Thursday, 12 September 2013

Key MS research priorities

Ignore the black swan at your members peril. #MSBlog #MSResearch

"I received the email below from the MS Society. You may find the research priorities interesting, or not! My one criticism is the priorities make no mention of cause or causation; the whole exercise seems to have be done within the current paradigm or "autoimmune dogma". This will make it hard for the Charcot Project to get any support from the MS Society. These research priorities do not acknowledge, or make any allowances for, a black swan."


"I am interested in finding out if the methodology the James Lind Alliance partnership uses takes into account black swan events or is it blinkered by consensus dogma? Black swan events are more common than we realise, and rarely if ever emerge from a consensus."



It is very hard to see a black swan from this perspective! 

Dear researchers

Key MS research priorities

In collaboration with several organisations, the MS Society has recently completed a James Lind Alliance partnership to set priorities for MS research important to people affected by MS and healthcare professionals: 


  1. Which treatments are effective to slow, stop or reverse the accumulation of disability associated with MS?
  2. How can MS be prevented?
  3. Which treatments are effective for fatigue in people with MS?
  4. How can people with MS be best supported to self-manage their condition?
  5. Does early treatment with aggressive disease modifying drugs improve the prognosis for people with MS?
  6. Is Vitamin D supplementation an effective disease modifying treatment for MS?
  7. Which treatments are effective to improve mobility for people with MS?
  8. Which treatments are effective to improve cognition in people with MS?
  9. Which treatments are effective for pain in people with MS?
  10. Is physiotherapy effective in reducing disability in people with MS?

The JLA have an established process of bringing together healthcare professionals and people affected by health conditions to jointly agree research priorities for a particular health condition. Some of you would have been involved in this process, and we are delighted to announce these results. 

With 669 people affected by MS and health care professionals feeding into this process from the beginning we can be confident that this list of unanswered questions truly reflects the priorities of the MS community.

The MS Society is now working to identify how we will support research to address these priorities. This may be through our own funding mechanisms, or through encouraging other funders to support and adopt these priorities. We will be in touch with more information on our strategies to address these priorities once they are finalised.

These priorities will complement our existing research strategy, and applications to future grant rounds that specifically address these priorities will be considered more favourably. However we do not intend to exclusively restrict our funding to these priorities, and will continue to support research into the causes of MS, and all aspects of treatment and care for people affected by MS.

Previous partnerships using this process in other conditions have a track record of turning priorities into research projects by securing funding through other organisations. This is really encouraging news and we will be working to make this happen with these new priorities.

You can find out more information on our partnership here: www.mssociety.org.uk/jla.

Best wishes,

MS SocietySwitchboard: 020 8438 0700



Black swan post:



06 Sep 2013
Have we got the autoimmune paradigm of MS wrong? #MSBlog #MSResearch “I was involved in a heated discussion yesterday at a meeting in Germany that centred on the current, and future, DMT market for MS. The opinion ...

55 comments:

  1. Prof G,

    Although you regularly refer to the auto-immune dogma, you have made a good career out of it. Attendances at huge numbers of international conferences, recipient of huge volumes of grants on various funders, personal consultancy fees from most of the big pharma companies. I didn't here you dissing th auto-immune theory when picking up a cheque from Biogen.

    If you want to keep hold of the nice earner which is MS research, don't bite he hand(s) that feed you!


    I look forward to seeing the results of the Charcot project. However, as with most research I'm expecting the following: trial was under- powered, more research required, drug combination needs to be reassessed. Please surprise me.

    I'm a person with MS who believes that EBV is the culprit - it's been theorised as such for 30 years. It's the tortoise pace of the MS research world that's been the real scandal. At ECTRIMS when you have time to think, think about people with MS who just want to live a normal life. I have no interest in Black Swans, just an interest in stopping my disease and encouraging some repair. If only researchers had focused on such practical things and not wasted decades coming up with theory after theory.

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    1. Using the doctrine of Karl Popper on which much of science is based to try and disprove the hypothesis.

      Therefore, to disprove the autoimmune hypothesis you have to work on autoimmunity.

      However, as a point here. You are so wrong when you say ProfG is a proponent of the Autoimmune Theory.

      I have known ProfG for many years and he has never been a proponent of autoimmunity and has always maintained that it is something else (Virus) that is the central problem.

      Will the Charcot Project fail, lets hope not, but there is a possibility.

      As to the power, this is statistically based but not infallible but with each participant there is a cost and it is massive, so I think we should be applauding the Prof Gs (UK and Down Under) for having the "jajce" to get off their bums, and do something they are passionate about.

      If all neurologists were like this you would have a lot more options.

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  2. The most important question I want answered is what causes MS? All the fund raising money that is wasted on the obvious is disgraceful. If you've had the disease for over 30 years, you may have been told MS doesn't cause pain. If patients had been listed to, maybe we would not need expensive projects.

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  3. I took part in this JLA day at MS soc HQ in July time (it would be handy if the MS soc could put on their website that there are 2 Edgeware roads but that's a different topic for discussion somehwere else!)

    It felt like a very democratic process but the outliers get cast aside and when the middle of the bell curve is a bit of a black hole then those outliers could be important, I agree with the black swan comment.

    the most heartening thing i took from the day was when, in the last half hour when people had a chance to make a claim for the pet project to e investigated further the young neurologist researcher was laughed out of town at his suggestion for more research dollar to go to the auto-immune theory.

    I chose to see that as the best part of a very long and at times frustrating day.

    The Cause of MS was included as one of the 30 questions at the beginning of the day (to be whittled down to the final 10) but I guess, in much the same way as the Siskin CCSVI research not getting off the ground in Canada, people are more concerned with their own here and now: there apparently weren't enough takers for the study which would have had a blind placebo controlled aspect to it.

    People directly affected by MS can say finding the cause is important but on the day there are more pressing questions to be answered?

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  4. 'scuse the typos in my comment above but my main thought is: Anonymous(es?), bring your name to the debate.

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  5. How many of these are Pharma answering?

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  6. Isn't Q2 (can MS be prevented) at least partly rleated to cause?

    Hear hear re MD comment at 12.35 12 Sept re charcot Project

    Thanks as always

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  7. We need to spend more money on CCSVI trials. A lot more money. All of the MS money. The neurologists and big pharma are keeping the truth from being told!!!!!

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    1. If enough people had found this of sufficient importance to bring this to the table then maybe it would have made the top ten, so perhaps a failing in mobilising support.

      I wonder if anybody has every requested funding to do any studies within the UK, I can't remember seeing any from MS Society. So is their any body out there who will put in the effort to do definitive studies rather than siphon cash using private practise

      However to spend all the money on just one thing is frankly rather short sighted. I thought there were trials ongoing so why do we want any more, one was stopped because of worsening. By the time this would be put forward surely results will be shown.

      As for stopping truth being told....tell me how?

      Big pharma are not going to be bothered with CCSVI unless it is druggable. If it is they will have taken a long hard look at it but how are they keeping stuff quiet. Are they frightened that their revenues will be hit by the resounding success.... I have not seen much evidence of this yet!

      Are the neurologists conspiracy stopping studies being published because they say something positive....I think not there are enough outlets to get this stuff aired and failing that you use the media.

      The Canadian CCSVI fraternity will be meeting soon will this reveal something new. The truth is we have to wait and see what the trials show, when they report we will move forward.

      Delete
    2. If you're being sarcastic, it helps if you can make it plain, there are symbols to indicate this [!] is just one of them.

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    3. Stick 'em in square brackets and we'll get the message.

      Delete
  8. Replies
    1. HaHa You Got me! Happy to know it, I wonder though if some people agree with your joke

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  9. It is shocking that the MS societies, both in the UK and here in the US, seem uninterested in funding studies looking for the root causes of the disease. I recently spoke with a prominent US MS neurologist who noted the same incredible omission. He had recently spoken to the medical director of the NMSS, who told him that they were no funds currently being directed at studies looking for the cause of multiple sclerosis.

    Shocking and obscene, IMO…

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    1. Yes it is shocking, but not unsurprising. The people there have MS and many may have reached SPMS so their perspective would be very different to neurologists and researchers.

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    2. I have SPMS and I posted the comment 9:15 anon regarding the cause of MS. I was 21 when I was diagnosed over 35 years ago. I do not want to see the constant misery of young people struck down with this horrible disease. It would be great to be well, but I would love to see this disease eradicated and this can only be done by finding the cause. The current research into treatments is for after the horse has bolted. It is short sighted to not look for prevention.

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    3. Question 2. How can MS be prevented?

      By knowing the cause?

      The genetics studies are focused on cause, the charcot project

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    4. Tell me if I am missing something.

      MS is caused by attack of the immune system on the meylin sheath which provides trophic support the the underlying axons. When enough of the meylin sheath is destroyed the axons eventually begin to die which ushers in progressive disease.

      In PPMS, meylin is attacked in a continuous manner without any recovery.

      Where is the mystery?

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    5. The idea that MS is an initially an attack on the myelin sheath is not a given (see post on MS is a grey matter disease?) that's the problem with MS research the complete pathology is unknown.

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    6. Demyelination leads to axonal loss which leads to the death of the neuron. So yes MS is also a disease of the grey matter but there is little evidence that it is the primary driver.

      www.jhasim.com/files/articlefiles/pdf/asm_9_2_p37_41.pdf

      http://www.ncbi.nlm.nih.gov/m/pubmed/20855416/

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    7. So we know what happens, but do we know what causes us to develop MS?

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    8. It is pretty clear what the root cause of MS is. It is an autoimmune disease. Preventing people from getting it in the first place or at least identifying those that are likely to get it still needs to be worked on. But to those that are diagnosed today, the treatment options available means that it can be managed if treated appropriately.

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    9. Is it clear? Why is it acceptable, that just because some patients respond well to treatment, prevention is not a priority? Thankfully, scientists had the knowledge to prevent the major diseases last century. MS more difficult, but why give up on the search?

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    10. I think the ultimate goal would be to prevent people from getting MS, it does take time to unravel the mysteries of the immune system. 30 years ago there was nothing available for people with MS and now there are numerous treatments, including HSCT which can halt disease in over 50% of the worst cases of PPMS'ers to date. Imagine how they would be if they were treated early?

      So even though MS is not cured I am glad I have the options available to me since being diagnosed in January. I wasted no time getting on a DMD and if this does not work I have other options to me, but I will not give in to the mass hysteria belief that science and big pharma are out to screw me. I have a mind and I can think. And as far as the great strides in the last century in other diseases, all I can say is at least I don't have cancer.

      http://m.youtube.com/watch?v=1EMKoaBysOk&desktop_uri=%2Fwatch%3Fv%3D1EMKoaBysOk

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    11. Anon 12:46
      That was the point of the paper on MS as a grey matter disease.........initial event may not be attack on myelin. CSF proteins in early stages show degradation not associated with myelin. Not that myelin is not targeted at some later time. Myelin loss leads to clinical symptoms. But how long has the disease been simmering?

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    12. As one of my cancer surgeons said to me "your MS is much more of a problem to you". Not always a killer, just like MS.

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    13. Simply saying that MS is an "autoimmune disease" is a huge copout. The aberrant immune response seen in MS is a SYMPTOM of an underlying disease driver. It's not as if your immune system just decides one day to go ahead and start attacking the body's own cells.

      The whole concept of autoimmunity has led to a massive throwing up of the hands by researchers (largely funded by the pharmaceutical companies), who instead of looking for what ignites the aberrant immune response instead seek to minimize the damage done. This is akin to putting out fires caused by an out-of-control blowtorch, but never stopping to turn that blowtorch off, or even looking for the blowtorch.

      In a sense, all of the available MS DMT's are only sophisticated symptom managers. We must learn what causes the immune system to go haywire in order to ultimately cure the disease.

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  10. Is this a failing of using a mechanism such as the JLA? ie that a topic whilst seemingly unimportant to the people involved, is only unimportant because the implications (of not knowing the cause) haven't been adequately thought through? This may be because those people are involved in their everyday lives rather than taking a step back from research and realising that finding the cause could be a key to unlocking treatment. Just a thought.

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  11. The Disgruntled MS ResearcherFriday, September 13, 2013 12:45:00 pm

    This JLA exercise is very disappointing. Most of the priorities are, or will be, addressed by the drug industry.

    Did you know that the MS Society had the opportunity to address "Is Vitamin D supplementation an effective disease modifying treatment for MS?"? a few years ago? A UK consortium had a very well designed study rejected by the MS Society. The UK was meant to partner with the Australians on this study so that they would have enough power to get a definitive answer. Despite being let down by the Brits, the Australians are going ahead with their study. Good on them. I suspect it won't give a definitive answer. Talk about shooting yourself in the foot guys not to mention potentially wasting money down under with a under-powered trial!

    Lets go through the priorities one by one.

    Which treatments are effective to slow, stop or reverse the accumulation of disability associated with MS? BIG PHARMA will answer this!

    How can MS be prevented? REALLY; how can you prevent something if you don't know the cause?

    Which treatments are effective for fatigue in people with MS? ASK BIG PHARMA TO TEST THEIR COMPOUNDS ON FATIGUE.

    How can people with MS be best supported to self-manage their condition? I AGREE A WORTHWHILE POINT; READING THIS BLOG AS A START.

    Does early treatment with aggressive disease modifying drugs improve the prognosis for people with MS? HASN'T THIS BEEN ANSWERED ALREADY? BEST TO SPEND YOUR MONEY GETTING THE NHS TO ACKNOWLEDGE THIS.

    Is Vitamin D supplementation an effective disease modifying treatment for MS? LET'S WAIT FOR THE AUSTRALIANS, CANADIANS AND DUTCH TO ANSWER THIS IT IS CHEAPER.

    Which treatments are effective to improve mobility for people with MS? DOESN@T FAMPRIDINE DO THIS ALREADY? THIS IS A PHARMA ISSUE.

    Which treatments are effective to improve cognition in people with MS? ANOTHER PHARMA ISSUE. THE MS SOCIETY DOES NOT HAVE THE BUDGET TO DEVELOP DRUGS. MAYBE YOU CAN ADOPT AND PROMOTE THE MS TRUST'S STAYING SMART PROGRAMME?

    Which treatments are effective for pain in people with MS? ANOTHER BIG PHARMA PROJECT. THE MS SOCIETY DOES NOT HAVE THE MONEY TO DEVELOP DRUGS.

    Is physiotherapy effective in reducing disability in people with MS? I AM SURPRISED THAT THIS MADE IT INTO THE TOP 10. NOW THAT IT HAS LET'S HOPE THE MS SOCIETY PUT THE MONEY WHERE THEIR MOUTH IS AND HAVE A PHYSIOTHERAPY CALL.

    So the two priorities that get my vote by default are SELF-MANAGEMENT AND PHYSIOTHERAPY with PREVENTION coming third.

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    1. Dear Disgruntled MS Researcher

      I have a good idea who you are.

      The point I want to make by referring to the black swan is that MS research is stuck in a rut and the MS Society should act as a catalyst. It should fund off-the-wall, blue sky, ideas. Research is a creative enterprise and relies on motivated, bright, people pushing the boundaries by working on new ideas. The other ingredient is serendipity. Most advances in science are unpredictable and come from outside the field. A consensus exercise like the JLA simply entrenches the current dogma and modus operandi. It reminds me of the maxim 'the camel is a horse designed by committee'. Let's hope I am wrong.

      Delete
    2. I wonder what the JLA exercise cost the MS Society? I suspect a lot of money; hard-earned money that could have been spent on funding a research project.

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    3. As we know the MS Society are regular visitors to this Blog, perhaps they would care to comment?

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    4. Prof G if you ask most people with an illness, they will more often than not ask for money to be spent on anything helps their own problem. I have sat in on hospital and PCT forums, where this is the case. I find this disturbing. I feel the disgruntled researcher has a point. I don't ask to be cured, I follow a healthy lifestyle and physiotherapy, I just want the next generation to be MS free.

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    5. Prof G, have you got any realistic ideas on how to get this paradigm shift debated/accepted/acted upon? I'm sure there are people more than willing to add their name/weight/energy to somehow get this message across. This post has similarities to your 'where are the activists - differences between MS and HIV' post a few months ago.

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    6. We need people power.....most cost effective may be lobbying central government to change...get the BPA in action, incentivise pharma and NHS to support some studies.

      Delete
    7. To address all the issues would need a massive budget, more I suspect than any one MS society has or wider. Likewise one pharma could not address the issue.

      I think I could give a fair answer to the "disgruntled scientists" point about vitamin D but the MS Society would need to comment on that and this is perhaps not the forum.

      However, as can be seen according to the Researcher there are three studies ongoing does each country need to answer the same country.
      How many worms studies are ongoing?

      Each country surely cannot just keep following scientific FADS/Dogma
      Sure they need to address the wants of their members and this is in part where this repetition comes, but they cannot do everything, unless Bill Gates becomes a supporter.

      The UK MS Society has been lamblasted for not really funding anything on CCSVI. The Canadian MS Society has put millions into CCSVI. Millions therefore that cannot be directed elsewhere. But it is not sensible to blow all you global budgets on the same thing.

      What next?

      I will put money on "Faecal (fecal) transplants", I bet it is on the table. Yep you will be asked to eat it.

      However, let's be warned as this could be done without the need for a neuro, just irrigation, anti-biotics and abit of pooh. I can see the clinics springing up now....

      Has anyone done this already? I bet they?
      Just get a few testimonials on youtube and off we go again..
      mark my word.

      In this case above I am not joking

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    8. Faecal transplants what do you mean?

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    9. Fecal transplants are for IBS, do you see this as potentially useful for MS?

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    10. The microbiome is everywhere and not just for bowel problems, trust me there are people out there up to their elbows in it. Rats fed on human stools...em

      Is this useful for MS if I say yes do I start a fad? if I say no do I get "sent to Coventry" for heresy.

      Delete
    11. http://en.wikipedia.org/wiki/Send_to_Coventry

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    12. If I wanted to make money from getting people to eat poo, I'd go after the weight-loss crowd, not MSers. I'm guessing we'll start seeing the miracle diet ads in the next week or two ...

      http://www.nytimes.com/2013/09/06/health/gut-bacteria-from-thin-humans-can-slim-mice-down.html?pagewanted=all&_r=0

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    13. Does a mechanics turn away someone who wants a light bulb or window wiper changed, difference is a mechanic may not charge the labour costs. Punters are punters.

      Yes you need gut flora for digestion and without it there are problems,

      Delete
  12. I believe we have found the cause of MS already; EBV. What we need to do is test whether preventing people getting EBV or infectious mononucleosis or glandular fever prevents MS and whether suppressing EBV is an effective treatment for MS.

    By the way one of the most effective class of drugs in development for MS are the anti-CD20 (and by inference anti-CD19) monoclonal antibodies and they are potent anti-EBV agents. Are we missing something here?

    Trying to get our anti-EBV trial funded has been difficult, but we will keep trying. Clearly there is no space on the MS Society's list of priorities for this strategy.

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    1. Although I do believe EPV is probably the trigger that initiates an autoimmune attack in MS I do not believe it directly attacks the meylin sheath or its related cells as you have sugessted in previous posts. If your assumption is correct then Tsybari should have zero effect since its primary role is to prevent lymphocytes from crossing the BBB. If EBV infected b cells reside in the CNS the virus would do its damage regardless of a BBB breach.

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  13. I participated in the MSS - JLA debate as neurologist and MSologist. A very interesting process that I enjoyed. However when I made the case for the importance of 'cause' research and the importance of infections, it wasn't a winner!

    Bruno Gran

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    Replies
    1. So I'm not the only one who thinks that prevention is better than cure. Can't understand the JLA. Maybe, our donations should be sent directly to the institutions where we are confident our money is being spent wisely.

      Delete
  14. Wow! what a response. Perhaps we shouldn't just jump in and bash the JLA and MS Society so quickly. Like all new methods this is a process not appreciated or understood by all and it needs time to provide the evidence that this process is useful. There were many more extremely important 'priorities' short listed which did not make it into the 'top 10' but every question submitted is published on UK DUETS and has not been lost to the research community. The MS Society has also pointed out that these 'top 10' will influence their funding direction but by no means exclude topics not listed. Out of over 1000 questions submitted these were whittled down to just 10 through a previously described and transparent process.

    I would also like to point out that the 'young MS researcher' was not 'laughed off', the final workshop was conducted in a very 'grown up' manner with no criticism of individuals allowed. The majority of participants considered it to be an unusual but rewarding and valuable process.

    An earlier post mentioned some of the priorities should be answered by big pharma. This could only be so if big pharma suddenly decide to work together. How likely is that to happen? Looking at comparisons between the effects of existing treatments on things like mobility and cognitive function will be very difficult to answer. Does this mean the question should not be posed?

    Some of the questions can be interpreted in various ways. For example 'How can MS be prevented' could well be seen as a causation question. I would also point out that questions are worded according to how they were originally submitted and most are a combination of many similar questions. The priority about early therapy with aggressive drugs is just that - use of aggressive treatments- i.e those which have great promise but significant side effects, early on in disease. It is not referring to aggressive treatment early on in the disease with the drugs with few side effects. This is clearly a controversial issue which was debated at MS Frontiers and needs to be addressed.

    The JLA exclude pure researchers and pharma for the very reason that they are already significant influencers of the direction of research. Here priority is given to consultancy of a wide representation of those people, carers, people with MS, clinicians, nurses, physiotherapists, complementary therapists, fundraisers, volunteers... affected daily by MS in some way, these people are without financial or personal research 'pet' agendas.

    The JLA priority setting partnership is a carefully managed and inexpensive process using mostly volunteers. (I do not have a personal conflict of interest here!)

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    1. JLA stands for political correctness. Excluding basic researchers and the drug industry from the process is simply dumb and is the reason why the MS Society has a list of priorities that will result in mediocre outputs.

      Delete
    2. "'grown up' manner with no criticism of individuals allowed"

      The problem identified in a sentence; the JLA process clearly lacked the necessary criticism and debate.

      Delete
    3. To Disillusioned and Bored.;..

      Get yourself down to Basildon (tonight) to be INSPIRED.

      Delete

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