Bioequivalence and Bioavailability Forum

dear hs and dlabes !

thanks for your comments; the example criteria "met all inclusion criteria" can of course be dropped and/or limited to specific criteria (i.e. explicitly defined major protocol violations) important for a specific study and yes I would exclude a subject from the PADS even when one vial is broken (ICH E9: the availability of measurements of the primary variable).

however, you can also specify a specific pharmacokinetic analysis set (PKAS) using the following example criteria for a cross-over trial:

pharmacokinetic analysis set: subjects received both study treatments and have suitable data for PK analysis (a) samples are available at pre-dosing and 15 min post each study drug administration (b) for at least x out of y time points specified in the protocol, etc. etc.

using this approach you don't have to run PK analyses for the FADS and PADS. you have to define your method how missing values are handled for this data set only. however, I have seen both approaches in practice (a) analyses of FADS and PADS separately and (b) analysis of PKAS only.

regarding the importance of FADS and PADS: the FADS should reflect the clinical situation in practice better than the rather artificial PADS and is according to my point of view more important. I personally think that the importance of a data set should not depend on the hypothesis and/or parameters investigated. I have to admit that I am not fully convinced by the ICH E9 in this respect but I may have to think about this topic in more detail.

best regards & thanks for the very interesting discussion

martin