Following the news of the null result of the Norwegian Phase III trial, and interest in how this impacts the planned UK trial, I thought it might be useful to open a thread for this. The microsite for this UK rituximab trial and associated B-cell research is on Invest in ME Research Centre of Excellence website, so anyone wanting to know the background may follow the links here: http://www.investinme.org/ukrtbcell-ce-index.shtml The plan was for the Haukeland team to visit the UK team again before the end of this year, once the codes for the Phase III trial had been broken in October, and following from their visit to Norwich in January (which included public talks) to discuss a UK trial to begin in 2018. It's been reported that announcement of the null result was made early for the sake of patients, as particpants receiving placebo had been promised attempts to include them in a new trial if rituximab had proved effective, so it wouldn't be fair to keep them in false hope for months until publication; and they wanted to avoid patients going for treatment outside of clinical trials and with unselected patients, which they have always advised against. Likewise, one of the reasons for delay in starting a UK trial is because the preceding B-cell research, as advised by Jonathan Edwards and led by Jo Cambridge at UCL, was aimed at being able to identify a subset of likely responders to rituximab in the ME/CFS patient group, while being useful research in its own right, so this work has proceeded with great care and caution to the credit of all the researchers involved. So, at the time of writing, the B-cell research is ongoing, and Invest in ME Research stated that they hope (as originally planned) to meet with the researchers soon. This was their initial statement in response to the news from Norway of a null result: http://www.investinme.org/IIMER-Newslet-1711-03.shtml EDITED 12th February 2018 to add statement by Invest in ME Research: http://www.investinme.org/IIMER-Newslet-1802-01.shtml (in short, they will not be going ahead with a UK trial of rituximab).
The Phase III Rituximab News thread: https://www.s4me.info/index.php?threads/phase-iii-rituximab-trial-news.1153/
So is this still a likelihood? Is there some sort of subset, just much smaller than expected? Or will the UCL work now be focused on more general understanding instead? I’m finding it hard to accept the previous studies and anecdotal reports were simply placebo effect or fluke. I don’t think we should waste money on repetitive dead end research, but will possible reasons for a false negative result be looked into? It would be awful if the difference in results is explainable and everyone abandons rituximab as a knee jerk reaction. In the previous thread about the announcement I found the terminology confusing. What is meant by the term ‘responders’? Were there no responders, or did 30% respond (not reaching the threshold of 50% to make it a success)? Or did 30% improve, exactly the same as the placebo arm?
Hi @Jenny TipsforME I agree with you and this is the problem of the early reveal of the null result, albeit quite rightly done for all the right reasons, but it does mean that until a close analysis of the data is done and the teams meet to discuss, we await with more questions than answers.
Dear Jenny, It is important to remember that the official result from the previous study, in terms of the primary endpoint, was also negative. The apparent difference at six months was interesting enough to justify a further trial but I do not think this result has come as a big surprise to any of the researchers - just a disappointment. Apparent 'responses' unrelated to drug are commonplace in trials. There are almost never none in a placebo arm.
Which I suppose highlights the importance of having a placebo arm, as a datum for comparison. So long as all the arms are subject to the same 'noise' then it can be nulled out.
Or maybe it will go towards Jo Cambridge, Fane Mensah etc at UCL, as their work on B cells has been done with collaboration From F & M?
I think it makes sense to look at specific blood cell populations. Until recently a lot of work has been done on unsorted peripheral blood mononuclear cells and I think that is likely to be problematic because they vary in proportions so much. There is now interest in T cells and I think it makes sense to do parallel studies on B and T cells - which can easily be achieved if the same material is looked at by labs with special expertise in one or other or both.
