Bioequivalence and Bioavailability Forum

Hi d_labes,

❝ In very short: All effects fixed, that means without loss of generality no period, no sequence and no subject effects (! according to EM ) i.e. all set to zero.

He is right, that's a bit easier than adding constants that later on cancel out anyway. What a clever person.

❝ Normal distribution of the log(PKmetric) with µT = log(GMR) + µR and s²_wT for the period a subject receives Test and µR and s²_wR for the periods a subject receives Reference. s²_wX as usual = log(1.0 + CVwX^2).

I can't really see if that's correct. I would do
logPK=F+S+error
where F is the treatment effect, S is the subject effect and even though we evaluate it as a fixed effect we model it as random here (this is justified, although it perhaps sounds silly). So basically the S is normal with mean zero and variances s²_b.

Let's say a particular subject is in seq RRT:
Derive one random Gaussian with variance s²_b (it is the same you re-use for one subject).
Derive three within's, two for ref and one for test. To generate three observations add the formulation effects to the three different withins and the between for the subject. Done. It may come to the same thing as what you did, I can't tell...

Hang on... I need to think more about this. I have a feelign I might be editing this post again soon