Bioequivalence and Bioavailability Forum

❝ I don’t agree. IMHO it is better to invest your intellectual horsepower in the protocol, than to state sumfink ambiguous and have to come up with “creative” ideas in the analysis. If the protocol is written by a genius, the analysis can be done by a dummy. I’m not sure whether it always / easily can be done the other way ’round. Creative solutions might be interpreted by assessors as the first step of cherry-picking:

“Oh, the study passed by applying Method X. But there are alternatives. Would the study have failed with Method Y? Let’s ask the applicant for a justi­fi­cation, …”.

Such a request can turn out to be a show-stopper. Methods are based on different assumptions, which are difficult – if not impossible – to proof given the limited sample size in BE studies. So you might be forced to come up with a lot of in your response, which might be accepted – or not…

Helmut: Then we need a structured data analysis plan for our clinical protocol.
Well let us assume that we can make a general statement in the clinical protocol that covers the eventuality of “drop out” subjects when using Phoenix WinNonlin. “if a subject drops out during the reference period of the study then the corresponding test pharmacokinetic data (Cmax and AUC) from that subject can be omitted from the data set prior to BE data analysis irrespective of whether the study is a two or three way cross-over study. On the other hand if one subject drops out during a test period then the following applies:
For a two way cross-over study the corresponding reference period can be omitted from the data set.
For a three way cross over study the one remaining test data set available is included with the reference in the study.
So how does that sound for a start?

Angus

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Edit: Full quote removed. Please delete everything from the text of the original poster which is not necessary in understanding your answer; see also this post! [Helmut]