Biotech Values

[iwfal]

Adaptive trials - when is an alpha send not an alpha (i.e. why adaptive trials are like 3 card monte with the disappearing alpha - or why you have to look really carefully when someone talks of alpha magic).

Take the case of a trial where:

1) They want to test 4 different drug protocols against one another in part a

2) After enrolling and randomizing 100 patients into those 4 arms (non placebo) they then measure PFS and

3) for part b they take the best protocol forward to be testing in 200 patients randomized 1:1 for placebo vs the best protocol.

4) In the final analysis they want to use not just the 200 patients - but also the 25 patients that were in the carried forward protocol in part a. I.e. it ends up being 125 patients in the treatment arm and 100 patients in the placebo arm.


Note that there is no p value comparison against an assigned alpha at the end of part a (because there was no placebo group), but because you looked, you acted and you want to use those patients in the final analysis the final alpha will not be 0.05. I.e. there was an alpha spend even through there was no 'alpha' 'used' at the 'interim'.

And more complicated adaptive trials get a lot odder/messier.