NorthWest Biotherapeutics Inc (NWBO)

[john1045]

Very well stated Doc!!

Living longer does not help a trial end when the end depends on events. Lowering the entrance requirements to speed up PFS eventing results, as the Germans did, does help speed up event rates but can only help to a small degree as the treatment arm must supply the majority of events. There are 2 theorhetical primary completion medians for PFS. One is for SOC theorhetical cohort (N=83) PFS and the other for treatment arm theorhetical cohort (N=165) PFS. This is theorhetical based on no treatment difference. The trial expects, of course, that actual eventing will be coming much more quickly from the SOC cohort which is why 348 patients were expected to enroll. The problem is that if everyone is living longer, even if 116 SOC PFS events happen, the trial still needs 132 treatment PFS events to occur to reach primary completion. The reality is that SOC could be approaching 100 events and event rate tailing off and treatment should be tailing compared to SOC from the beginning of enrollment. This puts the trial in the dilema of tailing from both cohorts and obviously needs more events from the treatment arm which in immunotherapy treatments has a tendency to drop off very quickly once moving past a critical inflection point. We are at 13+ months past last patient treated and we still don't have a declared primary completion which we were told was expected sometime in November. Might 13 months also correlate to a critical inflection point on the Kaplan Meijer curve for the entire group of patients in this trial where the majority of patients that progress after this point begin to stretch out the entire patient population eventing tail? Look at Rkmatters' recent post about SOC PFS and you see her expected range of 11-13 months SOC PFS which reflects inclusion criteria and improved methods and treatments for SOC. If we accept her rational as reasonable, this means we should have a clear SOC PFS in the books. The problem with great treatment success and SOC expectations that are too low is that it puts too much pressure on the treatment arm events to end the trial. Expectations for treatment benefit that are insufficient to end the trial timely and SOC tailing due to any pseudos who made it in and longer lived subsets means that treatment events need to make up the difference but are only able to do so very slowly. This would result in the expected primary completion date to be pushed back multiple times perhaps. Now where have I seen that happen. Hmmm, I guess you could say that this dilema is not really helping the trial.. finish. Best wishes.