Dear NONMEM users,
Currently I am working on the simulation of a bio-equavalence trial. For
the reference compound a population PK model has been derived on basis
of data from 100 patients. Values for between-and within-patient
variability are available for all PK parameters. The simulation
comprises a randomized cross-over study with 12 patients taking the
test and reference compound. Two-hunderd trials are simulated and
summarized. During the simulations I noticed that truncation of the
simulated of PK parameters significantly influences the power of the
study to confirm bio-equivalence. For instance truncation of simulated
oral clearances of both compounds from a range of 1-300 L/hr to 5 - 30
L/hr doubled the number of positive trials (due to decreased within-
patient variability). Post-hoc estimates form the popPK study indicated
that clearance values of the reference compound are all within the
latter range of 5 to 30 L/hr. I expect that oral clearance of the test
compound will not differ more than 5% from the reference compound. In my
opinion simulation of trials with the smallest range will produce more
reliable estimates of the power to detect bio-equivalence.
I would greatly appreciate your comments on this subject.
Best regards,
Ron Mathôt
Department of Hospital Pharmacy and Clincal Pharmacology
Erasmus University Medical Center
Rotterdam
The Netherlands
