GETSET (white) in Lancet 22/06/17

[Sean]

Sorry for my ignorance folks but even if you ignore all the issues over the way it's set up if you take it on face value is this really only saying that the "benefit" of GET over standard treatment is only that participants scored 4% lower on the fatigue scale at the end of 12 weeks. Does that really even register as significant.

Not. Even. Close. In any practical real-world sense.

They are playing games with words and statistical thresholds.

Secondly does this actually help back up the reanalysis of the PACE data which showed a similar very small effect.
In which case - despite the media coverage around publication - maybe this actually can help with debunking PACE. Or am I just being exceptionally naive.

No, I think this adds to the increasing pile of damning evidence about poor methodology and clinical results, and questionable reporting of those results.

 

[alex3619]

Given the clear methodological biases then I wonder if the effect size is so small there is actually a negative result that the biases are hiding.

 

[Hutan]

Looks like a poor control group in that most people saw a doctor once and then were sent surveys at 12 weeks and 12 months. That was the trial for them. Its more like a waiting list control group and certainly doesn't try to set similar expectations.

Participants in the control group were no more likely to receive SMC sessions during the trial than those in the GES group. In the GES group, 28 (26%) of 107 patients attended one session, two (2%) attended two sessions, and none attended three sessions; in the control group, 28 (27%) of 104 patients attended one session, two (2%) attended two sessions, and two (2%) attended three sessions (χ2 2·126; p=0·54).

Specialist Medical Care??? Where 72% of the GES group and 69% of the control group didn't see any specialist at all? Not once! That's more accurately termed 'Virtually No Medical Care'. And that's in a trial where the participants might have expected slightly better medical care than the run-of-the-mill patient.

So in NiCE terms can the cost of GET programmes continue to be justified for such a minimal effect on the minority who perceive a benefit. And given the negative impact report by a significant number with the consequences for individuals and cost to the economy.

Indeed. Here's a radical idea. Stop the pfaffing around with GET and use the funds saved to get people with chronic fatigue in front of proper doctors who have a comprehensive approach to diagnosis including being allowed to run tests, who know how to treat things like autoimmune conditions, POTS and sleep disorders and who can give advice on activity management.

That's one of the kinds of trial I'd like to see: for the people referred to chronic fatigue clinics, a comparison between 'Standard (ie 'virtually no') medical care' and 'Informed Diagnosis and Caring Medical Care'. (With objective outcomes ). I'm pretty sure a bit of real medical effort would show an economic benefit.

 

[Sean]

They have modified the intention-to-treat so that it is no longer an intention to treat but the set of people who gave follow up data. That is not intention to treat at all and highly misleading.

Not a good look, is it.

 

[user9876]

Could that be because Oxford doesn't require PEM but NICE does?

But they select first by NICE so everyone should have PEM and then they look for Oxford. Hence they have a subset of around 85% who meet both but around 15% who meet Nice but not oxford. I suspect it is because for Oxford fatigue needs to be the primary symptom and not say pain or PEM but it is unclear.

And of course the time period as @Dolphin pointed out. As with the other values they don't give ranges so we don't know the minimum time that people have been ill for.

NICE of course is not intended as a diagnosis method suitable for trials and maybe this is telling here.

 

[Karen Kirke]

[side question] we're currently working on a research survey for the Chronic Illness Inclusion Project. Which questionnaires/scales of do you think are worth the paper (or pixels) they're written on?
.

The Clinician's Guide to the Institute of Medicines report has a nice list that could be worth working through to see what might suit your purposes? From p.13 of this document: http://www.nationalacademies.org/hmd/~/media/Files/Report Files/2015/MECFS/MECFScliniciansguide.pdf

 

[Cinders66]

For me, the outrage of this is that Peter white and the media are still framing our illness as essentially chronic disabling fatigue of unknown cause, that's how they chose to characterise it and the telegraph picked that up I think. I'm very severely ill now and boy these numpties would have a shock if they saw my life and heard my experiences but even when I was mild to moderate this is not a fair way to characterize what a lot of us are suffering.
And they are not just igmoramuses having a private uninformed opinion, they are Drs working with patients but not listening & failing to understand why we are as outraged as people with distressing complex illness like MS would be, having their illness simplistically and trivialisingly portrayed in the media. THEY are the ones who turned UK ME into this and here we are in 2017 STILL victims of a false narrative but supposed to rejoice that just 1 in 5 ambulant patients who feel up to trying exercise can feel a bit better through it, what about the rest of us?. The telegraph delivering this as something positive whilst we have creaked and groaned under nothing but advice to do more for years.

 

[RogerBlack]

NICE of course is not intended as a diagnosis method suitable for trials and maybe this is telling here.

The NICE criteria are not at all bad really, if followed. https://www.nice.org.uk/guidance/cg53/chapter/1-Guidance#diagnosis

They are rather similar to Fukuda, for example, but with the addition that PEM is mandatory in NICE.
With fukuda, you have more symptoms that can be taken into account for a diagnosis, but do not have to have PEM. (four or more of cognitive, sore throat/lymph/muscle/joint/headache,sleep or PEM.).
http://www.cfids-me.org/cdcdefine.html

The NICE guidance is really pretty good. If you don't look at the CBT and GET sections.

• Challenging thoughts and expectations that may affect symptom improvement and outcomes.
  
  
• Addressing complex adjustment to diagnosis and acceptance of current functional limitations.
  
  
• Developing awareness of thoughts, expectations or beliefs and defining fatigue-related cognitions and behaviour.
  
  
• Identifying perpetuating factors that may maintain or exacerbate CFS/ME symptoms to increase the person's self-efficacy (sense of control over symptoms).
  
  
• Addressing any over-vigilance to symptoms and related checking or reassurance-seeking behaviours by providing physiological explanations of symptoms and using refocusing/distraction techniques.

Snip this out, and the CBT section would almost be reasonable.

 

[RogerBlack]

but supposed to rejoice that just 1 in 5 ambulant patients who feel up to trying exercise can feel a bit better through it,

I note many people quoting the "1 in 5" figure. (there are other problems with this figure)

If you take into account the improvements of people in the control group, it's more like "1 in 9".

In fact, being in the control group is a significantly more cost-effective intervention, with much more positive outcome for money spent.

 

[Cinders66]

NICE require PEM OR PEF. Post exertion fatigue or feeling extra tired after pushing themselves - I'm sure many unfit or chronic fatigued people get that, is totally different to global exacerbation of symptoms, which for many would include various out of increased pain, temperature control issues, sleep disturbance, flu feelings, OI, headaches etc.

 

[trishrhymes]

They are rather similar to Fukuda, for example, but with the addition that PEM is mandatory in NICE.

Here's what they say about the NICE criteria in this paper:

'The NICE criteria require at least 4 months of clinically evaluated, unexplained, persistent, or relapsing fatigue with a definite onset that has resulted in a substantial reduction in activity and that is characterised by postexertional malaise or fatigue, or both. They also require at least one of ten related symptoms: difficulty sleeping, headaches, cognitive dysfunction, general malaise or flu-like symptoms, painful lymph nodes, sore throat, physical or mental exertion making symptoms worse, dizziness or nausea, palpitations, or multisite muscle or joint pain without evidence of inflammation'

Note particularly 'at least 4 months' - this may explain why some did not meet the Oxford criteria which require 6 months.

Note also:

and 'characterised by postexertional malaise or fatigue or both'

I'm not sure this therefore mandates PEM, since post exertional fatigue could be simply what healthy people feel like after playing sport.

And they only require one other symptom - so someone fatigued by depression and sleeping badly who feels tired after exercise could be seen to fit their definition.

 

[Karen Kirke]

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.

I wrote about this before - they recurited many patients very close to the recovery threshold on SF-36 - they admitted this, but they didnt drop those patients as not meeting the inclusion criteria, no they simply added the Chadler scale

The GES self-help guide itself is very instructive as to the type of patients envisioned by the clinicians/researchers http://www.wolfson.qmul.ac.uk/images/pdfs/getset/GET guide booklet version 1 22062010.pdf (This is the booklet given to the patients who took part in the GES arm of the trial.)

Here’s what “Julie” (see p.11 of booklet) can do in a week (after she’s stabilised her boom-bust pattern, before she starts exercising):


Works 10am-6pm Mon –Fri

Walks for 20 mins 4 days a week, a yoga class once a week, a walk with friends once a week, and shopping twice a week

Goes out after work on a Thursday night for 3 hours

Goes out on a Saturday night for 2 hours

Does housework and ironing in 3x 1 hour slots at the weekend

Studies for just shy of 4 hours spread out over the week


Lucky Julie is allowed to lie in till 8am at the weekend, and after her shower and breakfast she’s rewarded with an hour of housework on Saturday and nearly two hours of study on Sunday.


On Friday evening, after her full working week and having been out the night before, Julie is allowed to cook/eat for an hour and then, I kid you not, she studies for an hour. On Friday evening.


We learn less about "Joe" (see p.20-21 of booklet), but his goal is to build up to being able to walk for 30mins so that he can go to the High Street and return with two small bags. He then “has had a busy time recently, with family staying and a few late nights, which has caused an increase in his symptoms that could be classed as a CFS/ME related setback”. His setback can’t be too worrying, since options in his setback plan include to continue his current level of exercise “even though this will feel more difficult” or knock 3 mins off his walking time.


I find it concerning that clinicians might consider this level of activity feasible for most patients, when I think this is far from being the case.


I’m also concerned that the intervention seems to be envisioned for high-functioning patients with boom and bust patterns, but is being recommended for all. Clinically very problematic. It would explain why even in this trial, whose sample could not be considered representative of the ME/CFS population, 85% of patients in this study saw minimal change in their "CFS" after GES, and only 14% reported a positive change in their "CFS", just 8% more than the "control" group (table 6).


Julie's scheduled to be shopping right now. I wonder will she bump into Joe and his two bags on the High Street?

 

[RogerBlack]

I'm not sure this therefore mandates PEM, since post exertional fatigue could be simply what healthy people feel like after playing sport.

And they only require one other symptom - so someone fatigued by depression and sleeping badly who feels tired after exercise could be seen to fit their definition.

characterised by post-exertional malaise and/or fatigue (typically delayed, for example by at least 24 hours, with slow recovery over several days)

I can't read that as other than meaning PEM and PEF mean the same thing.

 

[Dolphin]

But they select first by NICE so everyone should have PEM and then they look for Oxford. Hence they have a subset of around 85% who meet both but around 15% who meet Nice but not oxford. I suspect it is because for Oxford fatigue needs to be the primary symptom and not say pain or PEM but it is unclear.

And of course the time period as @Dolphin pointed out. As with the other values they don't give ranges so we don't know the minimum time that people have been ill for.

NICE of course is not intended as a diagnosis method suitable for trials and maybe this is telling here.

The Oxford criteria also require both physical and mental fatigue:

The fatigue is severely disabling and affects physical and mental functioning

 

[NelliePledge]

The GES self-help guide itself is very instructive as to the type of patients envisioned by the clinicians/researchers http://www.wolfson.qmul.ac.uk/images/pdfs/getset/GET guide booklet version 1 22062010.pdf (This is the booklet given to the patients who took part in the GES arm of the trial.)

Here’s what “Julie” (see p.11 of booklet) can do in a week (after she’s stabilised her boom-bust pattern, before she starts exercising):


Works 10am-6pm Mon –Fri

Walks for 20 mins 4 days a week, a yoga class once a week, a walk with friends once a week, and shopping once a week

Goes out after work on a Thursday night for 3 hours

Goes out on a Saturday night for 2 hours

Does housework and ironing in 3x 1 hour slots at the weekend

Studies for just shy of 4 hours spread out over the week


Lucky Julie is allowed to lie in till 8am at the weekend, and after her shower and breakfast she’s rewarded with an hour of housework on Saturday and nearly two hours of study on Sunday.


On Friday evening, after her full working week and having been out the night before, Julie is allowed to cook/eat for an hour and then, I kid you not, she studies for an hour. On Friday evening.


We learn less about "Joe" (see p.20-21 of booklet), but his goal is to build up to being able to walk for 30mins so that he can go to the High Street and return with two small bags. He then “has had a busy time recently, with family staying and a few late nights, which has caused an increase in his symptoms that could be classed as a CFS/ME related setback”. His setback can’t be too worrying, since options in his setback plan include to continue his current level of exercise “even though this will feel more difficult” or knock 3 mins off his walking time.


I find it concerning that clinicians might consider this level of activity feasible for most patients, when I think this is far from being the case.


I’m also concerned that the intervention seems to be envisioned for high-functioning patients with boom and bust patterns, but is being recommended for all. Clinically very problematic. It would explain why even in this trial, whose sample could not be considered representative of the ME/CFS population, 85% of patients in this study saw minimal change in their "CFS" after GES, and only 14% reported a positive change in their "CFS", just 8% more than the "control" group (table 6).


Julie's scheduled to be shopping right now. I wonder will she bump into Joe and his two bags on the High Street?

this sounds like my life before I was ill

 

[Deepwater]

The GES self-help guide itself is very instructive as to the type of patients envisioned by the clinicians/researchers http://www.wolfson.qmul.ac.uk/images/pdfs/getset/GET guide booklet version 1 22062010.pdf (This is the booklet given to the patients who took part in the GES arm of the trial.)

Here’s what “Julie” (see p.11 of booklet) can do in a week (after she’s stabilised her boom-bust pattern, before she starts exercising):


Works 10am-6pm Mon –Fri

Walks for 20 mins 4 days a week, a yoga class once a week, a walk with friends once a week, and shopping once a week

Goes out after work on a Thursday night for 3 hours

Goes out on a Saturday night for 2 hours

Does housework and ironing in 3x 1 hour slots at the weekend

Studies for just shy of 4 hours spread out over the week


Lucky Julie is allowed to lie in till 8am at the weekend, and after her shower and breakfast she’s rewarded with an hour of housework on Saturday and nearly two hours of study on Sunday.


On Friday evening, after her full working week and having been out the night before, Julie is allowed to cook/eat for an hour and then, I kid you not, she studies for an hour. On Friday evening.

QUOTE]

 

[Dolphin]

'Graded exercise focusses on improving routines and changing physical activity patterns, and it may even require an initial reduction in activity. The aim is to progress carefully to improve, under the supervision of a CFS-experienced therapist, rather than pushing people too hard and towards a setback. Offering the therapy as a self-help approach, supervised by a physiotherapist, could increase access and avoid the fatiguing effects of travel for the intervention.'

http://www.qmul.ac.uk/media/news/items/smd/198480.html
If there is an actual improvement, we don't know what causes it.

It could be because people have actually reduced how much they do. And have more rest periods and generally a more balanced activity and rest pattern rather than much to do with increasing activity.

 

[BurnA]

It could be because people have actually reduced how much they do.

So without any objective measurement pre-trial we don't actually know if people have reduced their activity levels and hence are feeling better.

In other words the Telegraph headline could read :
"Reduced activity could help chronic fatigue syndrome, study shows"

 

[Dolphin]

https://twitter.com/i/web/status/878617185538772992

 

[Large Donner]

This is really quite fascinating when you think of it, physiotherapy over the phone. I wonder if they can do radio massage next.