according to the EMA’s BE-GL Section 4.1.8:
Exclusion of data cannot be accepted on the basis of statistical analysis or for pharmacokinetic reasons alone, because it is impossible to distinguish the formulation effects from other effects influencing the pharmacokinetics.
The exceptions to this are:
- A subject with lack of any measurable concentrations or only very low plasma concentrations for reference medicinal product. A subject is considered to have very low plasma concentrations if its AUC is less than 5% of reference medicinal product geometric mean AUC (which should be calculated without inclusion of data from the outlying subject). The exclusion of data due to this reason will only be accepted in exceptional cases and may question the validity of the trial.
- Subjects with non-zero baseline concentrations > 5% of Cmax. Such data should be excluded from bioequivalence calculation […].
Setting up a workflow for #2 is straightforward. However, I have no clue for #1 (currently I’m doing it in R). Any suggestions appreciated.
Bonus question: What about replicate designs where data might be incomplete (i.e., missing periods)?