Replies to post #277234 on Avid Bioservices Inc (CDMO)

[exwannabe]

Why isn't all the data from those patients considered blinded?

The analysis of all 592(?) patients up to Feb(?) was the final analysis of the formal blinded trial.

At that point in time, the trial was unblinded. Patients were told if they were on treatment or not. PPHM continued to follow the patients (as is normal), but that data is follow-up, not the formal data endpoint.

But all this is a nit on the story. The trial endpoint was OS in the entire population. That failed, and failed badly (OS 10.7 vs 10.8 months).

At that point searching through bunches of subsets is worthless for FDA approval. And despite what CP says, 200-240 was a subset. And likely one of several dozen. With 20+ such, you would be reasonably likely to find one with P<.05. Just like the blue jelly beans.

There was never a SUNRISE BLA in the cards. Garnick gave the correct answer to that idea when he laughed.

[Protector]

jbainseky, the data must remain blinded even AFTER enrolment (incl. treatment and AFTER treatment maturation). The patient (mainly if we consider placebo effects) may NOT know while he is still part of the trial (before eventing or progression) that he had Bavi or placebo. Even progressing patients are not told unless a Doctor asks (e.g. in function of another problem that must be treated or a 3rd ln treatment - in which case the DMC can call for isolated patients unblinding and PPHM had a procedure in place for that).

Since PPHM followed the advice of the DMC (STOP Sunrise at first look-in) we know that only 33% of the patients where at that point. Since STOPPING went hand in hand with unblinding (there may be a couple of weeks in between but that doesn't change anything) ALL DATA behind that point is considered NON-BLINDED.

Why: A patients alive in the test, hence not evented, and possibly not even progressing, is after unblinding considered to know in what arm he was because he must reply to the question if he wants further maintenance with bavituximab or not (the placebo patients do not get that question because there is no such thing as placebo maintenance).

Hence as of that point an effect may kick-in because the patient now KNOWS FOR SURE that he had Bavituximab or not. The FDA would therefor not want to consider that patient in the results. he may have lived longer because he knew that he got bavi or event earlier at the surprise he was in the placebo arm. This would kind of be the opposite of what the FDA wants to avoid entering the results because it would create an artificial spread between arms that is not due to Bavituximab.

Unfortunately, and the reason why there was NO STAT. SIG on the BLINDED part is that the Bavituximab patients often arrive in the part of the data collected/matured after unblinding. That is NORMAL in this case because bavituximab worked and performed as expected and hence these patients end up in the median table AFTER unblinding and helped achieve statistical significance for efficacy with 74% increase in overall survival.

That is were the matured data became stat. sig. and a correlation with biomarkers was possible. Unfortunately not in a way that is acceptable for the FDA but still unvaluable for PPHM.