Bioequivalence and Bioavailability Forum

Dear all,

I have a question regarding estimating intra-subject variability in a fixed sequence 2 period design (i.e. A followed by B).

This could be analyzed by a paired t-test or mixed model whereas the latter has some benefit in case of missing values in one period assuming that missing values are missing at random and I will focus therefore on the mixed model approach (although probably challenged by some regulatory agencies for that reason).

With the mixed model approach you model the subject as random factor and treatment as fixed and you get an estimate for the between subject variability and the residual error.

My question: on which premises can the residual error obtained from the mixed effects model to be interpreted as within subject variability?

Best regards & looking forward to an interesting discussion

Martin