GETSET (white) in Lancet 22/06/17

[slysaint]

probably on a thread somewhere:
https://www.google.co.uk/url?sa=t&rct=j&q=&esrc=s&source=web&cd=3&ved=0ahUKEwjvj9G7y9PUAhUJblAKHSHuD78QFgg2MAI&url=http://www.25megroup.org/Information/Medical/Margaret%20Williams/PROOF%20POSITIVE.doc&usg=AFQjCNEOdZfGooQDYdWqcAexEstf0YtTmA&cad=rja

PROOF POSITIVE ? (REVISITED)
Margaret Williams 14th September 2016


"
Another follow-up study of PACE participants is scientifically meaningless because there is no way of
taking into account the effect of other interventions which the participants may have used after the
PACE trial ended in 2009.

The GETSET trial (Graded Exercise Therapy guided SElf-help Treatment) for patients with chronic
fatigue syndrome/myalgic encephalomyelitis was described as a randomised controlled trial in
secondary care:
“This study will test the acceptability, effectiveness, cost effectiveness and safety of
Graded Exercise Therapy guided SElf-help Treatment (GETSET) for patients with CFS/ME attending
hospital clinics. GETSET has been designed to incorporate the best elements of GET provided by
current and previous research trials, paying particular attention to safety and acceptability”.

The methodology involved participants being given a booklet and interviewed by telephone or skype. Peter
White was the Chief Principal Investigator of GETSET; originally, it ran from 1st December 2011 to
30th November 2014 (ie. before he had been forced to release the PACE trial data) and funding was
£244,056.00 but Peter White changed the primary outcome measures and asked for the trial to be
extended until December 2015."

"
One question which needs to be addressed is whether his obsession with advancing his own ideology
may have caused him to place PACE participants at serious risk: PACE had no serial checks on
participants’ immune parameters even though in 2004 Peter White himself published a paper on this
important aspect (Immunological changes after both exercise and activity in chronic fatigue syndrome:
a pilot study. White PD, KE Nye, AJ Pinching et al. JCFS 2004:12 (2):51-66).
In that article, White et al stated:

“We designed this pilot study to explore whether the illness was associated with alterations in
immunological markers following exercise. Immunological abnormalities are commonly observed in
CFS…Concentrations of plasma transforming growth factor-beta (TGF-) (anti-inflammatory) and
tumour necrosis factor-alpha (TNF-) (pro-inflammatory) have both been shown to be
raised….Abnormal regulation of cytokines may both reflect and cause altered function across a broad
range of cell types…..Altered cytokine levels, whatever their origin, could modify muscle and or
neuronal function.
“Concentrations of TGF-1 were significantly elevated in CFS patients at all times before and after
exercise testing.
“We found that exercise induced a sustained elevation in the concentration of TNF-which was still
present three days later, and this only occurred in the CFS patients.
“TGF-was grossly elevated when compared to controls before exercise (and) showed an increase in
response to the exercise entailed in getting to the study centre.
“These data replicate three out of four previous studies finding elevated TGF-in subjects with CFS.
“The pro-inflammatory cytokine TNF-is known to be a cause of acute sickness behaviour,
characterised by reduced activity related to ‘weakness, malaise, listlessness and inability to
concentrate’, symptoms also notable in CFS.
“These preliminary data suggest that ‘ordinary’ activity (ie. that involved in getting up and travelling
some distance) may induce anti-inflammatory cytokine release (TGF), whereas more intense exercise
may induce pro-inflammatory cytokine release (TNF-) in patients with CFS”.
This important information was withheld from participants and therapists alike (the Therapists’
Manual on GET was dismissive of studies showing immune dysfunction in ME/CFS).

In the light of this knowledge, it is notable that there seems to have been a cavalier disregard of safety
for GET participants, even though Peter White was aware that three days after exercise, TNFremains
elevated and that this probably accounts for the “sickness behaviour” and “weakness, malaise,
listlessness and inability to concentrate”.

 

[user9876]

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.

They don't seem to give the range for SF36 PF scores but the averages and were 47 and 50 for the different groups with a SD of 22 so it doesn't look like they were high. Perhaps there were one or two who were but that isn't clear. I wonder what the ethics committee was told?

 

[Grigor]

Does anyone know what type of entry criteria they've used? Is it our beloved Oxford? CDC??

 

[Keith Geraghty]

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

now ask yourself this, why would a person have ME/CFS and be near 85 of physial function SF-36? SF-36 is a clear indicator of poor health - how would measuring fatigue help if you are already close to normal physical health?

social problems and cognitive problems - how without physical health worsening ?

they recruited selectively

 

[lilpink]

The problem is can you come up with a single accepted scientific advancement in the treatment for ME since the last NICE review.

Not the treatment per se, but surely the Snell/ Van Ness work is good enough to illustrate that relying on exercise therapies might be a one way ticket to a class action in time.

 

[trishrhymes]

Looks like they learned a lot from PACE.

Don't do any objective tests like 6 minute walk or step test or actometers because they might reveal the truth.

Don't have a meaningful control group like the FINE trial, because that turned out to be a null trial,

Set the end point for reporting results at 12 weeks because that was the peak point for between group differences in FINE and PACE, and the between group effects might disappear by long term follow up, as they did with those trials.

Add in the Chalder Fatigue scale to primary outcomes, because that is more likely to be influenced by therapist effect than Physical functioning.

Set the significance level for between group differences so low as to be meaningless (a 5 point difference on SF36 is not, in my eyes, anywhere near clinically significant).

Continue to use a definition that will include people with, for example, temporary post viral fatigue, poor sleep habits or depression.

The most surprising finding of the trial is that, despite adding all these faults to the long list of faults of the PACE trial, they still managed to get such pathetic between group differences.

 

[lilpink]

We have just witnessed the power of the establishment in action ! boy oh boy do they play hard

Oh yes! But their sins might find them out in time... (for eg: http://www.telegraph.co.uk/news/201...s-colluded-disgraced-bishop-peter-ball-cover/)

 

[lilpink]

I would assume without checking that the ethics committee involved

I can't see from a cursory skim which ethics committee was used. It wasn't South West Frenchay was it?

 

[AndyPR]

Comment from AfME - for them I thought it was surprisingly strong.

Action for M.E. comment on GETSET study in Lancet

Some people with M.E. report that using a guided self-help version of graded exercise therapy (GET) helps improve symptoms, says a study published yesterday in the Lancet.

Two hundred people with M.E. (diagnosed using criteria set out in the NICE guideline) took part in the 12-week study. Half were randomly assigned to receive specialist medical care alone, such as prescriptions or advice regarding medication. The other half received guided graded exercise self-help (GES) in addition to specialist medical care; this involved slowly building up physical activity levels, after establishing a daily routine, with the support of a specialist physiotherapist by phone or Skype.

Results indicate that:

• 42% of participants in the GES group adhered to the programme “well” or “very well”
• the mean fatigue score in the GES group was four points lower than in the group receiving specialist medical care alone; the mean physical function score was six points higher in the GES group
• when rating their overall health, 18% people in the GES group reported feeling “much better” or “very much better,” compared to 5% in the specialist medical care group
• 10 of 97 participants in the GES group dropped out of the study, compared to two in the specialist medical care group.

Action for M.E. comment


Sonya Chowdhury, Chief Executive, Action for M.E., says, “People living with M.E. urgently need access to appropriate care to support them in managing complex and challenging symptoms. While this study shows moderate improvements for those taking part, it’s essential to note that only a minority of patients – one in five – reported feeling much or very much better.

“Limitations to this study are made clear in the paper – in addition to these, we note that the most commonly chosen activity by those taking part was walking. This indicates that those bed and/or housebound with the more severe form of M.E., who are frequently too ill to undertake basic self-care, were unlikely to have been included: even carefully managed activity is rarely, if at all, possible for this very vulnerable patient group.

"It is extremely frustrating to see the study being reported by the Telegraph with the headline Exercise can help chronic fatigue syndrome. Exercise as it's generally understood - going for a run, playing football - is NOT the same as graded exercise therapy, which is a specialised symptom-managed approach that should be delivered by an experienced professional. To conflate the terms plays down complexities involved in managing M.E. and perpetuates misunderstanding about this devastating condition.

“On a related note, the authors state that ‘relative efficacy of a behavioural intervention does not imply that CFS is caused by psychological factors.’ But it cannot be denied that the continuing emphasis on behavioural treatments for M.E., particularly when we know so little about the biology of the condition, contributes to continuing misunderstanding and stigma that prevents children, families and adults affected by M.E. accessing the care and support they need.

“This situation will only change if we see significant mainstream investment into collaborative research that helps us stratify the illness, identify biomarkers, and ultimately lead to targeted treatments for everyone with M.E., not just a minority.”

https://www.actionforme.org.uk/news/action-for-me-comment-on-getset-study-in-lancet/

 

[lilpink]

Politicians are always ready to cut friends out if circumstances change

This has always been my contention. Whilst I'm sure their own faulty cognitions tell them otherwise, the BPS school is essentially the puppet, the patsy ...its strings being pulled by the government / Establishment but always vulnerable to being scape-goated and thrown away when their usefulness is over.

 

[lilpink]

Not exactly a ringing endorsement is it?

No but it IS a political strategy by the SMC... feigning 'balance'.

 

[Forbin]

Does anyone know what type of entry criteria they've used? Is it our beloved Oxford? CDC??

They say:

...we recruited adult patients (18 years and older) who met the UK National Institute for Health and Care Excellence criteria for chronic fatigue syndrome...

This appears to be it. It's from 2007 and seems to list things that the patient might have that would make you "suspicious" of "CFS/ME." It also lists things that should make you question a diagnosis of CFS/ME if they are not present.
https://www.nice.org.uk/guidance/cg53

It's been around a while, but I don't recall seeing it before (but maybe that's just me)..

 

[lilpink]

Comment from AfME - for them I thought it was surprisingly strong.

Re-positioning. I think it speaks volumes. They know the end is nigh. I must stop with these biblical allusions !

 

[user9876]

now ask yourself this, why would a person have ME/CFS and be near 85 of physial function SF-36? SF-36 is a clear indicator of poor health - how would measuring fatigue help if you are already close to normal physical health?

You can separate physical fatigue (and hence function) from mental fatigue and function. However to admit they are separate and potentially vary independently is to admit that the CFQ is not an interval or even an ordinal scale and hence their stats are invalid.

 

[Londinium]

Comment from AfME - for them I thought it was surprisingly strong.

https://www.actionforme.org.uk/news/action-for-me-comment-on-getset-study-in-lancet/

Am I reading that right? Over 50% of the GES group didn't report either 'well' or 'very well' in terms of adhering to the protocol? That's poor.

If I were to sum up, the only improvement on PACE is less egregious outcome switching, which explains the poverty of the results - 18% improvement similar to the 20ish% seen in PACE under original trial protocol. Otherwise all the flaws are the same.

 

[Valentijn]

Comment from AfME - for them I thought it was surprisingly strong.

Chowdhury recently coming out about her son's ME, and her ability to say that Crawley is not currently his doctor, may indicate a bit of a rift between them, or at least an end of Crawley's direct influence over Chowdhury's son. And nearly all patients who pin their hopes on CBT/GET at first inevitably become disillusioned with it when perceived improvements fail to hold up.

 

[Valentijn]

If I were to sum up, the only improvement on PACE is less egregious outcome switching, which explains the poverty of the results - 18% improvement similar to the 20ish% seen in PACE under original trial protocol. Otherwise all the flaws are the same.

Based on the comment by @Keith Geraghty this trial did much worse than PACE in selecting patients who were not physically disabled:

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.

At least PACE required a SF36-PF score of 65 or lower for recruitment. It looks like the quacks are retreating to using physically healthy people for their studies, as they did prior to PACE and FINE. And now there's the added novelty of dropping the objective outcome measurements they used to use with the healthy patients.

 

[slysaint]

Comment from AfME - for them I thought it was surprisingly strong.

Maybe, but no condemnation of GET as a therapy, just explaining it is not the same as what is generally understood as exercise.

 

[Grigor]

They say:


This appears to be it. It's from 2007 and seems to list things that the patient might have that would make you "suspicious" of "CFS/ME." It also lists things that should make you question a diagnosis of CFS/ME is they are not present.
https://www.nice.org.uk/guidance/cg53

It's been around a while, but I don't recall seeing it before (but maybe that's just me)..

Ah super thank you. So atleast PEM had to be considered. Not sure if they've actually used a then...that's a little vague.

 

[Jenny TipsforME]

It wasn't South West Frenchay was it?

Do you have knowledge of this ethics board? Apart from just seeing what questionable ME studies they've waved through?