The reference scaled average bioequivalence (RSABE) Phoenix templates are currently being developed by Ana Henry to run on the new version of Phoenix 6.4. We look forward to this excellent initiative. Meanwhile a new Guidance for Methylphenidate has appeared. The new Guidance (attached) is focused on Concerta as the reference. It focuses on requiring 3 partial AUC metrics plus AUC to inf and Cmax as BE metrics.
Additionally a requirement for the (subject-by-formulation interaction) variance, which is the variation in the average T and R difference in PK parameter between individuals. {A 4 period design with equal replication of R and T is recommended}.
The RSABE Pharsight templates were based on a prior FDA document relating to Progesterone and the subject by formulation interaction by variance parameter was not included.
I posted this to Helmut’s forum (see below) and had some very helpful comments regarding estimating this (subject by formulation) variance parameter in Phoenix 6.4 (Step3 in Guidance)
http://forum.bebac.at/mix_entry.php?id=13848&page=0&category=0&order=last_answer&descasc=DESC#p13861
I am coposting it here wondering if there is other information regards calculating step 3 and also step 4 of this FDA Guidance using Phoenix 6.4. Step 4 describes the requirement for 95% upper confidence interval of the (subject by formulation) variance. Helmut has commented that the basic information is all there.
Ana was not sure but thought the individual BE routine may be useful in this regard. She remarked that others at Pharsight were better qualified to comment on this statistical issue
Any comments are most welcome,
Angus