The UK Rituximab Trial: A Study in a Hurry

August 12, 2013

by Sasha

Photo: fussy onion/Flickr

London: site of the proposed UK Rituximab trial
Photo by fussy onion/Flickr

On June 6, the Norwegian Medical Research Council agreed to give a large enough grant to the Haukeland Rituximab trial for the study to begin. Later that day, the charity Invest in ME announced that they were initiating a UK Rituximab trial. It seemed to come out of nowhere. There were no details – cost, size, location, research team – but there didn’t need to be. The ME community started throwing money at the trial and trusted Invest in ME when it said it could be done.

This trust was surely based on the reputation that Invest in ME has established for itself in its few short years of existence. The newest UK ME charity, run entirely by volunteers, it set up in 2006 an international annual conference on biomedical research into ME – not CFS, but WHO-defined ME – that is now attended by most of the major research groups from all over the world and is a focus for information-sharing and collaboration-building among ME researchers.

At the most recent conference, Drs Fluge and Mella presented their follow-up study of a new Rituximab dosing schedule on the control patients from their Norwegian pilot study. The results are still embargoed until publication but apparently positive. Drs Kogelnik and Scheibenbogen, who are planning US and German Rituximab studies, respectively, were also there. No-one could doubt Invest in ME’s sources of expertise and support in setting up a trial.

The community’s trust quickly paid off as the charity was able to make public a major coup. Jonathan Edwards, Emeritus Professor of Connective Tissue Medicine at University College London (UCL), had agreed to advise Invest in ME on all aspects of running a Rituximab trial (read his statement on the trial here). It was Professor Edwards who proposed in 1999 that self-perpetuating B lymphocytes drive autoimmune disease. He went on in 2004 to conduct the trials of Rituximab for rheumatoid arthritis that established the role of B cell depletion in treating autoimmune disorders, the same mechanism that Drs Fluge and Mella believe is operating in the treatment of ME with Rituximab.

Fresh from that victory, Invest in ME went on to announce their plans to have the trial conducted by an expert team led by Dr Jo Cambridge at UCL, with the intention of including other London sites and other collaborating researchers such as Dr Amalok Bansal, an immunologist with a research interest in B-cell abnormalities in ME.

Further details were announced. To the surprise of many, the proposed trial would not be of the magnitude of the 140-patient Haukeland confirmatory study but, with about 30 patients, would be roughly the same size as the Norwegian pilot trial. Professor Edwards explained that a small trial is appropriate when a large effect is expected, as indicated by the Haukeland pilot trial in which 67% of patients treated with Rituximab improved, compared to 13% of controls. A successful small trial would make a strong case for further studies that themselves may not need to be big. Several independent confirmatory trials will be needed if Rituximab is to be licensed for ME.

The small size of the trial makes for a relatively low-cost project. Details of the study protocol are still being hammered out but the current estimate is £350,000 ($540,000; €410,000). This is potentially a very achievable sum to raise within a short timeframe.

The UK has several advantages here. It has several large ME charities and, in a very welcome move, the ME Association has pledged nearly £60,000 to the trial, subject to its normal independent peer-review procedure. Action for ME have announced that their board of directors will be considering collaboration on the trial; the Irish ME Trust has pledged £1,000, setting a good example for smaller charities; and there are other UK charities that might also be expected to donate. Working together with Invest in ME, who have more support pledged, a very substantial chunk of that £350,000 could be found in short order.

Also, Invest in ME has many supporters and have already racked up about £20,000 in donations even though there has been no big launch or fanfare for the study. The Medical Research Council, thanks to years of pressure, is now finally funding biomedical ME research and might look favourably on this trial, if applied to.

And of course, Maria Gjerpe’s MEandYou Foundation raised something close to the total sum needed for the UK trial in only three months in a country with a tenth of the population of the UK. Her positive, fun, feelgood campaign made people want to join in and expanded the support base well beyond the ME community and into the general public. She raised awareness so effectively that the entire Norwegian football Champions’ League – the healthiest of the healthy – aligned themselves with us, some of the most stigmatised of the sick, and donated signed shirts for auction. We in the UK need to follow her example, work together, be ambassadors for our community, and welcome people in.

Not all elements of the trial are yet in place and Invest in ME, like MEandYou, have sensibly been transparent about what happens if, for some reason, the trial does not go forward. In that case, donations to their Rituximab fund will go into their general Biomedical Research Fund, where there’s no doubt they’ll do some very good things with it. But many – probably most of us – feel the same urgency as Invest in ME to get the money raised and in place, so that things can proceed as soon as possible, and with the £20,000 donated to Invest in ME and the £60,000 pledged by the ME Association, we’re already nearly a quarter of the way there. What can the rest of us do to help?

  • Donate! There are now two Rituximab funds raising money for this trial: Invest in ME’s fund and the ME Association’s fund (scroll down for donation instructions), and we can probably expect each collaborating ME charity to set up its own fund for the trial as they join in. UK taxpayers should Gift Aid their donations.
  • Join The Matrix (long black coat optional): be one of 100 people to make a pledge to raise £1,000.
  • Fundraise: people are doing all sorts of things to fundraise, from selling crafts to sponsored walks. Think about what you can do.
  • Raise awareness of the trial. Many people in the UK who have ME don’t belong to any of the charities and won’t know that there’s a trial to donate to or raise money for. Help them find out.

We’re very fortunate that Professor Edwards has joined the forums here on Phoenix Rising. He has already been giving fascinating answers to our many questions (on this thread, starting here) and has generously agreed to answer some more about the trial and how Rituximab might make sense for ME. If you have such a question, please post it in the comments section. I will collate the questions and present them to Professor Edwards for an interview article with him to appear later.

In the meantime, let’s get cracking. We can have a superb trial in the UK, one that will benefit patients all over the world – let’s get on with making it happen!

Remember that Phoenix Rising costs money to run and needs your donations to support it. Please hit the button below and donate!

Further resources

Invest in ME’s Rituximab trial website

Discover magazine’s April 2013 article on Rituximab, including comments by Professor Edwards

Fluge and Mella’s 2011 PLoSOne pilot trial of Rituximab

 

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54 comments

{ 54 comments… read them below or add one }

Nielk August 12, 2013 at 7:07 pm

Thanks Sasha for this article. It is real exciting news!

Desdinova August 12, 2013 at 9:22 pm

That's wonderful news to end my hectic day. Thanks Sasha I needed that.

Waverunner August 13, 2013 at 12:45 am

Good news.

lilpink August 14, 2013 at 1:44 am

Mmm MEA have pledged that money to be ring fenced for *A* Rituxan trial…but as far as I know they haven't offered it to 'THE' trial ie: THE Invest in ME trial.

Simon August 14, 2013 at 2:22 am

Thanks for a great summary of what's happening with Rituximab, I've found it all very confusing.

I still don't really understand why the study is so small. I know there is extensive discussion of this on the main thread – which I've only dipped into – and Jonathan Edwards seems to be saying that a small study can be more tightly controlled than a large multi-centre one. I can see the logic that a smaller replication study would have been a better place to start, but given that the large study is already largely funded and plans are well-developed for it, I do wonder how much 'value' a smaller study will add in practice. Any pointers on this appreciated.

Sasha August 14, 2013 at 2:44 am
lilpink

Mmm MEA have pledged that money to be ring fenced for *A* Rituxan trial…but as far as I know they haven't offered it to 'THE' trial ie: THE Invest in ME trial.

Hi lilpink – Charles Shepherd clarified on the MEA Facebook page that this is the same trial, i.e. the one initiated by Invest in ME, for example in this statement:

https://www.facebook.com/permalink….comment_id=5247930&offset=0&total_comments=77​
Yes, this is the trial that Professor Jo Edwards is advising on​
Yes, this is the trial that Invest in ME are fundraising for​
Yes, this is the trial that the MEA is very happy to help fund (we have around £60,000 raised so far) – provided it passes the peer review procedures referred to in my 10 point statement and the MEA website statement​

So, a superb achievement by IiME in initiating the trial, an excellent example set by the MEA early in the game for other UK charities who might donate and speed up this whole process. If the charities work together, we could have very substantial funds for this within a few months. I don't know if there's any scope for work to begin before full funding is obtained as has been the case in the Norwegian trial (it's not yet fully funded) but clearly, the sooner we get big money together, the sooner this is going to happen.

Sasha August 14, 2013 at 2:46 am
Simon

Thanks for a great summary of what's happening with Rituximab, I've found it all very confusing.

I still don't really understand why the study is so small. I know there is extensive discussion of this on the main thread – which I've only dipped into – and Joanathan Edwards seems to be saying that a small study can be more tightly controlled than a large multi-centre one. I can see the logic that a smaller replication study would have been a better place to start, but given that the large study is already largely funded and plans are well-developed for it, I do wonder how much 'value' a smaller study will add in practice. Any pointers on this appreicaited.

Thanks, Simon – one for Jonathan Edwards there!

Oh, oops – actually that's a good one for the interview, I'll bung that question on the list.

Firestormm August 14, 2013 at 2:50 am
lilpink

Mmm MEA have pledged that money to be ring fenced for *A* Rituxan trial…but as far as I know they haven't offered it to 'THE' trial ie: THE Invest in ME trial.

Maybe because there is no trial?

At least at present. Once something has actually been proposed by UCL, and if a Trial recommendation or other form of research (see Prof. Edwards' thread and comments from him), is outlined; then the other charities might – once peer reviewed – invest with IiME or directly with UCL.

You have to remember that the other charities need to do right by their own members – the ones who actually entrusted the money to them. There are rules they need to follow.

Currently, IiME have said they would effectively 'own' all funds donated to their Rituximab Fund and if a Trial did not proceed they would then reinvest within their own organisation's 'biomedical' research programme.

Such a thing is probably not acceptable to the other charities who in such an event might want the money back.

I sincerely hope it can all move forward and become clearer when we hear something concrete from UCL. I suspect we are talking months rather than weeks – but maybe Professor Edwards will reveal more or Dr Cambridge once he returns from Norway.

Heart Face August 14, 2013 at 2:56 am

Great write up Sasha and very accurate – thank you! Just one comment to make. If Action for ME do make a donation, there will be NO collaboration. This is my opinion. Action for ME and a few other charities have already joined A collaboration of which Invest in ME will have nothing to do with since the likes of Simon "I didn't say that" Wessely and Esther "only poor people who have been abused as children get ME" Crawley – are involved. I should think that as with the ME association, a donation will need to be made and then Invest in ME can be left to do what they do best: what many of the patients need, and what many of the patients want.

Sasha August 14, 2013 at 3:02 am
Firestormm

Once something has actually been proposed by UCL, and if a Trial recommendation or other form of research (see Prof. Edwards' thread and comments from him), is outlined; then the other charities might – once peer reviewed – invest.

You have to remember that the other charities need to do right by their own members – the ones who actually entrusted the money to them. There are rules they need to follow.

Currently, IiME have said they would effectively 'own' all funds donated to their Rituximab Fund and if a Trial did not proceed they would then reinvest within their own organisation. Such a thing may not be acceptable to the other charities who in such an event might want the money back.

I agree that no charity is likely to want to donate to another charity – I've never seen research funding work that way and in fact there's no need for it or advantage to it. In joint funding, charities donate via the research team's parent body (some bit of UCL in this case, probably). As you say, if other charities all donated to the IiME Rituximab fund and for some reason the trial doesn't come off (and it's only responsible to have a fallback plan for that), Invest in ME would end up holding tens of thousands of pounds that the original donors had given to the original charities and that would hardly be fair to those donors. The trustees of those charities might be in trouble in such a case.

I don't think we'll see donations at this point – in a sense, even IiME haven't donated their own money to the trial, unless they've already paid money over to UCL. They're quite correctly ringfencing it in their dedicated Rituximab fund – but someone please correct me if I'm wrong. The normal thing to do at this stage, when there's no protocol in place ready for submission to charities' peer grant-giving processes, is to ringfence it, and that ringfencing is very, very welcome indeed. The MEA have made it clear that they're keen to fund this, subject (responsibly) to peer review, and I expect other charities will be too. In the meantime, ringfencing funds gives a big signal to all donors that this is a viable project that they should donate to. It will also give a big signal to the MRC.

Sasha August 14, 2013 at 3:28 am
Heart Face

Great write up Sasha and very accurate – thank you! Just one comment to make. If Action for ME do make a donation, there will be NO collaboration. This is my opinion. Action for ME and a few other charities have already joined A collaboration of which Invest in ME will have nothing to do with since the likes of Simon "I didn't say that" Wessely and Esther "only poor people who have been abused as children get ME" Crawley – are involved. I should think that as with the ME association, a donation will need to be made and then Invest in ME can be left to do what they do best: what many of the patients need, and what many of the patients want.

Thanks for the kind comments, Heart Face. I think we cross-posted and my comments on the post below yours address this issue of why other charities wouldn't be expected to donate directly to IiME for this project, but rather directly to the trial (i.e. the appropriate bit of UCL).

If AfME or any other charity ringfence funds for this, and donate to the trial (i.e. to the appropriate bit of UCL), that will be money direct to the trial. The only 'collaboration' going on is to collaboratively fund and whatever one thinks of any particular charity, it's all cash and it's going to speed up funding of the trial.

We've got to put the trial first in this. There's some difficult history in the UK, of course, but it would be a terrible shame to let that history delay or destroy our chances of moving forward quickly with the trial. If the results of the trial confirm the Haukeland findings and establish ME firmly in the public and medical mind as an immune condition treatable by an immune drug, everything changes for us and the psychosocial model gets left in the dust. Our disease will be validated as an immune disease, the research funding coffers will open, and our world will change. We've got to fund the trial as quickly as we can.

lilpink August 14, 2013 at 3:58 am
Sasha
lilpink

Mmm MEA have pledged that money to be ring fenced for *A* Rituxan trial…but as far as I know they haven't offered it to 'THE' trial ie: THE Invest in ME trial.

Hi lilpink – Charles Shepherd clarified on the MEA Facebook page that this is the same trial, i.e. the one initiated by Invest in ME, for example in this statement:

https://www.facebook.com/permalink….comment_id=5247930&offset=0&total_comments=77​
Yes, this is the trial that Professor Jo Edwards is advising on​
Yes, this is the trial that Invest in ME are fundraising for​
Yes, this is the trial that the MEA is very happy to help fund (we have around £60,000 raised so far) – provided it passes the peer review procedures referred to in my 10 point statement and the MEA website statement​

So, a superb achievement by IiME in initiating the trial, an excellent example set by the MEA early in the game for other UK charities who might donate and speed up this whole process. If the charities work together, we could have very substantial funds for this within a few months. I don't know if there's any scope for work to begin before full funding is obtained as has been the case in the Norwegian trial (it's not yet fully funded) but clearly, the sooner we get big money together, the sooner this is going to happen.

Mmmm but he still hasn't said for sure it's going to the Invest initiative. I think people need to be aware of that and if they want to donate to the Jonathan Edwards/ Invest in ME fund they must do it directly to Invest in ME and not presume that their money will get to this particular research initiative if given to the MEA. The MEA have been curiously unclear about their intentions. (I'm au fait wit the commentaries by CS et al on the MEA FB page etc).

lilpink August 14, 2013 at 4:01 am
Firestormm
lilpink

Mmm MEA have pledged that money to be ring fenced for *A* Rituxan trial…but as far as I know they haven't offered it to 'THE' trial ie: THE Invest in ME trial.

Maybe because there is no trial?

At least at present. Once something has actually been proposed by UCL, and if a Trial recommendation or other form of research (see Prof. Edwards' thread and comments from him), is outlined; then the other charities might – once peer reviewed – invest with IiME or directly with UCL.

You have to remember that the other charities need to do right by their own members – the ones who actually entrusted the money to them. There are rules they need to follow.

Currently, IiME have said they would effectively 'own' all funds donated to their Rituximab Fund and if a Trial did not proceed they would then reinvest within their own organisation's 'biomedical' research programme.

Such a thing is probably not acceptable to the other charities who in such an event might want the money back.

I sincerely hope it can all move forward and become clearer when we hear something concrete from UCL. I suspect we are talking months rather than weeks – but maybe Professor Edwards will reveal more or Dr Cambridge once he returns from Norway.

I'm glad you've made it clear Firestormm that the MEA has not actually promised this money to Invest in ME for the Invest in ME trial. It does need to be made clear. I think everyone who wants to move this forward must ensure that Invest in ME are able to reach the total needed to start the process as quickly as possible without interference from outside influences which may slow things down. Thus it would seem reasonable to donate directly to Invest in ME where the mandate is clear and unambiguous.

lilpink August 14, 2013 at 4:04 am

Here's the link to ensure this trial (with Jonathan Edwards on board) goes ahead. Please donate..it's in all our interests to do so: http://ldifme.org/donate/

Sasha August 14, 2013 at 4:35 am
lilpink

Mmmm but he still hasn't said for sure it's going to the Invest initiative. I think people need to be aware of that and if they want to donate to the Jonathan Edwards/ Invest in ME fund they must do it directly to Invest in ME and not presume that their money will get to this particular research initiative if given to the MEA. The MEA have been curiously unclear about their intentions. (I'm au fait wit the commentaries by CS et al on the MEA FB page etc).

Hi lilpink – I honestly don't see any room for confusion there, given that statement from Charles Shepherd. The only circumstances under which money donated to the MEA's Rituximab fund wouldn't go to the Jonathan Edwards study that IiME initiated would be if Prof Edwards's team produced a protocol that failed the MEA's peer review process and, given the MEA's strongly expressed wish to have the trial happen, and the expertise of Prof. Edwards and his willingness to take peer review comments on board, I think the chances of that are extremely remote.

Here's Charles Shepherd again on this topic:

https://www.facebook.com/permalink….comment_id=5250558&offset=0&total_comments=77​
I can assure you, as I have assured Professor Edwards on the phone this week, that the MEA wants to speed up the process of getting this clinical trial moving at UCL​
That is why we have (so far) put together a package of almost £60,000 to help fund a clinical trial of Rituximab​
As far as I am aware this is the largest contribution from any ME/CFS research funding charity at present​
As Professr Edwards has indicated in the above posting he is very happy to take on board suggestions regarding the protocol – which is now being prepared at UCL​
He is also very happy to approach the MRC​
This is all part of the scientific process – as is peer review for a potential funder whereby a finalised research proposal is critiqued by other experts in the field ​
Peer review will not hold up the process of getting the Rituximab study moving – the delay will almost certainly come from the time it takes to raise around £400,000​
And although I'm sure a good ethics committee will have questions to ask (and I'm familiar with ethics at UCL from our work with the ME Biobank) I don't think this will be a factor in the delay either​
Yes, it all boils down to funding – which is why I will say yet again that there ought to be a joint charity fundraising effort to get this trial moving​

It seems to me that all roads lead to Rome on this.

It's a huge achievement that IiME have pulled off in initiating this trial. I'm extremely grateful to them for all the hard work that must have gone into that – they can be very proud indeed of what they've done. But we're into a new stage now and IiME will need the help of other charities to get this done quickly. It's a huge compliment to IiME that the MEA want to help fund the trial that they've initiated. Whatever IiME can do to encourage more charities to do the same and set up their own funds that their own supporters can donate to, the better.

Bob August 14, 2013 at 5:10 am
Simon

I still don't really understand why the study is so small. I know there is extensive discussion of this on the main thread – which I've only dipped into – and Jonathan Edwards seems to be saying that a small study can be more tightly controlled than a large multi-centre one. I can see the logic that a smaller replication study would have been a better place to start, but given that the large study is already largely funded and plans are well-developed for it, I do wonder how much 'value' a smaller study will add in practice. Any pointers on this appreciated.

Hi Simon, Jonathan Edwards addresses these questions here:
http://forums.phoenixrising.me/inde…uximab-trial-30-july.24499/page-8#post-377254

lilpink August 14, 2013 at 5:10 am
Sasha
lilpink

Mmmm but he still hasn't said for sure it's going to the Invest initiative. I think people need to be aware of that and if they want to donate to the Jonathan Edwards/ Invest in ME fund they must do it directly to Invest in ME and not presume that their money will get to this particular research initiative if given to the MEA. The MEA have been curiously unclear about their intentions. (I'm au fait wit the commentaries by CS et al on the MEA FB page etc).

Hi lilpink – I honestly don't see any room for confusion there, given that statement from Charles Shepherd. The only circumstances under which money donated to the MEA's Rituximab fund wouldn't go to the Jonathan Edwards study that IiME initiated would be if Prof Edwards's team produced a protocol that failed the MEA's peer review process and, given the MEA's strongly expressed wish to have the trial happen, and the expertise of Prof. Edwards and his willingness to take peer review comments on board, I think the chances of that are extremely remote.

Here's Charles Shepherd again on this topic:

https://www.facebook.com/permalink….comment_id=5250558&offset=0&total_comments=77​
I can assure you, as I have assured Professor Edwards on the phone this week, that the MEA wants to speed up the process of getting this clinical trial moving at UCL​
That is why we have (so far) put together a package of almost £60,000 to help fund a clinical trial of Rituximab​
As far as I am aware this is the largest contribution from any ME/CFS research funding charity at present​
As Professr Edwards has indicated in the above posting he is very happy to take on board suggestions regarding the protocol – which is now being prepared at UCL​
He is also very happy to approach the MRC​
This is all part of the scientific process – as is peer review for a potential funder whereby a finalised research proposal is critiqued by other experts in the field ​
Peer review will not hold up the process of getting the Rituximab study moving – the delay will almost certainly come from the time it takes to raise around £400,000​
And although I'm sure a good ethics committee will have questions to ask (and I'm familiar with ethics at UCL from our work with the ME Biobank) I don't think this will be a factor in the delay either​
Yes, it all boils down to funding – which is why I will say yet again that there ought to be a joint charity fundraising effort to get this trial moving​

It seems to me that all roads lead to Rome on this.

It's a huge achievement that IiME have pulled off in initiating this trial. I'm extremely grateful to them for all the hard work that must have gone into that – they can be very proud indeed of what they've done. But we're into a new stage now and IiME will need the help of other charities to get this done quickly. It's a huge compliment to IiME that the MEA want to help fund the trial that they've initiated. Whatever IiME can do to encourage more charities to do the same and set up their own funds that their own supporters can donate to, the better.

Hi Sasha, I think you may be a little naive about Uk ME politics. This is clearly a manoeuvring by MEA to try to take the reins on this project (imo and many others)..hence why they make proviso after proviso. It's worded in such a way to sound reasonable to most folks, but you can't get any sort of firm reply from the MEA to the question 'so are you going to give your ringfenced money to the Invest in ME initiative or not'? If you have have seen a 'yes' or 'no' to this I'd be grateful for the link.

A "joint charity fundraising effort to get this trial moving" would be ideal if it weren't for the concerns over the motives and machinations of the UKRC to which most of the other charities now belong. It would be nice to see the MEA *pledge* the money they have ringfenced (which would not, I believe, preclude them from changing their plans if the trial parameters were not to their liking, but would show true faith in this initiative) ..then, and only then, might many of us who have a better understanding of the social nuances that pervade UK ME interactions accept their affirmations in good faith.

Bob August 14, 2013 at 5:20 am
lilpink

I'm glad you've made it clear Firestormm that the MEA has not actually promised this money to Invest in ME for the Invest in ME trial. It does need to be made clear. I think everyone who wants to move this forward must ensure that Invest in ME are able to reach the total needed to start the process as quickly as possible without interference from outside influences which may slow things down. Thus it would seem reasonable to donate directly to Invest in ME where the mandate is clear and unambiguous.

lilpink

Hi Sasha, I think you may be a little naive about Uk ME politics. This is clearly a manoeuvring by MEA to try to take the reins on this project (imo and many others)..hence why they make proviso after proviso. It's worded in such a way to sound reasonable to most folks, but you can't get any sort of firm reply from the MEA to the question 'so are you going to give your ringfenced money to the Invest in ME initiative or not'?

It's fair enough (and probably sensible) to ask and encourage people to donate directly to Invest in ME if they want to contribute to the Rituximab study, but I believe that Charles Shepherd has been crystal clear about the MEA's intentions…

The MEA are enthused by, and are in support of, the UCL Rituximab study, that Invest in ME have organised.
And the MEA have ring-fenced their funding pot, waiting to receive the peer-reviewed protocol for the proposed study from UCL.
Once they've received and assessed the protocol, then they'll release the funding. (Assuming that the protocol is of adequate quality, which it will be because it's being drawn up by the experienced UCL team.)
I don't think it could be any clearer.

That's my interpretation of their position, anyway.

Sasha August 14, 2013 at 5:24 am

Hi lilpink – after several decades of having ME in the UK I've watched the politics and discussed them with others and have formed my own understanding of them. I see a field in which, as in any contentious issue, people faced with the same facts can (and do) come to different conclusions according to their temperaments, life experience, social circle of contacts, and general assumptions. I don't think we're likely to agree on these issues but we've both set out our arguments and I think we can leave people to make up their own minds.

Bob August 14, 2013 at 5:27 am
lilpink

A "joint charity fundraising effort to get this trial moving" would be ideal if it weren't for the concerns over the motives and machinations of the UKRC to which most of the other charities now belong. It would be nice to see the MEA *pledge* the money they have ringfenced (which would not, I believe, preclude them from changing their plans if the trial parameters were not to their liking, but would show true faith in this initiative) ..then, and only then, might many of us who have a better understanding of the social nuances that pervade UK ME interactions accept their affirmations in good faith.

I think it's good to always be sceptical and questioning of motives, and to be aware of the UK politics. And I think this project is definitely best left to IiME to organise along with the UCL. (Too many cooks spoil the broth.) And other than offering funding without any interference, I certainly don't want AfME having anything to do with it, given their track record and their current medical advisor. But I don't personally mistrust the MEA. Actually, I have come to respect and appreciate the MEA as I've learned more about them over the past couple of years.

Firestormm August 14, 2013 at 5:39 am
lilpink

I'm glad you've made it clear Firestormm that the MEA has not actually promised this money to Invest in ME for the Invest in ME trial. It does need to be made clear. I think everyone who wants to move this forward must ensure that Invest in ME are able to reach the total needed to start the process as quickly as possible without interference from outside influences which may slow things down. Thus it would seem reasonable to donate directly to Invest in ME where the mandate is clear and unambiguous.

You are not reading what I have said in my comment above – or choosing not to I don't really know which.

IiME are saying that any donations – from whatever source – will be 'owned' by them to do with that they wish. In the event of this 'Trial' which is little more than an idea at the moment – it has no concrete foundations yet – not happening; IiME will retain all the donations to do with as they please.

This is not a position that other charities will find palatable for very obvious reasons but especially as there is nothing on the table yet. The funds that the MEA – for example – have in their fund were donated to the MEA who have expressed a desire to fund further research into Rituximab and a Trial should one be deemed feasible.

Other charities have indicated their similar interest in funding further research around Rituximab should a proposal be forthcoming from at this point in time UCL; and should it pass independent peer-review.

Whether the money comes from IiME and their funding efforts or from other sources; it doesn't matter. Once the proposal is agreed upon then others may choose to fund it.

Who cares where the money comes from? The main thing you should be focusing on is that the research proceeds if it is deemed worthwhile – by UCL and by those who are willing to fund it.

I think once a proposal is on the table – you will see concerted efforts from ALL charities who have expressed an interest.

At the moment they are waiting to see what happens i.e. what UCL and Professor Edwards come up with by way of recommendation.

Bob August 14, 2013 at 5:58 am

To address the confusion about the MEA's position, I've looked up the clearest details that I could find…
I'll post the details below, and then leave it for others to interpret…

These quotes are taken from Charles Shepherd's posts on MEA's Facebook account.
I've extracted the most relevant info, and provided links to the full information…

(my bolding)

Charles Shepherd

4 I have again been discussing the possibility of a UK clinical trial with Professor Edwards (and others, including Professor Stephen Holgate) before going away on holiday and had a further very helpful telephone conversation with Professor Edwards this morning
5 I am very happy with the ideas he is putting forward for a small clinical trial which will hopefully turn into a formal proposal for funding at a later date
6 Provided the proposal meets the high standard of peer review that all research funded by the MEA RRF insists on we will be very happy to help fund a trial at UCL – which is where the ME Biobank is also situated
7 When I first discussed the possibility of a UK clinical trial with other research colleagues it emerged that the likely cost could be in the region of £400,000 – which is why we have suggested that the best way to get this moving would be a joint charity fundraising effort
8 I have already discussed this with most of the UK ME/CFS research funding charities and written to Invest in ME to suggest that it would be helpful to have a meeting of interested charities to see how a joint fundraising effort could be taken forward
9 I also confirmed to Professor Edwards this morning that the MEA RRF would be very happy to consider any funding proposals for preliminary work on immune function etc that may well be required before a clinical trial takes place

https://www.facebook.com/permalink….omment_id=5246064&offset=50&total_comments=77

And then there's further clarification here:

Charles Shepherd

I'm sorry if my further 10 point statement regarding the proposed clinical trial of Rituximab at UCL still isn't clear to you

Yes, this is the trial that Professor Jo Edwards is advising on

Yes, this is the trial that Invest in ME are fundraising for

Yes, this is the trial that the MEA is very happy to help fund (we have around £60,000 raised so far) – provided it passes the peer review procedures referred to in my 10 point statement and the MEA website statement

As already noted, we have also taken advice from Professor Edwards dating back to 2011 and I spoke to him again in some detail yesterday

It should also be noted that a trial of this nature will require quite a lot of preliminary work, possibly including some further work on immune status, before a final protocol for the trial can be prepared

Professor Edwards has retired from UCL and my understanding is that the protocol will be developed by the Clinical Trials Unit at UCL

It then has to gain ethical approval – which may take a bit of time given the potential for this drug to cause serious adverse effects. So we are almost certainly looking at 2014 rather than 2013.

My understanding is that UCL is not involved in fundraising and £400,000 is an awful lot of money – so this is why I have suggested that a joint charity fundraising campaign is carried out by those ME/CFS charities who want to see a Rituximab trial carried out here in the UK sooner rather than later….

Both myself and our Chairman (Neil Riley) have been in correspondence with Invest in ME on the subject of inter charity collaboration – possibly in the same way that the very successful ME biobank at UCL is now being funded and organised. And I would be very happy to set up a meeting of interested charities (and there are others who might be willing to help).

I hope all is now clear but do come back if anything is not.

https://www.facebook.com/permalink….comment_id=5247930&offset=0&total_comments=77

lilpink August 14, 2013 at 6:21 am
Bob
lilpink

I'm glad you've made it clear Firestormm that the MEA has not actually promised this money to Invest in ME for the Invest in ME trial. It does need to be made clear. I think everyone who wants to move this forward must ensure that Invest in ME are able to reach the total needed to start the process as quickly as possible without interference from outside influences which may slow things down. Thus it would seem reasonable to donate directly to Invest in ME where the mandate is clear and unambiguous.

lilpink

Hi Sasha, I think you may be a little naive about Uk ME politics. This is clearly a manoeuvring by MEA to try to take the reins on this project (imo and many others)..hence why they make proviso after proviso. It's worded in such a way to sound reasonable to most folks, but you can't get any sort of firm reply from the MEA to the question 'so are you going to give your ringfenced money to the Invest in ME initiative or not'?

It's fair enough (and probably sensible) to ask and encourage people to donate directly to Invest in ME if they want to contribute to the Rituximab study, but I believe that Charles Shepherd has been crystal clear about the MEA's intentions…

The MEA are enthused by, and are in support of, the UCL Rituximab study, that Invest in ME have organised.
And the MEA have ring-fenced their funding pot, waiting to receive the peer-reviewed protocol for the proposed study from UCL.
Once they've received and assessed the protocol, then they'll release the funding. (Assuming that the protocol is of adequate quality, which it will be because it's being drawn up by the experienced UCL team.)
I don't think it could be any clearer.

That's my interpretation of their position, anyway.

Mmm mmm..I think our different interpretations and perspective may be borne of a (very) long history of this illness and its politics in the UK, not to mention the incredibly long thread of questioning and answers by CS on FB to even arrive at that capitulation…

lilpink August 14, 2013 at 6:27 am
Bob
lilpink

A "joint charity fundraising effort to get this trial moving" would be ideal if it weren't for the concerns over the motives and machinations of the UKRC to which most of the other charities now belong. It would be nice to see the MEA *pledge* the money they have ringfenced (which would not, I believe, preclude them from changing their plans if the trial parameters were not to their liking, but would show true faith in this initiative) ..then, and only then, might many of us who have a better understanding of the social nuances that pervade UK ME interactions accept their affirmations in good faith.

I think it's good to always be sceptical and questioning of motives, and to be aware of the UK politics. And I think this project is best left to IiME to organise along with the UCL. (Too many cooks spoil the broth.) And other than offering funding without any interference, I certainly don't want AfME having anything to do with it, given their track record and their current medical advisor. But I don't personally mistrust the MEA. Actually, I have come to respect and appreciate the MEA as I've learned more about them over the past couple of years.

I agree with most of your assertions..but not the final conclusion re MEA. The longer I have been associated (as a member) with MEA the more I've become disillusioned and seriously in doubt re their intentions. Conversely, I have absolute trust in the integrity of Invest in ME, not to mention their ability to have transformed the world stage for dissemination of related science via their Conferences and pre-conference research workshops (all done since their inception in 2006 and done using only unpaid volunteers. The MEA have been 'at it' since 1976 and achieved ..well.. not very much. AfME have brought any notion of a patient centred charity into oxymoronic disrepute).

Bob August 14, 2013 at 6:38 am
lilpink

I agree with most of your assertions..but not the final conclusion re MEA. The longer I have been associated (as a member) with MEA the more I've become disillusioned and seriously in doubt re their intentions. Conversely, I have absolute trust in the integrity of Invest in ME, not to mention their ability to have transformed the world stage for dissemination of related science via their Conferences and pre-conference research workshops (all done since their inception in 2006 and done using only unpaid volunteers. The MEA have been 'at it' since 1976 and achieved ..well.. not very much. AfME have brought any notion of a patient centred charity into oxymoronic disrepute).

I totally agree with you about IiME and about AfME. But I have no reason, personally, to mistrust the MEA. MEA have a different style to IiME, and are member-focused, providing services to members. They don't have block-buster conferences, and their approach might not be quite as focused or indignant as IiME's, but I've not seen them supporting or promoting the psycho-social model since I've been a member. If I did, then I wouldn't be a member. In fact, Charles Shepherd has had letters published, attacking the PACE trial, for example. They also do a lot of work advocating for ME patients to get DWP/ATOS rules changed. I think this isn't an area that IiME gets involved in.

Bob August 14, 2013 at 6:57 am

Sasha, thanks for the great article. Very informative. :thumbsup:

Bob August 14, 2013 at 7:02 am

lilpink, I'm not sure if continuing a negative conversation about the merits of each UK charity will really help fund the Rituximab trial? So I'm bowing out of further discussion on this thread. We have differences of opinion, and that's fine.

lilpink August 14, 2013 at 7:09 am
Bob
lilpink

I agree with most of your assertions..but not the final conclusion re MEA. The longer I have been associated (as a member) with MEA the more I've become disillusioned and seriously in doubt re their intentions. Conversely, I have absolute trust in the integrity of Invest in ME, not to mention their ability to have transformed the world stage for dissemination of related science via their Conferences and pre-conference research workshops (all done since their inception in 2006 and done using only unpaid volunteers. The MEA have been 'at it' since 1976 and achieved ..well.. not very much. AfME have brought any notion of a patient centred charity into oxymoronic disrepute).

I totally agree with you about IiME and about AfME. But I have no reason, personally, to mistrust the MEA. MEA have a different style to IiME, and are member-focused, providing services to members. They don't have block-buster conferences, and their approach might not be quite as focused or indignant as IiME's, but I've not seen them supporting or promoting the psycho-social model since I've been a member. If I did, then I wouldn't be a member. In fact, Charles Shepherd has had letters published, attacking the PACE trial, for example. They also do a lot of work advocating for ME patients to get DWP/ATOS rules changed. I think this isn't an area that IiME gets involved in.

Mmm again. You don't feel there's a conflict apropos your assertion that they don't support or promote the psycho-social model and their membership of the UKRC? I personally feel that's a HUGE concern..but we must make our own minds up about that. I'd take umbrage with the use of the word 'indignant' if used pejoratively about Invest in ME, but not if used in the context that we all should rightly be incensed (and indignant) about the way in which those who suffer this illness have been treated….

Sasha August 14, 2013 at 7:13 am

We've got a bit bogged down here in an area of discussion where I suspect we're not going to make any progress in reaching agreement – which, as Bob says, is fine. We're all entitled to our opinions and the important thing, as far as I'm concerned, is that we donate to the trial – and everyone should donate to whatever charity they're happy to entrust with their money.

I suggest we move on to something more productive, namely: has anyone got any questions for Prof. Edwards that they'd like to put to him for the interview I'll be doing with him in the follow-up article?

Also: has anyone got any good ideas for fundraising projects for the trial? Is anyone doing anything special?

lilpink August 14, 2013 at 7:17 am
Sasha

Hi lilpink – after several decades of having ME in the UK I've watched the politics and discussed them with others and have formed my own understanding of them. I see a field in which, as in any contentious issue, people faced with the same facts can (and do) come to different conclusions according to their temperaments, life experience, social circle of contacts, and general assumptions. I don't think we're likely to agree on these issues but we've both set out our arguments and I think we can leave people to make up their own minds.

I agree. I think you take a sensible and measured approach. I'm not sure all the details can be addressed within this forum….maybe we will have to wait for history to tease them apart and examine them more openly and ruthlessy. Without full disclosure, from all sides, it's nigh impossible to to create a properly coloured-in picture…but I'd like to think my colouring book has a more detailed 'dot to dot' drawing than some, and more than just 'black' and 'white' to paint with…
So people can make up their minds..of course..that's what we are all entitled to do… but the amount of information provided here isn't enough of a resource to provide a full understanding of the situation (imo of course! :) )

lilpink August 14, 2013 at 7:20 am

I'm happy to leave the conversation at this point..I simply wanted to ensure that the facts were presented properly..without spin. Thanks, Sasha, for the article. Hope to see more of the same when the trial is up and running.

Bob August 14, 2013 at 7:20 am
lilpink

I'd take umbrage with the use of the word 'indignant' if used pejoratively about Invest in ME, but not if used in the context that we all should rightly be incensed (and indignant) about the way in which those who suffer this illness have been treated….

'Indignant' was definitely not used pejoratively. I couldn't think of a better word to use to describe IiME's 100% focus on the injustice in the way ME patients are treated. I totally support IiME, and always have done.

Sasha August 14, 2013 at 7:30 am
lilpink

I'm happy to leave the conversation at this point..I simply wanted to ensure that the facts were presented properly..without spin. Thanks, Sasha, for the article. Hope to see more of the same when the trial is up and running.

Thanks – yes, I hope to be writing more articles as things progress and of course I'll be presenting the interview with Prof. Edwards soon (if anyone gives me any questions to ask him, that is!).

Dolphin August 14, 2013 at 7:53 am
lilpink

Mmm again. You don't feel there's a conflict apropos your assertion that they don't support or promote the psycho-social model and their membership of the UKRC? I personally feel that's a HUGE concern..but we must make our own minds up about that.

I don't interpret the MEA joining of the UKRC as evidence that they support or promote the "psychosocial model" (and my views are similar in terms of ME Research UK joining it). I believe both have joined with the hope that it will lead to a lot more biomedical research.

Saying that I am concerned that it may lead to problems. So in my view, it may turn out to be a good thing in the long wrong, or it may cause more problems than it helps in the long term. But I don't interpret a charity getting involved with it as evidence that they support or promote the "psychosocial model" (and my view would be similar of an individual who was supportive of it).

So I accept that people may believe that the UKRC will cause more problems than it solves, and hence could be unhappy with a charity getting involved. But for me, it doesn't provide strong evidence of a charity's support or promotion of the "psychosocial model". I think what charities do and say in other areas give us a better idea of their positions on this (and similarly with individuals who are supportive of it).

Sasha August 14, 2013 at 8:02 am

Can I suggest that any discussion of the UKRC goes onto another thread? I think it probably already has its own thread somewhere. Like I said, I don't think we're going to resolve all these thorny issues here and I think we're in danger of getting a long way off the topic of the Rituximab trial. :)

Legendrew August 14, 2013 at 8:15 am

Good article – well written and well informed!

Bob August 14, 2013 at 8:31 am

Here's an alternate thread for discussions re the UK Research Collaborative:
http://forums.phoenixrising.me/index.php?threads/uk-research-collaborative-means-business.23574/

lilpink August 14, 2013 at 9:32 am
Bob
lilpink

I'd take umbrage with the use of the word 'indignant' if used pejoratively about Invest in ME, but not if used in the context that we all should rightly be incensed (and indignant) about the way in which those who suffer this illness have been treated….

'Indignant' was definitely not used pejoratively. I couldn't think of a better word to use to describe IiME's 100% focus on the injustice in the way ME patients are treated. I totally support IiME, and always have done.

Good to know :) Support well placed .

lilpink August 14, 2013 at 9:33 am
Sasha
lilpink

I'm happy to leave the conversation at this point..I simply wanted to ensure that the facts were presented properly..without spin. Thanks, Sasha, for the article. Hope to see more of the same when the trial is up and running.

Thanks – yes, I hope to be writing more articles as things progress and of course I'll be presenting the interview with Prof. Edwards soon (if anyone gives me any questions to ask him, that is!).

Good to know too :)

Simon August 14, 2013 at 2:41 pm
Bob

Simon said:

I still don't really understand why the study is so small. I know there is extensive discussion of this on the main thread – which I've only dipped into – and Jonathan Edwards seems to be saying that a small study can be more tightly controlled than a large multi-centre one. I can see the logic that a smaller replication study would have been a better place to start, but given that the large study is already largely funded and plans are well-developed for it, I do wonder how much 'value' a smaller study will add in practice.

Hi Simon, Jonathan Edwards addresses these questions here:
http://forums.phoenixrising.me/inde…uximab-trial-30-july.24499/page-8#post-377254

Thanks, Bob

Though it might help if I summarise that Jonathan Edwards interesting post below. He was replying to a post by Esther12 about the value of a small study given the larger Norwegian one.

His answer seems to boil down to a concern that the larger Norwegian study might find a lesser effect next time around [which often happens after a big bang initial result], and that could derail Rituximab. Wheras if that did happen, but a UCL study found a clear sub-group that responded well to Rituximab, then it would still be a live game.

If the total response rate for unselected ME turned out to be 40% (or less), taken with all the uncertainties about objective monitoring I think regulatory authorities would be very cagy about licensing until there was other information to help the case. For this sort of reason my view is that we should try very hard to find a different sort of trial design.

So one of my main thoughts about design is not to do a mini-Norway. It would be much better if we could find a way of testing whether rituximab works for some people with ME from a different angle and one that might get at least one step further towards finding out who those people might be and why they respond.

what I would like to see is a focus on the longer term objective of making sense of a B cell story for some of ME. In that sense I agree with a lot of other people’s comments, especially Firestormm. If the big Norway study is a bit disappointing we want to make sure the real value of a B cell approach, if there is one, is not lost. In five years time there may not be the same mix of people in a position to collaborate.

So it seems to me the argument for a small UK study is partly as insurance in case five years down the line the Norwegian results are 'complicated', and partly to better understand how the B-cell approach fits different patients.

Please correct me if I have got this wrong.

Bob August 14, 2013 at 3:53 pm

Sasha, FYI, your article is quoted, and linked to, by the NICE Guidelines blogspot:
http://niceguidelines.blogspot.co.uk/2013/08/professor-jonathan-edwards-b.html

Dolphin August 14, 2013 at 4:52 pm

If it was a question of a small trial costing a relatively small amount of money and a big trial costing the size of the current proposed study (in the ball park of £350,000-400,000), then there would be a stronger case for a bigger trial. However, a bigger trial at the moment would likely cost £1m+, the sort of money which might be too much to raise, or might only be raised with virtually nothing else being funded for a period. So the situation is maybe more a case of a small study in the UK versus no study in the UK.

I'm hoping that because it's a small trial, there will be a reasonable number of biological measurements taken at baseline (useful to try to work out characteristics of responders/non-responders) and ideally a few biological measurements during and after the trial. By having small numbers, this would seem more affordable.

Firestormm August 14, 2013 at 11:25 pm
Simon

Thanks, Bob

Though it might help if I summarise that Jonathan Edwards interesting post below. He was replying to a post by Esther12 about the value of a small study given the larger Norwegian one.

His answer seems to boil down to a concern that the larger Norwegian study might find a lesser effect next time around [which often happens after a big bang initial result], and that could derail Rituximab. Wheras if that did happen, but a UCL study found a clear sub-group that responded well to Rituximab, then it would still be a live game.

So it seems to me the argument for a small UK study is partly as insurance in case five years down the line the Norwegian results are 'complicated', and partly to better understand how the B-cell approach fits different patients.

Please correct me if I have got this wrong.

Seems correct to me.

One of my thoughts about this would be whether or not samples could be taken from the initial Norway trial, by UCL and used to drill-down and try and better understand why those who responded did so.

What I mean to say is, would rituximab need to be tested again on UK patients in a replication trial; or could UCL 'simply' perform a better analysis of the existing data?

If on the other hand, a UK n=30 attempt at replication is being estimated as costing c. £400k – and this is deemed necessary to gain data before you can better analyse reasons: then we might be looking at more money, not less?

If you intended gathering better data, perhaps you could spend less on a smaller replication, in order to spend more on data analysis and in trying to discover the reason why?

Hard to know really at this point. Am certainly awaiting news from UCL with baited breath. All very exciting.

Sasha August 15, 2013 at 1:10 am

Independent replication by several different investigators is going to be key to getting Rituximab licensed, if the good results are confirmed – it won't be enough to analyse the Haukeland data or samples over and over. One way or another, we need more studies and it's important that there's also a German and US one planned.

The US (OMI) study will cost $7.65 million so I suspect the UK one will be underway faster…

I've got no info on the German trial.

user9876 August 15, 2013 at 1:18 am
Firestormm

Seems correct to me.

One of my thoughts about this would be whether or not samples could be taken from the initial Norway trial, by UCL and used to drill-down and try and better understand why those who responded did so.

What I mean to say is, would rituximab need to be tested again on UK patients in a replication trial; or could UCL 'simply' perform a better analysis of the existing data?

If on the other hand, a UK n=30 attempt at replication is being estimated as costing c. £400k – and this is deemed necessary to gain data before you can better analyse reasons: then we might be looking at more money, not less?

If you intended gathering better data, perhaps you could spend less on a smaller replication, in order to spend more on data analysis and in trying to discover the reason why?

Hard to know really at this point. Am certainly awaiting news from UCL with baited breath. All very exciting.

I think the real value is in the people at UCL thinking through the autoimmune angle and using their experience to interpret it. In the past they have been shown to have good intuition and forming the right questions and hypothesis is the hard part of science (running the experiment is easy). But its the intuitions with the knowledge of auto immunity that will lead to taking the right measurements that can be used to give greater understanding.

Fluge and Mella are oncologists and as such were using Rituximab for treating cancer which I get the impression is quite different. So it seems very important to have additional, very good, people with different backgrounds and understanding involved in a study. I suspect the things they will measure will be very different from that which Fulge and Mella would have measured when they designed their protocol many years ago.

Firestormm August 15, 2013 at 1:56 am
user9876

I think the real value is in the people at UCL thinking through the autoimmune angle and using their experience to interpret it. In the past they have been shown to have good intuition and forming the right questions and hypothesis is the hard part of science (running the experiment is easy). But its the intuitions with the knowledge of auto immunity that will lead to taking the right measurements that can be used to give greater understanding.

Fluge and Mella are oncologists and as such were using Rituximab for treating cancer which I get the impression is quite different. So it seems very important to have additional, very good, people with different backgrounds and understanding involved in a study. I suspect the things they will measure will be very different from that which Fulge and Mella would have measured when they designed their protocol many years ago.

Morning User :)

So you thinking they'd run a smaller replication Trial but with their angle of expertise it would be 'better' designed and measured? If so, then yeah I can see that too I guess.

Fingers are crossed :)

user9876 August 15, 2013 at 2:16 am
Firestormm

Morning User :)

So you thinking they'd run a smaller replication Trial but with their angle of expertise it would be 'better' designed and measured? If so, then yeah I can see that too I guess.

Fingers are crossed :)

I wouldn't necessarily use the phrase better designed but rather designed to explore a different angle from Fluge and Mella. And an angle that might lead to explanation.

Thats a very different thing from a multi-site trial exploring a hypothesis of the amount of benefit to be gained by Rituximab.

Both types of research are interesting. Unfortunately its hard (or costly) in science to do a mega experiment that answers all questions well.

Firestormm August 15, 2013 at 2:28 am
user9876

I wouldn't necessarily use the phrase better designed but rather designed to explore a different angle from Fluge and Mella. And an angle that might lead to explanation.

Thats a very different thing from a multi-site trial exploring a hypothesis of the amount of benefit to be gained by Rituximab.

Both types of research are interesting. Unfortunately its hard (or costly) in science to do a mega experiment that answers all questions well.

Thanks.

I am thinking that we have Rituximab, right, and we know something about how it works and what it does, right? So we are starting our search for why it should help those it did – with something more than we might have had before in other research seeking to determine mechanisms.

From what Prof. Edwards has been saying though, we don't know everything about Rituximab and how it can effect individuals: so we can't entirely say that if Ritux. is believed to have resulted in e.g. remission from a diagnosis of ME, that it is down to X. Like we might be better able to do with Rheumatoid Arthritis.

But we can begin with the drug itself and that's a start. Though we would still need to screen patients before and after treatment: but UCL know what to look for and with help from Norway – the search is narrowed.

To what extent patient selection at this point will matter – beyond the means by which they were selected in Norway – I don't know. It would make sense to select based on e.g. NICE on the one hand, then separately on other criteria perhaps: thinking ahead and down the road.

Also to have a further set known who have recognised abnormalities (with an ME diagnosis) that are deemed more/most likely to respond to Ritux.

Just thinking…

Firestormm August 15, 2013 at 2:36 am

Oh and a cohort who have abnormalities in a control group perhaps – but don't have a diagnosis of ME.

Hmm… if the abnormalities were the same in the control and in that part of the ME cohort; I think this might work – wonder if they might have e.g. RA patients in a control or another disease that has the abnormalities and is known to respond?

My thinking being, that you need to try and equate response to Ritux. to remission in ME symptoms (and what is considered the disease known and diagnosed as ME); if you see what I mean?

Can treatment and remission with Rituximab mean something else other than remission in ME? As we don't know what ME is really – or the mechanisms behind it or in each individual case: I think it would be good to know more.

user9876 August 15, 2013 at 2:41 am
Firestormm

To what extent patient selection at this point will matter – beyond the means by which they were selected in Norway – I don't know. It would make sense to select based on e.g. NICE on the one hand, then separately on other criteria perhaps: thinking ahead and down the road.

I think NICE is extremely broad. But all the diagnositic guidelines are predicated on an exclusion diagnosis (i.e. the removal of people with other diseases). To me this is where things get difficult as its often unspecified. NICE lists a set of blood tests and also says anything else that seems relavent to the particular case but I think this last bit often gets lost. The problem is that the semantics of the ME, CFS labels come from the diagnositic system that includes these undefined or poorly defined exclusions.

Personally I would start a trial with severe cases as where there is remission the effects should be blindingly obvious (non of this statistical significance and very small movement in measures) and also as I would expect markers to be more obvious with greater changes.

Firestormm August 15, 2013 at 2:48 am

Yeah I realise that about NICE. But they also break down the illness into categories. My point really would be that this study could be an opportunity to also demonstrate if the NICE criteria adequately select those most likely to respond to this treatment (compared to other criteria such as CDC and CCC).

Of course the more complex the recruitment protocol the more expensive. But we are talking about a UK Trial with one aim being UK approval for the drug. So… NICE should be considered in some definite way, (though it could be argued CDC equates to NICE I suppose).

OverTheHills August 17, 2013 at 8:27 pm
Sasha

….. has anyone got any questions for Prof. Edwards that they'd like to put to him for the interview I'll be doing with him in the follow-up article?

Also: has anyone got any good ideas for fundraising projects for the trial? Is anyone doing anything special?

I'm really really enjoying reading Prof Edwards ongoing dialogue on the ' invest-in-me-prof-jonathan-edwards-statement-on-uk-rituximab-trial-30-july' thread. It is generous of him to spend so much time in these discussions. A very refreshing change to feel we are being treated like a group of sane adults with varying views and knowledge; being respected in other words.

What I would like to know is what he is getting out of his presence on PR? is it working for him? is there anything else we can do that will be useful to him (aside from fundraising).

I hope that some of our questions are thought provoking for him. From my own experience I know that teaching is sometimes a good way to clarify my thoughts on a subject.

OTH

Bob September 4, 2013 at 4:05 pm

IiME's Quick Overview of the IiME/UCL Clinical Trial
http://www.ukrituximabtrial.org/IIMEUKRT Summary Sep13.htm

I wasn't sure which thread to post this on!
Not much new info, but perhaps a little new info, as follows…

  • Invest in ME have agreed to fully fund the preliminary study by UCL which is a pre-requisite to the full clinical trial. This will begin shortly.
  • The preliminary study will be a small study which will confirm the earlier work of Dr Amolak Bansal [1] on B-cells but using a different cohort of ME patients.
  • Professor Edwards believes this is a useful study in its own right and a pre-requisite for the clinical trial.
  • Meanwhile work is continuing on the design of a protocol which will be finalised after the trip to Bergen that IiME and Professor Edwards have arranged.

Bob September 4, 2013 at 4:07 pm

Meanwhile, the fundraising Matrix is taking shape:
http://www.ukrituximabtrial.org/IIME UK Rituximab Trial Matrix 01.htm

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