NorthWest Biotherapeutics Inc (NWBO)

[flipper44]

Yes Smokey, the 148/149 events are used to power the trial more strongly.

Perhaps your answer already acknowledges the point/question I am submitting, but let me explain it. Pyrr and AVII are diehards about stating that in the past, enrollment must be completed on PFS prior to the first interim analysis. Meaning, for instance, if 348 enrollment had not been met, they would have to wait beyond 149 events to conduct the first interim analysis.

While FDA policies often change, NWBO would not take chances and vary from tradition, unless the resizing negotiations with regulators also agreed to 2 separate enrollments.

Even though the confirmatory trial in DCVax-L's case is likely to be the same phase III trial (plus some satellite data assistance from trials out there conducted by UCLA, IMHO), think of the confirmatory trial as a separate trial, even though it is not.

I think a researcher named Fleming once quoted someone who stated, who is unlucky enough to enter a placebo confirmatory trial after the treatment is initially approved through AA?

The point is, FDASIA and others continue to try and perfect the transition from AA to full approval. One requirement is that the new/confirmatory trial already started before AA is granted on the surrogate trial. Companies and regulators over time learned that one trial could be used for both surrogate and confirmatory proof. (In some cases, the confirmatory trial can conclude single arm, but even better, enrolled while both portions of the trial were still blinded.)

My recollection is that, because of this, the surrogate endpoint is often overpowered. We know we have strong powering for the primary endpoint. So that fits, but to create a more level powering playing field between surrogate and confirmatory portions of the trial, perhaps the surrogate portion of the trial reached full enrollment at 300.

Anyway, if that were the case, then we already reached full enrollment in the surrogate/AA portion of the trial.

(Of course, if this is the case, it means we already had first interim success.)