ME/CFS meeting at the Royal Society of Medicine - March 18th 2015

[rosamary]

Sonya C. Hosted a symposium on the severely affected a while ago.it was pretty awful.I wouldnot want her to speak for me.,

Why was it awful? I am very interested. I was just extremely pleased that she had taken on board the fact that the severely ill are so neglected and attempted to get the focus on them for a change.

 

[charles shepherd]

Can someone tell us how that compares to effective treatments, e.g. Rituximab or LDN? It doesn't sound a lot to me. £1500 is about 2243.8 US dollars according to one on-line converter.

I don't have any figures to hand (Jonathan probably has) but Rituximab is a very expensive form of treatment when compared to other drugs that have been used to try and treat ME/CFS. So it is not something that the NHS is going to touch for ME/CFS, or NICE is going to recommend, without safety and efficacy being robustly confirmed in a number of large clinical trials.

What I would caution is stating that these are 'effective' forms of treatment in our current state of knowledge

We have some very interesting positive results from one small but well conducted clinical trial in Norway in relation to Rituximab. But this is only one positive clinical trail so far. Hopefully, we will see a UK clinical trial starting this year….

LDN is a very speculative and unproven form of treatment. Feedback to the MEA has been very mixed.

 

[Snow Leopard]

Bit of an aside, but Lenny Jason is a psychologist. Not that he proposes psychology as a treatment, but he does a lot of interesting work looking at patterns of disease and stigma and social behaviours. It has its place when done intelligently.

The difference between Lenny and the (infamous) others, is that Lenny actually listens to us and our experiences. He works with us, not independently of us and that is the key difference.

 

[Ecoclimber]

@charles shepherd

I appreciate you informative response to my questions although one wonders why then the vigorous debate between the Countess Mar and Prof. White, Wessely et al. as outline in one of our threads concerning the Pace Trial if you want to slog your way through 2500 replies.

I was also surprise given the dearth of medical research in the UK, how quickly WT funded the replication trial for xmrv after the so called 'ME/CFS breakthrough' (xmrv was associated with ME/CFS not a cause for ME/CFS as some patients misunderstood) was announced in Science. I don't believe the ink had dried yet on the pages of Science before the UK scientists jumped in to conduct their research studies as noted by many UK patients.

As you well know in the medical science field, replication studies are required before validation and acceptance. However, it seems as though medical professionals are willing to validate and accept studies within the psych/social field with far less stringent requirements for validation.

We have the authors of the PaceTrial who have refused repeatedly to release their datasets even under the FOIA so that a replication study could be conducted using their methodology. We also have a co-mingling of cohorts under the flawed Oxford criteria. We also have the objects of recovery as not one prior to illness onset but rather of one walking a short treadmill test and at that a most dismal recovery comparable to controls. (18% -24%) I believe.

Given the fact that Doctor’s Fluge and Mella with their 2009 case series and the 29-person 2011 study found that about 2/3rds of ME/CFS patients had a significant and positive response to the chemotherapy and autoimmune drug Rituximab. Even though a small study compared to the PaceTrial, replication is still required under a much larger study that would require the same positive results before it would be considered viable as a treatment option. They have not hidden their data.

One wonders why so many of medical professionals in the UK accept the PaceTrial as Gospel truth without a further replication study? To me, the PaceTrial does not rise to the level of scientific scrutiny to be valid.

Also, you might find of interest, a blog post written by Clinical Psychologist and Professor in the Department of Psychiatry, University of Pennsylvania, James (Jim) Coyne, PhD in PlosOne
BMC Medicine gets caught up in Triple P Parenting promoters’ war on critics and null findings

Undeclared conflicts of interest constitute scientific misconduct. Why we should be as concerned about conflicts of interest of interest in evaluations of nonpharmacological treatments, like psychotherapy.

I cede the floor to UK patients who know more about treatment options within the UK.

-

 

[Alison2]

Why was it awful? I am very interested. I was just extremely pleased that she had taken on board the fact that the severely ill are so neglected and attempted to get the focus on them for a change.

There was a discussion about it, in general me/cfs news.take part in our severe me symposium from home.
sorry dont know how to do link to it.

 

[eafw]

There was a discussion about it

http://forums.phoenixrising.me/inde...-in-our-severe-m-e-symposium-from-home.33473/

 

[Bob]

The Countess of Mar's speech has gone down very well. I think it's possibly the most number of 'likes' that I've ever received for a post.

I'm very grateful for Charles' and Jonathan's involvement as well. We forget to say thanks sometimes, when in the middle of discussions over details.

Looking forward to seeing the videos if they release them.

 

[rosamary]

http://forums.phoenixrising.me/inde...-in-our-severe-m-e-symposium-from-home.33473/

Thank you. I'll have a read through it to see whether Sonya should be on that interview panel.

She certainly attempted to highlight that ME was not cf on that the Mathew Wright Programme yesterday.

(If anyone saw that, who was that lady with the green eyeshadow and a very expressive face?)

 

[MeSci]

I don't have any figures to hand (Jonathan probably has) but Rituximab is a very expensive form of treatment when compared to other drugs that have been used to try and treat ME/CFS. So it is not something that the NHS is going to touch for ME/CFS, or NICE is going to recommend, without safety and efficacy being robustly confirmed in a number of large clinical trials.

What I would caution is stating that these are 'effective' forms of treatment in our current state of knowledge

We have some very interesting positive results from one small but well conducted clinical trial in Norway in relation to Rituximab. But this is only one positive clinical trail so far. Hopefully, we will see a UK clinical trial starting this year….

LDN is a very speculative and unproven form of treatment. Feedback to the MEA has been very mixed.

The point I was making in the last section of my post, albeit not very clearly:

Edit - when I say 'effective treatments' I mean treatments that have shown promise in clinical trials or treatments that self-selected groups, such as people here, have found to be effective and improve function, ability to work, etc.

As the 'evidence' which NICE and others claim indicates efficacy and safety for CBT and GET is, when scrutinised, really no better than patient self-report here, I see no excuse for them to stick to the position that CBT/GET should be recommended and the patients' preferred treatments should not, especially as patients also report in their droves that CBT/GET has seriously harmed them.

is that there is no more evidence, AFAIK, for CBT/GET than for the treatments that a substantial number of patients have reported to be helpful. I'm not surprised if reports are mixed for any treatment, as there are probably several subgroups who will require different treatments.

PACE involved self-reporting from a poorly-selected patient group, some of whom had been told that a treatment would benefit them, completely unblinded, shambolically conducted and misleadingly analysed.

That cannot be regarded as evidence, yet it is repeatedly cited and treated as such. Patients' direct self-reports here and elsewhere merit equal or even greater attention, in my view. And as someone else has pointed out, there is already more than one source of positive trial evidence for rituximab.

 

[eafw]

She certainly attempted to highlight that ME was not cf on that the Mathew Wright Programme yesterday.

I think that AfME/ Sonya C are realising that the tide is turning a bit and patients are able to speak up more publicly, Twitter etc. She gave a bit of a wobbly interview after the cytokines study came out and there was some discussion about it so hopefully this change is a genuine attempt to get on board with what sufferers have been saying for a while (still wouldn't have her on any clinical decision making panel right now though)

 

[Jonathan Edwards]

In response to Ecoclimber, I would second Charles's view that a grand conspiracy theory may not be the reality. Certainly in the UK we do cock-up better than conspiracy, even if there is often a bit of conspiracy, often rather cocked up conspiracy, lurking but not doing much.

I think the reason why UK ME/CFS clinicians fail when they do has a lot more to do with why relatives are negative and radio presenters screw up - they don't understand. And let's be fair, ME/CFS is not easy to understand. I have gone on record as saying that it is the most difficult intellectual puzzle I have ever encountered. In comparison, rewriting Leibniz's theory of the universe, which I do the rest of my time, is a piece of cake. The reason why no biological research has been funded is mostly that nobody has a clue what research to do. That is not entirely true because there have been good applications for infrastructure for basic data gathering work but I suspect these have fallen foul of the way the system divides up the types of funding (bureaucracy).

I think the reason why patients get referred for inappropriate therapy when they do is that it is the path of least resistance for clinicians who have no clue what they are trying to treat and are clutching at straws of theories that make sense in the way that Fox News or the Daily Mail seem to make sense. 'All in the mind' is easier if you cannot think of anything else. The instinct to 'minister unto', which leads on to paternalism and all that stuff is there in all of us and is easy to slip into. What I see in all these debates is mostly human nature, not conspiracy. I do not actually think that the 'biopsychosocial model' is held in any great esteem by anyone more than a few miles from the centre. I had never heard of it before I joined PR, nor the people who propound it.

Yes, we need a level playing field, and I am prepared to put effort into trying to achieve that, but I think this is less Star Wars and more people muddling along in the wrong direction. A lot of harm can come from muddling. I know from my own mistakes, but it should not be mistaken for malice.

 

[eafw]

The reason why no biological research has been funded is mostly that nobody has a clue what research to do.

One of the things that puzzles me is why researchers are not looking at or drawing on work that has already been done in similar(ish) conditions: MS, RA, post encephalitis and other viral aquired brain injury, HPA issues and so on. At least they don't seem to be joining the dots much with studies that are already there in other illnesses. Maybe you would say it's not knowing which dots to join, but there have been clues for years - for anyone listening to the patients.

I do not actually think that the 'biopsychosocial model' is held in any great esteem by anyone more than a few miles from the centre.

Esteem or not it is what informs nearly everyone a ME sufferer will encounter in the both NHS and the popular consciousness, even if they don't name it as such. This is why from our end it is such a big deal.

 

[Sidereal]

Whoever cracks this disease and figures out the biological mechanism could well end up with the Nobel. CFS is considered a prime example of psychosomatic illness. The entire "medically unexplained symptoms" paradigm would come crashing down.

 

[Roy S]

The reason that more biological science has not been done is lack of funding. There are reasons that has happened and is still happening. Some people have made it happen. Others have allowed it to happen.

Even using the word conspiracy can imply insanity.

 

[Jonathan Edwards]

The reason that more biological science has not been done is lack of funding. There are reasons that has happened and is still happening. Some people have made it happen. Others have allowed it to happen.

I disagree. I managed to nail the fact that rituximab is useful for autoimmunity with essentially no funding (nobody would fund it). For the pilot study that got it off the ground I bought the rituximab myself with some money my father had given me because he wanted to see me succeed in my career where he had been disappointed. Otherwise I did everything myself - put up the IVs, took the blood pressures and the blood samples, since I had no staff. If people really want to find the answer to a question they will. We need the right people to be interested.

One of the things that puzzles me is why researchers are not looking at or drawing on work that has already been done in similar(ish) conditions: MS, RA, post encephalitis and other viral aquired brain injury, HPA issues and so on. At least they don't seem to be joining the dots much with studies that are already there in other illnesses. Maybe you would say it's not knowing which dots to join, but there have been clues for years - for anyone listening to the patients.

The problem is that when people have looked - and people have looked and it has been forgotten - if they are honest they found zilch. Zilch in the brain, zilch in the serum, zilch in the blood cells, zilch in the ... (At least in terms of replicated findings that is where we still are by and large.) That maybe because they are looking for the wrong things or because they are making methodological mistakes or it may be that the sorts of things you find in the other diseases just do not show up in ME. And when things do turn up a bit out of line, like cortisol levels, it does not seem to lead anywhere. However much you listen to patients if you cannot get any repeatable results in the lab that suggest a sensible hypothesis you are stuffed.

It is perfectly possible that all that is because researchers have been too focussed on the wrong theories and have missed things staring them in the face (that is the usual situation in biomedical science). But I do not actually think that MS and RA are necessarily sufficiently similar to be a good starting model when it comes to finding ME biomarkers. ME is in some way quite different from the others. As I said before, it is the hardest thing I have come across. But that does not make it impossible. As I have said many times what I think it needs most of all is lots of up front debate about theories like we get on PR.

And the other thing I suspect it needs is what usually tips things in lab science - somebody comes out of the lab into the coffee room and says - hey this is weird, I was expecting X to be up but its down - what the heck is going on. (Note that what not to do is repeat the experiment until you get the up result you thought you wanted, and publish.)

 

[A.B.]

@Jonathan Edwards since we're talking theories, what do you think about macrophagic myofascitis?

Aluminum oxyhydroxide (alum) is a crystalline compound widely used as an immunological adjuvant of vaccines. Concerns linked to the use of alum particles emerged following recognition of their causative role in the so-called macrophagic myofasciitis (MMF) lesion detected in patients with myalgic encephalomyelitis/chronic fatigue/syndrome. MMF revealed an unexpectedly long-lasting biopersistence of alum within immune cells in presumably susceptible individuals, stressing the previous fundamental misconception of its biodisposition. We previously showed that poorly biodegradable aluminum-coated particles injected into muscle are promptly phagocytosed in muscle and the draining lymph nodes, and can disseminate within phagocytic cells throughout the body and slowly accumulate in brain.

Accumulation of alum in the brain presumably leads to chronically activated microglia.

About 50% of MMF patients meet the international consensus criteria for ME.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4318414/

 

[Aurator]

I managed to nail the fact that rituximab is useful for autoimmunity with essentially no funding (nobody would fund it). For the pilot study that got it off the ground I bought the rituximab myself with some money my father had given me because he wanted to see me succeed in my career where he had been disappointed. Otherwise I did everything myself - put up the IVs, took the blood pressures and the blood samples, since I had no staff.

That's a remarkable example of dedication, especially in this day and age, though I'm not entirely surprised by it given your evident motivation to get to the root of things, whatever it takes.

I accept that ME is currently an enigma and that even you may not have a clear idea of where research efforts should be focused. If you were suddenly given a budget of £100 million, though, and had to use it or lose it in the next five years, where would you throw the money?

I know you have other things to do besides answering these sorts of naive questions. Even a brief answer will do.

 

[charles shepherd]

@charles shepherd

I appreciate you informative response to my questions although one wonders why then the vigorous debate between the Countess Mar and Prof. White, Wessely et al. as outline in one of our threads concerning the Pace Trial if you want to slog your way through 2500 replies.

I was also surprise given the dearth of medical research in the UK, how quickly WT funded the replication trial for xmrv after the so called 'ME/CFS breakthrough' (xmrv was associated with ME/CFS not a cause for ME/CFS as some patients misunderstood) was announced in Science. I don't believe the ink had dried yet on the pages of Science before the UK scientists jumped in to conduct their research studies as noted by many UK patients.

As you well know in the medical science field, replication studies are required before validation and acceptance. However, it seems as though medical professionals are willing to validate and accept studies within the psych/social field with far less stringent requirements for validation.

We have the authors of the PaceTrial who have refused repeatedly to release their datasets even under the FOIA so that a replication study could be conducted using their methodology. We also have a co-mingling of cohorts under the flawed Oxford criteria. We also have the objects of recovery as not one prior to illness onset but rather of one walking a short treadmill test and at that a most dismal recovery comparable to controls. (18% -24%) I believe.

Given the fact that Doctor’s Fluge and Mella with their 2009 case series and the 29-person 2011 study found that about 2/3rds of ME/CFS patients had a significant and positive response to the chemotherapy and autoimmune drug Rituximab. Even though a small study compared to the PaceTrial, replication is still required under a much larger study that would require the same positive results before it would be considered viable as a treatment option. They have not hidden their data.

One wonders why so many of medical professionals in the UK accept the PaceTrial as Gospel truth without a further replication study? To me, the PaceTrial does not rise to the level of scientific scrutiny to be valid.

Also you might find of interest, a blog post written by Clinical Psychologist and Professor in the Department of Psychiatry, University of Pennsylvania, James (Jim) Coyne, PhD in PlosOne
BMC Medicine gets caught up in Triple P Parenting promoters’ war on critics and null findings
Undeclared conflicts of interest constitute scientific misconduct. Why we should be as concerned about conflicts of interest of interest in evaluations of nonpharmacological treatments, like psychotherapy.

I cede the floor to UK patients who know more about treatment options within the UK.

-

Two quick points:

The PACE trial has, of course, caused a great deal of debate (including a House of Lords debate initiated by the Countess of Mar), concern and anger here in the UK.

Not surprisngly, many of these criticisms were repeated at the RSM meeting by various speakers - including myself.

So PACE is not going to go away…..

But this debate is one small part of the very messy mix of views that help to decide what happens to ME/CFS from both the clinical and research perspective here in the UK

One of the other encouraging aspects to this RSM meeting was the fact that we had doctors, not just myself and Jonathan, questioning the meaning and validity of these unblinded trials. Dr Luis Nacul spent quite a lot of his time with a more detailed critique of the trials - which I hope will appear in due course on the RSM website

Without going back to a very large XMRV file I can't recall at what point the Welcome Trust ageed to fund an XMRV study. But it wasn't published till January 2011 (the XMRV paper was published in October 2009)

It's worth noting that there was a lot of concern and scepticism about all the hype (ie XMRV was the cause of ME/CFS and expensive commercial blood testing for XMRV started) that began to surround the XMRV paper here in the UK - and I include myself here.

In fact, it wasn't too long after publication that I went up to the MRC at Mill Hill to see Jonathan Stoye and Kate Bishop, both leading experts on retroviral infection, so see if they would be willing to do a validation study - which was then carried out:

As a result, the MEA and myself received a lot of criticism - some of which was actually very unpleasant!

The XMRV sceptics (who included several doctors who are firmly in the biomedical camp) were proved correct in the end on this one....

 

[Jonathan Edwards]

I accept that ME is currently an enigma and that even you may not have a clear idea of where research efforts should be focused. If you were suddenly given a budget of £100 million, though, and had to use it or lose it in the next five years, where would you throw the money?

I know you have other things to do besides answering these sorts of naive questions. Even a brief answer will do.

I have been thinking hard about that and was thinking more in terms of a budget of £20 million over ten years as a starter. What I would put top of the list is the identification of a ring fenced population based cohort in a region of the UK based on primary trawling of an entire population base using multiple sets of criteria but with a focus on patients with something like Canadian criteria disease (maybe IOM). I would set in place resources for longitudinal analysis of the cohort. I would then look to replicate basic findings like NK function, cytokine profiles, B cell function and antibodies, and HPA axis disturbance to see if these really are replicable and if so look at detailed mechanisms using the longitudinal analysis. I would also want to look at the demographics in detail in terms of incidence patterns to try to pin down genetic , environmental and stochastic components

That may all sound very boring but I think it needs doing so that we know which of these 'leads' is really worth pursuing.

With the next £20 million you offer I would get my friends at Queen Square National Hospital for Nervous Diseases (who would lap up the grant money) to home in on fMRI analysis of ME brains longitudinally - again trying to replicate, but also go further than, the interesting studies already in print from Baraniuk, Stanford and the University of Sussex (effects of interferon and fatigue). We could do some PET studies too.

As for the next £60 million - there are plenty of drug trials we could do and maybe even with dose response curves that would really give something hard.

No surprises really, but then the girl in the lab hasn't come into the coffee room just yet.

 

[lansbergen]

But I do not actually think that MS and RA are necessarily sufficiently similar to be a good starting model when it comes to finding ME biomarkers. ME is in some way quite different from the others. As I said before, it is the hardest thing I have come across. But that does not make it impossible. As I have said many times what I think it needs most of all is lots of up front debate about theories like we get on PR.

And the other thing I suspect it needs is what usually tips things in lab science - somebody comes out of the lab into the coffee room and says - hey this is weird, I was expecting X to be up but its down - what the heck is going on.

Scientific curuosity and a bloodhound nose. .