Re: sequential PK/PD

From: Mats Karlsson Subject: Re: [NMusers] sequential PK/PD Date: Thu, 02 May 2002 16:16:13 +0200 Dear Joga and Sriram, Actually the three approaches that Janet Wade and I compared were: 1) Posthoc PK parameters only to drive the PD 2) Simultaneous PK and PD analysis 3) Simultaneous PK and PD analysis but where the *population* PK parameters were fixed to values found in an analysis of the PK data alone. We found that 2 and 3 behaved equally well under the (limited) circumstances we tried whereas 1 behaved slightly worse. The rational for 3 can be made as follows: We may to fix some PK parameters a) to speed up computation, or b) to assure that misspecification of the PD model doesn't translate into misspecification of the PK parameters. The choice of fixing on the population parameters can be justified because these are often determined with good precision (as opposed to the individual posthoc parameters, which in addition are biased with sparse data). Surprisingly to many (incl. us in the beginning), the PK data will influence the population PD parameters for method 3, even if the FO method is used. The reason is that all data are included in the calculation of the objective function value. The work was presented at PAGE, Saintes, 1999 Best regards, Mats -- Mats Karlsson, PhD Professor of Pharmacometrics Div. of Pharmacokinetics and Drug Therapy Dept. of Pharmaceutical Biosciences Faculty of Pharmacy Uppsala University Box 591 SE-751 24 Uppsala Sweden phone +46 18 471 4105 fax +46 18 471 4003 mats.karlsson@farmbio.uu.se