Trial by Error, Continued: More on Graded Exercise from Peter White and The Lancet

Kati

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David (Tuller) posted a new blog post today regarding GETSET. He asked on twitter to leave comments on the blog:

http://www.virology.ws/2017/06/28/t...ded-exercise-from-peter-white-and-the-lancet/

He consulted with statistician Bruce Levin and quoted him (in his post)

Exerpt:

Professor Peter White and colleagues have published yet another study in The Lancet promoting graded exercise as an appropriate intervention for the illness they refer to as “chronic fatigue syndrome” but that is more appropriately called “myalgic encephalomyelitis.” (Two compromise terms, ME/CFS and CFS/ME, satisfy no one.) This new article exhibits the range of problems found repeatedly in this body of research, including the reliance on subjective outcomes for an open-label trial, unusual outcome-switching, and self-serving presentations of data.

In short, this latest study seeks to bolster the crumbling evidence base for the PACE/CBT/GET paradigm by reporting modest benefits for graded exercise. But as with previous research espousing this approach, even the unimpressive results reported here cannot be taken seriously by scientists who understand basic research standards.

Much more at the link above.
 
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Tom Kindlon

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I don`t think this comment is that significant.
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“It is important to note that this trial was not designed to test causative factors in chronic fatigue syndrome, and the relative efficacy of a behavioural intervention does not imply that chronic fatigue syndrome is caused by psychological factors,”
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Peter White has used "causes" before (e.g. 10 years ago on a discussion list with me) to refer to what initially caused the illness e.g. an infection. He sees what perpetuates the condition as something else.
 

A.B.

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obscurantism
1. opposition to the increase and spread of knowledge.
2. deliberate obscurity or evasion of clarity.

That the PACE authors continuously fail to mention important biomedical findings in their papers is a form of obscurantism.

The PEM literature is highly relevant to any discussion about exercise. I'm fairly sure it has never been acknowledged in any paper by the CBT/GET proponents. One can only conclude that they wish to keep readers in the dark and shield their cherished therapy from highly inconvenient facts.
 
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lilpink

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Surely Prof Levin's observation "Obviously they were looking at baseline data in order to notice that “too many” subjects had non-disabled physical functioning" is the most damning of all? Assuming I have understood the context correctly then the GET-SET PI's have by their own foolishness accidentally revealed that they did look at baseline data. It wasn't blinded? And their mid stream changes might amount to research fraud?
 

dangermouse

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I reckon GetSetJulie will be one of their biggest errors, it's so blatantly obvious that whoever dreamed up Julie's diary has not got a clue about the nature of ME and how it impacts the human body.

Even prior to getting ME I'd have struggled to keep up with Julie's timetable of activities!

The more exposure GetSetJulie gets the better! She's proof of how flawed the whole thing is.

It's so ridiculous it's laughable.

Ah, she likely claps hands and reminds herself not to "do" ME throughout the day, that'll be it.
 

slysaint

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Brightened my day a bit............David Tuller the Magnum PI of the ME world:heart:

" The investigators mention patient surveys on reported harms from graded exercise, but they choose to ignore the growing peer-reviewed literature from leading medical research centers around the world. They also ignore the major 2015 report from the U.S. Institute of Medicine (now called the Academy of Medicine), which identified “post-exertional malaise” as the cardinal symptom, in the process renaming it “exertion intolerance.”

One for the NICE guidelines I hope. (fingers crossed emoji)
 
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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.
 

TiredSam

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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).
The date of the booklet's publication is 2009. In the light of research since then (obviously sufferers' testimonies before and since then have counted for nothing due to their "skewed perceptions") it should be withdrawn as a matter of urgency.
 
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The date of the booklet's publication is 2009. In the light of research since then (obviously sufferers' testimonies before and since then have counted for nothing due to their "skewed perceptions") it should be withdrawn as a matter of urgency.
I couldn't see a publication date - can you let me know where it is? And did you see one on the patient booklet too?
 

TiredSam

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From the patients' booklet:

If your setback is CFS/ME related then you should try and continue exercising at your current level to the best of your ability. It is often incorrectly assumed that an increase in symptoms equals harm. It doesn’t. If you continue at the exercise level you are on now you may well find that you feel no worse, and after a short while you may actually feel better. 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 that you have made. Setbacks are a normal part of recovery and so it is important to remain as positive as possible. As you get stronger you will find that you have fewer setbacks and they are less severe and last a shorter time.

Forming a setback plan
Managing a setback is a matter of using common sense but you will find it helpful to work out a plan of action in advance. When developing a setback plan there are important points to remember.
• Try to maintain as much physical activity as you can even if this seems difficult.
• Resting too much will probably worsen your condition in the long run. Even resting for a week can make it much harder to get back to where you were on the GET programme.
• If you cannot do your exercise in one go break it into two or
more sessions.
• If you have had to stop an activity or an exercise get back to it as soon as you can.
Absolutely insane. They just made it up.
 

Wolfiness

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The original protocol had only one primary outcome measure, the SF-36 PF. However, when some eligible participants were found to have high SF-36 PF scores at randomisation (because of their illness affecting cognitive or social functions but not physical function), we decided to also include fatigue, using the CFQ, as a co-primary outcome.
Again? "We only realised halfway through the trial that the methods we've been using for decades to assess patients are inadequate." AGAIN?! Fascinated by their genuine stupidity.
 
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The link to the therapist manual in your post didn't work for me, so I've only seen the patient booklet. Publication date is August 2009, on page 36, the last page.
Thank you! I see it now. It's a while ago, eh? Yes I saw that the therapist manual link wasn't working so I replied to my own comment giving links again.

Hopefully this will work:
http://www.wolfson.qmul.ac.uk/images/pdfs/getset/GETSET therapists manual with appendices.pdf

If not, navigate to both therapist manual and patient booklet from here http://www.wolfson.qmul.ac.uk/current-projects/getset-trial#links
or here http://www.wolfson.qmul.ac.uk/current-projects/getset-trial#trial-information
 

slysaint

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From the therapists manual, Re: Use of heart monitor:

"Most people with CFS/ME have a higher RPE score than normal subjects for the same heart rate, so they cannot rely on their subjective RPE ratings to determine optimal exercise intensity. However, in the GET booklet heart rate is not used to measure exercise intensity, but distance covered. If a participant is particularly interested in using a heart rate monitor to determine their exercise intensity, you can provide advice within the time you have, but will need to inform the participant that you do not have much time to dwell on it.

You could provide them with the following information: once participating in 30 minutes of physical activity or exercise on at least 5 days of the week, they should aim to be working between 60 and 75% of their predicted heart rate maximum.

Participants may decide to use heart rates to measure the intensity of their exercise. So this information is for your general knowledge, but does not need to be used with participants unless they require this information so that they are exercising safely.

The participant’s target HR zone is calculated from a universally accepted and understood method; a method used for normal, healthy people (220–age, X 0.6-0.75). Where 0.6 to 0.75 correspond to 60% and 75% of predicted maximum heart rate."

So did the participants wear heart rate monitors?
 
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From the patients' booklet:



Absolutely insane. They just made it up.
The example of what to do during a setback is also interesting (p.21 of patient booklet http://www.wolfson.qmul.ac.uk/images/pdfs/getset/GET guide booklet version 1 22062010.pdf).

Fictional "Joe" is supposed to be walking for 17 minutes 5 days a week, but he has a fictional ME/CFS "setback" so he follows his setback plan, doing one of the following (wording is mine - see p.21 for wording in booklet):

1. Keep walking for 17 minutes 5 days a week "even though this will feel more difficult".
2. Keep walking for 17 mins 5 days a week, just go slower.
3. Keep walking for 17 mins 5 days a week, with a 5 min rest in the middle.
4. Go for two walks 5 days a week: walk for 10 mins in the morning and 7 mins in the evening.
5. Walk for 17 mins 4 days a week, splitting it or taking a rest if needed.
6. For one or two days, reduce length of walk to last week's duration: 14 mins, then go right back to 17 mins.
7. Reduce length of walk to last week's duration: 14 mins, and do it 5 days a week.

In case Joe didn't get the message, his setback plan ends with "I should aim to return to the 17-minute, pre-setback walk as soon as possible."

It might explain why only 42% of participants adhered to GET completely or very well, 30% moderately well, 29% slightly or not at all (p.8 of the GETSET paper).
 

BurnA

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However, in the
GET booklet heart rate is not used to measure exercise intensity, but distance covered
. If a participant is
particularly interested in using a heart rate monitor to determine their exercise intensity, you can provide
advice within the time you have, but will need to inform the participant that you do not have much time to
dwell on it.
OMG.

I thought using a heart rate monitor for measuring distance covered would be the craziest thing I read today. But then i read how therapists shouldn't dwell on it.

Imagine dwelling on an objective measurement of whether or not the exercise was suitable for the patient.
Or dwelling on the fact the a participant may suffer heart problems during the trial, Noooo definitely not to be dwelled upon.


Seriously isn't this negligence.?