Bioequivalence and Bioavailability Forum

¡ Hola ElMaestro !

❝ "Exclusion of data can never be accepted on basis of stat analysis or for PK reasons alone."

Sure – although debatable.
But Ratnakar’s and Atish’s posts dealt with exclusion of subjects based on missing values. If three samples in the area of the expected C_max were broken in centrifugation we probably will fall into a deep pit (especially if CV_intra is low and the sample size is small – a single ‘outlier’ will kill the study). Unless we start fiddling around with cubic splines we will never be able to get a reasonable estimate of C_max. All NCA methods will grossly underestimate C_max – which may blow the study. C_max is nasty in many respects. Even if just a little ‘noise’ is present, PK modeling regularly has its problems getting close to the measured data in this region.
IMHO defining ‘critical regions’ of the profile in the protocol is not a bad idea. No “[…] PK reasons alone”, but common sense added!
If one wants to come up with a hard-core justification of the ‘critical regions’: perform PK modeling (pilot study or literature data) and plot the partial derivatives of parameters vs. time; extremes (min/max) will indicate most influential time points. Remark: never seen this in a protocol – maybe freaks like me do it at home.