HI Abeta:
I'm quite confused myself. Don't have any answers and the March, 2017 data analysis did not correlate Mes, PN, Class and Neural. Only looked at big picture M+/M-.
But having said that, the March, 2017 data appears very promising to me. Let's look at it this way:
For M+, N=131 and we know that the blended results portend that DC VAX is effective. If the agreed upon by 69 authors historical control stake of 21.7 months is used, my calculations show that the delta to TX is about 20 months with a blended 34.7 months. Even if you use 29 months, which may be an outlier(as I think 34 months is too from a 2018 small study), then the TX is still about 9+ months. This is impressive when you consider that pro-neural is M+. So the vaccine seems to work well here. I cannot correlate this success vis-a-vis the LL/RP clinical findings that showed to them that the vaccine had little to no effect on this group. The March, 2017 analysis does not go into these weeds. So, it would be interesting to hear from LL/RP what they think.
Now turning to M-, we know that MES is predominantly in that category. We also know that the MES sub-group is relatively quite large and a large recent study indicated that MES could constitute about 50% of the stage IV glio population. Being conservative, let's assume that it is 30% of the ITT. Then, N=100 for this group. LL/RP said that they found the vaccine quite effective in this relatively large grouping. We also know that CLASS is M- and that it constitutes about 20%-30% of all stage IV glios. Again, let's assume conservatively that CLASS is 15% of the ITT or N=50. Neural is a rather small % of stage IV glios, so let's discount this group where N=0. These are very conservative assumptions and the M- N=200 approximately or about 60%. We know that M-is very aggressive and so is MES, so the agreed upon historical control stake of 12.7 months is reasonable. Blended is 19.8 months and TX delta would be around 9 months. Even if you used 14.6 months used by Bosch(I don't know why he referred to this parameter in the case of M-), the delta would still approach 7 months. Still rather impressive.
Essentially what you have is N=280 where the vaccine is effective across M+ and M- and across the major sub-groups. This constitutes about 85% of the ITT population. Effect seems to be widespread and any approval would be likely to be broad rather than limited to a particular sub-group.
Insofar as the control stakes are concerned, I believe that cross over confoundment will be de minimis for the reasons Flipper has articulated. We should have sufficient and SS separation. We also have a non-cross over group of about 14% as another evaluative control stake.
Thus, I believe the March, 2017 data portends success and the 2018 data will more than confirm this. Accordingly, I have to believe that the spring refresh of 2018 is the last data collection. They will wait till November to end the trial and we will hear results in early 2019 or in about 6 months. I am pretty certain that we won't have a funding overhang because, most likely, there will be a sale/lease back of property which is non-dilutive and enough to carry the trial to completion and to a meaningful(and sustained) rise in the pps. The ball game is FDA broad approval. NWBO wants to leave no stone unturned to achieve this goal. Failure is not an option. This is what I believe the game plan is and why LP/LG are so relatively confident. The data will be mature in a matter of a few months, IMHO.
Caveat: all the above is JMHO.
AI
