GETSET (white) in Lancet 22/06/17

[Sean]

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.

 

[Sean]

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.

Just worth repeating.

 

[slysaint]

More for David Tuller to tear to shreds

Pretty please let this be his next target (anyone notified him?)

 

[Esther12]

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/

Really? I found that so frustrating.

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.

I wouldn't say that the seriousness of the limitations with this study are made clear in the paper. Does this study really show that GES led to moderate improvements? I'd say that the limitations of the study mean that we cannot claim that - maybe these limitations were not made clear to Sonya?

"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.

White and colleague choose to call it exercise therapy. Action for ME seem to constantly turn a blind eye to the role researchers play in generating the headlines that they find so frustrating. If it happens oncsistently, maybe the researchers are playing some role in it?! Time to criticise the people who matter rather than just the soft targets.

“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.

When Peter White, lead investigator for GETSET, was providing a training session for his employers at Swiss Re on the PACE trial and it's implications how to manage CFS claims, he explained the importance and finacial implications of this point:

A final point specific to claims assessment, and a question we’re often asked, is whether CFS would
fall within a mental health exclusion, if one applies to a policy. The answer to this lies within the precise
exclusion wording. If the policy refers to functional somatic syndromes in addition to mental health, then
CFS may fall within the exclusion. If the policy doesn’t refer to functional somatic syndromes as well as
mental health then it would be difficult to apply. The point made is that a diagnosis of Myalgic
Encephalomyelitis or ME (a term often used colloquially instead of CFS) is considered a neurological
condition according to the arrangement of the International Classification of Diseases (ICD) diagnostic
codes whereas CFS can alternatively be defined as neurasthenia which is in the mental health chapter
of ICD10.

https://drive.google.com/file/d/0B1hvPDijFCa3bFEyVXl6djFnZjg/view

“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.”

The situation will not change until patient groups start calling out those reponsible for conducting poor quality work and then misrepresenting results. It will be very difficult to change things while Action for ME continues to have influence.

 

[Demepivo]

One small positive in the SMC Press Release from Prof Chris Ponting at Edinburgh University who is is involved in MEGA. Quite a few patients have been in contact with him about MEGA, PACE & related matters.

Prof. Chris Ponting, Chair of Medical Bioinformatics and Principal Investigator at the MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, said:

“The beneficial effect was for fewer than 1 in 5 individuals, for an unblinded trial, and there was no consideration of long-term benefit or otherwise. The study could also have exploited actometers that would have more accurately measured participant activity.”

 

[Demepivo]

The situation will not change until patient groups start calling out those reponsible for conducting poor quality work and then misrepresenting results. It will be very difficult to change things while Action for ME continues to have influence.

AfME & the MEA don't really have much influence. They go along to the CMRC and other meetings and nothing changes.

AfME take the minutes to avoid having to voice an opinion. So what does the MEA do?

 

[wdb]

Results

Is it possible to calculate from this the mean scores at baseline of the 10 participants who dropped out ?

I'm getting odd numbers, if the final mean is 19.1 and the difference is -4.2 is the mean at baseline of the 97 that completed 23.3 ?

 

[Countrygirl]

David Tuller


More crap out this week in The Lancet from the CBT/GET ideological brigades...I will blog about this nonsense in the next few days. A great reason to continue supporting my crowdfunding campaign to help me bust PACE!

 

[Jenny TipsforME]

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

[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?

It's not a trial, so we're not measuring improvement, we'd definitely be doing something objective if we were. Physical function measurement isn't central to it, it's more political about representing patient voice. We want something (brief and) comparable though so when we're writing up we can say "our participants had worse scores than people suffering from x".

SF36 is used a lot but it has issues with Floor Effects for the severity of our participants. I suppose that would be alright for just showing people are very limited and nothing more, but I've never been a fan when I've filled it out myself.

BTW it will be across energy limiting illness disability, basically Spoonie criteria, so not specific to ME.

 

[John Mac]

More crap out this week in The Lancet from the CBT/GET ideological brigades...I will blog about this nonsense in the next few days. A great reason to continue supporting my crowdfunding campaign to help me bust PACE!

Done

 

[trishrhymes]

Done

Me too. My response to this ghastliness this morning was to give a bigger donation to David Tuller than my first one. The fight goes on.

 

[Barry53]

Lets not just assume NICE will be keen to use this as a reason to not review their guidelines... we've got plenty of fight in us yet. The battle has just begun!

I suppose inevitably there is no underlying data for this released. Is it possible for some clever folks to do some analysis of it based on what is known? Especially regarding the notion of people who volunteer for a GET programme may, for whatever reason, belong to as-yet identified sub-groups less likely to experience severe harm.

 

[user9876]

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.

It could be why they don't report the harm that happens elsewhere. If they are careful not to push too hard then some people will follow the protocol and others will claim/believe they do (for example through activity substitution). But it brings doubt to any harm figures.

 

[helperofearth123]

So 1 in 5 patients can have a small improvement by doing GET. Not exactly a very positive result. It can probably be explained by some sufferers under-estimating how much exercise they are capable of as when your energy goes down a lot because of this illness you have to estimate your new activity limits. So there probably isn't ANY real physical improvement going on, even in those who benefited. They are simply realizing they can do slightly more than they thought and then report that as an improvement when their illness hasn't actually improved at all.

e.g. Before the GET they may have thought they could walk 10 minutes a day. Then by the end of the GET they find they can actually walk 20 minutes a day. They report that they can now walk twice as far and thus it seems like they have improved. Whereas in reality they could walk 20 minutes a day the whole time and just estimated how far they could walk wrong in the first place because we can only guess/estimate how far we can walk without triggering a post exertion malaise reaction. So it's really merely changing their perspective on their illness rather than actually improving it.

 

[Daisymay]

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.

Placebo ? Wanting to please the therapist ?

 

[A.B.]

The Chalder fatigue scale is less tied to real world abilities than the SF-36 physical functioning scale. One could say it's highly subjective. The more subjective, the more bias and wishful thinking can influence results. It is therefore not surprising that they emphasized the fatigue score.

Amusingly they first added the Chalder fatigue scale score at 12 weeks and 1 year as outcome, then changed that to Chalder fatigue scale score at 12 weeks. Apparently the wishful thinking wears off rather quickly.

 

[user9876]

At least PACE required a SF36-PF score of 65 or lower for recruitment. It looks like the quacks are now 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.

I saw their statement as one of misleading the ethics committee rather than that they recruited healthy people. The average was around 50 with SD of 22 but SD may not be a valid measure. The table didn't have a range. But I suspect only a few were high scoring. I suspect high scoring for them is >=60 given that is recovered.

 

[user9876]

I can't see from a cursory skim which ethics committee was used. 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?

I thought the ethics board was an east london one - It was London Bridge Ethics committee.

[Edit] I was wrong

The study was approved by the UK National Research Ethics Service Committee London—London Bridge (reference 11/LO/1572) on the Nov 23, 2011.

 

[user9876]

I wouldn't say that the seriousness of the limitations with this study are made clear in the paper. Does this study really show that GES led to moderate improvements? I'd say that the limitations of the study mean that we cannot claim that - maybe these limitations were not made clear to Sonya?

The limitations of the study are so severe given only subjective measures on an open label trial the only conclusion that can be drawn is that the trial wasted money since it would only produce uninterpretable results.

 

[user9876]

I suppose inevitably there is no underlying data for this released. Is it possible for some clever folks to do some analysis of it based on what is known? Especially regarding the notion of people who volunteer for a GET programme may, for whatever reason, belong to as-yet identified sub-groups less likely to experience severe harm.

Data may be available in a controlled form perhaps @Keith Geraghty could explore.

At the time of publication, approvals were being sought to make suitably anonymised data available for external researchers to request through the Yale University Open Data Access (YODA) Project, which is prepared to share these data. The YODA Project is an independent organisation that advocates for the responsible sharing of clinical research data. Data from available clinical trials are shared through the YODA Project with registered users with approved proposals for scientific research.