Friday, 5 August 2016

#ThinkHand: spreading hope

Oh no ProfG, not another MS campaign! #ThinkHand #PoliticalSpeak

"I was criticised this week for having launched yet another MS campaign, #ThinkHand, without defining the objectives of what we are trying to achieve with the campaign. This campaign is really quite long in the tooth and elements of it have been appearing on this blog for several years, but more on that later. What you have to realise is that our blog is really now an MS rag, therefore it is entirely appropriate to be a vehicle for MS-related campaigns. I am also sure that you the reader can engage with multiple simultaneous campaigns at once."

"Because we are focusing on hand function this month does mean that our Treat-2-Target of NEDA, Brain Health, Essential Off-Label DMTsCharcot Project (preventing MS), Digesting Science (children of pwMS education), ClinicSpeak (MSer education and self-management), NeuroSpeak (healthcare professional education) and Holistic Management of MS (improving MS services) campaigns should be abandoned. In reality these are all complementary; all we are trying to do is improve the lives of people with MS and their families."


"As always with any campaign on our blog there is not one but several objectives to the campaign. SPREAD-HOPE is the acronym that captures the objectives of #ThinkHand succinctly."

SPREAD

S is for Scientific: to establish the length-dependent axonopathy and therapeutic lag hypotheses as the main theoretical construct for explaining progressive MS and for designing progressive MS clinical trials.

P is for Political: to create a lobby of relevant stakeholders to push the #ThinkHand agenda.

R is for Regulator: to convince the regulators that hand function is very important to people with MS and that they should accept the 9-HPT as the primary outcome in phase 3 progressive MS trials.

E is for Economic: to show that loss of hand function has a greater economic impact to people with MS, and society, than loss of lower limb function.

A is for Awareness: to increase awareness in the MS community and the general public about how important upper limb (hand and arm) function is for people with MS. It is arguably orders of magnitude more important than lower limb function.

D is for Debunk: to debunk the dogma that once a person with MS has lost lower limb function that nothing can be done to stop them from progressing further. This has real-life implications for pwMS, for example in the UK we are meant to stop DMTs in pwMS who have lost lower limb function and have started using a wheelchair. What is the evidence to support this stopping criterion? 


HOPE

H is for Hand: to focus on hand function as an outcome measure in progressive clinical trials and to develop a new and more appropriate patient-related outcome measure (PROM) that captures elements of hand function that are important to pwMS
. The current PROMs our out of date and not necessarily MS-relevant. 

O is for Optimism: to give people with progressive MS hope; simply because you have progressive MS does not mean that nothing can be done for you. Emerging evidence suggests we have been doing our progressive clinical trials incorrectly. If we had used upper-limb function as the primary outcome in earlier trials we would have had a licensed DMT for you years ago.

P is for Promise: to finally deliver on our PROMISE 2010 programme and deliver effective treatments for people with progressive MS. This means designing, getting funded and doing our own clinical trial focusing on people with more advanced MS; yes, we are proposing including wheelchair users in our trial. We also want pharma to take up the challenge and revisit progressive MS and to start doing clinical trials in more advanced MS using upper limb function, in particular hand function, as the primary outcome measure.

E is for EDSS: to get neurologists to remove and throw away their ‘EDSS blinkers’ and to stop looking at MS-related disability as defined by the EDSS. The EDSS is really not fit for purpose and we really should get rid of it, in particular as an outcome measure in progressive MS trials.

"I sincerely hope SPREAD-HOPE will allow you to buy into the objectives of our #ThinkHand campaign!"

18 comments:

  1. As a example is the Ascend trial based on abstracts published at
    the EDSS failed 48% progressed in placebo and 44% progressed with natalizumab. Trial is a failure and no treatment option for SPMS.

    However it hand function was important placebo 25% progressed on placebo and 13% on natalizumab p=0.0012. Success and treatment option for SPMS

    Will it be cost effective that is another issue but it says aspects of SPMS is modifiable with immunomodulating DMT and by slowing loss of hand function it those people with SPMS it will given them independence for longer. So do something suboptimal as we do need neuroprotection in there as well or do nothing and progression continues.
    This is the choice.

    We can wait for pharma to do this, but will Biogen be brave enough to do ASCEND II, or we can do it now and DrK will tell you how. However is actively a pre-requisit or not this is an important question and are people with SPMS really never active or can we just not see it with MRI

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  2. Prof G what about your #OffLabel campaign? Have you stopped that one as well?

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    1. Apologies, I have added the Off-Label campaign to the list. This is ongoing and has several strings to it as well. I have to admit that we need help on this front. I may call in the volunteers.

      Please note we are recruiting interns and volunteers to help us at Barts-MS.

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    2. Re interns and volunteers : I would if I lived near Barts MS. I'm changing my MRes to researching MS. I spend so much time researching MS as I have MS, I thought why not. I've got a few ideas that are lacking in research.

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    3. If we can help in any way let us know

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  3. I'm not sure whether this fits here, in your EAE benefits of exercise post or somewhere else completely. Anyway, I wanted to point up the benefits of passive stretching on blood sugar levels, heart rate and energy expenditure. This means that PWMS who have lost the ability to exercise their own legs can get great benefit from someone else exercising their legs for them. Maybe this is already widely known - it was news to me. The link to the work on this is here:
    http://www.bbc.co.uk/programmes/articles/5vVy8G7R5Q9gx4MgZNSf1XW/could-having-my-muscles-stretched-have-health-benefits

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  4. Prof G,

    I'm suffering from campaign fatigue. All these activities are laudable, but we really need some treatments - neuroprotectants or repair agents. Promise 2010 was 6 years ago. When does it become Broken Promise 2010? When I get to the stage where I start feeling grateful for still being able to wriggle my index finger, I should be put down. Any thoughts on when any of tbeset activities will result in real treatments?

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    1. Re: "neuroprotectants or repair agents..."

      We have them already; if you switch off inflammation you allow the brain and spinal cord to repair itself. The ability to repair depends on the amount of pre-existing damage. I orginally thought this was limited to early MS, but we are even seeing it in more advanced MS.

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    2. Re: "Promise 2010 was 6 years ago..."

      I know we have already completed a postive phenytoin neuroprotective study and are still running the PROXIMUS and SMART studies. All of these studies were done using insights from our work on PROMISE 2010. In addition, there are several other neuroprotection trials running at present. You have already heard from Biogen that their second anti-LINGO-1 study, targeting remyelination, was negative. However, Biogen hope there will still be some interesting data hidden in the study outcomes. I think these results will be presented at ECTRIMS.

      Please note that science is a slow process.

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    3. What was the promise?
      I think we can hold our head up with regard this one bit we needed promise 2015 or promise 2020 to follow on, I think the UK have made a real effort to push the neuroprotective agenda on since then, but things stall once clinical studies start.

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    4. MS,

      Promise 2010 started fund raising started fundraising in 2007. The work I was interested in was nervous system repair and protection. I gave my dollars on the words used by the NMSS 'rolling back the ravages of MS'. Here is the link:

      https://secure.nationalmssociety.org/site/PageServer?pagename=HOM_RES_research_targetedrepair

      9 years on there is no therapy to repair the nervous system or to protect it. It is another example of the MS societies making big promises to draw in the money, MS research teams putting in the grant applications etc. etc. Until such therapies are available for my doctor to prescribe, Promise 2010 has not delivered. Of course we now have the Progressive MS Alliance. We seem to go from one initiative to the next. Please note: this is not a criticism of Team G but the system. There is little urgency, or risk taking and the bureaucratic hurdles mean it is near impossible for researchers to get a promising cheap therapy to patients. You Brain Health initiative and push for early effective treatment are excellent.

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  5. Prof G it will never be cost-effective to treat patients with MS in wheelchairs. The issue is that by the time they are in wheelchairs that usually cognitively impaired and umemployed. It is better to focus your attention on early treatment. I wouldn't be surprised that delaying the rate of progression in patients in wheelchairs will increase costs as it will extend life expectancy.

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    1. Re; "I wouldn't be surprised that delaying the rate of progression in patients in wheelchairs will increase costs as it will extend life expectancy."

      Have you got a heart. Medicine is also about relieving suffering and improving quality of life. I have numerous patients who have lost lower limb function, and some who have even lost upper limb function, and have a very good quality of life. You need to be careful projecting your worldview of life onto people with MS. It is clear to me pwMS become more disabled they adjust and reset their worldviews.

      I simply can't buy into your position. In addition, how do you know that it is not cost-effective? We have been looking at the evidence on this and we can't find any. Which is why one of objectives is to study this in more detail.

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    2. I strongly agree with Dr G here. It is simply not true to say that by the time people are in wheelchairs they are "usually cognitively impaired". This is blatant and obnoxious prejudice against disabled people. FYI, Anonymous, I use a wheelchair and have an IQ of 154 and a research job.
      Even if it were true, that many PWMS who are in wheelchairs are cognitively impaired, that would still not be a reason for thinking that helping them to have the best quality of life possible is not a worthwhile goal.
      Let's hope, Anonymous, that you don't end as a wheelchair user, given your beliefs about the value of the lives of wheelchair users.

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    3. "Prof G it will never be cost-effective to treat patients with MS in wheelchairs".

      Wake up and smell the roses people read december 25th 2015 post.

      Subcutaneous cladribine costs £165 per 10mg in the UK in the US this can be from $32 to $120 and in our lab digest the I saw a person in the wheelchair who got six doses and went from new 28 lesions on their scan to no new lesions.

      Is this regression to the mean and would those lesions naturally disappear, maybe they would but if you do nothing what is going to happen?

      If your neuro is willing to try something rather than nothing then £1,600-£2,000 is not doing to break the bank. Is your neuro willing to do something off label (maybe not) or do they want to wait 7 years for pharma to do a trial and it will probably not be cost-effective in the UK unless someone does their sums.

      Ideally we can do a trial to get the evidence to convince people that it is worth treating people in wheelchairs. Can we get support for CHARIOT?

      Look through the blog for details....


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    4. Is this approach science fictio?n...yes because we do not have the knowledge to back it up completely the way to get that knowledge is to use it.

      Yo say it has risks...of course it does but balance these against doing nothing.

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    5. Interesting the post was Anonymous.

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    6. Who would want to be associated with such a negative view?

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