Recovery from CFS after treatments given in the PACE trial - unpublished letters

[Dolphin]

I think it would be better if there wasn't much discussion on this thread, so that it can be nice and compact, with people able to find the letters quickly. Most points will probably fit better on the main thread for this paper: http://forums.phoenixrising.me/inde...ter-treatments-given-in-the-pace-trial.21628/

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(it's not necessary to read all of the following before posting your letter)
When the Lancet paper on the PACE Trial was published (White et al., 2011), a total of 44 letters were submitted.

8 were published and 38 were not.
We set up a thread http://forums.phoenixrising.me/inde...rs-that-were-not-accepted-by-the-lancet.9761/ to highlight the unpublished letters as they often summarised well points on the trial and sometimes included points that were not covered in the published letters.

Another paper has recently been published on the PACE Trial is:

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

P. D. White, K. Goldsmith, A. L. Johnson, T. Chalder and M. Sharpe

Psychological Medicine January 2013, pp 1-9

http://journals.cambridge.org/psm/White

and I know some people are sending in letters (although the numbers submitting letters seem way down from the Lancet paper, which is disappointing).

Anyway, I thought I'd start this thread so people could post letters if they are turned down. If, for some reason, you don't want to post your own letter, I can post it for you or you can get another member of Phoenix Rising to do some.

Note: don't post a letter until you have decided you are not submitting any more letters and everything you have submitted has been refused. That is to say, if you have a letter refused, but you re-submit another letter that is in any way similar to the letter that was turned down, don't post either here until all the letters have been turned down (if that occurs). The journal already said it was not publishing a letter Dr. Shepherd submitted as it was on the ME Association website and they could apply this to first drafts too.

 

[Tom Kindlon]

My letter was turned down with the following comment:

We have received a considerable amount of correspondence regarding this paper, and as a number of the letters essentially duplicate the same comments we are unable to publish them all. The points you make have already been raised in an earlier letter we have received. Unfortunately therefore I am afraid we will not be able to accept this letter.

Good news that they are publishing some esp. if all the points I made are made, though I will wait to see the published letters before accepting this has occurred.

Title (possible): Changes to the recovery criteria have not improved their validity*

When one publishes a protocol for a trial, as the PACE Trial investigators have done (White et al. 2007), there needs to be compelling reasons to deviate from it (Evans, 2007). White et al. (2013) claim that the revised recovery definition is conservative, with the changes being made to "more accurately reflect recovery". Is this true with regard to the Chalder Fatigue Questionnaire (CFQ) and SF-36 physical functioning (SF36 PF) criteria?

The new CFQ criterion, a score of 18 or less (Likert scoring), was chosen because it represented the mean plus 1 standard deviation in a community sample (Cella & Chalder, 2010). The CFQ scores were not normally distributed but we know that only 13.6% of the sample scored higher than 18. However, it does not follow that this threshold represents a reliable cut-off for fatigue-caseness as fatigue problems are common in the general population. For example, in the paper the authors referenced when discussing symptoms in the general population (McAteer et al. 2011), 41.3% reported “feeling tired/run down” while 23.1% of a representative sample of the Norwegian population had high levels of fatigue (Lerdal et al. 2005). That is to say, it is quite possible that more than 13.6% of the sample in Cella & Chalder (2010) were experiencing significant fatigue problems.

The recovery criteria described in the protocol require a score of 3 or less (bimodal scoring) which is a validated definition for the absence of fatigue (Chalder et al. 1993). Although exact translation between Likert and bimodal scores is not possible, it can be shown that such a score is stricter than the new criteria because it translates to a Likert score between 6 and 17. Therefore, when compared against the established definition of fatigue-caseness, a Likert score of 18 always indicates the presence of abnormal levels of fatigue.

Furthermore, the trial's entry criterion for fatigue, a CFQ bimodal score of 6 or higher, translates to a Likert score between 12 and 23 meaning that participants could have baseline scores which were already 18 or less so that no improvement was required for them to recover according to the new criteria. Indeed, 17.6% of patients diagnosed with CFS at the Chronic Fatigue Unit at the South London and Maudsley NHS Trust had scores of 18 or less on the CFQ before treatment for their fatigue.

For SF-36 PF scores, the protocol required a score of ≥85 for recovery, whilst the newer criteria require a score of ≥60. Again, participants could score 60 or more at baseline which suggests the new criterion is neither conservative nor "more accurately reflects recovery".

Also, while I have not undertaken an exhaustive search, in all the other trials that I am aware of that used the SF36 PF to operationalize CFS criteria, a score of 60 would have been sufficiently low to meet each trial's requirements for a diagnosis of CFS (e.g. Stulemeijer et al. 2005; Tummers et al. 2012; van't Leven et al. 2010; Wearden et al. 2010).

White et al. (2013) used the formula of mean minus one standard deviation (sd) from data on the UK general population from Bowling et al. (1999) to derive the threshold of SF-36 PF ≥60. However, CFS is not unique in causing reductions in this domain, with Bowling et al. noting that 22% in the same survey reported a long-term health problem while 16% reported having an acute illness. Moreover 28.6% were aged 65 or more; population norms from these age groups are of questionable relevance to the PACE Trial cohort (mean (sd) age at baseline: 38 (12)).

In summary, the CFQ and SF-36 PF criteria that constitute White and colleagues' new definition of recovery have been revised such that they are less strict than those contained in the published protocol. These changes suggest that it is not safe to conclude that the new criteria are either conservative or more accurately reflect recovery than those published in the trial's protocol.

* Feel free to change the title if you want.

Tom Kindlon
Information Officer (voluntary position),
Irish ME/CFS Association,
PO Box 3075, Dublin 2, Ireland.

Declaration of Interest
I do various types of voluntary work for the Irish ME/CFS Association.

References

Cella M, Chalder T (2010). Measuring fatigue in clinical and community settings. Journal of Psychosomatic Research 69, 17–22.

Chalder T, Berelowitz G, Hirsch S, Pawlikowska T, Wallace P, Wessely S (1993). Development of a fatigue scale. Journal of Psychosomatic Research 37, 147–153.

Evans S (2007). When and how can endpoints be changed after initiation of a randomized clinical trial? PLoS Clin Trials 2, e18.

Lerdal A, Wahl A, Rustøen T, Hanestad BR, Moum T (2005). Fatigue in the general population: a translation and test of the psychometric properties of the Norwegian version of the fatigue severity scale. Scandinavian Journal of Public Health 33, 123-30.

McAteer A, Elliott AM, Hannaford PC (2011). Ascertaining the size of the symptom iceberg in a UK-wide community based survey. British Journal of General Practice 61, e1– e11.

Stulemeijer M, de Jong LW, Fiselier TJ, Hoogveld SW, Bleijenberg G (2005). Cognitive behaviour therapy for adolescents with chronic fatigue syndrome: randomised controlled trial. BMJ 330, 7481–7486.

Tummers M, Knoop H, van Dam A, Bleijenberg G (2012) . Implementing a minimal intervention for chronic fatigue syndrome in a mental health centre: a randomized controlled trial. Psychological Medicine 42, 2205-15

van't Leven M, Zielhuis GA, van der Meer JW, Verbeek AL, Bleijenberg G (2010). Fatigue and chronic fatigue syndrome-like complaints in the general population. European Journal of Public Health 20, 251-7

Wearden AJ, Dowrick C, Chew-Graham C, Bentall RP, Morriss RK, Peters S, Riste L, Richardson G, Lovell K, Dunn G; Fatigue Intervention by Nurses Evaluation (FINE) trial writing group and the FINE trial group (2010). Fatigue Intervention by Nurses Evaluation (FINE) trial writing group and the FINE trial group. Nurse led, home based self help treatment for patients in primary care with chronic fatigue syndrome: randomised controlled trial. BMJ 340, c1777.

White PD, Goldsmith K, Johnson AL, Chalder T, Sharpe M; PACE Trial Management Group (2013). Recovery from chronic fatigue syndrome after treatments given in the PACE trial. Psychological Medicine Jan 31:1-9. [Epub ahead of print]

White PD, Sharpe MC, Chalder T, DeCesare JC, Walwyn R; PACE trial group (2007). 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 Central Neurology 7, 6.

 

[Tom Kindlon]

Quelqu'un a traduit ma lettre. Je n'ai pas cherché pour trouver des erreurs - ce serait trop fatigant pour moi. Si quelqu'un voit des erreurs dans la traduction, je vous serais reconnaissant si vous aurait faites le moi savoir.

Les bonnes nouvelles qu'ils publient quelques esp. si toutes les observations que j'ai faites sont faites, mais je vais attendre de voir les lettres publiées avant d'accepter cela s'est produit.

Titre (possible): Les modifications apportées aux critères de rétablissement n'ont pas amélioré leur validité *

Quand on publie un protocole pour un essai, que les enquêteurs de première instance ont fait l'APCE (White et al. 2007), il doit y avoir des raisons impérieuses de s'écarter de l' (Evans, 2007). White et al. (2013) affirment que la définition révisée de récupération est conservatrice, avec les modifications apportées à «refléter plus fidèlement la reprise». Est-ce vrai en ce qui concerne le questionnaire de fatigue Chalder (CFQ) et SF-36 fonctionnement physique (SF36 PF) critères?

Le nouveau CFQ critère, un score de 18 ou moins (Likert de notation), a été choisi car il représentait la moyenne plus 1 écart-type dans un échantillon communautaire (Cella et Chalder, 2010). Les scores CFQ n'étaient pas distribuées normalement, mais nous savons que seulement 13,6% de l'échantillon obtenu plus de 18 ans. Toutefois, il ne s'ensuit pas que ce seuil représente un système fiable de coupure de fatigue cas existe aussi des problèmes de fatigue sont fréquents dans la population générale. Par exemple, dans le document, les auteurs référencés lors de l'examen des symptômes dans la population générale (McAteer et al. 2011), 41,3% ont déclaré "se sentir fatigué / run down" alors que 23,1% d'un échantillon représentatif de la population norvégienne avaient des niveaux élevés de fatigue (Lerdal et al. 2005). C'est-à-dire, il est fort possible que plus de 13,6% de l'échantillon à Cella & Chalder (2010) avaient des problèmes de fatigue importants.

Les critères de recouvrement décrites dans le protocole exigent un score de 3 ou moins (score bimodale) qui est une définition validée pour l'absence de fatigue (Chalder et al. 1993). Bien que la traduction exacte entre Likert et les scores bimodales n'est pas possible, on peut montrer qu'un tel score est plus stricte que les nouveaux critères, car elle se traduit par un score de Likert entre 6 et 17 ans. Par conséquent, lorsque comparée à la définition établie de la fatigue cas existe, un score de Likert de 18 indique toujours la présence de niveaux anormaux de fatigue.

Par ailleurs, le critère d'entrée de l'essai de fatigue, un CFQ note bimodale de 6 ou plus, se traduit par une échelle de Likert note comprise entre 12 et 23 ce qui signifie que les participants pourraient avoir des scores de base qui étaient déjà 18 ans ou moins qu'aucune amélioration était nécessaire pour eux de récupérer selon les nouveaux critères. En effet, 17,6% des patients diagnostiqués avec le SCF à l'Unité de fatigue chronique à la London South et Maudsley NHS Trust avaient des scores de 18 ou moins sur le CFQ avant le traitement de leur fatigue.

Pour SF-36 PF, le protocole requis un score de ≥ 85 pour la récupération, tandis que les critères les plus récents exigent un score ≥ 60. Encore une fois, les participants ont pu marquer 60 ou plus au départ ce qui suggère le nouveau critère n'est ni conservateur ni "reflète plus fidèlement la reprise».

Par ailleurs, si je n'ai pas entrepris une recherche exhaustive, dans tous les autres essais que je suis conscient de qui a utilisé la SF36 PF pour opérationnaliser les critères du SCF, un score de 60 aurait été suffisamment faible pour répondre aux besoins de chaque procès pour un diagnostic de SFC (par exemple Stulemeijer et al. 2005; Tummers et al. 2012; van't Leven et al. 2010; Wearden et al. 2010).

White et al. (2013) a utilisé la formule de la moyenne moins un écart-type (SD) à partir de données sur la population britannique en général de Bowling et al. (1999) pour calculer le seuil du SF-36 PF ≥ 60. Toutefois, le SFC n'est pas unique en entraînant une diminution dans ce domaine, avec Bowling et al. notant que 22% dans le même sondage a signalé un problème de santé à long terme, tandis que 16% ont déclaré avoir une maladie aiguë. En outre 28,6% étaient âgés de 65 ans ou plus; normes de la population de ces groupes d'âge sont d'une pertinence douteuse pour la cohorte de première instance de l'APCE (moyenne (écart-type) à l'âge de référence: 38 (12)).

En résumé, la CFQ et SF-36 PF critères qui constituent blanc et la définition de nouveaux collègues de récupération ont été révisés de sorte qu'ils sont moins strictes que celles contenues dans le protocole publié. Ces changements suggèrent qu'il n'est pas prudent de conclure que les nouveaux critères sont soit conservateur ou mieux refléter la récupération que ceux publiés dans le protocole de l'essai.

* N'hésitez pas à changer le titre si vous voulez.
Tom Kindlon Information Officer (position facultative),
Irish EM / SFC Association, PO Box 3075, Dublin 2, Irlande.

Déclaration d'intérêt.
je faire différents types de travail bénévole pour les Irlandais EM / SFC Association.

Références

Cella M, Chalder T (2010). Measuring fatigue in clinical and community settings. Journal of Psychosomatic Research 69, 17–22.

Chalder T, Berelowitz G, Hirsch S, Pawlikowska T, Wallace P, Wessely S (1993). Development of a fatigue scale. Journal of Psychosomatic Research 37, 147–153.

Evans S (2007). When and how can endpoints be changed after initiation of a randomized clinical trial? PLoS Clin Trials 2, e18.

Lerdal A, Wahl A, Rustøen T, Hanestad BR, Moum T (2005). Fatigue in the general population: a translation and test of the psychometric properties of the Norwegian version of the fatigue severity scale. Scandinavian Journal of Public Health 33, 123-30.

McAteer A, Elliott AM, Hannaford PC (2011). Ascertaining the size of the symptom iceberg in a UK-wide community based survey. British Journal of General Practice 61, e1– e11.

Stulemeijer M, de Jong LW, Fiselier TJ, Hoogveld SW, Bleijenberg G (2005). Cognitive behaviour therapy for adolescents with chronic fatigue syndrome: randomised controlled trial. BMJ 330, 7481–7486.

Tummers M, Knoop H, van Dam A, Bleijenberg G (2012) . Implementing a minimal intervention for chronic fatigue syndrome in a mental health centre: a randomized controlled trial. Psychological Medicine 42, 2205-15

van't Leven M, Zielhuis GA, van der Meer JW, Verbeek AL, Bleijenberg G (2010). Fatigue and chronic fatigue syndrome-like complaints in the general population. European Journal of Public Health 20, 251-7

Wearden AJ, Dowrick C, Chew-Graham C, Bentall RP, Morriss RK, Peters S, Riste L, Richardson G, Lovell K, Dunn G; Fatigue Intervention by Nurses Evaluation (FINE) trial writing group and the FINE trial group (2010). Fatigue Intervention by Nurses Evaluation (FINE) trial writing group and the FINE trial group. Nurse led, home based self help treatment for patients in primary care with chronic fatigue syndrome: randomised controlled trial. BMJ 340, c1777.

White PD, Goldsmith K, Johnson AL, Chalder T, Sharpe M; PACE Trial Management Group (2013). Recovery from chronic fatigue syndrome after treatments given in the PACE trial. Psychological Medicine Jan 31:1-9. [Epub ahead of print]

White PD, Sharpe MC, Chalder T, DeCesare JC, Walwyn R; PACE trial group (2007). 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 Central Neurology 7, 6.

 

[Bob]

Rejected letter, with standard response:
"The points you make have already been raised in an earlier letter we have received."



Generalisability of recovery outcomes based on the Oxford criteria.

One of the components for the PACE Trial’s main ‘recovery’ criteria (White et al. 2013), was exclusion from the Oxford criteria (Sharpe et al. 1991) for CFS (chronic fatigue syndrome.)

Unlike internationally recognised diagnostic criteria for CFS (Reeves et al. 2003; NICE 2007) the Oxford criteria require that ‘fatigue’ must be the ‘principal symptom’.

A trial participant would be excluded from the Oxford criteria, thus fulfilling one of the criteria for a trial ‘recovery’, if any other of the common symptoms seen in CFS (for example: malaise, impaired memory, impaired concentration or pain) (Reeves et al. 2003; NICE 2007, VanNess JM et al. 2010; Van Oosterwijck et al. 2010), became the ‘principal symptom’, even if the participant’s physical disability deteriorated after treatment.

The unique feature of the Oxford criteria for CFS, such that the prominence of common symptoms in CFS is used as an exclusionary criterion, raises a question over the generalisability of ‘recovery’ outcomes based on the Oxford criteria.





References:

NICE (2007). Chronic fatigue syndrome / Myalgic encephalomyelitis: full guideline. Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (or Encephalopathy): Diagnosis and Management of CFS/ME in Adults and Children. National Institute for Health and Clinical Excellence (NICE) Clinical Guideline 53. (http://guidance.nice.org.uk/CG53/Guidance/pdf/English)

Reeves WC, Lloyd A, Vernon SD, Klimas N, Jason LA, Bleijenberg G, Evengard B, White PD, Nisenbaum R, Unger ER ; International Chronic Fatigue Syndrome Study Group (2003). Identification of ambiguities in the 1994 chronic fatigue syndrome research case definition and recommendations for resolution. BioMed Central. Health Services Research 3, 25.

Sharpe MC, Archard LC, Banatvala JE, Borysiewicz LK, Clare AW, David A, Edwards RH, Hawton KE, Lambert HP, Lane RJ, Mann A, McDonald L, Mowbray J, Pearson D, Pelosi A, Peto T, Preedy V, Smith A, Smith D, Taylor D, Tyrrell D, Wallace P, Wessely S, White PD (1991). A report– chronic fatigue syndrome : guidelines for research. Journal of the Royal Society of Medicine 84, 118–121.

VanNess JM, Stevens SR, Bateman L, Stiles TL, Snell CR. (2010) Postexertional malaise in women with chronic fatigue syndrome. Journal of Women’s Health 19:239-44.

Van Oosterwijck J, Nijs J, Meeus M, Lefever I, Huybrechts L, Lambrecht L, Paul L. (2010). Pain inhibition and postexertional malaise in myalgic encephalomyelitis⁄chronic fatigue syndrome: An experimental study. Journal of Internal Medicine 268:265-78.

White PD, Goldsmith K, Johnson AL, Chalder T, Sharpe M. (2013). Recovery from chronic fatigue syndrome after treatments given in the PACE trial. Psychological Medicine Jan 31:1-9 [Epub ahead of print.]