NorthWest Biotherapeutics Inc (NWBO)

[longfellow95]

Hi Senti.
Thanks for laying out the treatment schedules again.

I agree with your remarks, but there are still some uncertainties for me, about what actually happens in practice, after a treatment patient crosses over. Does such a patient actually start getting a placebo dose after all their treatment doses are exhausted?
Certainly, some have stated that a placebo dose would definitely not be given to a patient who started out on treatment and then crossed over. I really don't know, but suspect that was the case. And if patients were told their doses have run out, perhaps that indicates that placebo doses were not given (to anybody) after crossover.
It's just an anomoly for me, that it would be good to know the answer to.
If you have seven of the treatment doses and then progress (as you suggested), you will quickly use the remaining 3 doses of active drug. I think it is more likely that that was when patients were told of doses having run out, rather than being switched onto the placebo doses.
And that being the case, it would mean that the patient and the doctor would realize what arm they started out on.
So that would be a slight compromise of the blind, but I can't see how they would have a practical way to avoid that.
And of course, it wouldn't compromise the blind at all, as regards PFS.

Then again, I keep thinking about the shelf life issue. Patients who were late crossovers (maybe after 3yrs) could conceivably run up against this issue, whichever arm they started out on.

And the minimum number of doses required is another one where I have seen hints of inconsistency.
You stated that a minimum number of 5 manufactured doses was required to get in the trial. You maybe got that from a version of the protocol.

In JTM however, it implies that 10 doses are required:-

In general, approximately 2 g of tumor tissue was needed to produce the full ten doses for the 36-month treatment and follow-up schedule. The vaccine was aliquoted in individual doses and cryopreserved at?<?150 °C [22]. The doses were stored centrally, and shipped individually to the clinical trial sites.

I'm just cogitating really about procedures following crossover.
Because I think there may be a link with the partial hold, and crossover provisions that one of the regulatory bodies might have deemed as deficient in some way.

Certainly, I'm thinking the hold was less likely to be about safety or efficacy per se, and more likely to be about some kind of technical deficiency with the crossover arrangements.


Just thinking out loud.