Replies to post #124093 on NorthWest Biotherapeutics Inc (NWBO)

[longfellow95]

Inflammation looks like progression on a scan according to both Macdonald and RANO (not sure which they're using). Assuming PFS failed I'm hoping they've thought this through and have a plan. If this is the case, convincing data to show to the FDA could include demonstration that this is typically pseudoprogression. I assume they are monitoring the tumours in these patients semi-real time so after progression they can show that months down the line that progression reverts.

I don't make the same assumption about the PFS endpoint, but they are reviewing all patients by visits in person to all the 80+ trial sites.
They are reviewing medical files, MRI images, and other documentation, so I think it's safe to say they are reviewing progression calls. They will have to do this with all subjects from both arms, except perhaps non-progressors. And the site visitors will still be blinded. Quite a big undertaking. So yes, they have a strategy to overcome the issue of pseudo-progression being called as progression. And they're probably doing this after consultation with the FDA.

From 6 Feb 2017 PR:-

The external parties managing the Trial are now moving forward with the process to reach data lock. In this process, all data from all of the treatment visits and follow up visits for all 331 patients in the Trial, must be subjected to quality control checking. The process involves in-person monitoring visits to all of the 80-plus sites in four countries to review the files onsite, as well as other documentary confirmation and checking of all MRI images. As such, it is a multi-month process. While this process is under way, OS and PFS events will continue to accumulate.

https://www.nwbio.com/nw-bio-announces-lifting-clinical-hold-dcvax-l-phase-iii-trial-fda-progression-free-survival-events-reached-overall-survival-events-not-yet-reached/

I think in several years once the field has matured a bit it will become clear that progression is the absolute worst endpoint to use in an immuno oncology trial.

Basically agree with you here. Unless progression is measured in a much more meaningful way ie not a simple longitudinal measurement of tumor.
At the very least, tumor density should be calculated, along with the broader clinical picture.