Does this mean there where no placebo problems at all?
No, it means there where no problems at all with the control arm and it's placebo labeling and distribution but is doesn't exclude that people in Bavi arms didn't receive some placebo. However, it is very unlikely they did because for that to happen we need more then just coding and labeling errors, for that we would also need more delivery of placebo and therefor somewhere production and ordering errors because one cannot label what he hasn't received. The other way around it is excluded that control arm patients received Bavi because there is no Bavi in circulation in these arms.
What coding discrepancies are remaining possible then?
The most obvious would be that patients didn't receive the 1mg and 3mg doses as assigned and that symmetric mix-ups occurred. For each error in the 1mg arm there is one in the 3mg arm. It would be hard to believe that docetaxel would have been labeled Bavi or the other way around? Normally the SOC comes in standard pre-labeled and only the Bavi must be dealt with by the CRO. All arms receive docetaxel. What could also be is that some 1mg or 3mg Bavi wasn't administered at all but then there would be some spare Bavi around somewhere or that some patients received higher doses but then Avid must have delivered them or they must have been taking from patients with follow-up treatment. All possible but unlikely compared to symmetric dose mix up.
How did Peregrine discover this?
Peregrine checked the patient's sample test results and patient treatment code assignments and by correlating them found the discrepancies for some, not all, patients.
In English please!
In a randomized double blinded clinical trial patients have a treatment code that is assigned randomly and that classifies a patient in a treatment group that receives a certain treatment. This is called patients treatment code assignment and neither Peregrine, Clinics or patients can derive what arm they are part of from this coding. During the clinical trial sample tests are performed and their results recorded. When correlating these test results of each patient with the coding it becomes possible to keep track if the patient really received what the coding indicated he/she should have received. Peregrine discovered there where major discrepancies between these sample test results and the coding for some patients in the Bavi arms of the trial.
When did Peregrine discover this, why so late?
Peregrine discovered this on and about SEPT 20, 2012 as they claim in their lawsuit filing. The data was unblinded in MAY 2012, so 3 to 4 months after unblinding. The holiday season and the fact that reviewing clinical trial data is a hard job and needs a lot of time are certainly the major causes. Peregrine was, by FDA test standards, not allowed any involvement or data access during the clinical trial and could therefore not be aware of these discrepancies any earlier. It therefor only discovered them during review, part of the course of preparing for an end-of-phase II meeting with regulatory authorities (FDA).
Has this anything to do with patients censoring?
No, the recent reworked republishing of old articles about patients censoring have completely nothing to do with this. The best argumentation to refute these unprofessional, often manipulative, articles is found in this post that explains in point 7 that Peregrine is not in charge of censoring in a double blind gold standard clinical trial but that this is done by the IDMC and clinicians. Furthermore is discloses the comparison of the censoring in a study that is 90% stage 4 death sentence patients to other studies of stage 1,2,3 which is really forcing ones case. Finally it emphasized that censoring is not a bad thing and occurs for many reasons including the obvious one that patients die before they can get a course of treatment or placebo.
Who is this CRO and why did they hire them?
Peregrine has 3 Bavi related Randomized clinical trials. For this FDA Gold Standard Randomized, Double Blinded 2nd Line NSLC clinical trial they hired a contractor, Clinical Supplies Management Inc (e-mail). CRO's are licensed by the FDA to perform these kinds of Gold Standard clinical trials and need to be hired because Peregrine itself is not allowed any direct or indirect (3rd party auditing on their behave) access to the data as long as it hasn't been unblinded. The CRO has to make sure of that and will not allow other parties to look into the data either (clinics, patients,etc). CSM is a US based company (Fargo, N.D.) which Peregrine can act upon in the US without complex and long oversea procedures. This master contractor does as well the randomized patients assignment as the coding/labeling and distribution for the 3 arms within the boundaries of applicable FDA clinical trial procedures.
Is Avid involved?
No, Avid just delivers Bavi to the CRO for labeling and distribution. For Avid to be involved it must have delivered something else then Bavi. If it was the case Peregrine wouldn't have started a lawsuit pointing out the problem and assigning the blame.
What about the trial?
Quote:
Plaintiff: Peregrine Pharmaceuticals Inc (our attorney)
Defendant: Clinical Supplies Management Inc and e-mail
Case Number: 8:2012cv01608
Filed: September 24, 2012
Court: California Central District Court
Presiding Judge: Josephine Staton Tucker
Referring Judge: Arthur Nakazato
Full Filing html text
What do we learn from the filing?
First it confirms that we are really talking about discrepancies in the data and that this company was only responsible for 1 of 3 the trials (3 = 2 x Lung Cancer and 1 time Pancreatic). It confirms that there is no impact on any other Bavi trials. It removes all uncertainties about who is claimed responsible for what, a US or overseas contractor, whether there are more then one direct contractors, and it takes Avid completely out of the equation.
Secondly and most importantly that Peregrine files for "Neglect", not sabotage, malicious intend, etc. This is important because Peregrine asks for damages due to loses/cost/expenses related to all this and the fact that it had to rescind it's prior announcements resulting in loss of goodwill (e.g.: load retraction) but ONLY ADDITIONALLY for CSM's breach(s) of contract that may cause a delay in bringing Bavituximab to market (that includes doing the clinical trial all over).
What now!
Peregrine intends to communicate further as soon as it is able to determine the impact of this issue, in weeks not months. An undisclosed external body is conducting an investigation (probably the FDA). For now Peregrine advises not to rely on previous announcements.
Personal Evaluation
As the cards are on the table at this moment my concern is not about the legal office investigations, class actions, the price per share, the loan retraction, the cash flow or what soever. Not even about reputation loss or creditability, those are easily grasped excuses while everything shows Peregrine had to pick a contractor out of an FDA licensed list and stay out of the picture until the end of PII.
The chronology of facts from SEPT 10 to SEPT 21 even confirms that on SEPT 12, two days after the quarterly and CC, Peregrine wanted even to go to Credit Swiss and that only on SEPT 19th they must have known for sure. Given the time needed to talk with legal counsel, set-up a strategy to address this, write PR's etc, AND BEFORE ALL to avoid people trading on leaks they very probably planned the announcement on black Monday at 7:30am as they did.
In my mind and based on reasoning i discarded all types of Peregrine BoD/Management and employees involvement in a set-up to make personal profit out of this situation based on stock or option trading. If there was a reasonable chance that this would be the case the SEC would have announced an investigation to the public by now as they always communicate early and call for information. All those riding that track want the keep the attention from the basis of the case so they can use this window of opportunity of uncertainty till OCT 28 to play the stock, hoping that most people will act as bears! They like to throw speculation, assumptions, conjection or words like that around for the smallest peace of information in a detailed reasoning while their own cases, advertised as one liners and, are mostly based on assumptions or self proclaimed trued such as that management are scammers, Bavi doesn't work, or others they can probably shuffle through uninformed reader throat's. As to the newbies on this board, we know they always show up and why. By their comments we know they hardly know that Peregrine is a bio-pharm company. Sell now, it's going to go down, watch and learn, the next dip is coming, etc, etc Saving us from ... from what actually! From keeping our shares! Why is it so d..m important to them that we longs sell our shares? Why are they prepared to lie and spread nonsense to achieve that goal! Why do they not just buy option calls and leave us alone, no, they specifically want us to sell our shares! Why, Why, Why!
I concentrate ONLY on the possible impact on announced results of the clinical trial. The market has reacted as if the results are going to be worse, possibly because it often is in such cases. Of course they reacted in minutes after the announcement. Many on here commented on the large volume in the next days and the fact that the stock isn't trading at 10 cent! Probably the market did the D&D and came to the conclusion that they may have overreacted.
I posted on black Monday, and I repost now with more up to date information, that i see no way for the results to get worse, on the contrary they should get better. I requested for scenario's where the results would get worse but saw no posts, unless posts where all kinds of statements of the sources mentioned at the top of these post had to be unvalidated to make the scenario's work. I am still interested in a post with a clear and detailed scenario which would result in worse results and which acknowledges the facts, such as PR text and lawsuit filing text.
