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Somebody seeks info on objective results from Graded Exercise Therapy studies

Tom Kindlon

Senior Member
Messages
1,734
Somebody has asked me the following. Feel free to reply below (my preference). Alternatively free feel to private message me or email me at tomkindlon @ Hotmail dot com with responses:
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I'm preparing a brief (which I hope to send to our Chief Medical Officer) about GET (it's really a PEM-GET primer). I'm looking for some academic sources which used objective outcome measures in GET interventions, specifically ones which showed no improvement following GET. I've included the PACE measures, but would like to reference other studies too, so that it's not just PACE, but more broadly GET.

Are you able to point me to anything?
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Snow Leopard

Hibernating
Messages
5,902
Location
South Australia
As far as I know, there is no such data - they've never bothered. This shows you their attitude towards the science - who cares about strong evidence, all they care about is subjective self reports in unblinded (uncontrolled) trials.

Fulcher/White posted "number employed", but it was a crossover study and they never stated the employment rate of the control group at baseline, so it's not really valid for comparison.

As for other methods, the 6 minute walking test is actually fairly worthless as a objective measure as it highly reflects motivation as well as anything else.

The step test has a strong association with physical fitness (VO2Max), but graded exercise therapy IS NOT DESIGNED TO INCREASE FITNESS (caps for emphasis).

This may seem hard to believe, but unless you have been extremely deconditioned (bedbound), going for a few walks each week will not increase your fitness. Multiple recent studies has shown that increasing your fitness requires your heart rate to reach upwards of 80% of max heart rate for short bursts, at least once a week (and resting for a few days afterwards - note this recommendation is for healthy people!!!). See here: http://www.ntnu.edu/cerg/physical-exercise

Graded exercise therapy is a psychological therapy, it is designed to change peoples behaviours with regards to exercise and activity, hence it is very very very very very (very emphasised) strange that actigraphy is not the primary outcome measure during and after treatment.

The two day VO2 test would be interesting - not for improvments in fitness, but improvements in being able to reproduce the same ventilatory threshold, heart rate rise and recovery curves as the day before. But the VO2 test is very hard and can cause temporary adverse effects. (and biases participation towards less ill patients)

Improvements on concentration (using reasonably long test intervals) on neuropsychological tests is also interesting, but expecting patients to sit there doing tests for hours also biases participation towards less ill patients.
 

A.B.

Senior Member
Messages
3,780
How does cognitive behaviour therapy reduce fatigue in patients with chronic fatigue syndrome? The role of physical activity.
https://www.ncbi.nlm.nih.gov/pubmed/20047707

Although CBT effectively reduced fatigue, it did not change the level of physical activity. Furthermore, changes in physical activity were not related to changes in fatigue. Across the samples, the mean mediation effect of physical activity averaged about 1% of the total treatment effect. This effect did not yield significance in any of the samples.

In other words, subjectively rated fatigue decreases, objectively measured activity levels don't change. The idea that fatigue could decrease without a resulting change in activity levels is not credible. The effect of CBT on fatigue is therefore an artifact of poor methodology. However the authors spun this as "The effect of CBT on fatigue in CFS is not mediated by a persistent increase in physical activity".

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There is also a report from the Belgian government with interesting information on ME/CFS rehabilitation centers with similar results. This report is noteworthy because they measured fitness with cardiopulmonary exercise testing, finding no improvement after therapy.

The systematic outcome registration in the four centres revealed that the main complaint of the patients, their fatigue, had improved significantly at the end of the therapy and 6 months later.

Physical capacity (maximal or sub-maximal according to the patient’s possibilities) did not change between start and end of the treatment.

Employment status decreased at the end of the therapy, from an average of 18.3% of a 38h- working week, to 14.9%. However, it should be noticed that this was not one of the preset goals of the interdisciplinary treatment, and that no specific occupational rehabilitation was foreseen. The percentage of patients living from a sickness allowance increased slightly from 54 to 57%.

Page 80
https://kce.fgov.be/sites/default/files/page_documents/d20081027358.pdf

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Medicine has long accepted that subjective outcomes without blinding are unreliable and create the false appearance of a treatment being effective. This is why we require placebo controlled trials as proof of a drug being effective. Some psychologists and psychiatrists are still under the illusion that their unblinded trial with subjective outcomes is more than an exercise in documenting human bias.
 
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Messages
15,786
@Tom Kindlon - FINE was supposed to include a step-taking test and maximum heart rate, as a secondary outcome, but they seem to have dropped that, or at least omitted it from the published results.

But generally they've avoided objective measurements like the plague, especially when not allowed to use fatigued psych patients. And I wouldn't be surprised if they've been burying a lot of data over the years which contradicts their beliefs.
 

Tom Kindlon

Senior Member
Messages
1,734
That reminds me that we do have this information on the FINE Trial.

"There were no between group differences in any of the step test measures at 20 or 70 weeks"(1).

Reference:

Wearden AJ1, Emsley R. Mediators of the effects on fatigue of pragmatic rehabilitation for chronic fatigue syndrome. J Consult Clin Psychol. 2013 Oct;81(5):831-8. doi: 10.1037/a0033561.

It was buried in a subsequent publication, not the main paper. Indeed, in reply to a letter of mine they said the following in the BMJ:
Kindlon points out that we have not analysed all the outcomes that we measured.3 We reported our primary outcomes and the related secondary clinical outcome data that we thought would be of interest in judging the clinical effectiveness of our intervention. We did not report the step test as an outcome because of a large amount of missing data. Further papers will examine exercise capacity and illness beliefs as potential mediators of the effects of pragmatic rehabilitation. We will also be reporting on predictors or moderators of treatment response; among the variables we will examine will be criteria fulfilled (Centres for Disease Control, London ME), ambulatory status, and comorbidities. Other papers will examine economic outcomes and barriers to delivering these treatments. All papers will use the acronym FINE and have the same ISRCT number, so can be linked to the BMJ paper.
 

Sean

Senior Member
Messages
7,378
Graded exercise therapy is a psychological therapy, it is designed to change peoples behaviours with regards to exercise and activity, hence it is very very very very very (very emphasised) strange that actigraphy is not the primary outcome measure during and after treatment.
If I may quote a noted authority on the subject:

An increase in activity "must ultimately be the aim of any treatment".

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1371151/pdf/brjgenprac00083-0040.pdf

It must surely therefore follow that the most relevant outcome measures are of activity levels, and that those measures must be as robust as possible.

But generally they've avoided objective measurements like the plague, especially when not allowed to use fatigued psych patients.
The one thing they have learned is to avoid using robust outcome measures.
 

alex3619

Senior Member
Messages
13,810
Location
Logan, Queensland, Australia
If I may quote a noted authority on the subject:
A bit of sly sarcasm there. :) Just for those who do not click on the link, it was Simon Wessely who emphasized objective outcome measures in 1999.
It is true that in the later stages of treatment patients are encouraged to increase their activity (which must ultimately be the aim of any treatment) but therapy does not involve the simple prescription of set amounts of exercise.
 

RogerBlack

Senior Member
Messages
902
In other words, subjectively rated fatigue decreases, objectively measured activity levels don't change. The idea that fatigue could decrease without a resulting change in activity levels is not credible.

To take the devils advocate POV - being better able to manage the condition such that there was no activity increase, but fatigue was reduced would be a positive, even if this diddn't lead to increased activity ability. (but this assumes that lifestyle change is even possible for some)
 

A.B.

Senior Member
Messages
3,780
To take the devils advocate POV - being better able to manage the condition such that there was no activity increase, but fatigue was reduced would be a positive, even if this diddn't lead to increased activity ability. (but this assumes that lifestyle change is even possible for some)

How would you better manage the condition without a change in activity levels? One would have to evoke some purely mental effect that can't be measured objectively and supposedly occurs in the same circumstances biased reporting of symptoms is known to occur (for which we actually have objective evidence, at least in other illnesses).
 
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RogerBlack

Senior Member
Messages
902
How would you better manage the condition without a change in activity levels? One would have to evoke some purely mental effect that can't be measured objectively and supposedly occurs in the same circumstances biased reporting of symptoms is known to occur (for which we actually have objective evidence, at least in other illnesses).

'Better manage' was incorrect. I meant 'some treatment could be found that'.
Mental performance is valid too - performance on objective scales like n-back, ...
Actiometers aren't the end. Sorry - particularly fuzzy ATM.
 

Pendergast

Spain
Messages
82
Location
Spain
Sorry for asking this ( maybe I'm a little bit naive and sure I'm clueless :confused:).

But, how can researchers blind these kind of studies? And what kind of objetive measures would be the best if we don't have biomarkers nor clear parameters to test for -yet-?

It's only curiosity and to have an answer if I'm asked the same question by any skeptical Dr.

I want to make it clear that I hate this CBT, GET, PACE trial stuff. :cautious:
 
Messages
2,391
Location
UK
If you really set out to objectively trial the effects of GET on ME sufferers, it would unequivocally show that a significant number of participants were harmed by GET. Such a trial would of course have serious ethical issues. No surprises therefore I suppose, that GET-like trials are left to those committed to unblinded trials with subjective outcome measures, and are prepared to swear that black is white.
 

anciendaze

Senior Member
Messages
1,841
The question about blinding is a real problem, but I'm going to let others reply to that part.

Questions about objective measures are another matter. Even without the kind of convenient biomarkers researchers would like we can easily show that physical performance of ME/CFS patients is far below any reasonable standard of health. The PACE researchers compared data with data from a study of the general population which was not limited by age, and did not exclude patients with serious diseases like heart failure, even though their cohort of subjects did exclude extremes of age and quite a number of physical illnesses. They further pretended that those performance measures from the general population were normally distributed when this was manifestly not true. This then resulted in claiming the patients in the study were only one standard deviation below the mean in performance, which wouldn't sound very serious to anyone thinking in terms of normal distributions. Results on a "walk test" grouping these patients together with those having stage II heart failure should change opinions. It undermines the argument for this approach that the same authors then altered the threshold for entry by 5 points, saying that this difference did not invalidate the study. If a change of 5 points for entry was insignificant, so would a change of 5 points for recovery be insignificant evidence of any therapeutic success.

Recent work by the CDC also shows ME/CFS patients they have chosen also have a very low standard of physical performance. What two small studies by Van Ness and Keller showed was that some patients exist who suffer a decrease in exercise capacity lasting more than 24 hours following exercise. This undermines the rationale for prescribing exercise for them, since they would not be able to engage in daily exercise without losing ground. We are now seeing that government researchers can define the disease and choose the patients to test in such a way that the prolonged decrease in function is not apparent, though the ability of even the patients they chose to benefit from exercise remains in doubt.

What gets lost in this dispute is that people having the characteristic drop in function during the time they report symptoms of PEM really do exist, and prescribing exercise for them within such a period should be contraindicated. I'm am willing to stipulate that 98% of the population does not show such a drop. If this were not so, experts in sports medicine would not have been shocked to discover exceptions at this late date. A completely separate study of patients reporting exercise intolerance with dyspnea showed that a significant percentage had low cardiac fill pressure, a very solid objective measurement. N.B. these patients did not have either pulmonary hypertension or classic heart failure.

Aside from questions about diagnostic criteria and cohort selection we have another question to deal with: how do you separate the patients who will suffer permanent damage from a therapy from those who will benefit? There is no reason to believe the fabled diagnostic eyeball could separate the patients seen by Systrom's group from those with less severe problems. Nor were most doctors who participated in the two other studies easily able to distinguish patients whose capacity for exercise would fall.

Official positions on this matter amount to claiming such patients do not exist because 98% of people are not like that. It might also be that governments do not care if a recommendation that benefits most other people causes long-term decline or even death in a few exceptions.

Added: Concerning the "few exceptions" above, you might compute 1 or 2% of your national population to estimate how many people could be harmed if exceptions are ignored. ("So official spokesperson are you trying to imply that you would be happy if several million Americans did not exist? Are these steps you are taking intended to make that true?")

Just as an old anecdote I will mention going to a young doctor for a previously scheduled check-up when I had a viral infection with "flu-like symptoms". I asked if this meant I should relax my regular exercise routine. (This was before I reached my current state of disability.) He suggested that it would do no harm to "push through". An experienced cardiologist said "absolutely not", since it would be impossible to tell "flu-like symptoms" from a more serious condition like viral myocarditis before doing permanent damage to the heart.

The problem is not that the advice would not benefit many other people, it is that the exceptions have major downsides.
 
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Messages
13,774
Sorry for asking this ( maybe I'm a little bit naive and sure I'm clueless :confused:).

But, how can researchers blind these kind of studies? And what kind of objetive measures would be the best if we don't have biomarkers nor clear parameters to test for -yet-?

It's only curiosity and to have an answer if I'm asked the same question by any skeptical Dr.

Always good to be asking probing questions to try and help understand things.

I don't think that you can really blind trials of treatments with CBT/GET, but this doesn't make the lack of blinding any less of an issue for its potential to distort results than it would be in a trial for a drug, homeopathy, etc.

Also, in PACE it's not just that there was no blinding, but also participants in the CBT+SMC and GET+SMC groups were told during the trial that these treatments had been shown to be effective, while those in the APT+SMC and SMC-only groups were not. That's super unblinded!

I think that there are also aspects of the treatments themselves, and the models which underlie them, which are likely to further increase problems with the sort of biases that leave people sceptical of the value of unblinded trials. eg: encouraging the view that patients can improve their symptoms by adopting the correct attitude and behavior is likely ot lead people to feel that they have greater control over their symptoms, and that therefore reporting fewer symptoms would reflect well on them, and more symptoms would reflect poorly.

re objective outcomes: the PACE researchers did say that they were using three objective outcomes - fitness, employment data and the 6 minute walking test. The addition of CBT led to null results for all three. The addition of GET led to a small improvement for 6mwt, and null results for the other two. PACE had planned to use actometers to objectively measure participant's activity levels, but they chose to drop this outcome measure after purchasing the actometers and using them at baseline. Results from actometers from 3 previous trials of CBT were then released, showing that CBT failed to lead to any improvement in activity levels.
 
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