Bioequivalence and Bioavailability Forum

Hi John,

❝ Apparently not...

Otherwise it would be boring, isn’t it?

❝ Question. If a study requires partial AUC at early phase of the plasma concentration-time curve, is it acceptable to implement in the protocol "Subject will be removed from the study if more than x blood draws cannot be collected within x min of schedule time during post-dose 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4 hours?"

Maybe; actually no qualified opinion.

❝ Given the fact that the variability of PAUC can be high, can the above be implemented at all?

Again – maybe. You will loose power what you terribly need for this metric…

❝ Obvious with the above example, the subject will be dropped out if he/she misses the 4 hr sample since PAUC0-4 requires 4 hour timepoint.

❝

❝ […] Tada, some CRO managed to screw up some early timepoint collection by as much as 35mins!

That’s a fucking lot! What happened? Normaly time deviations outside an “allowance window” stated in the protocol must be not only documented as such but also a comment in the CRF should be given justifiying the event. 35min?!

BTW, if you ask Phoenix/WinNonlin for partial AUCs (and sampling wasn’t performed exactly at the cut-off time point) an interpolation between two adjacent time points (before/after) is used; linear if C₂ ≥ C₁ and log/linear if C₂ < C₁. Makes sense, IMHO.