Doc logic,
Not to completely rehash this subject but knowing it was an important step in the NWBO story, I believe NWBO saw FDA basically as less of a partner than MHRA at the time. I have not known FDA to be very concerned about other RA's but they also do not want to do things that fly counter to advances being made in the global industry either.
It was FDA who required the crossover, which makes sense from a patient perspective though it greatly complicated the trial results, then it was FDA who applied the clinical hold when NWBO was accommodating the crossover and was concerned about the PFS and OS convolution of the data caused by the crossover and the additional pseudo-progression issue. One can see quite a corner FDA was creating for NWBO to be placed in even if it was not intentionally designed as such. (I will not expand into FDA internal workings, potential corruption and industry pressures and influences.) Now patients can pseudo progress and crossover or not and they can progress and crossover or not or they can not progress,... Even FDA does not always see the forest from the trees nor can they always navigate the forest of their own bureaucracy and regulatory framework in light of new medical advances such as what came to light during this trial in the relatively new immunotherapy field. The fact that it was tiny NWBO uncovering these things was not optimal for anyone in the short term but I believe it will be in the long term.
I have never been able to completely reconcile the FDA requirement to reduce the SOC/placebo population by 17 patients which NWBO still wanted to include for powering purposes since they still had the crossover option as the trial was designed to accommodate. Your explanation is feasible, I am just not so convinced it was the German influence I have no better solid hypothesis on this other than FDA became convinced there was little to be gained from more SOC/placebo crossover candidates and that was not in patient's best interests, though I think NWBO felt it may weaken their dataset, which is everything in such a trial. FDA always has the right to punt and say the ultimate responsibility rests with the sponsor and their guidance is just that. Sometimes there may be more or less motivation for FDA to find the optimum solution, sometimes they will punt and let the play continue after stepping back.
All in all, it is wrong to allow Wall St to have such a destructive effect on companies studying life threatening diseases who are breaking down historical beliefs, utilizing new tools and making truly breakthrough discoveries for the benefit of the health of mankind. Once it became obvious there would be timing delays with the trial by changing from a convoluted surrogate endpoint to the 'gold standard' of OS, the ultimate goal of all cancer therapies, the Wall St demons had their day. Unfortunately to Wall St this is a financial game while to brain cancer patients this is truly life and death. Maybe and hopefully US law will soon protect at least such medical advances from the Wall St demons.
Now NWBO has just about made it, we need the proverbial fat lady to sing that MHRA has approved DCVax-L for n and rGBM and maybe more! Then LP will open up her communications and all mankind will benefit.
GLTA and Happy New Year!
AI
