Is it possible that all cause mortality is the hard end point, whereas there can be error and subjectivity in the primary end point? Death is fairly straightforward to diagnose but I understand that determining the primary endpoints can be much more prone to error.
I agree that death is kind of the gold standard of end points in a way. The major difficulty is often studies don't have enough people to reliably detect a difference in death, so you use something like major adverse cardiac events (MACE). I think it looks like colchicine protects the heart, but possibly at the cost of something else.
We don't want to miss out on a drug that helps people if the all-cause data are just noise, but of course don't want to approve a drug that might be detrimental overall, so it's tricky. We also want to understand the downside. If the difference in deaths was all driven by pneumonia throughout the trials, we might chalk it up to neutrophil inhibition causing decreased immune response to infection, but there isn't a clear signal.
In my mind there needs to be a lot more data in this space.
Is it possible that all cause mortality is the hard end point, whereas there can be error and subjectivity in the primary end point? Death is fairly straightforward to diagnose but I understand that determining the primary endpoints can be much more prone to error.
Thanks for your analysis of this article.
I agree that death is kind of the gold standard of end points in a way. The major difficulty is often studies don't have enough people to reliably detect a difference in death, so you use something like major adverse cardiac events (MACE). I think it looks like colchicine protects the heart, but possibly at the cost of something else.
We don't want to miss out on a drug that helps people if the all-cause data are just noise, but of course don't want to approve a drug that might be detrimental overall, so it's tricky. We also want to understand the downside. If the difference in deaths was all driven by pneumonia throughout the trials, we might chalk it up to neutrophil inhibition causing decreased immune response to infection, but there isn't a clear signal.
In my mind there needs to be a lot more data in this space.