Replies to post #392959 on NorthWest Biotherapeutics Inc (NWBO)

[exwannabe]

Re: Pazdur speach

16:30 to 17:30 is where he talks about in the 80s the FDA set OS as the gold standard for oncology. The reason was based on the fact that chemo sucks so a benefit has to be real.

17:30 is where hs starts to explain the changing FDA thoughts:

Let's jump to the new millineum. With the advent of targeted therapies it became apparent that a revaluation of the dogma that OS was the only acceptable endpoint. that needed simply to be re-evaluated.

First, for the drugs demonstrating unprecedented response rates in early clinical trials in oncology with few therpuetic options for patients the ability to either a drug with a markedly improved durable response rate
vs. a toxic and marginally effective drug simply was not feasible and was of questionable value to either society or scientifically.

Equipose, a concept in modern medicine XXX in the concept of randomization simply did not exist in many situations.

If a randomized study is conducted in these situations investigators and patients requested crossover to the investigative drug at the time of disease progression in those drugs that demonstrated early unprecedented activity.
So, this request for crossover at the time of disease progression probably reflects that true equipose did not exist in the randomization process.

This crossover may ..confound the demonstration of improvement is OS because patients are basically patients were basically receiving in both arms the same therapy albeit in different sequences.

He goes on to state 2 more reasons. Longer OS in some settings and smaller populations with molecular selection of targets.

At 20:13 he sums it up saying the 3 features (the above 3 reason) may limit the use of OS in oncology so they needed to look for alternatives. He then goes on discuss alternative endpoints.