NorthWest Biotherapeutics Inc (NWBO)

[AVII77]

The reason I say this is your example shows a graph where all evidence for the period of time considered before a recommendation occurred pointed to positive trending.

The graph I worked off was unique in that there were many interims (8 or so planned). We are talking about what may have happened at the very first DCVax interim (0.6 on the x-axis below).

The DSMB does not base decisions simply on suppositions but actual data points.

I am asking, if you were on the DSMB and, at the very first interim, you saw PFS results plotting where that red dot is, what would you do?

Again: that red dot shows data indicating futility on the primary endpoint. A trend for benefit (no harm) but high confidence that if the trial continues it will not provide a conclusive answer.

though by your example I think you understand, your concern about a DSMB decision being cloaked by regulator action is not consistent with the qualifier "earliest appropriate time" in my statement.

In my opinion, certainly an appropriate time where action is required is if the results cross the boundary showing placebo is conclusively superior (if we demand conclusive evidence of superiority before stopping a trial for benefit, why not demand conclusive evidence of harm before stopping a trial for harm.) Now this depends on the endpoint measured, the disease and alternatives available to the patients. I think in MOST cases regulators would not allow treatment to continue in a futile trial if the "red dot" was below the z=0 line (trending negative). That's why I asked you to consider the special case here where there is a likelihood of the immunotherapy causing apparent progression and couple that with an interim OS trending positive.