RE:RE:RE:RE:RE:RE:RE:RE:RE:RE:RE:The list Nobody is turning things one way or the other. There are pros and cons to prescreening for Sortilin and excluding patients and you are not considering the cons. There are also technical reasons
a) as far as we are aware they don't have a validated assay for testing Sortilin. What's used at the R&D stage is often not suitable for the clinical stage.
b) they also don't have a cut off point. They don't have a SORT level at which to say this patient gets included and that patient gets excluded. You can guess, I don't think the fda is a guess driven organisation, or you can generate data to guide that decision. That means start with no exclusion criteria and seeing what the data tells them to do.
They will know if and when they need to introduce Sortilin screening based on what the data tells them not what some old guy thinks. I hope they don't need to do prescreening because that's the simplest and most valuable outcome. I will accept screening when/if it becomes necessary. I support managements choice atm because I don't see now being that time.
He preaches patience but can't be patient about this particular issue.
At no point do I think prescreening doesn't have some benefits but I see th3 benefits of not screening as outweigh prescreening atm. This phase is not just about accumulating responders (as much as we would like that). It's about learning the limitations of the drug. That unfortunately means sometimes failing in some circumstances.
jfm1330 wrote: Turn it the way you want, not directly testing patients for sortilin expression is clearly a subpar way to do this trial. Again, overexpression is relative, with the exact data about overexpression they would better understand what is going on and the relation with efficacy and they would not treat patient for nothing.
I understand this is early and that biopsy in most cases is painful for patients ans can involve some risks of internal hemorrhage. I know it, I got one from the liver and you need to lay down on a bed, not moving, for three hours to be sure it will not bleed inside your body. So I understand all they want is to treat patient with good odds of overexpressing sortilin, but they will have to do things differently in phase II and beyond.