VIRAS Stakeholder Comment on:
The NICE Guideline CG53, Review - July 2017

"1. Do you agree with the proposal not to update the guideline?"

Abbreviations
CBT cognitive behaviour therapy
CFQ Chalder fatigue questionnaire (or scale)
CFS chronic fatigue syndrome
GET graded exercise therapy
M.E. myalgic encephalomyelitis
NICE National Institute of Clinical and Care Excellence
PF Short-form 36 physical function subscale
QMUL Queen Mary University London
RA rheumatoid arthritis
SMC standardised specialist medical care (PACE Trial Control Group)

The NICE Guideline CG53 states
"6.3.1.1…
"CBT is an evidence-based therapy for CFS/ME. It is a collaborative approach that aims to reduce the levels of symptoms, disability and distress associated with CFS/ME. CBT or psychological approaches to CFS/ME do not imply that symptoms are psychological, 'made up' or in the patient's head. CBT is used as part of the overall management for many conditions, including cardiac rehabilitation, diabetes and chronic pain."

"6.3.1.2 Graded exercise therapy (GET)
"GET is an evidence-based professionally mediated approach to CFS/ME involving appropriate physical assessment, mutually negotiated and meaningful goal-setting and education. An achievable baseline of physical activity is agreed, followed by individually tailored and planned increases in the duration of exercise[…], with the objective of improving symptoms and functioning."

These statements contain inaccurate information that is likely to mislead doctors and patients. The PACE Trial (White et al. 2011) produced substantial evidence about the use of CBT and GET as therapies for CFS. The PACE Trial data (2016) shows unequivocally that these treatments provide no objective benefit to patients with M.E. or CFS. The data in Table 1 shows that the treatment effects with CBT and GET, are by convention and usage small to negligible and they do not reach clinical significance (Jacobson, Follette & Revenstorf. 1984).

Table 1

In the PACE Trial, the difference between CBT or GET compared to the SMC control group with the Chalder Fatigue Questionnaire (CFQ) is insignificant at a mere 3 points, as shown in Table 2. The minimum detectable change of the CFQ is ~9 points and 'normal' fatigue is 12 points or less (see appendix 1).

Table 2

The difference between CBT or GET compared to the control group with the SF-36 Physical Function subscale (PF) is negligible as shown in Table 3. The minimum detectable change for this measure is ~25 points, the general population mean for those not reporting long-standing illness is 92.5 and for those with long-standing illness it is 78.3. (see appendix 2).

Table 3

The PACE Trial data shows that the appearance of a treatment effect was created by a minority of only around 10% of participants. If CBT or GET were authentically able to "reduce the levels of symptoms, disability and distress associated with CFS/ME", then significant benefits should have been reported by the majority. The minority effect is evidently the result of poor participant selection, placebo, deference, coercion and other participation phenomena.

Furthermore, participants that provided subjective ratings indicating that they had improved on one measure, frequently had results in other measures which contradicted their claims to have improved. This was particularly evident with results from the only objective measure published, the Six Minute Walk Test, which frequently contradicted any reasonably good subjective ratings given for the Primary Outcome Measures. At outcome, the mean walk distance of >90% participants in all groups did not match the walking ability of an average, healthy person in their seventies. Only two participants reached the Casanova et al (2011) average for 40-49 year olds and one of those was in the control group.

Furthermore, 50% of participants in the control group improved five times more than 50% of either the CBT or GET groups with the CFQ and ten times more for the SF36 physical function measure. This difference was more than three times larger than the supposed overall 'treatment effect' of CBT and GET.

Therefore it is false and misleading to claim that "CBT is an evidence-based therapy for CFS/ME", and imply that this therapy can, "reduce the levels of symptoms, disability and distress associated with CFS/ME". The PACE Trial data shows unequivocally that CBT does not reduce the levels of patient's symptoms or disability.

It is false and misleading to claim that, "GET is an evidence-based professionally mediated approach to CFS/ME", thereby implying that this therapy can treat or benefit patients with CFS. The PACE Trial data shows unequivocally that GET made no difference to participant's symptoms or disability compared to normal medical care. Most significantly, one year of exercise therapy only produced a sub-clinical advantage in walking ability and left >90% of GET participants unable to match the walking ability of an average healthy person in their seventies.

 

"4. Do you have any comments on equalities issues?"

In February 2004, NICE accepted its remit for CG53 from the Department of Health and the Welsh Assembly: "Remit: To prepare for the NHS in England and Wales, guidance on the assessment, diagnosis, management of adjustment and coping, symptom management, and the use of rehabilitation strategies geared towards optimising functioning and achieving greater independence for adults and children of CFS/ME."

This remit, instructed the supposedly independent institution of NICE, to recommend the use of "rehabilitation strategies". NICE obliged by recommending CBT and GET. In the process, it confirmed to any reasonable person, that M.E. and CFS are indeed, "in the patient's head" and that patients are undisciplined and need to be told what to do because their actions and beliefs are causing their illness.

In its 'Comments Form', NICE graciously ask: "Do you have any comments on equalities issues?" In view of the fact that NICE accepted a highly discriminatory remit, which before the GDG was even started, was prejudiced against the interests of patients, and which would predictably be detrimental to their medical care, wellbeing and quality of life - Yes. There is an equality issue here because M.E. and CFS patients evidently are not 'equal' as far as NICE are concerned. Abundant evidence that recommendations in CG53 are false and misleading have been ignored by NICE themselves, making the institute unfit to pass judgement on its own prior and present conduct.

The remit that NICE accepted would have been rejected by any credible independent medical or scientific institution. It was loaded with competing interests that predetermined what the GDG should produce, but it did keep some NICE employees busy for some years and its final product did not inconvenience anyone important or 'equal'. So it is hardly surprising that now that NICE have the opportunity to virtually rewrite their own remit by way of a review, and pass judgement on its own earlier work, it would rather ignore the fact that CG53 misleads patients, doctors and the public and clearly prefers to maintain these seriously flawed guidelines.

This is despite the fact that the Centres for Disease Control and Prevention have removed all mention of CBT and GET from their pages for the public (Tuller, 2017. ME Association, 2017). And it is despite the fact that the PACE Trial, the FINE Trial, the GETSET trial and all similar efforts to establish GET and/or CBT as treatments, have provided incontrovertible evidence that these therapies are not treatments for M.E., or for CFS, or for 'Oxford CFS' and they provide no credible clinically significant benefit to patients.

VIRAS believe that pretending that these therapies can treat M.E. and CFS provides the public and some doctors with 'evidence' to support discrimination against patients and intentionally or not, even encourages abuse of patients as time-wasters and hypochondriacs. It protects the incomes, careers and reputations of the 'wessely-school', who created the illusion that CBT and GET are treatments for M.E. and CFS by: 1/ paper-pile publishing 2/ circular referencing, 3/ misrepresenting research data and 4/ the inveigling of every institution the old-boy network could access - to the extent that there is hardly an institution or individual in the field, which has not at some time or other either overtly or implicitly, supported wessely-school opinions. All these people, like NICE itself, now have a vested interest in maintaining the fantastical and disproved notion that M.E. and CFS can be rehabilitated with CBT and GET.

NICE Guideline CG53 is and always has been unfit for purpose, but NICE is not fit to conduct the review. The task must be assigned to a truly independent scientific body. NICE has demonstrated by its own conduct that they have bowed to, and continue to pander to the vested interests and undue influence of the wessely-school. The result is guidelines that have no credible scientific or medical basis influencing the medical care of thousands of seriously ill patients.

REFERENCES
Casanova C, Celli BR, Barria P. et al. 2011. The 6-min walk distance in healthy subjects: reference standards from seven countries. Eur Respir J. 2011 37: 150-156; doi: 10.1183/09031936.00194909.

Jacobson, N. S., Follette, W. C. & Revenstorf, D. 1984. Psychotherapy outcome research: methods for reporting variability and evaluating clinical significance. Behavior Therapy 15: 336-352.

ME Association. 2017. CDC removes CBT and GET as recommended treatments for ME/CFS. http://www.meassociation.org.uk/2017/07/cdc-removes-cbt-and-get-as-recommended-treatments-for-mecfs-11-july-2017/. Accessed July 13 2017.

PACE Trial data. 2016. QMUL. https://sites.google.com/site/pacefoir/pace-ipd_foia-qmul-2014-f73.xlsx. Accessed 26 October 2017.

Tuller, D. 2017. Trial By Error: The CDC Drops CBT/GET. Available at: http://www.virology.ws/2017/07/10/trial-by-error-the-cdc-drops-cbtget/. Accessed July 12 2017.

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): a randomised trial. 2011. Lancet. Mar 5;377(9768):823-36. doi:10.1016/S0140-6736(11)60096-2.


APPENDIX 1
Hoffman et al evaluated fatigue in 196 myasthenia gravis patients with the CFQ and reported a mean rating of 15.6(6.2). The PACE Trial Protocol states that a Bimodal CFQ score of 3 or less, is a "threshold having been previously shown to indicate normal fatigue". This converts to a median of ~12 in Likert scoring (0 to 33). Pouchot et al (2008) state that the CFQ has a "minimal clinically important difference" (MCID) of 9.9 in rheumatoid arthritis. Goligher et al (2008) found that the MCID with the CFQ was 7.0 (95% CI) in patients with systemic lupus erythematosus. Pettersson et al (2015) estimated the MCID with the CFQ was 9.42 (95% CI) in patients with systemic lupus erythematosus. Van Kessel et al was a clinical trial of CBT (n=35) and Relaxation Therapy (RT. n=37) for Multiple Sclerosis patients. 72 matched healthy controls had a mean CFQ score of 12.5 (5.24).


References
Pouchot J, Kherani RB, Brant R, Lacaille D, Lehman AJ, Ensworth S, Kopec J, Esdaile JM, Liang MH. 2008. Determination of the minimal clinically important difference for seven fatigue measures in rheumatoid arthritis. J Clin Epidemiol. 2008 Jul;61(7):705-13. 10.1016/j.jclinepi.2007.08.016.

Goligher E C, Pouchot J, Brant R, Kherani RB, Aviña-Zubieta JA, Lacaille D, Lehman AJ, Ensworth S, Kopec J, Esdaile JM, Liang MH. 2008. Minimal clinically important difference for 7 measures of fatigue in patients with systemic lupus erythematosus. J Rheumatol. April 2008,35(4)635-642. PMID:18322987

Pettersson S, Lundberg IE, Liang MH, Pouchot J, Welin Henriksson E. 2015. Determination of the minimal clinically important difference for seven measures of fatigue in Swedish patients with systemic lupus erythematosus. Scand J Rheumatol 2015;iFirst article:1-5. doi:10.3109/03009742.2014.988173

Van Kessel, Moss-Morris R, Willoughby E, Chalder T, Johnson MH, Robinson E. A Randomized Controlled Trial of Cognitive Behavior Therapy for Multiple Sclerosis Fatigue. Psychosom Med. February/March 2008 vol. 70 no. 2 205-213. 10.1097/PSY.0b013e3181643065.

APPENDIX 2
Ruta et al, carried out a test-retest reliability study of the SF36 in 233 British rheumatoid arthritis (RA) patients, representing 4 classes of RA with an average age of 56 and mean SF36 physical function score of 31. Ruta et al (1998) found that the "Size of individual SF-36 score difference with 95% confidence" is 23.8. Steffen and Seney (2008) studied 36 parkinsonism patients whose mean physical function score was 57 (SD.23) and determined that the minimal detectable change with 95% confidence was 28. Stulemeijer et al (2004) found that their adolescent control participants on the 'waiting list' for CBT, had 10 points improvement with the SF-36 physical function subscale at five months, which is 2 points higher than White et al's (2011) claim for a "clinically useful difference" rating. Population norms are 92.5 for no long-standing illness and 78.3 for those reporting long-standing illness (Jenkinson et al. 1993).

References
Jenkinson C, Coulter A and Wright L. 1993. Short form 36 health survey questionnaire: normative data for adults of working age. BMJ. 1993 May 29;306(6890):1437-1440. PMCID: PMC1677870.

Ruta DA, Hurst NP, Kind P, Stubbings A. 1998. Measuring Health Status in British Patients with Rheumatoid Arthritis: Reliability, Validity and Responsiveness of the Short Form 36-Item Health Survey (Sf-36). Br J Rheumatol. 1998;37:(4):425-436. PMID:9619895

Steffen T, Seney M. 2008. Test-Retest Reliability and Minimal Detectable Change on Balance and Ambulation Tests, the 36-Item Short-Form Health Survey, and the Unified Change on Balance and Ambulation Tests, and the Unified Parkinson Disease Rating Scale in People With Parkinsonism. 2008. Phys Ther. 2008; 88:733-746. 10.2522/ptj.20070214.

Stulemeijer M, de Jong LWAM, Fiselier TJW, Hoogveld SWB, Bleijenberg G. 2004. Cognitive behaviour therapy for adolescents with chronic fatigue syndrome: randomised controlled trial. BMJ. bmj.38301.587106.63v1. 10.1136/bmj.38301.587106.63. doi: https://doi.org/10.1136/bmj.38301.587106.63

White PD, Goldsmith KA, Johnson AL, 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. 2011. Lancet. Mar 5;377(9768):823-36. doi:10.1016/S0140-6736(11)60096-2.

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