NICE ME/CFS guideline - Stakeholder submissions to the draft and NICE responses - published 29th October 2021 - discussion thread

I wonder how usual it is for NICE to refer to future decision making in updates of a guideline that is still undergoing its first full review for over a decade?

It seems that NICE are starting to look at reasons for patient drop outs from treatments and the high rate of them in research trials for ME/CFS. I think therefore, patient groups need to advocate strongly for formal monitoring of the ME/CFS clinics so that they accurately record the drop out rates for any patient undergoing a 'non-GET' activity management or exercise programme, and also for the CBT take-up. If they can't present a full picture of their outcomes as part of the formal evidence collection in the next guideline review, including recording all the patients who are not finding their options 'useful' or even being harmed by them, then NICE should consider removing these currently non-evidenced treatments in future updates of the guideline. The onus should be on the specialist ME/CFS clinics to objectively prove the effectiveness of any treatments they are offering.

 

i've got to the royal colleges (p678), i'm going to have a break

 

Ok, back with the occupational therapists, who's support for the guideline i assume rests on the fact that, come rain or shine, it will doubtless be implemented by them anyway

This HPA stuff is something i see a lot of these days. One would think that working to poorly evidenced models and regarding them as facts would be something of a cautionary tale considering the way things have gone but apparently not

 

i cannot emphasise how damaging it is to patients' (my) mental health to have someone turn up pretending they know what to do, only to find out that they haven't the faintest idea what they're doing. This is the thing that, in my experience, "limits engagement" with the therapeutic process. OTs would do very well to be upfront about poor understanding of the condition, rather than peddle woo about the HPA axis and act all surprised when they manage to do genuine damage to patients

 

OTs keep making the (very good) point that there are physiological things known about the illness that it might be useful for patients to know about, then keep obsessively diverting back to autonomic dysfunction which probably plays not much more than a minor role if anything. This is not helpful to anyone but people peddling quack cures

 

I had several rounds weak positive ANA. Told no Lupus due to the ‘weak’ part.

I have little idea what it meant re lupus. I had various suspicions due to butterfly rash etc but nothing certain.

However given my symptoms had triggered these particular tests, that they do not seem keen to do, multiple times, seemed to me better not to rule out autoimmune causes general outside “CFS/FM”.

Sometime later tested RF very high positive where they cut off counting +100? consecutive tests ever after all same result.

This discovery 4/5 years ago.
No rheumatoid arthritis or other autoimmune diagnosis given.

I have symptoms pain pattern, signs blisters on knuckles and test confirmation.

I lack one out of three requirements, there was no inflammation visible on single MRI & ultrasound scan.

My rheumatologist has told me it’s my ‘Chronic Fatigue’ and Central Sensitisation that is keeping me up at night weeping from bone pain etc.

I have had an ME diagnosis for decades. I knew well it barred me from medical investigation.

When I fought my GP for help and they offered common blood tests I didn’t expect any to be+.

Having reach to stage of an unequivocally positive laboratory finding I didn’t expect that it would make no difference to my diagnosis or treatment.

When you have an ME diagnosis perhaps even your blood is not to be trusted?

I am increasingly severely affected, illness state seems to be deteriorating steadily.

I unexpectedly started crying reading your post. Yours is the outlook I expected from my own Drs.

Whenever I am particularly careful and patient in my explanations to them, and when they briefly sound or look unsure or wavering in their dismissal or occasionally show some concern, I feel anticipation. Perhaps we are at the point of break through?

Each time a rapid reset takes place. We begin again at the beginning. ‘How is your mood?’

I think it is relatively easy to understand the incentives for discrimination and exclusion when you’re not in the same room as the person who is practicing this on you. When I am I feel so disoriented.

I do not think it is easy to explain what the practical outcomes of stigma against patients with ME symptoms are.

I took more words than I thought to give outline to one aspect here.

@Jonathan Edwards I wish you weren’t the exception. Yet exceptional you remain. Thank you for your curiosity and for acting upon this.

I have absolute trust others will one day experience better medical interaction than I.

This will come sooner thanks to your speech on behalf of the evidence and we who carry it in our bodies.

 

The Association of British Neurologists seem to have been absent from the years since 2007 to the present. They gave this gem in their stakeholder feedback:

 

That's priceless!

 

You deserve a medal

 

i'm tired, but i couldn't face any more anyway. i just had a flick thru, there's over a thousand pages and the royal colleges stuff is excruciating. Not even funny, just deeply stuck in an idea of CFS that's never been relevant

 

I'm still on page 12...

 

There were others that defended The Lightning Process including the Royal College of General Practitioners who wrote:

"We note that the committee has decided to make a recommendation against the use of the Lightning Process as a psychological/behavioural intervention.

There has been a recent systematic review of the Lightning Process, published in August 2020. It found a variance in the quality of studies from good to fair and in reported patient outcomes. It concluded, however, that all studies evidenced a level of benefit from the intervention, commonly for the majority of participants.

https://www.sciencedirect.com/science/article/abs/pii/S155083 0720302330 Other relevant evidence can be found at: https://adc.bmj.com/content/103/2/155 https://lightningprocess.com/research/ Based on the review, it is unclear whether NICE has sufficiently considered this evidence"
​

This is from the Royal College of Physicians (RCP):

Our experts note that the decision on LP is particularly arbitrary as it was supported by data from the only RCT, and used a diagnostic definition that meant that all participants had to have the symptom of PEM So it has been banned solely on the basis of qualitative data, which seemed to be mixed. […] there is also evidence from case studies and one RCT that some patients report benefit from LP.​

Royal United Hospitals Bath NHS Foundation Trust:

This table provides good evidence from 100 children that the Lightning Process in addition to specialist medical care was better than specialist medical care alone. This was downgraded because of risk of bias and imprecision presumably due to self report. However, self report is recommended in these guidelines. And in children, no other form of outcome has been recommended. This evidence is therefore stronger than a qualitative study of 9 children and the personal opinion of the committee members (who have, to our knowledge) not had the LP. Therefore, this appears to be a form of bias.... ​

 

On this last one, it's simple: we wouldn't prescribe a drug if we didn't know the ingredients. Why should LP be any different?

 

Jonathan Edwards testimony must have made an impression. Several stakeholders refer to it in their submission, often attacking him and his reputation in an aggressive way (especially the comments by the RCP are inappropriate).

Here's a selection of what I'd stumbled upon but there might be more (too much to read all, could only skim):

Newcastle upon-Tyne Hospitals NHS Foundation Trust:

We are particularly concerned by the testimony of Prof Edwards […] We are not convinced that Prof Edwards has the necessary expertise and knowledge in clinical trials of non-pharmacological interventions to make this assessment. For example, it is flawed logic to suppose that a trial of CBT or other psychological therapy should somehow attempt to separate the effect of the therapy per se from the effect of the therapeutic relationship. In real clinical practice, it is impossible to have one without the other, and a trial must reflect this reality​

With reference to Professor Johnathan Edwards – he demonstrates, in his comments and arguments, a lack of understanding of the factors associated with a positive outcome of therapies, which include developing a personal relationship with caregivers. A positive, optimistic, and empathic relationship with therapists are shown to be important for a positive patient experience and outcome.​

More specifically, he states: “The central difficulty for trial design in ME/CFS is the high risk of systematic expectation bias in a fluctuating condition with subjective core features”. This is essentially true, but the same applies to mental health problems (fluctuating condition with subjective core features) where psychological treatments are considered valid options, yet the trials may share some similar design issues.​

If the committee are to take into account Professor’s Edwards views on the role of subjective core features in a therapy based research trial, then they also need to take into account the subjective role of the qualitative studies they have claimed as ‘evidence’.​

North Bristol NHS Trust - CFS/ME Service:

It is not clear why the expert testimony were included from Professor Jonathan Edwards. It is clear that Prof Edwards’ expertise is in pharmacological research, and not in research into non-pharmacological interventions. It would have been more useful to have an expert witness who understood the issues related to non-pharmacological interventions rather than one who focussed primarily on the problem on non-blinding. At one point (page 6) he criticises studies which do not show objective improvements and then immediately criticises the studies which did show objective improvements: “Some exercise studies show objective changes in indices of fitness but that does not necessarily imply a reduction in illness or disability”, domains which are typically assessed using subjective measures. The impression is of someone who wants to have his cake and eat it.

Prof Edwards states that “unblinded trials with subjective outcomes are specifically considered unreliable.” If NICE as an organisation were to generalise this opinion across all guidelines for example those for back pain, osteoarthritis and multiple sclerosis, what would the impact of this opinion be on these other guidelines? Prof Edwards puts forward the idea that placebo is due to “positive thinking” but does not seem to acknowledge the biological element of placebo, and the element associated with training. It would be advisable to find an expert who could offer a more informed view of non-pharmacological issues, rather than one whose expertise is in a different field.​

Register of Lightning Process Practitioners:

Professor Jonathan Edwards claims to have no conflict of interest or bias. However, he does admit to being a board director for a ME/CFS patient forum (Expert testimony p 13) and this may explain his adoption of a, possibly unconscious, bias as evidenced by this statement: “I think it is important to establish certain simple facts. The Lightning Process is a commercial product whose nature is secret and whose value is unproven – thus qualifying as an ‘alternative therapy’. Yours faithfully, Jonathan Edwards, Professor Emeritus, Division of Medicine, University College London” https://www.virology.ws/2020/05/30/trial-by-error-two-letters-to[1]dagbladet-about-its-me-coverage/. Letters to Dagbladet About Its ME Coverage, 30 MAY 2020: This can also be observed in his desire to devalue the statistically significant result of the SMILE RCT by claiming them to be ‘apparent positive results for the Lightning Process’. This inaccurate commentary on the LP, whilst having no direct experience of it or awareness of the published papers or books on it, brings into question his lack of impartiality and his suitability for the role of expert.​

The Royal College of Psychiatrists:

Professor Jonathan Edwards was asked to give evidence on the methodological issues around non pharmacological trials and outcomes. His main contribution concerned non- blinded interventions and what he called “subjective” outcomes (which we prefer to call “patient reported”), contrasting them unfavourably with those that he considered to be “objective” His argument is that trials that are unblinded and have self[1]reported outcomes cannot be trusted or used. Because some unblinded trials are not replicated by subsequent blinded ones, which is true, then all unblinded trials are not replicated, which is not true. His point is that patients who main symptoms are self[1]reported do not give an accurate account of those symptoms after any intervention which is non-blinded. For that reason objective measures, such as biomarkers, exercise testing and so on, which are superior to self-report measures, could be used.​

We do not accept this.

We do not accept this. Indeed, the general direction of travel is more in the opposite direction – for example in responding to the views of patients about what matters to them, NICE and others have steadily increased, not decreased, the importance of self-reported outcomes, also known as Patient Reported Outcome Measures (PROMS). The issues around complex interventions that cannot be blinded has been addressed in the MRC Guide to Assessing Complex Interventions, used by most triallists in this field. He also did not mention that these issues are already included in the Grade System as outlined in the Methods Section of this review, including both unblinding and performance bias. Instead he implied that his views represented something new and additional for the committee to take into account.​

Do NICE agree?​

ME/CFS to the head of medicine at UCH his only comment was that for ME/CFS we would need to be 100% sure of blinding.” His “claims to the contrary” is a systematic review of the placebo effect in ME/CFS https://pubmed.ncbi.nlm.nih.gov/15784798/. “In contrast with the conventional wisdom, the placebo response in CFS is low. Psychological-psychiatric interventions were shown to have a lower placebo response, perhaps linked to patient expectations”. This finding casts doubt on his main thesis, which is that “subjective outcomes are to be particularly distrusted in trials of CBT and GET in ME/CFS” - the evidence points the other way.

Could NICE please comment?​

Royal College of Physicians (RCP):

“There are three expert testimonies. We note that one of the testimonies is from a recognised advocate against trials and evidence in interventions who has served on the Board of Phoenix Rising. Their career and academic standing is based on laboratory research and pharmaceutical interventions, as opposed to guidelines development or pragmatic trial designs for health and social interventions. Our experts believe that the testimony shows a lack of understanding of this area of research. The fluctuating nature of the illness is a problem in RCTs, but if they are sufficiently powered it should not be a problem. Again, these trials cannot be blinded. Respondent bias is recognized in trials, and this is not a reason to dismiss them; and it is possible then to match up those where respondent bias may be a problem, with other measures of functioning or exercise that can be independently assessed. Our experts believe that a lack of understanding on how the theoretical model is simply used to think about the processes that might be in play to explain why the intervention may be effective; in itself, the theory should not be used to dismiss the results of a trial after the trial is completed simply because the reader doesn’t agree with it. Our experts believe that the comment about Cochrane and peer review is misplaced; this review was extensively peer reviewed. Our experts believe that the methods are being criticised here as belief disconfirmation bias is being experienced. Our experts believe that to dismiss all the evidence from trials in ME/CFS is idiosyncratic and that the detail of this presentation is largely anecdotal. Our experts believe that the chair of the guidelines panel or the Director of NICE needs to instruct the panel to dismiss this expert witness as it stands against the whole NICE evidence-based process in general for complex interventions.​

 

Many of these stakeholder comments are a depressing read: often very aggressive and dismissive.

Some question whether ME/CFS is any different from fatigue. Post-exertional malaise is seen as unscientific cause everyone gets fatigued after exercise. Some deny there are harms or controversy about GET. They argue that the guideline will cause harm because of its pessimistic message. Instead, it should encourage hope so that patients will take control of their own recovery.

Here's for example what Barts Health NHS Trust wrote:

We believe that the general effect of this guideline will be to maintain disability, increase the duration of illness, reduce hope of recovery, and lead to decommissioning of existing specialist services​

Others attacked patients or accused the committee of being biased.

Here's for example what Newcastle upon-Tyne Hospitals NHS Foundation Trust wrote:

“Most patients who use specialist services report that online information and ME groups have frightened them and many patients felt that online information from patient groups are ‘all doom and gloom’ and that Facebook Groups are all ‘very angry’ people.”

[...]

“We would not support patients accessing information from ME organisations as we do not share the same model of CFS/ME”​

 

The comments make clear that there's a lot that needs to change in the British ME/CFS healthcare system. Deepest sympathies to patients who have to navigate this Scylla and Charybdis.

Hope the NICE guideline will bring some real improvements.

 

Yet we know they are all busy developing impersonal apps to save the NHS money and to make some for themselves along the way....

 

Yes, it is salutary to re-read those character-assassinations of me.

It makes it easier for me to gather the effort to write that book after all. It was going to be about PACE but it will cover rather more now. I spent this afternoon drafting a new chapter on NICE guidelines.

If anyone needs someone to persuade them that these people are incompetent they need go further than these people themselves.