United Kingdom: ME Research Collaborative (MERC) [was CMRC] news

Interesting @Cinders66 thanks for that info i was still fairly new to the field back then.

Yes thank you indeed @Jonathan Edwards, what can we do to help?

 

More from Eileen Marshall and Margaret Williams :

http://www.meactionuk.org.uk/Problems_and_Solutions.htm

No way of telling if the quotes are accurate.

 

I would be very surprised if that were so Adam. Patient priorities and viewpoints are supposed to be listened to but I cannot see that anecdotes and testimonies should come in to the actual formulation of recommendations.

I am very aware that this is all politics but that is precisely why I am encouraging people to be tactical and take aline that the committee cannot fault. It may fail but the alternative is bound to fail.

To put it another way, I have lived in the community of medical experts all my life. I know how they think. If you want to convince these people to remove the stuff based on poor evidence you need to convince me because I am going to be five times easier to convince than them. Asking for NICE to treat anecdote equally alongside trials is a non starter for me.

 

That is hugely useful @Cinders66. I now understand some stuff I could not quite make sense of.

The bit you quote actually seems fair to me. I would agree that searching for a causal trigger should have low priority. I guess this was a reaction to people trying to track down viruses in the 1990s. I am less impressed that understanding mechanisms should be low priority but considering the failure to that date it might look sensible.

I agree that it seems a pity that PET scanning had not been taken up. Campos Costa did a SPECT study, which is similar, but I am not sure it was very illuminating. Remember that PET is a general technique and that the Japanese study sues it to look for something very specific. It is very expensive because you have to make isotopes that emit positrons and then build them into reagents. But it is certainly a pity it has been so slow to evolve.

 

I know this is a public space but I am going to make it public that I think Colin can be naïve at times. I think he knows I think that. What is so weird is that none of the MRC people seem to have seen how incompetent the methodology was.

 

I can fully appreciate that. This next question is purely for my own interest, and not disputing what you say: How do you go about ethically trialling if, and by how much, a treatment might harm people?

 

BTW, one of the great things about this forum is the number of patients with long memories and real expertise in the detailed history of PACE and lots of BPS-related stuff. If you're ever struggling for a reference or some background, starting a new thread with a specific question would give you a good chance of getting a rapid answer.

 

Not much except keeping me chafing at the bit. And feeding me all the right quotes. I am trying to collate this stuff systematically and am aware that certain people have put a huge amount of time in to researching all this.

 

Most treatments that can do a significant amount of good can do harm. The standard thing in industry is to do an initial phase 1 study looking for harms before you start looking for benefit. I am not sure that is a good model. The worst example was at Northwick Park where they gave the first dose to six healthy people (who could not even get a benefit) all at the same time and they nearly died.

The most difficult case i came across was a trial of a collagenase inhibitor where the side effects were likely to be indistinguishable from the condition being treated, at least for a good while. I resigned from the project as I could not see how it could be performed ethically.

The more common situation is where a treatment looks to be doing something useful in early trials but you need to identify occasional unwanted effects in large studies that might be really serious. There is as far as I know no formula for weighing benefit against damage but the general rule is that harms greatly outweigh benefits in terms of significance.

Where it gets difficult is the situation for something like GET where you might expect people to move both up or down a line of activity. If you take the mean or median level as your outcome measure then at least you might be able to show that improvements outweigh worsening but if the scale is non-linear which is likely the result may be very misleading.

In other words it is very complicated. Lots of studies under-report harms. How you guard against that is partly matter of being very sensitive to harm and partly making sure your measures reflect it adequately. But there is often not much motivation to do things properly.

 

So if NICE can only be convinced by trials evidence of harm from GET, but trialling techniques are not able to reliably acquire such evidence, where does that leave us? Do we need to step back and reappraise if better trialling techniques could be developed?

 

I don't think harm from GET is essential to the argument, or even in frame for the NICE discussion. The issue is that there is no usable evidence of benefit.

To demonstrate harm from GET would run into the same problems as demonstration of efficacy with PACE type designs although subjective bias would be under different forces. But completely different trial techniques for therapist-based treatments are needed anyway.

But then I see no argument for doing any more exercise trials since we have no good reason to think it works or is likely to work.

 

@Tom Kindlon points out that in PACE, fitness didn't improve in any group so activity probably didn't either and so there wasn't really an adequate test of safety.

All the evidence of harms comes from patient surveys, which of course aren't 'gold standard' evidence - but it's our everyday experience that activity makes us worse, and the survey data seems to reflect that experience.

My question is, given that from our point of view, it seems likely that patients are being harmed right now by GET, how can we best persuade NICE to remove GET (and CBT) from its recommendations without waiting until 2020?

Why don't NICE seem to appreciate the urgency? Is it the issue of surveys not being 'gold standard'? Have they not understood (or looked at) Tom's argument?

 

I don't think there is anyone at NICE in a position to make a decision. Decisions have to be taken after due deliberation of 'independent experts'.
That would be overridden if a drug company expressed concern about their drug and legal issues were involved. Or some evidence of harm appeared in an academic journal. As things are I do not see them overriding the rules.

 

What sort of evidence?

Flagging @Tom Kindlon.

 

Hey, Yes, I was under care of Peter Behan at neurology clinic in Southern General in Glasgow in mid 1980s. Behan also wrote the preface to Melvin Ramsay's 1986 book 'Postviral Fatigue Syndrome: the sage of Royal Free Disease', perhaps that is where the confusion came in!

 

That is the difficult bit. For there to be convincing anecdotal evidence of harm the harm would need to be something not normally encountered with the condition itself. And worsening of ME is very often encountered with the condition itself. Harm from drugs like vioxx, which increased the rate of stroke, were only accepted once large surveillance studies had been done, because stroke is normally encountered in the sort of people who tok vioxx.

 

Yes, Behan was one of the few doctors diagnosing ME in 80s. I realise I am quite unusual in having the validation of a neurology diagnosis. And of course I had never heard of ME - or Coxsackie - when I got ill. No one had heard of ME!

 

Can this really be an unsolvable problem? A perverse therapy, equivalent to trying to cure diabetes with sugar, worsens the condition and yet harm can't be ascribed to it?

The provision of GET by the NHS really worries me. There are plenty of people on this forum who say that they've been made severely and permanently much worse by GET. Surely there's something we can do to protect the newly diagnosed patients who are going to the NHS clinics right now and being prescribed GET? Now that the tide has turned against PACE? I don't know what the throughput of patients is but that could be a lot of lives permanently and unnecessarily ruined.

If this is a difficult problem, where and how can we raise it as a difficult problem that urgently needs addressing?

 

Does get complicated doesn't it! To prove something like that you would presumably need to demonstrate significantly different patterns of worsening, which could take an awful lot lot of proving.