Bioequivalence and Bioavailability Forum

Dear HS,

(emphasis by me)

❝ Problems arise from the ‘pseudo randomisation’ – there’s only one product and sequences in a conventional 2×2 cross-over will be fixed a priori like this:

❝  S/P |  I  II
❝ -----+-------
❝   1  | R1  R2
❝   2  | R2  R1

❝ Of course the assignment to ‘R₁’ is ‘R₂’ is arbitrary; any other then the chosen one in the protocol will result in another PE and CV_intra…

I cannot imagine any criterion to decide what R1 and R2 is, if it is the same product, same batch and so on.

What you have is only
  S/P  |  I  II
 ------+---------
   RR  | µR  µR+p
with µR the mean for R (your Reference product) and p a period effect.
Within a subject you have to add an error term to specify the full model.

Thus you cannot and need not randomize any arbitrary sequences.

I would just run an ANOVA with a fixed period effect and a random subject effect. The residual error is then what you are looking for, I think.