exwannabe,
Exceptions to adequate and well controlled studies allows for changes, when done prior to unblinding, when measures utilized to distinguish treatment effect from comparator, in this case SOC/placebo, turn out to be unreliable. The fact that regulators had a say in trial design, which included crossover to a potentially active treatment, created a situation that all parties had to make adjustments for when treatment effect, as noted by pseudoprogression, made these changes an absolute necessity. This necessity became even more apparent when the Germans no longer allowed their patients to join in the SIC/placebo arm. This arm was likely determined to be a lessor treatment (Fraunhofer’s claim that enrollment occurred only to the point statistically necessary) especially for low absolute lymphocyte patients which were only allowed into the trial from that country and typically would progress more quickly. The fact that not all of them did progress quickly was noted in the interim blinded data presented as being part of the longer lived patients. Early treatment advantage for low ALC patients had to have been clear very early when typical progression happens at about 7 months and treatment induced pseudoprogression can be noted by 8 weeks. Kind of a big deal that no one is talking much about but clearly was a distinct possibility and likely a high probability because it would explain all other actions taken quite well, including Les trying to cover up the enrollment discrepancy for the sake of data maturation and blind. Try again!; ). Best wishes.
