Validation

From: "Piotrovskij, Vladimir [JanBe]" <VPIOTROV@janbe.jnj.com> Subject: Validation Date: Wed, 3 Feb 1999 13:11:10 +0100 Dear all, It was nice to see so intensive discussion on the issue that hardly deserve it. I would suggest another topic, to me much more essential, and I believe the exchange of opinions will be even more intensive: Validation. FDA's Guidance for Industry "Population Pharmacokinetics" which is still draft (as far as I know) says: "The issue of validation of population models remains unresolved". The list of validation methods includes: - Prediction errors on concentrations: "This method can be used when only one sample per subject is obtained. ... The method does not take into account the correlation of observations within subjects" - Standardized prediction errors: "The use of the approach is discouraged" (when and by whom?) - Validation through parameters: What are 'true' individual parameters for a subject sampled 2 or 3 times and the model has, say, 5 structural parameters? - Plot of residuals against covariates: Just a visualizing technique? - Plot of residuals against covariates and Validation through parameters: Bootstrap is recommended with at least 200 replicates. It will take months for a model of medium complexity with the data set typical for industry (N hundreds if subjects) unless you have access to a supercomputer. - Posterior predictive check: Has any body experience with this new technique in the field of population PK-PD? Any comments? Best, Vladimir -------------------------------- Vladimir Piotrovsky Clinical Pharmacokinetics, ext 5463 Janssen Research Foundation 2340 Beerse, Belgium e-mail: vpiotrov@janbe.jnj.com