I had a thought today that I’m pretty sure none of us have discussed. It came to me as I was thinking about what might be going on behind the curtain.
In May 2014, the pseudoprogressor trial arm filled at 32 and the EAP (Expanded Access Protocol) trial began.
The 32 pseudoprogressors were, of course, randomized.
Now… many of us know that arm was intended to be around 48 (and that the sponsor projected it would take 72 or so patients to get to find 48 pseudos).
And for those that are newer here, it was to be 280 main arm + 48 pseudoprogressor to equal 312. So they really only increased the trial by 36. But, because the pseudos were now taken out of the count of 312, the main arm was really increased by 68 patients (280 + 68 = 348).
So… why make that pseudo arm only 32 patients? Especially when they enlarged the main trial from 280 to 348? One would think they would want to increase the pseudo arm as well.
Oh… unless they knew by then that the pseudo arm was performing as if L was a near cure for those patients. Then, you’d not only NOT want to increase the number from 48 to a higher number, if you could, you’d decrease the number.
Why? Well so none of those patients were give a placebo. Why give a placebo to a patient for which the product is going to be a cure?
Pseudos… they can wreak havoc on a trial you know.
If that’s the case… they would start funneling BOTH rapid and pseudos into the EAP - which is what they did.
And rapids were already going there because they were disqualified from the trial.
As they funneled more pseudos into the open label EAP trial, they start to see with an unblinded view just how well L is performing with these patients - who are all mesenchymal, by the way.
Now… I keep wondering why Linda L could say that they were still blinded to the trial on October 15, 2015? By then, whatever data they were submitting to the regulatory agency, how could they do that without unblinding the trial.
I’m thinking they could have unblinded the pseudo progressor arm by June 2015. If they did that, wouldn’t that keep the blind on the main arm? I think it would.
In unblinding the this arm, they may have decided it would be prudent to submit for a BLA for this group. I don’t know if they would ask for all mesenchymal patients or just pseudos… however, I’d think with all the sub typing going on at Adaptive Biotechnologies (which may have been done to provide data to support asking for the full mesenchymal group and not just pseudos), and Dr. Prins presentation… if this theory is correct, then I’d suspect they are asking for the entire group.
Meanwhile, they keep the main arm blinded and that trial goes to the end. And they halt screening because they are so close to 348 that it doesn’t matter… and so that no more mesenchymal patients are put into the trial to possibly be randomized as a control patient. And if, for some reason, they are refused at this time on the pseudo patients, the main arm's blind isn't compromised.
Kinda works, no?
