UK NICE guideline consultation open 10 July 2017 until Friday, 21 July 2017.

[charles shepherd]

THE NICE GUIDELINE SAGA - MEA SUMMARY OF KEY RECENT EVENTS

For anyone who has not been following the NICE guideline saga........

Like some (but not all) of the UK ME/CFS charities, the MEA has always regarded the 2007 NICE guideline on ME/CFS as being unfit for purpose - but it does have a few positive points

Over the past ten years we have made several attempts to try and get a revision of the NICE guideline - as have other ME/CFS charities and individuals. But without any success

NICE decided to park the ME/CFS guideline in its static list back in September 2013:
http://www.meassociation.org.uk/201...mecfs-any-time-soon-unless-26-september-2013/

The MEA then sent in a very comprehensive critique which dealt with a large number of reasons why this decision was wrong:
http://www.meassociation.org.uk/201...nice-mecfs-guideline-on-hold-23-october-2013/

At the same time the Forward ME group of ME/CFS charities, under the chairmanship of the Countess of Mar, decided to try a more joined up approach

We had meetings and on-going correspondence with Professor Mark Baker from NICE - who accepted that there was a need to look at the guideline again:
http://www.meassociation.org.uk/201...statement-by-the-me-association-10-july-2014/

But Prof Baker 'passed the parcel' to NHS England - who have become the key player when it comes to ordering a NICE guideline revision

We met (and had correspondence with) Dr Martin McShane, Director of Long Term Conditions at NHS England, to try and achieve a change of mind:
http://www.forward-me.org.uk/15th July 2015.htm

There is also some interesting internal correspondence involving Professor Baker at NICE and Dr McShane at NHS England, which was clearly not intended for public consumption, from around this time. This was obtained under an FoI
http://www.meassociation.org.uk/201...eedom-of-information-request-24-october-2016/

I can only assume that a combination of continual pressure at a charity, individual and parliamentary level has forced a change of mind at NHS England and at NICE - resulting in the current situation

As has already been pointed out, NICE announced some time ago that they would be reviewing all the relevant evidence to see if a review of the NICE guideline is now needed

And it's important to note that NICE are not really interested in research into causation of ME/CFS - they provide guidance to doctors on clinical assessment, diagnosis and management of illnesses

So they want to see and review research evidence and clinical trial evidence that relates to the above three topics

Unfortunately, there isn't a huge amount of new high quality papers to put in front of them

The Forward ME Group and the Countess of Mar have, however, been in very regular contact with Professor Baker and have been forwarding what we feel is important evidence that needs to be taken into consideration - the Wilshire re-analysis of PACE trial data, the MEA 'patient evidence' report on CBT, GET and Pacing, the Rituximab trial papers and the new paediatric primer (co-authored by MEA paediatric adviser Dr Nigel Speight) are all good examples

The most recent development, which is the subject of this thread on PR, is the announcement that stakeholders in the NICE guideline on ME/CFS (the MEA is one) are being consulted in July. We will therefore be sending in a further response in line with what we are being asked to provide in the way of evidence

This evidence gathering process is supposed to be terminating around September or October - after which NICE will announce if a guideline revision will take place

My guess, and this is purely guesswork, is that they will decide to carry out a review

If this takes place, it will presumably start in early 2018

How long it will take is debatable. So we could have a result in 2018. Or it could take till 2019

If NICE decide that a review is not necessary, we are back to square one and will once again be banging our heads against a very thick wall….

I hope people find this summary helpful

Dr Charles Shepherd
Hon Medical Adviser, MEA

 

[Binkie4]

I can only assume that a combination of continual pressure at a charity and parliamentary level has forced a change of mind at NHS England and at NICE - resulting in the current situationg

@charles shepherd

It should also be recognised that individuals as well as some charities and parliamentary members have been pressing NICE to review CG53.

 

[Barry53]

Yes.. I think I agree. But if that's the case we need more psychiatrists speaking out against them, and loudly refusing to deliver GET and CBT programmes to ME patients. So far we are not getting that - or not getting it enough to make a real difference....

Yes I also agree. Makes you wonder if there are one or two on the verge and just need a bit more support.

 

[Jo Best]

I hope people find this summary helpful

Thanks yes, that summary from the MEA perspective is helpful.

@charles shepherd
It should also be recognised that individuals as well as some charities and parliamentary members have been pressing NICE to review CG53.

Indeed and goes to show the uphill struggle by patients and families in this matter.

 

[charles shepherd]

@charles shepherd

It should also be recognised that individuals as well as some charities and parliamentary members have been pressing NICE to review CG53.

Correct!

I have just amended the wording…..

CS

 

[Londinium]

Presumably NICE would need to at least acknowledge the Rituximab papers published thus far? Even if only to say 'these are only Phase II trials and are insufficient at this time'? I've certainly seen other drugs assessed by NICE where the advice is 'shouldn't be used outside of a clinical trial/audit due to insufficient evidence' but if Rituximab even got that it would seem, IMHO, to be progress. It would at least mean an acknowledgement from NICE of a potential, albeit unproven, pharmacological treatment.

(Thsi would be good for me personally as my GP has a fairly militant approach of if NICE didn't say it then it's not worth reading about)

 

[NelliePledge]

how will the very low 4 % reported reduction in fatigue in FITNET play in to this, it doesnt actually back up PACE does it - at best it shows GET is of limited effectiveness so can the cost of delivering programmes of GET continue to be justified is this an argument that will have any traction with NICE?

 

[charles shepherd]

Presumably NICE would need to at least acknowledge the Rituximab papers published thus far? Even if only to say 'these are only Phase II trials and are insufficient at this time'? I've certainly seen other drugs assessed by NICE where the advice is 'shouldn't be used outside of a clinical trial/audit due to insufficient evidence' but if Rituximab even got that it would seem, IMHO, to be progress. It would at least mean an acknowledgement from NICE of a potential, albeit unproven, pharmacological treatment.

(Thsi would be good for me personally as my GP has a fairly militant approach of if NICE didn't say it then it's not worth reading about)

Yes, NICE will certainly have to take note of the clinical trails that have been carried out, or are in progress (i.e. the phase 3 trial in Norway) in their review of the evidence

But they won't be able to go any further than state something along the lines of:

- these are important preliminary results and we await the results of the phase 3 trial with interest

As I've stated elsewhere, the UK will need to have at least three large and high quality clinical trials (one from the UK for definite and preferably one from USA which satisfies the FDA) confirming both safety and efficacy in ME/CFS before this drug could be granted a product license for use in selected people with ME/CFS as well as it being given a positive recommendation from NICE for use in ME/CFS

Even if all goes to plan, I would be very surprised if this can be achieved in less than 5 years from now…….

CS

 

[BurnA]

As I've stated elsewhere, the UK will need to have at least three large and high quality clinical trials (one from the UK for definite and preferably one from USA which satisfies the FDA)

Charles,
I can understand having FDA approval ( somewhat ) but EMA governs the approval of drugs for EU, to quote its website :

The European Medicines Agency (EMA) is a decentralised agency of the European Union (EU), located in London. It began operating in 1995. The Agency is responsible for the scientific evaluation, supervision and safety monitoring of medicines in the EU.

EMA protects public and animal health in 28 EU Member States, as well as the countries of the European Economic Area, by ensuring that all medicines available on the EU market are safe, effective and of high quality.

EMA serves a market of over 500 million people living in the EU.

Therefore why or under what remit can NICE decide it wants to have a UK trial ?
Is this the norm for other diseases ?

Thanks

 

[charles shepherd]

Someone on the MEAF discussion is asking if NICE could be taken to court

So worth noting that there was a judical review of the NICE guideline back in 2008

MEA report:
http://www.meassociation.org.uk/200...rt-rules-that-a-judicial-review-can-go-ahead/

High Court Decision (March 2009):
http://www.bailii.org/ew/cases/EWHC/Admin/2009/452.html

CS

 

[charles shepherd]

Charles,
I can understand having FDA approval ( somewhat ) but EMA governs the approval of drugs for EU, to quote its website :



Therefore why or under what remit can NICE decide it wants to have a UK trial ?
Is this the norm for other diseases ?

Thanks

NICE reviews published evidence relating to the treatment of the conditions it covers

It does not commission, initiate or fund clinical trials

So NICE is not going to be involved in moving this process forward here in the UK

The licensing authorities take note of results from clinical trials. They also take note of what other regulatory authorities are doing

So if the FDA in America were to license a new drug treatment for ME/CFS the UK and European authorities would take note of this fact. But just because the FDA approves a drug, this would not mean that this decision would automatically apply here in the UK.

CS

 

[charles shepherd]

The information below applies to new drug treatments. Where a drug is already in use and is being assessed for another condition (as is the case with Rituximab) there will be changes to the protocol set out below.

Licensing of medicines
Before a medicine can be widely used in the UK, it must first be granted a licence.

While no medicine is completely risk free, a licence indicates all the proper checks have been carried out and the benefits of a medicine are believed to outweigh the risks.

UK medicine licences
Licences are only granted if high standards of safety and quality are met during the whole development and manufacture of a medicine.

The product must also work for the purpose it is intended for if it is to be licensed.

In the UK, licences can be granted by:

• the Medicines and Healthcare Products Regulatory Agency (MHRA)– which can grant licences for medicines only in the UK
• the European Medicines Agency (EMA) – which can grant licences for medicines in the European Union (EU)

Before a licence can be granted, the medicine needs to be developed and tested.

Developing a medicine

Potential medicines are thoroughly researched using tissue culture, computer analysis techniques and animal testing.

All new medicines are required by law to be tested for safety, quality and effectiveness.

Data is needed from two separate species of animal before a medicine can be used in clinical trials involving humans.

Clinical trials

Clinical trials are research studies carried out in human volunteers and patients. They carefully test the safety and effectiveness of medicines using strict criteria.

If clinical trials are going to be carried out in the UK, the manufacturer of the medicine must first apply to the MHRA for permission to test its medicine.

In the UK, clinical trials are sponsored by:

• the NHS, through the National Institute for Health Research
• the Medical Research Council
• the Department of Health and other government departments
• medical research charities
• pharmaceutical and other healthcare companies

Finding and developing new medicines takes around 10 to 15 years. It is a very expensive process. Estimates vary, but it can cost more than £1 billion to develop a new medicine, from its discovery to gaining a licence.

Read more about clinical trials and medical research.

Stages of research
Four stages of clinical trials are used to investigate a new medicine:

• phase 1 – the medicine is tested in small numbers of healthy volunteers (up to 100 people) to find out how it works in the body and whether side effects increase at higher doses
• phase 2 – the medicine is tested in moderate numbers of people (several hundred) with a particular condition or disease to see how effective it is and identify common short-term side effects
• phase 3 – information about the medicine is gathered from a larger number of people (often several thousand) to see how well it works and how safe it is
• phase 4 – this happens after a licence has been granted, and involves studies to monitor the medicine on an ongoing basis to see if there are any unexpected side effects, or if it causes problems in certain categories of people

Read more about the phases of clinical trials.

What information does a licence include?
The licence for a medicine includes information such as:

• what health condition it should be used to treat
• what dose should be used
• what form it takes – such as a tablet or liquid
• who can use the medicine – for example, only people above a certain age
• how long treatment with that medicine should last
• warnings about known safety issues – such as side effects and interactions with other medicines
• how the medicine should be stored
• when the medicine expires

This information is usually included in the summary of product characteristics. This is a leaflet that comes with the medicine to inform healthcare professionals about how it should be used.

As well as a summary of product characteristics, medicines should come with a patient information leaflet. This leaflet provides patients with certain facts about the medicine. However, a patient information leaflet is not necessary if all of the information fits on the medicine label.

 

[slysaint]

Yes, NICE will certainly have to take note of the clinical trails that have been carried out

I understand that they could not agree to Ritux being used as a treatment before all the relevent trials etc are completed, but will they take into consideration the findings of this and other biomedical research; that ME sufferers illness is due to a problem with the bodys energy production and exacerbated by exertion, making the current treatment of increasing exercise totally inappropriate.
At the very least there should be some form of physical/biological monitoring of patients as opposed to questionnaires if they[patients] are subjected to these 'therapies'.

 

[Jo Best]

Presumably NICE would need to at least acknowledge the Rituximab papers published thus far? Even if only to say 'these are only Phase II trials and are insufficient at this time'? I've certainly seen other drugs assessed by NICE where the advice is 'shouldn't be used outside of a clinical trial/audit due to insufficient evidence' but if Rituximab even got that it would seem, IMHO, to be progress. It would at least mean an acknowledgement from NICE of a potential, albeit unproven, pharmacological treatment.

(Thsi would be good for me personally as my GP has a fairly militant approach of if NICE didn't say it then it's not worth reading about)

Hopefully, NICE will acknowledge the published Phase II trial papers and impending publication of the Phase III trial, although unless they rush the review process (I mean the actual review, assuming they conclude from this consultation that a review is warranted) then I think it's possible that the Phase III trial will be published in time for consideration, not that that will be sufficient for recommendation by NICE, but will be important information.

So I hope that will put your GP on notice of a potential pharmacological treatment option, as you say, and bearing in mind the Norwegian CycloME trial ends in July, so that may be referred to by NICE depending on timing, and does your GP know that a UK trial is planned to begin by the end of 2018 (even if that's not mentioned by NICE)? This is the page on the Quadram Institute website with the January 2017 update: https://quadram.ac.uk/mecfs-talks-held-in-norwich/

The Bergen team will be visiting again in the autumn and a post for a Senior Research Associate to assist with clinical trials has been advertised: http://www.investinme.org/ce-news-1706-03.shtml

The B-cell research is ongoing prerequisit to the UK trial, in collaboration with the Norwegian and other European researchers and Christopher Armstrong (Melbourne).

 

[Londinium]

So I hope that will put your GP on notice of a potential pharmacological treatment option, as you say, and bearing in mind the Norwegian CycloME trial ends in July, so that may be referred to by NICE depending on timing, and does your GP know that a UK trial is planned to begin by the end of 2018 (even if that's not mentioned by NICE)?

Thanks Jo, I have certainly mentioned it (part of a conversation on whether specialist referral was worth it if all that's offered is GET - I was trying to gauge whether referral would give me a better chance of being eligible for this or future trials).

Would the CycloME trial be considered by NICE if it's only Phase II? I always had the impression they waited until Phase III before really considering (if that's not the case, is it just the fact that the previous NICE guidelines are so old that they predate the earlier Phase II Rituximab trials?).

Just straying a little OT: when you say the UCL/Armstrong B-cell research is a 'prerequisite' of the UK trial, are you saying that the UK trial cannot start (get ethical approval?) before we have a way of identifying potential responders better?

 

[Jo Best]

Thanks Jo, I have certainly mentioned it (part of a conversation on whether specialist referral was worth it if all that's offered is GET - I was trying to gauge whether referral would give me a better chance of being eligible for this or future trials).

I wouldn't have thought it worth a referral to a UK specialist clinic to improve your chance of getting on to a future trial, but you can decline the offer of any treatment (such as GET) so it might be worth asking around about other patients' experiences of the clinic you may be referred to and weigh up the pros and cons.

Would the CycloME trial be considered by NICE if it's only Phase II? I always had the impression they waited until Phase III before really considering (if that's not the case, is it just the fact that the previous NICE guidelines are so old that they predate the earlier Phase II Rituximab trials?).

I was only thinking of the CycloME trial in terms of another pharmacological treatment trial, which may be mentioned by NICE, not in the sense of recommending it for consideration, but yes the original NICE guideline was published in 2007 and the first Phase II rituximab paper was published in 2011, after the NICE 3-year review decision ( https://www.nice.org.uk/guidance/cg...me-myalgic-encephalomyelitis-review-decision2 ) and then they decided to put it on the static list in 2013 (https://www.nice.org.uk/guidance/cg...ncephalomyelitis-static-list-review-decision2 ) stating (even though they were informed of the rituximab and other studies)..

"NICE is not aware of any important new studies likely to publish over the next few years which would contradict the decision to move this guideline onto the static list. Having considered the criteria again in light of all comments received we still do not feel that the evidence base is substantially evolving in this area at this time."

So it's impossible to predict what information they'll decide or agree to include in the next review.

Just straying a little OT: when you say the UCL/Armstrong B-cell research is a 'prerequisite' of the UK trial, are you saying that the UK trial cannot start (get ethical approval?) before we have a way of identifying potential responders better?

No sorry, what I meant is that it was decided by the UK rituximab research team to do preliminary lab work on B-cells before designing a UK trial, with the aim of identifying likely responders to rituximab (and so adding value to the Norwegian trials), but that's not a requirement for ethical approval for a UK trial.

 

[Jo Best]

Let the games begin....https://www.theyworkforyou.com/wrans/?id=2017-06-27.1519.h&s=nice get#g1519.r0
Jim ShannonShadow DUP Spokesperson (Health), Shadow DUP Spokesperson (Transport), Shadow DUP Spokesperson (Equality)
To ask the Secretary of State for Health, what steps his Department is taking to encourage people with chronic fatigue syndrome to exercise each day.

• Hansard source(Citation: HC Deb, 29 June 2017, cW)

Steve Brine The Parliamentary Under-Secretary of State for Health[/paste:font]

In 2007 the National Institute for Health and Care Excellence (NICE) produced the best practice clinical guideline, Chronic fatigue syndrome/myalgic encephalomyelitis (or encephalopathy): Diagnosis and management of CFS/MEin adults and children. The guideline, last reviewed in 2013, sets out best practice on the diagnosis, treatment care and support of children and adults with CFS/ME and supports local National Health Service commissioners and clinicians in the delivery of services.

The NICE guideline makes recommendations on the use of Graded Exercise Therapy (GET) in patients mildly or moderately affected by CFS/ME. GET is a structured exercise programme designed to gradually increase how long someone can carry out a physical activity. It should be tailored to a person's current level of activities and should be delivered only by a suitably trained GETtherapist with experience in CFS/ME under appropriate clinical supervision. The guideline also acknowledges that there is no one form of treatment to suit every patient and that treatment and care should take into account the personal needs and preferences of the patient. The guideline can be found at the following link:

www.nice.org.uk/guidance/cg53/resources/chronic-fatigue-syndromemyalgic-encephalomyelitis-or-encephalopathy-diagnosis-and-management-pdf-975505810885

To ensure its recommendations reflect the latest available evidence, NICE is currently reviewing its guidance to see if an update is required. A decision is expected shortly.

 

[SamanthaJ]

Let the games begin....https://www.theyworkforyou.com/wrans/?id=2017-06-27.1519.h&s=nice get#g1519.r0
Jim ShannonShadow DUP Spokesperson (Health), Shadow DUP Spokesperson (Transport), Shadow DUP Spokesperson (Equality)
To ask the Secretary of State for Health, what steps his Department is taking to encourage people with chronic fatigue syndrome to exercise each day.

How bizarre. It even seems like an excessively simplistic way to describe GET. Worrying that this party is now in a position to influence the government (although, of course, the government is always saying they have no influence over NICE anyway). Had a quick look at They Work For You, but couldn't see an obvious reason why this person would have it in for us. Can anyone shed any light?

ETA: Being discussed here http://forums.phoenixrising.me/index.php?threads/seeking-solutions-conference-in-belfast-great-new-development.51841/#post-870005 (Thanks, @Barry53) May be more to this than meets the eye.

 

[Barry53]

Let the games begin....https://www.theyworkforyou.com/wrans/?id=2017-06-27.1519.h&s=nice get#g1519.r0
Jim ShannonShadow DUP Spokesperson (Health), Shadow DUP Spokesperson (Transport), Shadow DUP Spokesperson (Equality)
To ask the Secretary of State for Health, what steps his Department is taking to encourage people with chronic fatigue syndrome to exercise each day.

• Hansard source(Citation: HC Deb, 29 June 2017, cW)

Steve Brine The Parliamentary Under-Secretary of State for Health[/paste:font]

In 2007 the National Institute for Health and Care Excellence (NICE) produced the best practice clinical guideline, Chronic fatigue syndrome/myalgic encephalomyelitis (or encephalopathy): Diagnosis and management of CFS/MEin adults and children. The guideline, last reviewed in 2013, sets out best practice on the diagnosis, treatment care and support of children and adults with CFS/ME and supports local National Health Service commissioners and clinicians in the delivery of services.

The NICE guideline makes recommendations on the use of Graded Exercise Therapy (GET) in patients mildly or moderately affected by CFS/ME. GET is a structured exercise programme designed to gradually increase how long someone can carry out a physical activity. It should be tailored to a person's current level of activities and should be delivered only by a suitably trained GETtherapist with experience in CFS/ME under appropriate clinical supervision. The guideline also acknowledges that there is no one form of treatment to suit every patient and that treatment and care should take into account the personal needs and preferences of the patient. The guideline can be found at the following link:

www.nice.org.uk/guidance/cg53/resources/chronic-fatigue-syndromemyalgic-encephalomyelitis-or-encephalopathy-diagnosis-and-management-pdf-975505810885

To ensure its recommendations reflect the latest available evidence, NICE is currently reviewing its guidance to see if an update is required. A decision is expected shortly.

See also quite a few posts re this in thread "Seeking Solutions conference in Belfast GREAT NEW DEVELOPMENT"
Sorry, really struggling with iPhone at moment.

 

[Barry53]

How bizarre. It even seems like an excessively simplistic way to describe GET. Worrying that this party is now in a position to influence the government (although, of course, the government is always saying they have no influence over NICE anyway). Had a quick look at They Work For You, but couldn't see an obvious reason why this person would have it in for us. Can anyone shed any light?

See my post above.