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The UK Rituximab Trial: A Study in a Hurry

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by Sasha


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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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.
 
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.
 
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 said:
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 said:
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
 
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.

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...
 
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).
 
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.
 
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....
 
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?
 
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! :) )
 
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.
 
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.
 
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!).
 
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).
 
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. :)
 
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 .
 
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 :)