Member comments wanted: Third section (What the guideline will cover) of the NICE ME/CFS guidelines draft scope

[Andy]

The consultation for the draft scope closes 26 July 2018 at 5pm. Therefore, we need members to look at each section of the draft scope and provide feedback, in order to inform any comment that S4ME may make on the draft. So please read the below and comment away!

(Full document can be found here, NICE webpage on the process is here, we did have an initial thread on the draft scope here but these individual threads are to capture comments on the individual sections of the draft.

Thread for the first part of the scope (Why the guideline is needed) can be found here, and for the second part (Who the guideline is for) here.)

3. What the guideline will cover

3.1 Who is the focus?

Groups that will be covered
People with suspected or diagnosed ME/CFS
Specific consideration will be given to:

• children and young people
• people with severe symptoms.

3.2 Settings

Settings that will be covered

All settings where NHS or social care is provided or commissioned, including health services related to education and occupational health.

3.3 Activities, services or aspects of care

Key areas that will be covered

We will look at evidence in the areas below when developing the guideline, but it may not be possible to make recommendations in all the areas.

1 Identification and assessment before diagnosis
2 Diagnosis of ME/CFS
3 Management of ME/CFS
4 Monitoring and review
5 Information, education and support for people with suspected and diagnosed ME/CFS, and their families and carers
6 Information, education and support for health and social care professionals.

Note that guideline recommendations for medicines will normally fall within licensed indications; exceptionally, and only if clearly supported by evidence, use outside a licensed indication may be recommended. The guideline will assume that prescribers will use a medicine’s summary of product characteristics to inform decisions made with individual patients.

Areas that will not be covered

1 The specific management of symptoms where NICE guidance already exists (see below for related NICE guidelines) and management is not expected to be different in ME/CFS

Related NICE guidance

Published

Lyme disease (2018). NICE guideline NG95
Neuropathic pain in adults: pharmacological management in non-specialist settings (2013). NICE guideline CG173
Headaches in over 12s: diagnosis and management (2012). NICE guideline CG150
Common mental health problems: identification and pathways to care (2011). NICE guideline CG123
Irritable bowel syndrome in adults: diagnosis and management (2008). NICE guideline CG61

In development

Thyroid disease: assessment and management. NICE guideline. Publication expected November 2019
Chronic pain: assessment and management. NICE guideline. Publication expected January 2020

NICE guidance that will be replaced by this guideline

Chronic fatigue syndrome/myalgic encephalomyelitis (or encephalopathy): diagnosis and management (2007) NICE guideline CG53

NICE guidance about the experience of people using NHS services

NICE has produced the following guidance on the experience of people using the NHS. This guideline will not include additional recommendations on these topics unless there are specific issues related to ME/CFS:
Medicines optimisation (2015) NICE guideline NG5
Patient experience in adult NHS services (2012) NICE guideline CG138
Service user experience in adult mental health (2011) NICE guideline CG136
Medicines adherence (2009) NICE guideline CG76

3.4 Economic aspects

We will take economic aspects into account when making recommendations.
We will develop an economic plan that states for each review question (or key area in the scope) whether economic considerations are relevant, and if so whether this is an area that should be prioritised for economic modelling and analysis. We will review the economic evidence and carry out economic analyses, using an NHS and Personal Social Services perspective.

3.5 Key issues and draft questions

While writing this scope, we have identified the following key issues and draft question related to them:

1 Identification and assessment before diagnosis
1.1 In whom should ME/CFS be suspected?
1.2 What is the most clinically and cost effective method of assessing people with suspected ME/CFS?
1.3 Can disability or assessment scales aid the identification of people with ME/CFS?
1.4 What are the barriers and facilitators to the identification of ME/CFS?
1.5 What are the precautionary management strategies that should be adopted before diagnosis?

2 Diagnosis of ME/CFS
2.1 What tests are clinically and cost effective in making a diagnosis of ME/CFS?
2.2 In people with suspected ME/CFS, what are the criteria used to establish a diagnosis?
2.3 What are the barriers and facilitators to the diagnosis of ME/CFS?

3 Management of ME/CFS
3.1 What is the clinical and cost effectiveness of pharmacological interventions for people with ME/CFS?
3.2 What is the clinical and cost effectiveness of non-pharmacological interventions for people with ME/CFS?
3.3 What is the clinical and cost effectiveness of self-management strategies for people with ME/CFS?
3.4 In people with ME/CFS, what is the clinical and cost effectiveness of different models of
multidisciplinary team care, including team composition?

4 Monitoring and review
4.1 What is the most clinically and cost effective method of monitoring people with ME/CFS?
4.2 What is the most clinically and cost effective method of reviewing people with ME/CFS?
4.3 What are the barriers and facilitators to the care of people with ME/CFS?

5 Information, education and support for people with suspected and diagnosed ME/CFS, and their families and carers
5.1 What information, education and support do people with ME/CFS and their families and
carers need?

6 Information, education and support for health and social care professionals
6.1 What information, education and support do health and social care professionals who provide care for people with ME/CFS need?

3.6 Main outcomes

The main outcomes that may be considered when searching for and assessing the evidence are:
1 Quality of life (for example, EQ-5D, SF-36)
2 Pain
3 Fatigue
4 Physical and cognitive functioning (a person's ability to do everyday tasks and activities)
5 Psychological wellbeing
6 Care needs
7 Sleep

ETA: Added text and a link back to the original thread on the draft scope release.

 

[Ravn]

There needs to be clarification how to handle conflicts between the existing guidelines for various conditions and ME/CFS guidelines. Highly likely existing guidelines like the “Common mental health problems” would recommend management strategies unsuitable in ME/CFS.

1 The specific management of symptoms where NICE guidance already exists (see below for
related NICE guidelines) and management is not expected to be different in ME/CFS
Related NICE guidance
Published
Lyme disease (2018). NICE guideline NG95
Neuropathic pain in adults: pharmacological management in non-specialist settings (2013). NICE guideline CG173
Headaches in over 12s: diagnosis and management (2012). NICE guideline CG150
Common mental health problems: identification and pathways to care (2011). NICE guideline CG123
Irritable bowel syndrome in adults: diagnosis and management (2008). NICE guideline CG61
In development
Thyroid disease: assessment and management. NICE guideline. Publication expected November 2019
Chronic pain: assessment and management. NICE guideline. Publication expected January 2020

{my Italics}

This is good if it leads to an emphasis on precautionary pacing as opposed to pushing exercise until a firm diagnosis is made.

1.5 What are the precautionary management strategies that should be adopted before diagnosis?

In the Main Outcomes section we're back to Fatigue, and no mention of PEM.

Not sure why some symptoms, pain, fatigue and sleep, rate individual mention and others such as autonomic dysfunction do not.
At any rate individual symptoms are factors in - and are therefore covered by - the broader categories. I suggest focus on only 3 broad categories:

1 Physical and cognitive functioning (a person's ability to do everyday tasks and activities)
2 Psychological & social wellbeing (addressing psychological & social effects of the illness)
3 Care needs

 

[MSEsperanza]

There needs to be clarification how to handle conflicts between the existing guidelines for various conditions and ME/CFS guidelines. Highly likely existing guidelines like the “Common mental health problems” would recommend management strategies unsuitable in ME/CFS.

The paragraph about the related guidelines also caught my eye. Managed to check only the one for IBS yet, which stresses @Ravn 's concern:

1.2.1.3 Healthcare professionals should assess the physical activity levels of people with IBS, ideally using the General Practice Physical Activity Questionnaire (GPPAQ; see appendix J of the full guideline). People with low activity levels should be given brief advice and counselling to encourage them to increase their activity levels. [my bolding]

https://www.nice.org.uk/guidance/cg61/chapter/1-Recommendations#dietary-and-lifestyle-advice

 

[Jonathan Edwards]

3.6 Main outcomes

The main outcomes that may be considered when searching for and assessing the evidence are:

I do not remember this being such a stark problem in a previous draft but may have missed it. The main outcomes to be considered for assessing evidence have to be OBJECTIVE ones, since at present all trials are effectively unblinded. Subjective measures as listed are important to the patient but they are of no value as evidence. Outcomes of value would include actimetry, walking times, return to work, level of benefit requirements, NOT questionnaires. It is crucial that the technical staff collecting data are aware of this.

Can we incorporate that into an S4ME response?

 

[Sasha]

I do not remember this being such a stark problem in a previous draft but may have missed it. The main outcomes to be considered for assessing evidence have to be OBJECTIVE ones, since at present all trials are effectively unblinded. Subjective measures as listed are important to the patient but they are of no value as evidence. Outcomes of value would include actimetry, walking times, return to work, level of benefit requirements, NOT questionnaires. It is crucial that the technical staff collecting data are aware of this.

Can we incorporate that into an S4ME response?

I agree with your overall point but again, wouldn't want to concede that "Subjective measures as listed are important to the patient" because the problems inherent with them render the measures meaningless. Fatigue and disability are important to patients, but ratings of fatigue and disability made by patients in a nonblinded trial aren't important to patients.

I think we've got to be very careful on our wording with these things, because people are so ready to leap in and offer us a sop - and if they think that these subjective ratings are important to us, it's a small step to seeing PACE as showing some value of CBT and GET.

 

[Sasha]

Sorry if I'm taking any of your points out of context, @Jonathan Edwards - I'm not able to read much at the moment (heat + dysautonomia).

 

[Jonathan Edwards]

Sorry if I'm taking any of your points out of context, @Jonathan Edwards - I'm not able to read much at the moment (heat + dysautonomia).

I think you are missing the point that to concede that subjective measures are important to individual patients is to pre-empt the inevitable argument from a therapist that objective measures are not necessarily what matter most to patients. (White and Sharpe do this all the time, as does Wessely.) I had hoped to make it clear that the key point is that we entirely agree with that but it is irrelevant to which outcomes should be searched for when looking for evidence from publications. If the technical people searching for data have not got this on board the whole thing is a farce.

Indeed it would destroy the whole point of having a re-assessment of the evidence!

 

[Adrian]

I do not remember this being such a stark problem in a previous draft but may have missed it. The main outcomes to be considered for assessing evidence have to be OBJECTIVE ones, since at present all trials are effectively unblinded. Subjective measures as listed are important to the patient but they are of no value as evidence. Outcomes of value would include actimetry, walking times, return to work, level of benefit requirements, NOT questionnaires. It is crucial that the technical staff collecting data are aware of this.

Can we incorporate that into an S4ME response?

I think this is the most important point in response to this document. We need to emphasize it and repeat it. I would be quite happy if this was the only point we raised. It feels absolutely fundamental if they are to search for evidence and allow subjective outcomes they will take PACE, and Smile at face value and we will end up with a continuation of bad and harmful guidelines.

Remove the subjective data and dig into the trials and the results change.

 

[Hoopoe]

I do not remember this being such a stark problem in a previous draft but may have missed it. The main outcomes to be considered for assessing evidence have to be OBJECTIVE ones, since at present all trials are effectively unblinded.

Agreed, but merely asking for "objective" outcomes could still leave the door wide open for misleading claims.

We need to clearly define what constitutes reliable outcomes and demand that current and future evidence be held to this standard. Any loopholes will be exploited.

While we are at it, fatigue questionnaire need to go, not just because of Chalder Fatigue Scale or the unblindedness but because a patient that is successfully pacing can still be severely limited while suffering from not particularly severe fatigue. The idea that constant fatigue is central to the illness is simply incorrect.

 

[Hoopoe]

I think it would be hard to make misleading claims if treatments had to demonstrate an increase in activity levels that is sustained for 8 months, with daily step count measurements taken for 1-2 weeks every 1-2 months, or an abnormal pre-treatment 2 day CPET that becomes more normal (possibly also repeated several times over several months to minimize random fluctuations).

Maybe this is still unreliable, or maybe it's over the top. I don't know.

Patients are susceptible to wishful thinking. It is when actually doing stuff that we learn what our limits really are.

PS: these primary outcomes would be intended for clinical trials that wish to test a treatment specifically for ME/CFS, rather than some comorbid condition.

 

[Jonathan Edwards]

@Andy,

Although I was stakeholder meeting rep I don't particularly want to take a lead role in a S4ME response to the consultation. The point above is probably the one thing I would want to have in a response but I would like to leave it someone like yourself to extract a consensus message in the long run.

 

[Andy]

@Andy,

Although I was stakeholder meeting rep I don't particularly want to take a lead role in a S4ME response to the consultation. The point above is probably the one thing I would want to have in a response but I would like to leave it someone like yourself to extract a consensus message in the long run.

OK.

 

[Hoopoe]

My message to NICE on this topic would be something along these lines:

Unblinded trials with subjective primary outcomes are unable to distinguish between ineffective and effective treatments. The ME guidelines rely on this kind of evidence and are for this reason unfit for purpose. Widespread patient discontent with the guidelines, loss of trust, preventable harm, and waste of resources are some of the consequences. We call on NICE to implement reforms which ensure that only reliable clinical trials inform the ME treatment guidelines. We propose the following reliability criteria ...

The exact reliability criteria (as I call them here) would be determined by Science for ME. They would not be controversial or innovative, but mostly what is done in other areas of research, with a few ME specific recommendations.

NICE should also be told that it's OK to have no treatment to offer. Sensible advice and rapid diagnosis are still valuable.

 

[Jonathan Edwards]

I had forgotten that there are of course double blind trials of drugs for ME/CFS in which subjective outmodes have been used appropriately. None of them show convincing benefit so in practice they could be ignored. However, it would be fair to say that subjective outcome measures could be used as a source of evidence if and only if trials are convincingly blinded.

 

[MSEsperanza]

I do not remember this being such a stark problem in a previous draft but may have missed it. The main outcomes to be considered for assessing evidence have to be OBJECTIVE ones, since at present all trials are effectively unblinded. Subjective measures as listed are important to the patient but they are of no value as evidence. Outcomes of value would include actimetry, walking times, return to work, level of benefit requirements, NOT questionnaires. It is crucial that the technical staff collecting data are aware of this.

Does anyone know of another comparable NICE guideline in which studies without objective measures were excluded?

Furthermore, If anyone could explain the differences/ comparabilities between "level of quality", "validity score"/ "importance" and "evidence", this would be highly appreciated.

Background:

In order to comprehend how NICE assesses evidence in other guidelines, I skimmed the NICE guideline for MS for treatment of fatigue.

It seems that all but one studies on which the NICE MS guideline bases their recommendations on fatigue treatment are of "low" or "very low" level of quality, but at the same time of "critical importance":

https://www.nice.org.uk/guidance/cg186/evidence/full-guideline-pdf-193254301 ,p.315 ff

I spent some time yesterday trying to understand the tools applied by NICE to assess the level of evidence/ level of quality/ validity score/ importance.

I couldn't find answers to my questions in the NICE guidelines manual, most probably due to my lack of basic knowledge of evaluation methodology in medical sciences (combined with my level of patience when reading manuals) . Then I tried to compare the evidence/ quality assessment of the included studies in the old NICE ME/CFS guideline to the MS guideline. They don't seem to apply the same assessment tools, though (in the ME guideline "validity score" vs. "level of quality" plus "improtance" in the MS guideline).

(The old ME guideline, Appendix 1, : https://www.nice.org.uk/guidance/cg53/evidence/full-guideline-appendix-1-pdf-196524110 , p. 54ff)

Regarding the set of problems arising from the evidence question, I think we could learn from the errors made in MS research and treatment. In the medical field of MS, highly disabling factors of the disease relevant for a majority of patients also have been neglected for decades and only recently been addressed in the generalizing and downplaying term of "fatigue". However, there are some clinicians who acknowledge this problem and are doing research, firstly based on differentiating between diverse types of fatigue and fatiguability (motoric, cognitive, mental, emotional), and secondly, driving to find objective measures (see: https://www.s4me.info/threads/objec...igue-and-fatiguability-lurija-institute.4241/ )

I haven't read the papers and they seem to be only small studies and presumably also "low evidence" studies so far. Nevertheless, to me they appear of importance, because they conceive the need for developing new measures, acknowledging that the existing measures are not appropriate for those symptoms which develop/ exacerbate only during or after exertion.

Objective measures in ME additionally face the challenge that the process of measuring the most reliably measurable indicators of disability could deteriorate the patient's condition in the long term.

Thus, especially physical exercise studies could only include the mildly affected, yet still with the risk of deterioration. Cognitive exercise studies might also include the moderately affected, though.

I would like to add my personal experience with neuropsychological testing in a neurological rehab facility. Standard cognitive / neuropsychological tests done before showed normal results. In the rehab I had to undergo a 3,5h testing. Only this long duration test showed the abnormally quick decline in concentration, despite small breaks which weren't sufficient for me.

I am aware of the problem that severely affected pwME could not do this test, and even I (mostly moderate with mild and severe phases) would not have been able to participate, if I had to get to a testing surgery from home and espacially to get back home). In the rehab, it took place in a building on the same grounds. After the testing, I skipped lunch and went to bed immediately, rested for the rest of the day. On the next day I was only slightly worse.

Apologies for serving a salad of aspects of evidence assessment, research concepts, and testing anecdotes. Still being in the dilemma of on the one hand thinking I could provide some helpful experiences from the episode when I had been treated as patient with MS, and on the other hand having restricted time for reading, comprehending, and writing here.

Returning to the question how NICE assesses evidence, when looking at the studies included in the old ME guideline and in the MS guideline I tend to be pessimistic that NICE could grade PACE and other GET studies as "null evidence" and exclude them. More likely IMO it could be achieved that they will downgrade PACE's level of quality/evidence (as assessed by Cochrane) and limit the grade of their recommendations of GET, warning of risks not only for the severely, but also for the moderately and mildly affected. It might also be helpful to point out that GET and CBT designed for ME is different from exercise and CBT interventions in MS and other diseases. Thus the evidence shown in exercise studies designed for other diseases does not suit to back the alleged evidence of PACE and other GET studies.

To query the inclusion of studies based on subjective measures per se would at the same time query a paradigm. Wheras it is needed to dismantle the paradigm, the NICE guideline IMO is not in the first place to conceive this.

 

[Jonathan Edwards]

Does anyone know of another comparable NICE guideline in which studies without objective measures were excluded?

To query the inclusion of studies based on subjective measures per se would at the same time query a paradigm. Wheras it is needed to dismantle the paradigm, the NICE guideline IMO is not in the first place to conceive this.

First of all it is important to be clear that studies without objective measures are only problematic if they are unblinded. Studies with non-objective pain outcomes are standardly included as evidence for licensing and guidelines if they are blinded.

I think there is an interesting double standard here that all our discussions have brought to light. For drugs unblinded studies with non-objective outcomes are discounted as evidence pretty much across the board. But for therapist-delivered treatments, surgery and 'medical devices and procedures' the situation is much murkier. I think the bottom line is that whether Ben Goldacre, Cochrane or NICE, we are dealing with people who have a belief that they need to protect people and the state from thieving pharmaceutical companies but not from thieving therapy service providers or, at least until recently, gung-ho surgeons.

So we are not querying a paradigm so much as querying shoddy practice based on prejudice leading to double standards. There is no paradigm that allows unblinded trials without objective endpoints but there is entrenched practice in some quarters. Which means that in a sense NICE (or Cochrane) is exactly the place to get this tackled because it is the place where the double standard is applied.

I would not be surprised if poorly evidenced therapist-delivered treatments crept into all sorts of guidelines like MS and maybe even RA. But they appear as afterthoughts that do not cause much grief. Maybe nobody will be bothered to address them. So maybe the ME NICE guideline is exactly where the problem has to be tackled.

 

[JemPD]

I do not remember this being such a stark problem in a previous draft but may have missed it. The main outcomes to be considered for assessing evidence have to be OBJECTIVE ones, since at present all trials are effectively unblinded. Subjective measures as listed are important to the patient but they are of no value as evidence. Outcomes of value would include actimetry, walking times, return to work, level of benefit requirements, NOT questionnaires. It is crucial that the technical staff collecting data are aware of this.

Can we incorporate that into an S4ME response?

This. And the rest of whats been said by JE in this thread re non blinding & subjective/objective measures.
I could rave on about all the pernickety bits that irritate me in this scope doc. But if our response made this point CRYSTAL clear i think it would be very good.
I know there is loads that could be pointed out wrong with this scope, but personally i think it'd be best to stick to one or 2 really strong, non-misinterpretable facts, that are simple & that NICE can get their teeth into. Better to single out a couple of things that have a hope of making the most constructive impact, than a lot of prevarication & getting hung up on finer points which (although valid & important in themselves) will provoke decision makers to 'glaze over' when reading.

I'm sorry i dont have any more strength to engage with this. I'm dealing with contractors in my house & the urgent & critical is crowding out the 'merely' important. But I know S4ME will produce something great whatever happens. Thanks in advance for people's efforts

 

[Barry]

Remove the subjective data and dig into the trials and the results change.

I fully agree of course with including all relevant objective data. But are we shooting ourselves in the foot if we insist on removing all subjective data? Hasn't our argument with PACE been that unblinded trials with subjective outcomes are OK provided you back up the subjective evidence with objective evidence as well? True, once you have objective outcomes then subjective ones may be completely superfluous, but for ME is is possible that subjective symptoms still have some worth, but only if backed up by objective ones.

 

[Adrian]

but for ME is is possible that subjective symptoms still have some worth

The problem is that subjective symptoms are not being measured. Something like the sf36 is not measuring subjective stuff but the questionnaire is subjective because the answers are subject to both perception and reporting biases. By that I mean that you can persuade someone that its normal to feel tired after walking up a flight of stairs and hence change the perception from an answer of 'with difficulty' to 'can do it'. The actual difficulty hasn't changed just the way it is reported. You could also slip in a 'on a good day'. Then there is an issue around reporting where someone gives an answer to keep those doing the trial happy or because they feel pressured to do so. These are factors that need to be controlled for and its very hard in an open label trial.

 

[Jonathan Edwards]

unblinded trials with subjective outcomes are OK provided you back up the subjective evidence with objective evidence as well?

You start running into issues about powering primary endpoints and things. And even with objective backup subjective components to composite measures would need to be handled with great care. At present I don't think there is anything out there that would pass muster. If you fail to get the objective back up, as in PACE then the subjective measures don't go anywhere anyway?