NorthWest Biotherapeutics Inc (NWBO)

[skitahoe]

Doc,

I believe in the future far more trials will be run the way this one was, but without the halts unless really necessary. The control will be historical data, the goals will be adjustable based on what's learned during the trial. In short, the trial sponsors, clinicians, DSMB, and regulators will be able to work toward success, rather than maintain a protocol and trial that's leading to failure. I believe this trial caught the attention of all involved regulators for several years, I suspect that discussions with them led the company not to end the trial till the last patient to enter was 5 years into the trial.

Not every trial will be OS based, but if pseudoprogression is found in other trials, and if it's not possible to differentiate between real progression and pseudoprogression the regulators will have no problem with simply dropping that goal completely in the future. You can't blame companies for trying for PFS, it can greatly reduce the duration of the trial, but it's clearly better to succeed on OS than fail on PFS even though a lot of trial patients are alive. I really wonder how many prior trials may have failed because of pseudoprogression and never knew it as the drug was abandoned after failing on PFS.

I would have to say that whether they admit it or not the entire industry has learned a lot because of this trial and it is resulting in numerous regulatory changes.

Gary