io
I watched the whole thing yesterday - but of course I don't know this stuff very well so won't get it right.
Cox results were barely mentioned in the initial DNDN presentation. I think the fact that some pts had been removed from the Cox dataset - supposedly because of lack of data on them for some Cox variables - completely vitiated the analysis.
The FDA biostats guys were really weak presenters. No offense to anyone, but Chinese with poor English and an apparent desire not to take clear positions. They did not reiterate the briefing doc poit that there's a 1 in 40 chance of 9901 OS being a false positive. Said there was simply no way to quantify the chance.
When DNDN's statistician addressed the panel (twice - once after it looked as if it was all over, with Hussain triumphant that she had shown that this trial was way indferior evidence to the Tax trial) he did not mention Cox at all. What he did say was that if in doubt about a false positive, look at the confidence interval. At 1.13 it was still ahead of the game. And he reminded them - though shockingly without citing the NCI paper and conference on this - that TTP was wrongly measured from randomization rather than from some time when kick-in might happen - so one should not see non stat sig as problematic.
Amazingly, the discussion centered for what seemed like forever on the CD54 data, which as all admitted had no bearing on efficacy or safety. Hussain tried to argue that DNDN was infusing god knew what into pts since the cell concentrations varied so much from pt to pt, and that anyway it was just the healthy guys who got the upreg and the whole thing was circular - healthy in healthy out.
What was alarming was that nobody had clear rebuttals for Hussain. Especially when she hissed just before the vote that Tax's 2.5 mos was for much sicker pts than Prov's 4.5 mos and that the comparison was completely baseless - a comparison made by the patients who spoke in the public comment. Arguably, she shot herself in the foot by being such a total bitch to everyone, including to Dr Whitten, whom she castigated for allowing such a poorly designed trial in the first place. I bet some of the other panelists decided they's be damned if they'd vote with her.
Hope that helps.
Anyway, it was better entertainment than a World Cup soccer final in overtime.
Best, Corpstrat
