Replies to post #439298 on NorthWest Biotherapeutics Inc (NWBO)

[Reefrad]

I agree. This hypothesis is beyond the realm of reasonable speculation. The idea that a regulatory body would look at data that is still randomized and force a company to stop placebo is way out there. Remember that all patients on placebo were still getting SOC chemoradiation.

The truth is probably much simpler, pseudoprogression caused major issues and then OS raised the issue of crossover.

[MI Dendream]

I am one of the originators of this thesis. In my thesis, neither investigators, patients nor company knew that placebo was removed. BTW this was my thesis in August of 2015 which I shared with everyone invested as a connection with me.

Evidence to this thesis is the FACT that the final 31-32 patients were only placed on treatment, no randomization to placebo. While this only directly ties to those not yet randomized, the rationale to do this creates a moral and ethical obligation to treat every human being who volunteered their life to the study of a potential therapy. There is an obligation to those patients to first do no harm and to progress with GBM is to die, at least if they stay on placebo, and at that point it is not known whether or not DCVax can rescue a portion of them after progressing, it was only known that it delays death before progression.

[skitahoe]

Senti,

I think it was clear that after the halt all patients added to the trial received the vaccine and they reduced the total number by those who otherwise would have received the placebo. By the time the decision was made, and the trial resumed to add people, all that were in the trial in the control group would have crossed over if they wished. I suspect we'll find that all who didn't cross over either died, or were too ill to do so by the time they had the opportunity, but we'll only know that when we get the data.

During the halt I'm sure that those already in the trial would have continued to be treated just as though the trial was continuing. No doubt many lined up to initiate the trial at the time of the halt were no longer eligible by the time the trial resumed.

I don't know if at the time of the halt the company and the regulators discussed changing the primary goal to overall survival, but clearly that wouldn't be something you'd want in a trial where the control could cross over on progression.

In the past I've seen trials that went bad because control patients lived longer than historical data justified. I believe it was clear that many of these people used other therapeutics once progression was determined and they did gain benefits. The drug in question was abandoned, I suspect it would have been approved if based on historical information. It did produce results that were better than the control, just not better enough.

Gary

[MI Dendream]

If patients and or physicians were to know that treatment was altered in any way, the company would then also know, and that destroys the integrity of the trial. It is the CRO that administers the blind.