Replies to post #107210 on Avid Bioservices Inc (CDMO)

[freethemice]

Thurly, I agree that comparison with the mean of the historic control arms would
make more sense, at least to me. The trial has really become a single arm trial, but
randomized and double-blinded at the same time. However, there is the logic that the
original control arm if corrected by removing treatments with 1 mg/kg would result
in an even smaller MOS than 5.6 months. That is why I think whatever happened didn't make
much difference at all. If the only requirements for moving to phase 3 are that treatment
with bavi is safe, and there is good indication of efficacy, then I think it can happen.

[geocappy1]

Maybe there will be multiple control groups. It seems like the best would be the 40 patients who received primarily SOC with a few rounds of SOC+ bavi

[Protector]

Thruly, whatever we may think of that comparison I cannot believe that Garnick takes something to the FDA's end of PII meeting that makes no chance of being considered by the FDA.

I mean by that that no matter what the outcome of a decision will be Peregrine knows upfront that what they forward to the FDA will be acceptable and evaluated. That doesn't mean perse that the results will be found sufficiently good.

Furthermore we will have to see how they composed that new arm. They may have removed SOC+Bavi patients (if any) from the control arm and added SOC+placebo patients (if any) from the 1mg arm and discarded all SOC+Bavi patients (if any) from the control arm and discarded the 1mg arm completely for the rest.

They would then have a control arm with only SOC+placebo patients and a 3mg SOC+Bavi arm to move to the FDA. This wouldn't even invalidate the statistics of randomized assignment because the criteria for reshuffling where based on an error that was made during the 'blinded' period and so any form of manipulation of forcing certain patients in a certain group can be ruled out, which is the point of the randomization.

So I think that the statsig of the 3mg arm will be the issue to tackle with the FDA. That is where survival data, updated MOS and possible Bavi's performance in other trials as well the 'kind of' moral feeling of involvement of the FDA in having licensed CSM, that should have made such errors if they follow procedures, will come inline.

So I think we'll move into a PIII where a larger group of patients and probably even stricter procedures will be design at which point or 77% MOS increase (after error correction) will very probably become 100% or more again.

If like Garnick you pass 19 key drugs of BP's through the FDA then you know what is possible and what not and you have your informal contacts. You call and say:
- Joe, if I would... and ... do you think that would be acceptable.

and Joe replies,

- Will if you would ... and ... then I see no problem, but if you ... then we will almost certainly reject.

A 3 months later Garnick sits with Shan and others in the FDA meeting and Joe sees that the file has been molded according the information he provided and you have an allie at the other side of the table if the data is good, ONLY IF THTE DATA IS GOOD. Joe is not going to stick his neck out for Garnick.

That is called the HUMAN factor, rules are as strict as the strictness with which they are applied.