It's my belief that the analysis plan and acceptance criteria is a part of the initial filing for a Phase 3 Trial, it may not have been called an SAP, I don't know, but the criteria was established before the trial ever started, and now they'd like to change the acceptance criteria based on what they've learned from the clinicians, even though the trial was not unblinded.
I'm certainly unclear on when pseudoprogression was originally determined, but I believe it was well into the trial. If that's the case, many of the initial patients in the trial would have been considered to progress, when in reality it was pseudoprogression. They may have lived well beyond when thought to have progressed, yet the primary goal in the trial as I understand it was TTP, so they were misjudged. OS is clearly how this trial should be judged, it might be the only criteria that's really meaningful.
Certainly if you were starting the trial today, perhaps true progression could be a criteria that would shorten the duration of the trial, as all who had pseudoprogression would not be wrongly thought to have progressed. No doubt it takes years longer to look at survival, but it is really the best criteria, but it often adds years, even decades, to the duration of a trial. I'm aware of elderly people diagnosed with prostate cancer who are untreated because the cancer is so slow moving old age will kill them before the cancer, and I'm talking decades. Clearly the cancer would be treated in a younger patient, but again clearly progression, rather than survival would be the desirable acceptance criteria, as otherwise the trial could take decades to run.
I frankly believe that many good drugs have been abandoned because they were tried on the deadliest of cancers, like pancreatic, as the sponsoring company couldn't afford the cost of a trial in a slow moving cancer that the drug could be more effective in. I frankly wish there was a Public Option for trials in which a company turned the drug over to the FDA for trials, and the FDA received royalties from the approved drugs to fund it's operations. I believe many tiny biotechs would choose such an option after demonstrating efficacy in a Phase 1/2. The FDA wouldn't enroll a drug in the program until at least a Phase 1/2 had been done. It would always be the drug developers choice, they could do it themselves, and the FDA would get nothing, or they could enroll in the program and the FDA would see royalties. Another advantage would be the FDA trusting trials they actually ran, perhaps they'd be of shorter duration and lower cost as the fear of the drugmaker somehow cheating would be eliminated.
In cancer, one size doesn't fit all. Testing a drug that might work in pancreatic, knowing it was better in colon, might get you a quick approval, but it's far more likely to fail. If the FDA were doing it, they might do both cancers simultaneously, and both could be shorter as they were doing it. I'm not eliminating the clinicians, but many would be working directly under the FDA.
Gary
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