what could go wrong?, page-64

Hey Cake,

I know I must sound like the biggest bear, however just note that I'm not saying the trial is invalid, or that it's not going to achieve it's goals, or that the results won't be statistically significant. All I'm saying is that based on the data from the Phase 2 study, then it's virtually impossible for median PFS in the HA arm to be 13 months, UNLESS there's something abnormal going on with the control arm aswell.

My Argument isn't really based on what I "perceive" as the company's expectations. Since the company's expectations and goals of the Phase 3 came from statistical analysis and modelling of the Phase 2 data, so there shouldn't really be that much variance from the Phase 2 results( and that variance will be in weeks not months). Phase 3 oncology trials are designed to pick up small differences* Hence why it's also powered to show a statical significance from a smaller improvement in PFS

You have to remember that the majority of Phase 3 Oncology studies fail to even meet a statistical significance( 62%*), and the efficiency is never usually as good as what was observed in the Phase 2. "Actual magnitude of benefit achieved in a clinical trial, is nearly always less than what was predicted at the time the trial was designed", as “investigators consistently make overly-optimistic assumptions regarding treatment benefits when designing RCTs.”

* http://jnci.oxfordjournals.org/content/104/8/568.long

If PFS in the HA arm is 13 months, then you have patients who have exceeded the median Overall survival of those on the Phase 2 study(10.1 months), aswell as exceeding the median OS of patients on any 2nd line mcRC treatment currently available(11.2 months). Median PFS of 13 months should modestly translate into median OS of 20 + months, so it would end up perhaps doubling the efficiency of any 2nd line treatment currently available. It's probably safe to assume that PFS improving so dramatically over the Phase 2, that it now exceeds what was median OS- is something that's never been seen before in a Phase 3 Oncology study. Also, Increasing efficiency (PFS/OS) of current treatments by 100%, could turn out to be one of the greatest advances in cancer treatment this decade. Which is what some on here seem to believe...

If anyone wants to keep believing that median PFS in the HA arm will be 13 months, then I'm not gong to stand in your way any longer, I'll let the odds do it for me. Good luck to you though- someone's gotta win the lotto.