This article cannot be considered on its merits or problems without due diligence to the many critiques that have been made about the PACE trial itself, which is subject to key problems in methodology that render the claims of the original Lancet PACE article, and this one, untenable.

I complained to the Lancet well over a year ago (still awaiting response) because of the dangerous ramifications for patients of the PACE trial and its problems. The substance of my complaint can be found here:

http://mywikibiz.com/imag...

While there are many problems with the PACE trial covered by various people, my own complaint related to safety issues. This is relevant to this article because the article claims PACE trialled treatments as cost-effective, which is not a plausible claim if the treatment is not safe in the first place.

The fundamental problem that needs to be addressed is that the evidence available shows that claims, the PACE trial did not adequately assess, or even address, safety of
CBT and GET, and this study did not disprove patients and doctors' valid and substantive concerns regarding the dangers of CBT and GET. One major discrepancy of the PACE trial and the resulting article was the failure to address the biomedical evidence available detailing serious organic physiological dysfunction in patients who receive a 'CFS' or 'ME' diagnosis. Another is the inadequate treatment of adverse outcomes within the trial.

There are specific concerns to be raised about the patient cohort as well. Evidence indicates that research cohorts
for ‘CFS’ or ‘CFS/ME’ appear to be obtained (by those promoting psychogenic explanations for these conditions) by excluding patients with signs and symptoms (especially neurological) found in Myalgic Encephalomyelitis case descriptions, or indeed other organic diseases (the ‘alternativediagnoses‘). The PACE trial used, not just one case criteria to exclude patients with symptoms and signs of organic disease from the trial, but three: ‘Oxford’ (Sharpe et al, 1991); Reeves et al (2003), and those from the NICE guidelines (see White et al, 2011: 2).
Of 3158 patients who had been referred to “six specialist chronic fatigue syndrome clinics in the UK National Health Service” (White et al, 2011: 2), 1187 patients (over a third) were actually excluded because they did not actually meet Oxford criteria for ‘CFS’. Confusingly, no figures are given for those meeting Reeves et al (2003) and NICE exclusionary criteria, though these are claimed as part of the exclusion process. This is possibly because the Oxford criteria themselves efficiently exclude those with signs and symptoms of neurological myalgic encephalomyelitis, to the point that the Reeves and NICE exclusionary criteria may well have been superfluous.
There are similarities of symptoms and signs of neurological dysfunction found in specific case
descriptions of myalgic encephalomyelitis (for example, Ramsay, 1988), or ‘ME/CFS’ (as defined by Carruthers et al, 2003), with other neurological conditions, for just one example, those found in Multiple Sclerosis (see, for example, Poser 2000). Therefore, to have included patients with neurological symptoms and/or signs might have meant there was a risk of other neurological
conditions (such as Multiple Sclerosis) being involved in the trial. Indeed, in his response to me on the biomedcentral site in 2006, Peter White discusses the need to keep people with neurological conditions out of the trial. But, crucially, the key problem here is that, from the evidence available (some of which is detailed by Professor Hooper), Professor White and his colleagues do not appear to believe 'ME' is a neurological condition in the first place, despite the acceptance of this by the
World Health Organisation and British agencies, and despite the evidence available to support this, and therefore seem unable to acknowledge that at least some people given an ME or CFS diagnosis have organic neurological and other deficits. It seems therefore likely that ME/CFS patients with signs and symptoms of neurological (and indeed other organic) dysfunction were actively excluded from the PACE trial.

Ironically, if this premise is accurate, White et al cannot have substantiated their claims for the safety and efficacy of CBT/GET for patients they claim such treatments are safe and efficacious, those given an ME or CFS diagnosis who suffer physiological impairments including neurological
deficits. It needs to be noted that the PACE article actually claims the results: “can be generalised to patients who meet alternative diagnostic criteria for chronic fatigue
syndrome and myalgic encephalomyelitis but only if fatigue is their main symptom” (citing the London criteria and Reeves et al 2003 as the ‘alternative diagnostic criteria‘).

This is a confusing statement, bearing in mind that: the ‘London Criteria’ used in PACE were not actually that as referenced by them (as the documentation from the PACE trial protocol shows); the Reeves et al criteria were supposed to have been used by them within the trial itself (so the question arises, why are they ‘alternative’?); and their conclusions, and that of Bleijenberg and Knoop and
others, presents a blanket claim of safety and efficacy for all people given a diagnosis of ME or CFS, contradicting this statement about “only if fatigue is their main symptom“. Indeed, it is notable that White et al, from the beginning of the trial and throughout, refused to use
the criteria of Carruthers et al (2003) to include people with symptoms (and possibly signs) of neurological dysfunction, although they used their own (specifically customised and therefore different) version of a set of criteria claimed to identify ME (the ‘London’ criteria), already controversial due to lack of peer reviewed publication, uncertainty in authorship, and the existence
of different versions. Indeed, as is evident from the PACE Trial protocol, the specifically customized PACE version of the ‘London’ criteria for ME bore close similarities to the Oxford criteria for CFS, and were fundamentally different to the Carruthers et al criteria (2003).

That so many patients (nearly a third), of whom had been referred to a ‘specialist chronic fatigue syndrome unit’ by their GP, were actually excluded from the CFS diagnosis favoured by these authors, is extremely important, and leads to the question: what happens to such patients? When the patient exclusion process of another project (the negative XMRV study by Erlwein et al, 2009) was
clarified by co-authors (Wessely et al, 2010), some clinical patients who had attended chronic fatigue/CFS clinics commented in response that they had not been investigated thoroughly in the way the research cohorts appeared to be (ironically in order to exclude organic disease), either at the clinic or by their GP. Another study by Newton et al (2010) found that 40% of patients referred to a ‘chronic fatigue syndrome unit‘ did not have ‘CFS‘, though, crucially, Newton was including, as ‘CFS’ patients, those with specific physiological conditions such as positional orthostatic tachycardia syndrome (POTS), which are associated with neurological dysfunction (Carruthers et al, 2003). If these patients had been also excluded from a diagnosis of CFS (which, according to the
Oxford criteria and indeed the Reeves et al criteria, they should), the amount of patients referred to British ‘chronic fatigue syndrome units’ (or, often, ‘chronic fatigue units‘), meeting the Oxford criteria for CFS and having no exclusionary conditions that suggest organic dysfunction, would appear to be very small indeed. But even patients excluded under the rubric of the Oxford criteria
from research, will now be exhorted to ‘try’ CBT and/or GET in a clinical context, because of the unsafe claims of the PACE trial.

In the circumstances, claims of cost-effectiveness are unsafe, when even the problem of treatment safety has not been addressed adequately.

I will supply a reference list to my citations here in another post.