interestingly, the Norwegian data were stratified by health condition (unfortunately, only means were published): “No disease/current health problem”: 11·2; “Past or current disease”: 12·1; “Current health problem”: 12·5, and “Disease and current health problem”: 14·2.

Furthermore, 17·6% of chronic fatigue syndrome patients diagnosed at the Chronic Fatigue Unit (South London and Maudsley NHS Trust) had a score of 18 or less before they were treated.4 This suggests either that the Chronic Fatigue Unit diagnoses and treats fatigue problems in patients with normal levels of fatigue or, alternatively, that the threshold of 18 to represent normal fatigue is not suitable.

Given this information, and the fact that those with a Chalder fatigue questionnaire Likert score of 18 could still meet the trial's entry criteria (bimodal score of 6 or more),1, 3 it would be good if White and colleagues would now recalculate the data using the original definition of “fatigue caseness”.2, 3

I declare that I have no conflicts of interest.

References

1 White PD, Goldsmith KA, Johnson AL, et alon behalf of the PACE trial management group. Comparison of adaptive pacing therapy, cognitive behaviour therapy, graded exercise therapy, and specialist medical care for chronic fatigue syndrome (PACE): a randomised trial. Lancet 2011; 377: 823-836. Summary | Full Text | PDF(309KB) | CrossRef | PubMed

2 Chalder T, Berelowitz G, Pawlikowska T, et al. Development of a fatigue scale. J Psychosom Res 1993; 37: 147-153. CrossRef | PubMed

3 White PD, Sharpe MC, Chalder T, DeCesare JC, Walwyn Ron 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. BMC Neurol 2007; 7: 6. CrossRef | PubMed

4 Cella M, Chalder T. Measuring fatigue in clinical and community settings. J Psychosom Res 2010; 69: 17-22. CrossRef | PubMed

5 Loge JH, Ekeberg O, Kaasa S. Fatigue in the general Norwegian population: normative data and associations. J Psychosom Res 1998; 45: 53-65. CrossRef | PubMed

a Liverpool ME Support Group, Bootle, Liverpool L20 9LD, UK

-----

Andrew James Kewley's letter

The Lancet, Early Online Publication, 17 May 2011

doi:10.1016/S0140-6736(11)60681-8

The PACE trial in chronic fatigue syndrome

Andrew James Kewley a

I am concerned by the change in assessment method between the published results of the PACE trial1 and the trial protocol.2 Seven secondary outcomes were not reported and there were changes in several of the measures that were reported.1, 2

In particular, the protocol stated that those with short-form 36 physical function subscale scores of 65 or less would be deemed ill enough to participate, and that those with scores of 85 or more would be regarded as “recovered”.2 However, the authors have questionably defined “normal” as a score of 60 or more,1 based on general population scores which did not exclude those reporting chronic illnesses. In the cited study of working-age adults,3 the mean physical function score for respondents without long-term health problems was 92·7 (SD 13·1). The mean physical function scores for those aged 75—84 years, including those with long-term health problems, was 57·9.3

The lack of objective data, such as hours employed or actometer results, is problematic, since Wiborg and colleagues4 showed that improvements on questionnaires are not reflected in an increase in activity, as would be expected if the patients had more energy.4

The only significant difference between treatments for the 6-min walking test was for graded exercise therapy. But the increase in walking distance is small when compared to the distance walked by healthy elderly people (mean age 65 years), which was shown to be 631 m (SD 93).5

Unfortunately, the overall results of the PACE treatments were unimpressive, and with only 41% of patients reporting “positive” change after cognitive behavioural therapy or graded exercise therapy, further biomedical research is imperative.

I declare that I have no conflicts of interest.

References

1 White PD, Goldsmith KA, Johnson AL, et alon behalf of the PACE trial management group. Comparison of adaptive pacing therapy, cognitive behaviour therapy, graded exercise therapy, and specialist medical care for chronic fatigue syndrome (PACE): a randomised trial. Lancet 2011; 377: 611-690. Full Text | PDF(70KB) | CrossRef | PubMed

2 White PD, Sharpe MC, Chalder T, et al. 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. BMC Neurol 2007; 7: 6. CrossRef | PubMed

3 Bowling A, Bond M, Jenkinson C, Lamping DL. Short form 36 (SF-36) health survey questionnaire: which normative data should be used? Comparisons between the norms provided by the Omnibus Survey in Britain, the Health Survey for England and the Oxford Healthy Life Survey. J Public Health Med 1999; 21: 255-270. PubMed

4 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; 40: 1281-1287. CrossRef | PubMed

5 Troosters T, Gosselink R, Decramer M. Six minute walking distance in healthy elderly subjects. Eur Respir J 1999; 14: 270-274. CrossRef | PubMed

a Faculty of Science and Engineering, Flinders University, SA 5042, Australia

-------

Letter from Bart Stouten, Ellen M Goudsmit & Neil Riley

The Lancet, Early Online Publication, 17 May 2011

doi:10.1016/S0140-6736(11)60685-5

The PACE trial in chronic fatigue syndrome
Bart Stouten a, Ellen M Goudsmit b, Neil Riley c

The findings of the PACE trial1 seem impressive, but the discrepancy between the definitions of improvement in the protocol2 and paper requires an explanation. In the paper “clinically useful differences” were defined as 0·5 SD changes in fatigue or physical functioning compared with baseline. However, the criteria for improvement published in the trial protocol were much more demanding (table).2 Use of a cut-off score of 75 on the short-form 36 physical functioning subscale, as originally proposed, would halve the number of “recovered” patients.

Table http://www.thelancet.com/journals/la...Type=lightBlue
Table image http://www.thelancet.com/journals/la...Type=lightBlue
Definition of positive outcome/improvement in the trial protocol and the final publication

Moreover, consulting the normative data for the scale reveals that the mean score of 58 after both cognitive behaviour therapy and graded exercise improved a patient's physical functioning to the level of someone 40 years older than himself.3

Is this a case of “outcome reporting bias”?4

We declare that we have no conflicts of interest.

References

1 White PD, Goldsmith KA, Johnson AL, et alon behalf of the PACE trial management group. Comparison of adaptive pacing therapy, cognitive behaviour therapy, graded exercise therapy, and specialist medical care for chronic fatigue syndrome (PACE): a randomised trial. Lancet 2011; 377: 823-836. Summary | Full Text | PDF(309KB) | CrossRef | PubMed

2 White PD, Sharpe MC, Chalder T, et alon 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. BMC Neurol 2007; 7: 6. CrossRef | PubMed

3 Bowling A, Bond M, Jenkinson C, Lamping DL. Short form 36 (SF-36) health survey questionnaire: which normative data should be used? Comparisons between the norms provided by the Omnibus Survey in Britain, the Health Survey for England and the Oxford Healthy Life Survey. J Public Health Med 1999; 21: 255-270. PubMed

4 Smyth RMD, Kirkham JJ, Jacoby A, Altman DG, Gamble C, Williamson PR. Frequency and reasons for outcome reporting bias in clinical trials: interviews with trialists. BMJ 2011; 342: c7153. CrossRef | PubMed

a Einsteindreef 67A, 3562 XT Utrecht, Netherlands
b School of Psychology, University of East London, London, UK
c Byways, Chichester Road, Dorking, UK

----------------

Tom Kindlon's letter

The Lancet, Early Online Publication, 17 May 2011

doi:10.1016/S0140-6736(11)60684-3

The PACE trial in chronic fatigue syndrome

Tom Kindlon a

Peter White and colleagues1 claim that, if cognitive behaviour therapy and graded exercise therapy are delivered as described, they are “safe” for chronic fatigue syndrome (CFS); the CONSORT statement on harms reporting recommends against such claims.2

If few participants are compliant with the intervention, harms-related data might not be reliable. Both cognitive behaviour therapy and graded exercise therapy are designed to increase activity; however, actometers were not used, so one cannot be sure how many patients were actually more active.1 Analysis of three trials of cognitive behaviour therapy found that activity levels before and after therapy were similar, despite improvements being reported on fatigue and other subjective measures.3 This finding suggests that patients might simply substitute the activity component of cognitive behaviour therapy for other activities;4 if this situation occurred in White and colleagues' study, we would not have information on the effects of actually increasing activity levels.

On the only objective test, the 6-min walking distance, the cognitive behaviour therapy group only improved by 21 m, suggesting that total daily activity might not have increased.1 The average increase for graded exercise therapy of only 67 m leaves open the possibility that many on that intervention did not achieve or maintain increased exercise or activity levels.

If, as seems likely, “real-world” graded exercise therapy practitioners expect higher yearly 6-min walking distance targets than a 379 m crawl (or higher weekly increases than 1·29 m), more adverse reactions could occur.

Given many patients' reports of adverse reactions from such interventions, the biological reasons why they might be problematic (eg, abnormalities in muscle and immunological response to exercise), and the fact that adverse reactions are often only noted outside of trials, the assumption that cognitive behaviour therapy and graded exercise therapy are “safe” is premature.2, 4, 5


I work in a voluntary capacity for the Irish ME/CFS Association.

References

1 White PD, Goldsmith KA, Johnson AL, et alon behalf of the PACE trial management group. Comparison of adaptive pacing therapy, cognitive behaviour therapy, graded exercise therapy, and specialist medical care for chronic fatigue syndrome (PACE): a randomised trial. Lancet 2011; 377: 611-690. Full Text | PDF(70KB) | CrossRef | PubMed

2 Ioannidis JP, Evans SJ, Gøtzsche PC, et alfor the CONSORT Group. Better reporting of harms in randomized trials: an extension of the CONSORT statement. Ann Intern Med 2004; 141: 781-788. PubMed

3 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; 40: 1281-1287. CrossRef | PubMed

4 Kindlon T. Harms of cognitive behaviour therapy designed to increase activity levels in chronic fatigue syndrome: questions remain. Psychother Psychosom 2011; 80: 110-111. CrossRef | PubMed

5 Twisk FN, Maes M. A review on cognitive behavorial therapy (CBT) and graded exercise therapy (GET) in myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS): CBT/GET is not only ineffective and not evidence-based, but also potentially harmful for many patients with ME/CFS. Neuro Endocrinol Lett 2009; 30: 284-299. PubMed

a Irish ME/CFS Association, PO Box 3075, Dublin 2, Ireland

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Mieko Shinohara's letter

The Lancet, Early Online Publication, 17 May 2011

doi:10.1016/S0140-6736(11)60686-7

The PACE trial in chronic fatigue syndrome

Mieko Shinohara a

A very controversial paper was published on March 5, 2011, about treatments for chronic fatigue syndrome (CFS).1 I have suffered from this disease for more than 20 years and have been nearly bedridden for the past few years. I hope that the study will be beneficial for patients with CFS.

Surprisingly, patients who participated in the study were young, and their symptoms were mild to moderate. Furthermore, their disease duration was short, and they were still in the process of adjusting to the fact that they had an illness whose cause is not known. Probably, the participants learned coping skills through self-help strategies.2
Cognitive behaviour therapy and graded exercise therapy can be effective for many chronic diseases other than CFS. As this study showed, it is reasonable that cognitive behaviour therapy and graded exercise therapy are effective for CFS. However, whether these treatments will be effective for patients with severe CFS who need medical support remains unknown. I am concerned that this study might lead to further misunderstanding of this disease.

In Japan, much research on fatigue in general has been done, but more severely ill patients have been totally overlooked. We need more research where those patients are involved. We are sincerely hoping that the researchers will focus on the biological roots of CFS, so that eventually a cure can be found.

I declare that I have no conflicts of interest.

References

1 White PD, Goldsmith KA, Johnson ALon behalf of the PACE trial management group. Comparison of adaptive pacing therapy, cognitive behaviour therapy, graded exercise therapy, and specialist medical care for chronic fatigue syndrome (PACE): a randomised trial. Lancet 2011; 377: 823-836. Summary | Full Text | PDF(309KB) | CrossRef | PubMed

2 Carruthers BM, van de Sande MI. Myalgic encephalomyelitis/chronic fatigue syndrome: a clinical case definition and guidelines for medical practitioners. http://sacfs.asn.au/download/consens...iew_me_cfs.pdf. (accessed May 6, 2011).

a Japan Chronic Fatigue Syndrome Association, Samei-biru 2B, 3-11-12 Takanodai, Nerima-ku, Tokyo 177-033, Japan

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Letter from Johan WS Vlaeyen, Petra Karsdorp, Rena Gatzounis, Saskia Ranson & Martien Schrooten

The Lancet, Early Online Publication, 17 May 2011

doi:10.1016/S0140-6736(11)60682-X

The PACE trial in chronic fatigue syndrome

Johan WS Vlaeyen a b, Petra Karsdorp b, Rena Gatzounis a, Saskia Ranson b, Martien Schrooten a b

Peter White and colleagues' sophisticated randomised PACE trial1 clearly shows that “adaptive pacing” is not more effective than specialist medical care in improving chronic fatigue outcomes. Although the results are in line with recent findings that activity pacing is not associated with disability in fibromyalgia,2 we raise several concerns about adaptive pacing therapy.

First, the basic assumptions that excessive task persistence in chronic fatigue increases symptoms and that regular pauses or activity alternation are needed are not supported empirically.3 The cognitive and motivational consequences of task interruption are largely unknown for fatigue and pain disorders.

Second, there is no clear definition of pacing as a treatment technique, probably because of the lack of an empirically tested mechanism of behavioural interruptions.

Third, activity pacing can involve at least three different approaches to task interruption. For example, symptom-contingent pacing uses fatigue or pain as signals for exertion, to avoid exacerbations. Time-contingent pacing encourages patients to interrupt when a preset time window has elapsed, irrespective of symptom change.4 Goal-contingent pacing guides patients in dividing higher-order goals into smaller, manageable pieces, with task interruption occurring after completion of lower-order goals, promoting a sense of control and mastery.5 Mixing of these different contingencies, as seems to occur in the PACE study, could create confusion in patients, reducing their unique effects.

Since the term “pacing” is widely used, but poorly defined, we would like to call for a better understanding and affective-motivational examination of the effects of task interruptions in the context of fatigue and pain.

We declare that we have no conflicts of interest.

References

1 White P, Goldsmith K, Johnson A, et al, on behalf of the PACE trial management group. 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: 611—90.

2 Karsdorp PA, Vlaeyen JW. Active avoidance but not activity pacing is associated with disability in fibromyalgia. Pain 2009; 147: 29-35. CrossRef | PubMed

3 Gill JR, Brown CA. A structured review of the evidence for pacing as a chronic pain
intervention. Eur J Pain 2009; 13: 214-216. CrossRef | PubMed

4 Fordyce WE. Behavioral methods for chronic pain and illness. St Louis: Mosby, 1976.

5 Nielson WR, Jensen MP, Hill ML. An activity pacing scale for the chronic pain coping inventory: development in a sample of patients with fibromyalgia syndrome. Pain 2001; 89: 111-115. CrossRef | PubMed

a Research Group Health Psychology, University of Leuven, 3000 Leuven, Belgium

b Department of Clinical Psychological Science, Maastricht University, Maastricht, Netherlands

 

[biophile]

That reminds me, Tom Kindlon said that he had sent a letter to both the authors, but never received a reply:

I'm shocked, SHOCKED, that CBT/GET apologists don't usually respond when they are called on their statements.