I posted this comment on David Tuller's blog, showing how the manuals clarify that the rationale for GES in GETSET is essentially the same as that for GET in PACE:
Thank you Dr Tuller and Prof Levin. I don't think there is a shift in rationale or hypothesis between PACE and GETSET, there is just a shift in where that rationale or hypothesis is explicitly stated, from the published paper and trial manuals to trial manuals only. This shift could reduce readership of that rationale or hypothesis and therefore reduce criticism of the trial. The GETSET trial therapist manual and patient booklet make it very clear that the rationale and theoretical model for GES in GETSET is the same as that for GET in the PACE trial (see below).
The therapist manual was authored by Clark, Tims and White and can be read here:
http://www.wolfson.qmul.ac....
The patient booklet was written by 9 NHS GET therapists, edited by Clark with thanks to White, Cunningham and Bavinton, and can be read here:
http://www.wolfson.qmul.ac....
The patient booklet sticks with the PACE rationale for graded exercise:
“After a period of illness…we tend to avoid physical activity and rest more than usual. When we do less each day our body loses fitness and strength in a physical process called deconditioning…The inability to function as before leads to frustration and an eventual lack of motivation for any physical activity. This starts a vicious cycle of avoiding activity and increased fatigue which then results in further deconditioning. The aim of GET is to break this cycle.” (p.4)
Patients are also reassured that no harm will come to them:
“Will GET do me harm? You may be worried that any increase in exercise or physical activity could make your condition worse. Be reassured – research has shown that a guided, gradual exercise programme can help people who suffer from CFS/ME without causing ill effects.” (GETSET patient booklet p.2)
Patient surveys famously contradict this claim of no harm – see figure 1 and table 1 of this article for an overview of UK survey data:
http://journals.sagepub.com....
A more nuanced explanation is given to the therapists. On p.7 of the GETSET therapist manual, Clark
et al state:
“It is not fully understood why GET helps many people with CFS/ME…One theory which can be used to explain GET, as outlined in the GET booklet is based on deconditioning…Another theory points to an altered perception of effort (this may be more significant than deconditioning) [NB Patient booklet does not refer to this more significant effort perception theory.] Participants are encouraged to see symptoms
as temporary and reversible, as a result of their current physical inactivity, and not as signs of progressive pathology.”
Mechanisms are discussed here:
"Apart from the behavioural and perceptual effects of graded exposure to previously avoided physical activities, there may be other mechanisms involved in the success of GET such as reversing deconditioning, including elements of habituation, and positive effects of re-engagement with important activities" (p.7-8, GETSET therapist manual).
"Preliminary research suggests that reduced symptoms (including fatigue) are related to simply participating in a GET programme, rather than necessarily getting fitter, whereas improved functioning is related to getting fitter and stronger" (p.7, GETSET therapist manual).
Therapists are told that "It is important to explain that although [patients] have an increase in symptoms, ‘hurt does not equal harm’ (GETSET therapist manual p.26). Patients are told "Remember that although you may not feel like exercising during a CFS/ME related setback, by resting too much you can quickly lose the physical gains you have made" (GETSET patient booklet p.20).
While Clark et al tell the GES therapists that the effort perception theory may be more significant, they tell therapists:
“The rating of perceived exertion…is not discussed in the GET booklet [for patients] and therefore is not something you need to discuss with the participant unless they mention it.” (p.49)
They go on to explain to the GES therapists that:
“[rating of perceived exertion] is a concept that is important to the participant in their overall success with GES because it is usual for CFS/ME patients to have higher Rating of Perceived Exertion (RPE) than those who do not have CFS.”
While some might think this is because the key feature of ME/CFS is exertion intolerance, to the extent that the Institute of Medicine suggested renaming it “Systemic Exertion Intolerance Disease”
https://www.ncbi.nlm.nih.go..., Clark et al explain to the GES therapists in their manual that:
“[CFS patients’ higher Ratings of Perceived Exertion] may be related to sleep disturbance, deconditioning, enhanced interoception (increased awareness of body sensations), or mood disturbance among other reasons.”
They then clarify for the GES therapists that:
“The RPE cannot therefore be used as an objective measure of intensity for this patient group…After an exercise programme, research has shown that the RPE in CFS patients is normalised, and can at that stage usually be reliable as a measure of intensity.”
To be clear, they have stated that a rating of a patient’s perception of how effortful things are relative to other things is an objective measure in some patient groups, but is not objective in CFS, because CFS patients differ from other patient groups in that they have skewed perceptions, perceiving things to be more effortful than they actually are. This skewed perception is fixed, according to the authors, by exercise programmes.
Perception rating scales are, objectively speaking, not objective; they are and will be subjective for every patient group that exists now and may exist in the future. All outcome measures in GETSET were subjective.
Thankfully other researchers are seeking to understand what ongoing pathophysiological process might be behind exertion intolerance in ME/CFS, taking patients’ experience/perceptions as their starting point, and using objective as well as subjective outcome measures.
