Replies to post #6992 on NorthWest Biotherapeutics Inc (NWBO)

[Pyrrhonian]

That's a decent summation ou. In the literature it says that prior to beginning a trial the sponsor meets with the FDA to determine a set of "stopping boundaries" for the trial. Should these boundaries be crossed before the end of the trial, the DMC will almost certainly recommend an early termination due to efficacy (which is why they were put in place to begin with), and the FDA will back it up. However, if they are not all crossed, but most are, the DMC can still recommend it, and the sponsor accept it, but they are warned by the FDA that such action "would increase the possibility of a type I error." The FDA may reject such a request. It is far better to wait until all are crossed. However, and for the sake of argument, let's suppose 8 of the 10 are crossed, and they surmise the other two will take another 10-14 weeks (from some 6 weeks into the review) to be crossed. Should the DMC simply advise a "continue" until the 88th event (possibly another 5-6 months away), or should they just wait it out? Of course, they cannot tell management of this (hence their response to the moaning public that the efficacy data is "pending," is "outstanding"). The steering committee/ firewalled employees are briefed by the DMC and make the call for NW management until they are able to unblind them to the data. I believe THAT is where we are now.

It makes logical sense to deduce that the steering committee was presented with the dilemma, they in turn approached the FDA seeking "clarification" (from FDA guidelines), the FDA unblinded the PEI according to the obligations of their arrangement, the PEI approved the vacc., enrollment is no longer needed there (halt is imminent), and we are simply waiting on an outcome that would prolong the lives of many more patients than halting now and risking the FDA finding something in the data (type I error) that would cause them to recommend another ph III trial. Whether or not it specifically involves the pseudo-progression group is just an educated guess, but what I outlined above is not. It's the most likely reason for such a lengthy delay (imo). All of the pieces fit this way (especially the 'timely' German approval).

[foxhound02]

Ou:

Keep in mind that your whole scenario is recounting The Flipper Epic, which may well be true. Alternatively, there may be issues with the data, which is the most common cause of a delay. The more time goes on the more I am leaning away from early approval. Too many parties would be involved to keep a secret. Price would be rising. Either way I am fine. If we take it in the teeth and need to expand (delay) completion, well, that is must what is bound to happen when I am invested in any biotech.

[Doktornolittle]

OU: Regarding evidence for your summary of the positive model some of us have developed/bought to explain the delay.

On the other side of the pond you have the Germans who have approved effective compassionate care in Germany for anyone, with insurance (to be worked out) for Germans. This would appear to create the situation where the only people in the German trial would be foreigners who could not afford the out of pocket compassionate use in Germany. They could only get the 67% chance of getting DCVax-L, for free, offered by the trial in Germany.

But this seems unlikely and one poster convincingly argued that they would definitely never do this due to the huge advantage to the wealthy. That such is a topic of discussion and resolve in Europe.

So if you buy those things... then you either have a trial in Germany without a placebo, or no trial in Germany. Add Flippers claim that the Germans had ruled out the pseudo-progression group for their trial... and you end up with a limited number of possibilities to explain what is going on here in the US. The explanation you outlined is one of them.

So what are the bad assumptions or logic above, and or what are the other possibilities that explain all this?