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The UK Rituximab Trial: A Study in a Hurry

Discussion in 'Phoenix Rising Articles' started by Mark, Aug 12, 2013.

  1. Simon

    Simon

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    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.
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  2. Bob

    Bob

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  3. Dolphin

    Dolphin Senior Member

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    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.
  4. Firestormm

    Firestormm Senior Member

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    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.
  5. Sasha

    Sasha Fine, thank you

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    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.
  6. user9876

    user9876 Senior Member

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    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.
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  7. Firestormm

    Firestormm Senior Member

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    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 :)
  8. user9876

    user9876 Senior Member

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    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.
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  9. Firestormm

    Firestormm Senior Member

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    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...
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  10. Firestormm

    Firestormm Senior Member

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    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.
  11. user9876

    user9876 Senior Member

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    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.
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  12. Firestormm

    Firestormm Senior Member

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    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).
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  13. OverTheHills

    OverTheHills

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    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
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  14. Bob

    Bob

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    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.
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  15. Bob

    Bob

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