Replies to post #439661 on NorthWest Biotherapeutics Inc (NWBO)

[meirluc]

4. (18 Distribution of final 31 patients): ALL PATIENTS WERE RANDOMIZED You can't just put a group in one arm or the other. NWBO had nothing to do with which patients ended up in which arm. Because of the large number of sites, the final randomization may not have been exactly 2:1 but may have been off by a few people one way or the other.

The final randomization was 2.34:1, and definitely more off by a few people from the planned 2:1 ratio.

It is also remarkable that the last group of about 108 patients (32.6 of the trial), ended up with at least 42 of the 93 (45%) post 36(+) months survivors, whereas of the preceding 223 patients only at most 51 (22.9%) were post 36 months survivors.

If the randomization pattern was roughly the same throughout the trial, what were the reasons for the later group's superior survival capacity?

During March 2017 when the data for the 2018 JTM article was collected, 62 of the 108 patients ( 57.4%) were still alive and 46 (42.6%) had died.
I am estimating that at that time the median time on trial for the last group of 108, was about 22 months and the mOS of that group, with 54 alive and 54 dead would roughly have occurred at 24 months. This would not be very different than the 23.1 months mOS of the entire trial. Therefore, at that time (2017-2018) that last group of 108 patients did not seem remarkable.

However, something remarkable must have happened thereafter because of those 62 March 2017 survivors belonging to the last group of 108 patients, at least 42 (67.7%) went on to survive at least 36 months.

If the survival capacity of that last group of about 108 was not related to an overrepresentation of Treatment patients, what were the reasons for this group's superior survival record?

[biosectinvestor]

They would not be told the randomization was otherwise. It would of course still go through the DSMB.

The answer makes no sense, the randomization is exact. They do not just end up with missing arms. His answer can be heard a lot of different ways. People heard it the way they heard it because they believed and still believe certain things. But we won't know until we and they know.

When for instance, the DSMB might be required to eliminate an arm, let's say for an ethical reason but not yet to break the blind, they can still "randomize" to another arm, it's just that neither are placebo. The company was blind all the way through, so there is NO WAY they an know anything specific about the randomization and of course they are going to continue saying that is the case, because as long as they were concerned, IT WAS.

Of course the FDA was involved in the HOLD. As I said, if ANY regulator places a hold, the FDA is immediately and automatically involved and the trial comes to a halt. But the original halt is still applicable as you can see from the very website that confirmed the change to the end points. The FDA's hold was not necessarily the CAUSE. Different issue than who was involved.

[MI Dendream]

Yep, I remember this all now. Thanks, Senti.

I’ll say it now if I didn’t say it exactly this way then. Hogwash.

I indicated then I am nearly certain that I believe FDA would consider the imbalance still randomized since everyone else involved did not know it occurred, assumed randomization happened and all remained blinded. In 2019, Les still remained blinded. Technically, until sites were locked down and sometime thereafter, they could not really see where imbalance even sat and I am sure it is spread over many sites, where the last 32 enrolled.

I picture this, Les, Marnix LP and a few others siting around a table discussing the possibilities that explain a 32 imbalance of patients who substantially weakened my study by taking 2:1 randomization up to 2.34:1. A study that I am also led to believe has regulators somewhere halting me for some, the gods of trial design only know, reason…oops I mean halted new screening as otherwise everyone else just carried on forward as if nothing in the world just happened. And I am suppose to believe this at a time when everyone still says FDA is making them use the original endpoints…LOOK OUT FOR THE POTTED PLANT.

Yes, I am certain that something like this came out of somebody’s mouth in that meeting…“I don’t know maybe some flaw some where happened during randomization and somehow the system that corrects imbalances by every damn factor known to man even regionally went wrong this one time by such a huge number that no clinical scientist on earth out there is gonna believe us, but yea maybe that did happen…pause…if that’s the case then what the hell do we do?” That followed one of them saying…

“We can all see they stopped putting patients on placebo, so how do we answer them to get them to move past it?”

That same person afterwards said probably said something like, “Ok, but I can’t sell that so which of you is saying that, and it isn’t you Marnix? We need plausible deniability.”

“Ok, put on a nice Hawaiian shirt at least please, Les. We have a long time coming still and it would be nice to maintain some valuation in case we get desperate again.”