Bioequivalence and Bioavailability Forum

Hi Ken,

❝ Yes. Do you mean similar to fully replicate design (2x2x4)? So, the design is as follows :-

❝

❝ Sequence 1 R - T(cap) - T(tab) - R

❝ Sequence 2 T(cap)- R - R - T(tab)

That is one way of doing it. I imagine Detlew will recoil in disgust and mention something about n'th order effects so let's not talk too loud for the sake of his blood pressure.
Ideally, in the best of all worlds to make everybody happy you would need all 12 sequences and also balance between them but of course that's absurdly difficult to achieve with certainty.

❝ Are the statistics and computations same as that of fully replicate design?

In principle yes. I believe -could be extremely wrong of course- that this is a normal linear mixed effects model with
s_total,tabs² on the diagonal of the covariance matrix where observations are with the test tabs.
s_total,caps² on the diagonal where observations are with the test capsules.
s_intra,Ref²+s_inter,Ref² on the diagonal where observations are with Ref.
s_inter,Ref² off-diagonal where Ref's coincide for a given subject.
0 elsewhere.
All in all four variance components.
Of course EMA's principle of mandatory fixed factors screws it up, but I am sure it can all be worked out with a linear model too.

No idea how to request that in SAS or WNL or R, or how to implement a linear model for the same. I can only do it manually in C.