Replies to post #211853 on NorthWest Biotherapeutics Inc (NWBO)

[CogDiss 1188X]

I did a very rough estimate on that and it seems like they might come up with 99 or less controls roughly 15% of the time, so not a crazy result. Someone who is better at stats want to give it a whirl?

[exwannabe]

Still scratching my head as to how the hell they ended up with 232 test patients and 99 control if they were randomly assigned as les said...

The only thing I could even possibly come up with is that used a randomization alg that was designed for a trial with many less sites (the original design). With only a handful of sites, it could not have gotten as far out of balance even w/o a design to force/nudge it back in balance.

But increase the number of sites, and the chance of a larger imbalance goes up. That is why trials with a large number of sites would have a strategy in place to keep the balance intact.

It it possible that they simply used a bad randomization design for the trial given the final number of sites?

Hodag (on the other board) who is clearly in the industry scoffed at this. And I totally understand his view. But I do not see the numbers this far out w/o something being out of whack.

Note: It was stratified by site and meth status. The site stratification might have been a bad choice with a large number of small sites, geography might have been better.

[doingmybest]

jammyjames, I agree, seems quite improbable. I think LG cannot talk to this now so he is limited in what he can say. You would have expected the randomization to have some of each arm still to fill, not 17-0. I have come to think there was a subtle mfg enhancement made which improved the therapy but was assessed by the company not to have any quality impact and did not violate the process validation and FDA had an opinion at the time that questioned whether more comparability testing should have been performed. It took more time for NWBO to convince FDA that all is fine and the product is technically unchanged. There is a lot of learning going on in industry and in FDA regarding mfg of biologics and cellular products.