NorthWest Biotherapeutics Inc (NWBO)

[Doc logic]

thermo,

The check off where exwannabe admitted “unknown” and the JAMA article is all that is really needed to put an end to this argument and knowing well ahead of time that the endpoints would need to be changed because of treatment induced pseudoprogression is also a huge consideration which is even more important than this being formally done at the end of the trial which is one of 2 guidance suggested times to do so.
NWBO was blinded to all data analyzed from 2015 on until likely late 2020. This fact and PFS argument for the halt on it’s own fails to adequately account for the screening halt and 17 missing SOC/placebo patients in my opinion. On the other hand, a blinded look at a link to improved OS at the expense of failed PFS held up to open label results as a mirror would explain what happened if regulators had looked more closely.
I believed then and now that those missing patients represented a down payment on approval based on what regulators saw not what NWBO was blinded to. A recommendation to halt the trial based on all evidence from within and outside of this trial (used as a mirror to give insight not added into these results) could have been made based on PFS failure being linked to OS benefit. This was a point AVII77 made back in the day that had merit but since then is not mentioned by those who look at this trial from the bear point of view as he did. Like you, I don’t think failed PFS automatically translates into known OS benefit either but if seen by a closer look by regulators, their actions in that light are understandable as are those of NWBO based on blinded data correlations, unblinded manufacturing movement in 2020 and the lack of concern by peers at JAMA.
The rational for doing what was done during the screening halt has seemed clear to me for quite some time. Due diligence going back to the Phase 1 results indicated that benefit would be found but not with identical results because of typical drop off in Phase 3s vs Phase 1s even though I hoped for close to identical for quite some time. Evidence of efficacy is why I also believed the enrollment discrepancy was related to missing SOC/patients before that was disclosed. Evidence without a proven acceptable measure to account for treatment benefit or a clear path forward to commercial scale manufacturing is a big problem, though, just as you realized and needed to make an adjustment for. Just glad it wasn’t too big for the Lindas ; ). Best wishes.