NorthWest Biotherapeutics Inc (NWBO)

[longfellow95]

Nobody knows because they are still trying to draw up a SAP that they can use to claim victory.

Not to 'claim' victory, but to achieve approval.

And what is wrong with that?
They are doing all that they can do to overcome the issues of pseudo-progression, crossover, and the depowering hold.
Would shareholders and all other stakeholders including patients, expect them to do anything else?

Let's not forget that the actions of the FDA have been instrumental in hamstringing this trial.
Firstly, by the apparent insistence on a crossover. This was where potential confoundment first came in.
Hindsight is wonderful, but this is when NWBO should have taken a raincheck.
With a planned ratio of 2:1, control arm size was already considerably smaller than ideal: add in a crossover and you also no longer have a clean OS comparison.
At that time, they perhaps should have gone for 1:1.
Or do what BMY did in 548. Start off with an OS primary, so no crossover, then change to a PFS primary down the line, when it is too late to have a crossover.

Then, an issue arises mid-trial leading to a recruitment hold.
FDA allows further recruitment to treatment, but not to control.
And prolongs the hold indefinitely, to the point where NWBO announces they can no longer keep recruitment open, due to all the logistics and expense.
Then and only then, the FDA lifts the hold. This further skews the ratio and caps the numerical size of the control arm to 99.
Too small..(From a powering point of view, it would have been much better if the recruitment post the start of hold, had all been to control.)
Thereby robbing the trial of chunks of statistical power.
The additional powering afforded by the 2014 enhancements is robbed away completely.

And then we have the independently powered game Dr B played om longs. Standard primary/secondary are independently powered. Dr B tossed this out because he knew longs would spin it to assume incorrectly it implies co-primaries. Disgusting.

Well, the 2014 enhancements already suggested that alpha spend had been split with reference to a p=0.02 PFS spend.
So, Dr B's comment may have been a simple statement of fact.

I view the FDA actions in relation to this trial with considerable cynicism and distaste, and 'bad actor' comes to mind..

Still, a rigorously adjudicated PFS will be clean, but a sizeable delta will be required to achieve nominal stat sig.