schedule time vs. actual time for ANVISA BE [Regulatives / Guidelines]

posted by ElMaestro  – Denmark, 2022-07-12 23:10 (31 d 14:21 ago) – Posting: # 23131
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Hi Shuanghe,

like others I like the actual timings best.
But there are reasons and even if they are not entirely in the public domain I am happy to shed a little light over it here. To catch the squirrel....

You are testing A versus B on behalf of a sponsor.
For Cmax you get a 90% CI of 86.44-118.20. Pass.
For AUCt you get a 90% CI of 113.87-125.04. Bugger. Angry sponsor.

You're royally screwed. But wait... no-one signed off on the pk+stats yet....

You go back into the source. You find the sheets with TPDs. You "update" them a little. It is safe because our clinical updates to the Sponsor only mentions how many were dosed, how many dropped out, how many had AEs, did they resolve. But the clinical updates to do not contain TPD details.
And now a second round of pk+stats.
For Cmax you get a 90% CI of 86.44-118.20. Pass.
For AUCt you get a 90% CI of 113.87-124.96. Pass. Happy sponsor.

And one day the agency gets wind of it. One case is enough. Agency wants to see analysis with scheduled timings. It is a sensitivity analysis now. If the analysis with actual timings gives another result than with scheduled timings then it can be argued the study was not well planned or well conducted (much like if AUCinf is wildly different from AUCt).

Bear in mind that AUCt(A) or AUCt(B) is not of interest in BE, but the ratio is. And the expected ratio is (can be said to be) independent of TPDs as long as TPD occur at random, i.e. with no treatment preference.

Pass or fail!
ElMaestro

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