Avid Bioservices Inc (CDMO)

[Protector]

The dust is lifting

exwannebe, reply to your three posts because the answers can be combined.
exwannabe 1 exwannebe 2 exwannebe 3

1) The September trial did not have the problem. As explained the more extreme the results are the less it can be obtained by chance in a clinical trial. The 13.2 MOS was double the SOC MOS and extremely high compared to the Historical SOC MOSes. So or it must have been Bavi or there is an error in the data analysis or there is some cheating involved, but by chance you don't double MOS.

2) You wrote:

If the problem with this trial was the ECOG=2 patients, ask PPHM why they even allowed them in the trial

The problem is WITHOUT ANY DOUBT the ECOG 2 patients. I cannot answer why they allowed them in the clinical trial. However it is not important because the trial was not seeking significance as FTM pointed out already and my post was a aimed at explaining why PPHM best didn't provide p-values WITHOUT providing also the full detail. The full detail is for a scientific conference, probably under embargo(ASCO?). You wrote in reply:

They failed to provide it for this trial becuase it was not good.

I anticipated:

As a consequence PPHM has all interest to provide p-value at a moment where they can FULLY attract the attention to the imbalance of ECOG=2 patients in the pancreatic trial. There where 3 times more ECOG 2 patients in the Bavi arm then in the Control arm.

check my original

And the following is incorrect, that claim hasn't been made, the words sex, age don't even appear in my complete post. I am glad you kind of bring it back to "overall tone" in your 3rd post.

Stratifying based status, age, sex, etc., is very common. To claim this can not be is nonsense.

ImaPseudonym,In your post I noticed that you didn't really get the point about the pseudo-positive. Not that it was impossible because others did and DrRocker even re-worded it in a TOP ON way.

I also see that you feel addressed by my post. Apparently you feel that the shoe fits you in some way.

Despite CP's recent warnings about people (me?) who try to distinguish carefully between what we know and what we are guessing about - here are a couple things to keep in mind.

Unfortunately for you, this statement in which you try to hi-jack to role of the careful house father holding the patent on the process to distinguish fact from speculation will not fly. You are on a board where most posters give intensive links, sources, reasoning and if not are challenged by others to do so if the claims are not part of the general knowledge. As you will find out below, just labeling a heading with "speculation" is insufficient to roll that wheel before the boards eyes.


But to the core of your post now.

In the original 9/7 report, which included p-values for the mos data. The data for the 3mg arm (compared to the soc alone arm) was not statistically significant. p-value was around .07. They were only able to report statistically significant results when they combined the 1mg and 3mg arms into one (increasing the number of subjects) which got the p-value well under the normally necessary .05 ... + 3 next paragraphs

I know you are no so long on this board but no so long ago, I was the one that raised the non-stat sig of the 3mg arm issue and popped the questions after another posters attracted the attention on the fact first. I was told by the most reputed posters on this board that it was irrelevant, that in PII we search safety, signal and not efficacy and that it was up to IBM to know if they they would continue with a PIII if the FDA agreed on safety and signal.
This post is the answer that I gave to oddone33320, which was about the impact of the discrepancy's in the interim data results of the 2nd ln NSCLC and not about future final results, nor stat sig of 3mg arm given the non importance of it for the progression to PIII.

As for your section marked speculation:

It could be that the additional data has come in since the early release such that, had there been no discrepency, the 3mg arm would have a higher mos and/or a better p-value. That might be enough to keep the results at par with the earlier ones after the corrections are made for the discrepencies.

- Discrepancies occurrence is irrelevant for the 3mg arm because it was not affected.
- The 3mg arm MOS on 50% passing away can NEVER improve because its median comes out of an ascending ordered series (logic, your specialty!)
- The only thing that could make it look better would have to be that the median of the control arm shifts more to the left then the median of the 3mg arm.
- With the MOS of the control at 5.6, only 0.4 away from historical low of 5.2 and Bavi pollution of the control arm sample it is not impossible but if, then there is not much to gain.
- MOS in the control arm was reached long ago, since it is assumed PPHM tells us the good and hides the bad, they would for sure have given that info if it would have occurred in their Sept 7th PR.

So the answer is : NO, the 3mg MOS can't get better, at the best the control arm could get some worse. What troubles me is that by all posters it is someone that teaches logic that asks this question, so yes I may have been subconsciously been offering you the shoe to try out and you just did a quite convincing attempt to make it fit!

It could be that they do not end up doing a full combine of soc + 1mg arms. Maybe the data they got about levels of bavi in the blood were enough to not have to put all 1mg patients into the control arm.

It could be that the FDA doesn't let them use their combined soc+1mg "control arm" (I don't think there is a lot of precedent for that) and they end up using historical soc data. I don't know what that will do to either the difference between 3mg and soc mos, or its significance.

They could use historic vs 3mg arm as Thruly suggested. The fact they officially loose dosimetry data isn't that important because it is a PPHM decision whether they, after an FDA end of PII meeting go, enter the cost of a PIII. For PPHM the 1mg arm data isn't lost completely because the know EXACTLY what the magnitude of the discrepancy are and for dosage decision they may isolate patients from the 1mg arm. As long as they don't go higher then 3mg.

It could be that there is a way to increase the margin of error in order to increase the statistical significance of the 3mg mos, by reporting that mos in a range. I don't know enough about how they run the stats in these things to know if that is really an option. If it is, that might mean that the reported number looks lower than before.

We don't need all that. Historical+3mg and safety will do fine. If PPHM goes for the conservative approach, combining control+1mg, then they know what they are doing and why. For all we know the aim for an FDA 'NO GO' so that CSM finances them a new trial and they can change the design based on what they learned from this one. That probably isn't the case, just demonstrating we don't know why PPHM choose the ctrl+1mg combination but they sure have a good reason.

It could very well be that the data is still strong enough to go to phase III (based at least in part on the strong safety factor). And none of these ways in which the 3mg arm data might be worse end up mattering at all. Potential partners and the FDA will have access to stuff we do not.

This includes the subtle suggestion that we are not going to be allowed a P III by the FDA, and that making it there would be a lucky shot. As for the bold part of the text I let it make it's own case and let the reader find out what 'non of these ways' refers to! There is one, and just one, way and that is censoring patients in the 3mg arm after the 50% MOS event occurred. In all other cases PPHM must have lied to us in the PR about the 3mg arm not being impacted by the discrepancies.

You see, when you try out shoes a few minutes later they already fit better.


Drumstick7591, hhmmmm.

finally a post that is not totally filled with some wishful thinking and conjecture and second guessing as I have been hearing from many here including Cloak.

Well there must be something wrong with your hearing because for starter my posts provide all reasoning and basic data available. They are positive, yes, absolutely correct but you cannot say that if there is some negative or ney to say I say it too. I didn't ignore the class action, the uncertainty about whether PPHM even filed for breakthrough, I pointed initially the 3mg non-stat sig out, i commented on BoD/Management's communication problems, etc, etc. I think I have a track record present in concrete under the form of un-deletable posts on IHub.

What I find low, and see as prove of the underlying agenda of your post, is that you have to attack Loof's contest, WHICH WE ALL KNEW WAS A GAME (you didn't really think Loof was going to send you 10 death Squirrels if you won, did you?) to make your point.

so this is mostly fun and games.

and the boards projections of when they were supposed to report data on the PC trials were all wrong as well.

The board used the corporate fact sheet and that projected Pancreatic in Q1/2013. I don't think the board did project many dates outside the Q1 of 2013, if any!


You where correct about ImaPseudonym's post.

finally a post that is not totally filled with some wishful thinking and conjecture and second guessing

Because indeed it wasn't filled with that, it was carefully writen, I agree. As demonstrated higher it was filled with "up front and generally know impossible positive speculations, such as the 3mg MOS becoming higher", farced we irrelevant intermezzo's such as "had there been no discrepency", which for the topic at hand the 3mg arm we knew it wasn't impacted, just helping to confuse the cat.

Would this qualify for pseudo positive coming from a poster who demonstrated that he for sure has the know-how to know the answer to the raised question?