Replies to post #253891 on NorthWest Biotherapeutics Inc (NWBO)

[flipper44]

Unless, you've already won, but early efficacy would doom your product for approval, so you'd want to make the case it really was a race to a blind audience. Many years ago Les said to me, patients go to the Optune trial to die, and they go to the DCVax-l trial for a chance at life. About the same time, LL stated it seems like everyone is living longer. The FDA has a duty to warn a company, before they end/test a trial for possible efficacy, that an early termination might prevent any chance at a marketing license. Of course it might have been all about early PFS confoundment (as opposed to early success), but the CROs apparently moved the last 31 patients toward the treatment arm and away from placebo. It's probably why a surly cast of characters have been on this board before and after. I know I anticipated the possibility of a lengthy trial long ago, but nothing like we have today.

I think God He stole the handle and
The train won't stop going
No way to slow down -- Jethro Tull

[Doc logic]

Lykiri,

If you look at what trial expectations were for median OS at around 17 months then Dr. Linda Liau's 2015 statement makes more sense. Since methylation status was unknown in some of the vanguard group I think her statement points to her belief that most of these were unmethylated which correlates to earlier eventing. As you point out, by 2015 there most assuredly was data coming in on the low absolute lymphocyte count patients and that must have been showing a strong separation with about a 2 to 1 confirmatory ratio. That would be a huge treatment benefit signal that would require further investigation of the data. Remember, the low absolute lymphocyte patients were being watched very carefully so this presented a possibility for a good snapshot of longer term treatment benefit based on outcomes from a patient group expected to event sooner. Best wishes.

[biosectinvestor]

I have always said that the placebo patients were likely not doing as well and it became apparent that their later dosing was harmful...but a full halt would undermine the trial, so the “partial halt” was indicated, without updating disclosures of any additional risks to patients. The Germans are more anxious about medical experimentation than Americans due to their history, though Americans should be at least as anxious for the same reasons. I think one of my earliest posts was about that ethical level of focus in Germany.

I do not think placebo patients were doing any worse than they would have otherwise, as someone tried to suggest in a response, only that it became obvious early on that DCVax patients both lived longer and were not subjected to any additional substantial risks due to the treatment. Ethically, it was the moral thing to do to end the placebo arm, in my opinion, and neither to notify the company or anyone else as to why... because that would spoil the trial, and that also is viewed as unethical experimentation.

This is all just my opinion, based upon inference and deduction.