If you have time, I suggest you look into the CHF phase III trial ... which I personally believe is very well designed.
It wasn't initially designed this way, you may recall.
Initially - when someone else was paying for it - they thought a 1,900-big cohort was the way to go. Then I think that reduced to 1,400.
Thereafter, I read about 900.
Given your view that it is now very well designed, it begs the question why they didn't just target the very sickest patients in the first place.
It would have saved a lot of money, as well as possibly averted some clinical signals that were not to their liking from the not-so-sick part of the trial cohort.
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