analysis of five Dutch hallmark studies

[Lou Corsius]

An analysis of Dutch hallmark studies confirms the outcome of the PACE trial:
cognitive behaviour therapy with a graded activity protocol
is not effective for chronic fatigue syndrome and Myalgic Encephalomyelitis.
Gen Med Open. 2017. 1(3): 1-12. doi: 10.15761/GMO.1000117.
Twisk FNM, Corsius LAMM.
Abstract
Myalgic Encephalomyelitis (ME) and Chronic Fatigue Syndrome (CFS)
are considered to be enigmatic diseases.
Several studies propose that
the combination of cognitive behaviour therapy with a graded activity protocol (CBT+),
justified by a so-called (bio)psychosocial (explanatory) model,
is an effective treatment option for CFS (ME).
Objective
A critical review of five Dutch hallmark studies that allegedly support this claim.
Methods
An analysis of the five CBT+ studies with special attention to
the patients studied,
the criteria (subjective and objective measures and cut-off scores)
used to select participants and to define improvement and recovery,
the consistency of the definitions of caseness (being diagnosed as a CFS patient at entry)
versus the definitions of improvement and recovery after CBT+, and
the objective effects.
Results
The studies investigated suffer from various methodological flaws.
Apart from these methodological shortcomings,
the claim that CBT+ is an effective treatment option for CFS
is not substantiated by the data reported.
Some studies investigated CFS patients,
other studies investigated CF patients, labelled as CFS patients, or
combinations of CFS and CF patients.
No study investigated the effect of CBT+
in a group of patients meeting the (original) diagnostic criteria for ME.
The effects of CBT+ on subjective measures, for example fatigue and disability,
if present, are insufficient to achieve normal values.
Impressive recovery and improvement rates
are based on very loose criteria for subjective measures.
Cut-off scores for subjective measures used to define improvement and recovery in studies
show overlap with cut-off scores for CFS caseness in one or more of the other studies.
More importantly, looking at the objective measures,
the proof of clinical improvement after CBT+ is lacking.
Conclusion
Solid evidence of effectiveness of CBT+ for CFS, let alone ME,
is lacking in the five hallmark studies.
The lack of objective improvement indicates CBT+ is ineffective.
This conclusion confirms the outcome of the large-scale PACE-trial in the UK.
Keywords:
Myalgic Encephalomyelitis, chronic fatigue syndrome, cognitive behaviour therapy,
graded exercise therapy, measures, effectiveness
http://www.oatext.com/pdf/GMO-1-117.pdf

 

[Sundancer]

Solid evidence of effectiveness of CBT+ for CFS, let alone ME,
is lacking in the five hallmark studies.
The lack of objective improvement indicates CBT+ is ineffective.
This conclusion confirms the outcome of the large-scale PACE-trial in the UK.

That's good, now we have to hope that the message seeps through to doctors and society.
Nice to see a landsman btw

 

[Tom Kindlon]

https://twitter.com/i/web/status/959934462325936130

 

[Tom Kindlon]

https://twitter.com/i/web/status/960255243400474624

 

[Dolphin]

Good to see the Knoop et al., 2007 full recovery paper being criticised.

Knoop et al., 2007

Knoop et al., 2007 [35] reported impressive recovery rates for CFS by CBT+: “After treatment, 69% of the patients no longer met the CDC criteria for CFS.”. But as the authors also acknowledge:” The percentage of recovered patients depended on the criteria used for recovery.“. According to Knoop et al., 2007 [35] 23% of the CFS patients fully recovered using “the most comprehensive definition of recovery”. First of all, looking at the co-morbidities reported, one could question the correct application of the diagnostic criteria for CFS [4] to select patients in this study [35]. The diagnosis CFS [4] is only applicable when the patient doesn’t experience medical and psychological comorbidities which can adequately explain “fatigue”. The criteria for ‘recovery from CFS (CDC)’ are very easily met, e.g. an improvement from 35 to 34 for CIS F (range 8-46) combined with an improvement from 700 to 699 for SIP 8 (range 0-5.799) are sufficient to be qualified as being ‘recovered from CFS’ (CIS F <35 and SIP8 <700) in this study. However, these scores are by far insufficient to achieve the ‘normal levels’ as defined by the same study (CIS F ≤27 and SIP8 ≤203). This is illustrated by the observation that the positive effect of CBT+ on the mean SIP 8 score is by far insufficient to reach ‘normal levels’ defined in this study (≤203). Not surprisingly, the criteria employed to define recovery largely determine the ‘recovery rates’. Using ‘more strict’ criteria for recovery (CIS F ≤27, SIP8 ≤203, SF-36 SF-36 PF ≥80, SF-36 Social Functioning subscore ≥75, SF-36 General Health subscore ≥65, and no factors scoring negative on the Fatigue Quality List), the recovery rate drops to 23%. However, even “the most comprehensive definition of recovery” isn’t based on stringent criteria. Curiously, the SIP 8 score, used as a criterion to select patients (caseness) in this study [35] and other trials [7], isn’t included in these two definitions of recovery. The study doesn’t report how many CFS patients reached ‘normal levels’ (≤203), but considering the size of the effect of CBT+ on SIP 8 in this study and other trials, few patients, if any, would reach ‘normal levels’. An important point of criticism on the ‘normal values’ used in this study and other studies by the research group relates to the method by which these ‘normal values’ are determined. The ‘threshold scores’ are defined as the mean +/- 1 SD of the healthy population. However, as the authors acknowledge the SIP 8 and SF-36 PF are not normally distributed but skewed [35]. The same applies to CIS F [16] and other SF 36 subscales [52,53]. Aaronson et al., 1998 [54], cited in Knoop et al., 2007 [35], showed a large ceiling effect of SF-36 PF: 31.9% of the Dutch population scored at the highest scale level. As Knoop et al. [35] state “Therefore one could argue that recovery according to the SIP8 has to be defined as scoring the same or lower than the 85th percentile of the healthy reference group.” Using percentiles as threshold scores instead of the mean +/- 1 SD for all subjective measures has a non-negligible negative effect on ‘recovery rates’: “[T] he recovery rate using the definition of having no disabilities in all domains [..] would decrease from 26 to 20%.”. Likely due to the use of the mean +/-1 SD algorithm for calculating ‘normal values’ and/or the use of non-presentative reference populations, the ‘normal value’ for SF-36 PF for the ‘young’ CFS patient group (mean age: 37.0 years) comes close to the mean SF-36 PF scores for healthy population of seniors aged 55 to 64 years [55], while the ‘normal values’ for SF-36 Social Functioning score resembles the mean score of older people aged 75 to 84 years [55] and the ‘threshold score’ for the SF-36 General health score is comparable with the mean of a population of 65 to 74 years [55]. If percentiles of representative populations were employed to define ‘normal values’ and the SIP 8 score was included in the “the most comprehensive definition of recovery” the ‘recovery rate’ based on the subjective measures used would drop dramatically.

The impressive recovery rates reported by the Knoop et al., 2007 study [35] aren’t justified by the data, since the study lacked a control group and non-intervention showed to have positive effects on the subjective measures in substantial patient subgroups in other studies [7-31]. Furthermore, the effect of CBT+ on the other symptoms defining CFS [4] aren’t reported. The study lacked objective measures to substantiate ‘recovery’. Finally, the study reported much lower recovery rates for patients with comorbidities, while many CFS patients experience comorbidities [56].