Re: [NMusers] truncation & simulation

Dear all,
Thanks for the responses. Upon closer inspection of my controlstream I
noticed that with the smaller range of 5 to 30 L/hr I also included a
total covariance matrix. The latter proved to be the cause of the
increased power as suggested by David. Further simulations (with
covariance matrix) revealed that parameter distributions can be
truncated from a 99.999 to a 95% interval without influencing the power
of the study.
Ron

Ron Mathôt wrote:
> 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
>
>
>

Received on Sat Apr 26 2008 - 11:49:49 EDT