IiME letter to Mark Baker (NICE) re: CBT & GET as recommended treatments

[Tom Kindlon]

I remember @Tom Kindlon put a huge amounting of time and effort into going through the MEA survey about PACE and the people whose conditioned became worse because of it. I know he posted about it on other forums.

Also there is Tom's paper on the under reporting of harms in PACE. When I had a consultant mention GET to me I gave him a copy.That was the end of that.

Thank you Tom

Thanks.
I posted them to this thread:
http://forums.phoenixrising.me/inde...ed-as-primary-treatments-for-me.37782/page-15

Also here:
ME/CFS: Graded Exercise Therapy. Experiences & Comments from 2015 (UK) MEA CBT/GET/Pacing Survey
https://www.pinterest.co.uk/tomkindlon/mecfs-graded-exercise-therapy-experiences-comments/

ME/CFS: Cognitive Behavioural Therapy. Experiences & Comments from 2015 MEA CBT/GET/Pacing Survey
https://www.pinterest.co.uk/tomkindlon/mecfs-cognitive-behavioural-therapy-experiences-co/

 

[large donner]

@Alvin, yes, but, whatever the authors actually did, PACE was anyway a bust scientifically in so many ways that we've an embarrassment of riches as far as discrediting it goes, so it ought to be impossible for NICE to justify using it it in the new guidelines.

Its going to be a real challenge for NICE to review issues with the PACE trial and continue with the current recommendations but at the same time by admitting PACE is flawed they will be admitting peer reviewed published work in the Lancet funded by the DWP is garbage.

As NICE have already replied that one trial doesn't disqualify all others the issue of the criteria used could be crucial in how we win this argument.

 

[Inara]

Why on earth would the BPS school risk including people in their trials that would potentially show less effect from their treatments? They use Oxford to deliberately exclude what would potentially be the condition they don't want in their studies.

Today a psychologist said to my husband (both in acadamia), that they pick data so as to give "good results" (I guess p < 0.05), and if they published raw data (as required for data archiving) people would see that they manipulated. That's why they cannot publish their raw data.

 

[Indigophoton]

Perhaps this paper by Nacul et al helps in arguing against the Oxford criteria,

Brurberg et al. (2014) also showed that the Oxford criteria (Sharpe et al., 2015) yielded the highest median prevalence across studies, 1.5 per cent, 15 times greater than that obtained using the Canadian criteria, albeit in different populations. If it is assumed that the Oxford criteria always capture Canadian-positive cases, then, based on the above figures, we expect that of a sample of 15 cases selected using the Oxford criteria, 14 will not meet the Canadian criteria. Therefore, if Oxford-positive cases are used to test a hypothesis related to a specific pathophysiological process observed in Canadian-positive cases, this could lead to the selection of 14 non-cases (false positives) for every 15 recruited; an unacceptable level of misclassification.

How have selection bias and disease misclassification undermined the validity of myalgic encephalomyelitis/chronic fatigue syndrome studies?

The seems like an argument for not using any evidence that relies solely upon the Oxford criteria, assuming one can argue that the CCC are useful.

Beth Smith et al. (2014, addendum 2016) recently reappraised the evidence for ME/CFS treatments. When studies using the broad Oxford criteria (Sharpe et al., 1991) were excluded, a virtual disappearance of effect for graded exercise therapy (GET), cognitive behaviour therapy (CBT) and other psychological therapies recommended by the NICE guidelines (National Institute for Health and Care Excellence (NICE), 2007) was revealed. Studies included the pacing, graded activity, and cognitive behaviour therapy: a randomised evaluation (PACE) trial (White et al., 2011) where psychological and exercise-based treatments had some efficacy against chronic fatigue as a symptom in the sample., but were shown to have little effect for those people with ME/CFS when defined according to more restrictive criteria (Beth Smith et al., 2014, addendum 2016; Geraghty and Esmail, 2016).

The revised understanding of the evidence will likely result in changes to ME/CFS treatment guidelines, illustrating the potentially far-reaching repercussions of diagnostic misclassification and selection bias.

Based on this, it does appear that if we can get the Oxford criteria thrown out, that would effectively knock out CBT and GET.

 

[Jonathan Edwards]

Based on this, it does appear that if we can get the Oxford criteria thrown out, that would effectively knock out CBT and GET

Nacul's argument is an important one.. The other thing that strikes me is that if it is agreed that PEM is central to the category of ME/CFS, CFS/ME or ME+CFS that the guidelines will be for then there is an immediate problem with studies that voluntarily recruit patients to possibly receiving GET. It is highly unlikely that People with PEM will want to be included. And Oxford allows all the people without PEM through, to have the effect of GET on them studied. This is a consistent problem with all the Oxford studies that include GET or GET and CBT.

So Oxford is no good if trial design biases out all (or even most of) the Canadians. So although Oxford is reasonable to use on a purely set theory basis, if we know that the probability of the right subset being included is seriously biased against we have a positive reason to reject an Oxford sample.

It might also be that people with PEM would not sign up for CBT since they would be the ones, in the BPS words, most convinced they have a physical illness (because it feels like it) and therefore sceptical about CBT.

I wonder if there is any chance of discovering the PEM status of the recruited and not recruited patients in any of these studies. I suspect not.

Edit: I realise that some of this is probably what Large Donner has been trying to persuade me of, but I needed to find a way of thinking it that required no need to prejudge ill intent.

 

[Inara]

So although Oxford is reasonable to use on a purely set theory basis

Would you be willing to explain this?

Also, I get confused. Didn't I understand you correctly that from a scientifc view it is correct to use Oxford criteria and transport the results to ME? I.e. didn't you mean that Oxford-CFS is a superset of ME? If so, I realize I didn't understand why that is correct?

 

[Jonathan Edwards]

Yes, despite Valentijn's reasonable protestations I think Oxford is roughly a superset of ME. So you can apply inferences drawn from an Oxford population to ME if you have no reason to think there is an important confounding factor that skews the probabilities. But if such a confounding factor is staring us in the face, and in fact we have debated it several times before, then the same inferences are not reasonable to apply.

 

[Inara]

I think Oxford is roughly a superset of ME

I think for a mathematician this is hard to understand. But I hope I start to understand your way of thinking nonetheless. Thanks for explaining.

 

[Invisible Woman]

I think this is where I have been confused as I haven't considered Oxford as a superset but as a large, loosely defined set where there are some common members with other separate sets such as ME.

As far as I can tell I would have been excluded from Oxford, even though there is little doubt about the diagnosis of ME /CFS.

 

[Hoopoe]

Yes, despite Valentijn's reasonable protestations I think Oxford is roughly a superset of ME. So you can apply inferences drawn from an Oxford population to ME if you have no reason to think there is an important confounding factor that skews the probabilities. But if such a confounding factor is staring us in the face, and in fact we have debated it several times before, then the same inferences are not reasonable to apply.

Doesn't Oxford criteria exclude those with neurological signs? This sounds like a permission to exclude many ME/CS patients, because I'm pretty sure that a determined doctor could easily find some neurological abnormalities. I can't walk straight with closed eyes for example (tandem gait test it's called I believe).

 

[Andy]

Reply from Mark Baker and response to it from IiME - http://www.investinme.org/IIMER-Newslet-1801-01.shtml#IiMER-reply18-1

The existing recommendations are carefully nuanced and crafted to give power and choice to patients. The problem is, I believe, in the unthinking and ill-informed manner in which the recommendations are imposed on people for whom they are not intended and/or not suitable. To this extent, some clarification may be required prior to the completion of the new guideline.

I was struck by some of the stories at the workshop about the misuse of the current recommendations and the disturbing extent to which they are imposed on people who are unlikely to benefit from them and for whom alternative approaches would be sensible. However, scrapping the entire guideline now would be massively counter-productive as it would almost certainly result in the withdrawal of the already dwindling number of services available to people with ME. Therefore, a rather more limited approach would be required to protect what is good whilst modifying what may be harmful.

"protect what is good" I've no idea what he's talking about here, I've yet to experience anything good from the NHS while I have progressed from mild to the severe side of moderate.

 

[large donner]

Doesn't Oxford criteria exclude those with neurological signs? This sounds like a permission to exclude many ME/CS patients, because I'm pretty sure that a determined doctor could easily find some neurological abnormalities. I can't walk straight with closed eyes for example (tandem gait test it's called I believe).

This is my whole point.

To declare you diagnosed with CFS to dump you they ignore all the observable neurological signs from the examination and fail to document them in your medical files hence it adds to the argument that you are medically unexplained and disqualifies you from testing.

Yet when they want to run a CBT GET trial to "prove" their treatments they wouldn't let you within a million miles of the trial because as White says in his own words.....

CFS defined simply as a principal complaint of fatigue that is disabling, having lasted six months, with no alternative medical explanation.

He couldn't make it any clearer that's what he means and its a built in disclaimer.

 

[Inara]

Doesn't Oxford criteria exclude those with neurological signs?

That's why I agree with @large donner and others that ME is not a subset of Oxford-CFS.
If I understood correctly, PEM is excluded in Oxford-CFS, but it's an ICC symptom. So, ICC-ME is no subset.

Yet when they want to run a CBT GET trial to "prove" their treatments they wouldn't let you within a million miles of the trial because as White says in his own words.....

The more I think about that - and having in mind Mr. Bakers words - the more I think that is correct. And in a way, it fits what the psychologist said about picking data to get nice results.

 

[Amw66]

Nacul's argument is an important one.. The other thing that strikes me is that if it is agreed that PEM is central to the category of ME/CFS, CFS/ME or ME+CFS that the guidelines will be for then there is an immediate problem with studies that voluntarily recruit patients to possibly receiving GET. It is highly unlikely that People with PEM will want to be included. And Oxford allows all the people without PEM through, to have the effect of GET on them studied. This is a consistent problem with all the Oxford studies that include GET or GET and CBT.

So Oxford is no good if trial design biases out all (or even most of) the Canadians. So although Oxford is reasonable to use on a purely set theory basis, if we know that the probability of the right subset being included is seriously biased against we have a positive reason to reject an Oxford sample.

It might also be that people with PEM would not sign up for CBT since they would be the ones, in the BPS words, most convinced they have a physical illness (because it feels like it) and therefore sceptical about CBT.

I wonder if there is any chance of discovering the PEM status of the recruited and not recruited patients in any of these studies. I suspect not.

Edit: I realise that some of this is probably what Large Donner has been trying to persuade me of, but I needed to find a way of thinking it that required no need to prejudge ill intent.

Perhaps this is why there are recent efforts to trace and check status of PACE participants? And NOD data?

 

[Indigophoton]

if it is agreed that PEM is central to the category of ME/CFS, CFS/ME or ME+CFS that the guidelines will be for

Then could we simply argue that Oxford is invalid because it does not require PEM?

Proving the need to use PEM in any criteria might be relatively straightforward, as there seems to be an increasing consensus on that.

For example, The BMJ Best Practice Review from just last month states that "PEM is the hallmark of CFS", and that the Oxford criteria are inappropriate:

Chronic fatigue syndrome

Last reviewed: December 2017
Last updated: November 2017
....

Definition
Definitions of chronic fatigue syndrome (CFS) have evolved from a focus on fatigue and impairment as described in the Centers for Disease Control (CDC) criteria, [1] to postexertional malaise (PEM)/exertional exhaustion in myalgic encephalomyelitis (ME)/CFS as defined by the Canadian Consensus Criteria, [2] [3] and systemic exertion intolerance disease (SEID) introduced by the US Institute of Medicine. [4] [5] These 3 definitions have compatible criteria that focus on PEM, disability, sleep, pain, and cognition.[6] [7]

Exertional exhaustion is the critical aspect that distinguishes ME/CFS from other nociceptive, interoceptive, and fatiguing illnesses. .....Consideration of “fatigue” as mental or physical tiredness is too simplistic to encompass the scope of impairment in CFS, and belies the inadequacy of the vocabulary of fatigue.

CFS is characterized by a sudden or gradual onset of persistent disabling fatigue, postexertional malaise (PEM, exertional exhaustion), unrefreshing sleep, cognitive and autonomic dysfunction, myalgia, arthralgia, headaches, and sore throat and lymph nodes, with symptoms lasting at least 6 months. [8]PEM is the hallmark of CFS. The fatigue is not related to other medical conditions, and symptoms do not improve with sleep or rest.

ME is more strictly defined than CFS. ME is defined by: disabling fatigue; postexertional malaise; sleep, pain, cognitive and autonomic dysfunction; and chemical irritant sensitivity.[6] [7]

Systemic exertion intolerance disease (SEID) was defined by the US Institute of Medicine (IOM). Diagnosis of SEID requires disabling fatigue, PEM, unrefreshing sleep, and cognitive and autonomic dysfunction that is persisting, moderate or severe, and present at least 50% of the time in order to denote the unique symptom spectrum. [4]

It is inappropriate to use the 1991 Oxford criteria of fatigue as an alternative for CFS because the Oxford criteria are based on “mild fatigue", do not require postexertional malaise, and allow inclusion of chronic idiopathic fatigue, depression, and other fatiguing conditions. [9] Up to 30.5% of the population have chronic fatigue [10] and would meet Oxford criteria for study inclusion. Studies that used the Oxford criteria are not representative of the more severe and restricted definitions of CFS that the CDC, Canadian Consensus, or SEID criteria define. Exercise and cognitive behavioral therapy studies that used the Oxford criteria for study inclusion are biased and misleading because people with true CFS are underrepresented, with excessive recruitment of people with chronic idiopathic fatigue and depression who are known to respond well to these modalities. [11]

http://bestpractice.bmj.com/topics/en-us/277

(My bold).

If PEM is agreed, and demonstrable as, essential to ME/CFS, and therefore to any trial criteria, then Oxford fails, the trials that rely on Oxford fail, and CBT and GET are gone.

So the question might be, is there any evidence to suggest that PEM is not a requirement in ME/CFS. If there is none, while there is plenty for it having a core role, or key place, in the condition, then Oxford doesn't have a leg to stand on.

 

[Graham]

It might also be that people with PEM would not sign up for CBT since they would be the ones, in the BPS words, most convinced they have a physical illness (because it feels like it) and therefore sceptical about CBT.

Looking at Figure 1 on the original PACE paper, after the first set of exclusions were carried out, it left 1460 patients. It seems as though 533 of those failed the consent part (mostly the patients refused, but 46 were on doctors' advice). We don't know why, but it's a substantial proportion (over a third). A further 29 were dropped for unrecorded reasons.

On the second run through, where the 1460 - 533 - 29 = 898 were further reduced to 722, a further 69 failed the consent part (mostly the patients refused to take part, but 2 were withdrawn on research assessors' advice). Together with a further 12 that were unrecorded, this brings the total down to the 641.

I'm sure there's a lot of interesting data in here, but we will never be able to get hold of it.

 

[BurnA]

Reply from Mark Baker and response to it from IiME - http://www.investinme.org/IIMER-Newslet-1801-01.shtml#IiMER-reply18-1

"protect what is good" I've no idea what he's talking about here, I've yet to experience anything good from the NHS while I have progressed from mild to the severe side of moderate.

It does seem as if we are getting a message through to him though.

However, scrapping the entire guideline now would be massively counter-productive as it would almost certainly result in the withdrawal of the already dwindling number of services available to people with ME.

This sounds like the something is better than nothing approach.

He doesn't seem to realise the ME services he is concerned about withdrawing may be the very ones offering CBT and GET.

 

[Valentijn]

I wonder if there is any chance of discovering the PEM status of the recruited and not recruited patients in any of these studies. I suspect not.

PACE authors claimed that about half of their Oxford patients also met London criteria, which includes a vague form of exercise intolerance:

A new onset of significantly abnormal levels of muscle fatigability and/or muscle weakness, precipitated by relatively minor levels of activity. Symptoms typically worsen during the next 24-48 hours.

So the question might be, is there any evidence to suggest that PEM is not a requirement in ME/CFS. If there is none, while there is plenty for it having a core role, or key place, in the condition, then Oxford doesn't have a leg to stand on.

I think it comes down to the disease being defined. NICE purports to describe diagnosis and treatment for ME/CFS, and sort-of requires PEM as a symptom. It's ridiculous for NICE to then use criteria for a different condition to determine treatments for ME/CFS. Oxford fatigue studies are applicable to patients with Oxford fatigue, whereas studies honestly using NICE criteria or similar (PEM or at least exercise intolerance sort-of required) would be applicable to patients who can be diagnosed by the NICE criteria.

I think part of the problem is that NICE is trying to combine chronic fatigue along with ME/CFS into one illness. On one side are patients who are principally fatigued, and on the other hand are patients who have a specific form of exercise intolerance. Both groups need descriptions, diagnostic criteria, and treatments, but mashing them together has resulted in bizarre recommendations that are unlikely to be particularly helpful for either group.

Perhaps what is needed is to show that Oxford and PEM patients are definitively distinct - different symptoms, different impact, different biochemistry, different needs. I think there has been research comparing symptoms and severity of different groups, but not biomedical or other measurements. However comparing different studies using different criteria regarding biochemistry, etc, might also be productive.

 

[Sean]

PACE authors claimed that about half of their Oxford patients also met London criteria

A modified form of the London criteria that has never been tested or used in any other study. So it is a useless sub-grouping exercise. Purely for show, IMHO.

 

[large donner]

A modified form of the London criteria that has never been tested or used in any other study. So it is a useless sub-grouping exercise. Purely for show, IMHO.

Also if they didn't report the results or provide the data separately for the two claimed different definitions why did they bother using two definitions.