Dasatinib EMA, April 2020 [BE/BA News]

posted by ElMaestro  – Belgium?, 2020-06-21 11:49 (129 d 19:33 ago) – Posting: # 21554
Views: 823

Hi all,

check this out.

"In order to avoid the bias introduced by the randomly occurring low-lier values under fasting conditions, it is considered acceptable that low-lier profiles can be excluded from statistical analysis of the fasted state study if they occur with the same or lower frequency in the test product compared to the reference product. The low-lier profiles are defined as those profiles with dasatinib AUC exposures < 10% of the geometric mean AUC obtained in the rest of the profiles. This should be predefined in the protocol."

Just think about it. It marks a novel and much needed way by which you can take the variability of the reference into consideration when deciding whether or not your Test product is BE to the Ref.

Technically, it could get a little involved: If you have n observations, of which m may be less than 10% of the (n-m) rest of observations, then identifying those m observations is computationally very different from anything else we usually encounter in BE. The approach can rightfully be called a kind of m'th order jackknife but we do not need to traverse all permutations to find the m observations.

I think it is a brave and much needed leap forward on the part of the regulators that they allow it. Dasatinib has caused lots of headaches and peptic ulcers at Sponsors and CROs globally. Those days may be gone. :-)

I could be wrong, but...

Best regards,
ElMaestro

No, of course you do not need to audit your CRO if it was inspected in 1968 by the agency of Crabongostan.

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