NorthWest Biotherapeutics Inc (NWBO)

[flipper44]

Thinking about sequential analysis again.

Warning: this is subtle.

This is the only "look" at data the DMC gets until the 2nd interim analysis. The 2nd analysis, as you know, will be triggered by 88 events. The DMC does not get an in-between extra peak. Thus, they are not waiting for a little more data to "see" if significance shows up. This would be strictly prohibited by sequential analysis.

That said, the sponsor could be waiting for a bit more data to accumulate that they will only "see" once the trial is unblinded. At 66 events, if they are confident there is statistical significance on their primary endpoint, and they also have statistical significance on their other endpoints, they may still want a little more "blinded" data to accumulate before the trial is officially unblinded. This would not be the DMC's idea, it would be the sponsor of the trial (those conducting the actual trial). They are certainly within their rights to think patients need this drug right now, and the trial should be halted for efficacy before the 2nd interim analysis, but they also may think once the data is unblinded, it might be very statistically sound to have accumulated somewhere around 70% - 75% blinded events in order to strengthen the powering for the FDA down the road.

This may seem counterintuitive, but I can see this playing out to protect current trial patients through early halt, in addition to protecting future patients by getting a tad more blinded data so that approval becomes a foregone conclusion.

Note: Futility does not become more probable as time goes on in between interim analysis, because the DMC does not get little "peaks" in between 66 and 88 events.