RE: Residuals and INTERACTION for simultaneous PK/PD,i mpos sible?

From: "Wang, Yaning" WangYA@cder.fda.gov Subject: RE: [NMusers] Residuals and INTERACTION for simultaneous PK/PD,i mpos sible? Date: Fri, April 15, 2005 4:48 pm Eleveld: In my opinion, you should be able to use INTERACTION even though the residual error model is additive error model (or homoscastic). My understanding is that the impact of INTERACTION is in the process of getting the posterior modes for those ETAs (Emperical Bayes, EB) if the residual error model is heteroscastic. Then, this impact will be carried into the estimation of the population parameters (THETAs) because the marginal likelihood is approximated around those EBs. When you use FOCE without INTERACTION for a heteroscastic residual error model, the posterior function of ETAs is approximated by assigning zero to those unknown ETAs in the residual error part of posterior function. When you use FOCE with INTERACTION, those unknown ETAs in the residual error part of posterior function will be replaced by the current EBs (ETAhat) instead of zero. But if your residual error model is an additive error model, the residual error part of posterior function does not involve any ETA. It does not matter whether you use INTERACTION or not. Try FOCE with or without INTERACTION to fit a dataset with an additive residual error model, you should get identical results. Yaning Yaning Wang, Ph.D. Pharmacometrician Office of Clinical Pharmacology and Biopharmaceutics Center of Drug Research and Evaluation Food and Drug Administration Office: 301-827-9763