Re: repeating cases

Date: Thu, 18 Nov 1999 11:32:01 +1300 From: Nick Holford <n.holford@auckland.ac.nz> Subject: Re: repeating cases Looks like an ideal case for using a Between Occasion Variability (BOV) model. These have been described by Karlsson & Sheiner as Inter Occasion Variability (IOV) but I prefer BOV. You can use the different covariates for the animal to predict *systematic* changes in CL from study to study but the BOV describes the *random* variability about the mean (covariate adjusted) CL for that individual. The code for describing Between Subject Variability (BSV) and BOV for CL could be like the following. OCC is a data item that indicates the occasion of the study e.g OCC=1 would be all concs and doses on study occasion 1 and OCC=2 would be all concs and doses on study occasion 2, etc. The $OMEGA BLOCK(1) SAME record allows the ETA to be different for each occasion for an in individual but ensures that all ETAs are sampled from a distribution with the same SD. It is not possible to identify BOV without this constraint. $INPUT TIME OCC AMT DV $THETA 1 ; CL $OMEGA BLOCK(1) .25 ;Occ 1 $OMEGA BLOCK(1) SAME ;Occ 2 ; Repeat the $OMEGA BLOCK(1) SAME record for each occasion after the first $OMEGA .5 ; BSVCL $PK IF (OCC.EQ.1) THEN BOV=ETA(1) ENDIF IF (OCC.EQ.2) THEN BOV=ETA(2) ENDIF ; Repeat above IF/ENDIF block for each occasion BSV=ETA(1) CL=THETA(1)*EXP(BSV+BOV) Karlsson, M. O. Sheiner, L. B. The importance of modeling interoccasion variability in population pharmacokinetic analyses. J Pharmacokin Biopharm 1993; 21:735-50 -- Nick Holford, Dept Pharmacology & Clinical Pharmacology University of Auckland, Private Bag 92019, Auckland, New Zealand email:n.holford@auckland.ac.nz tel:+64(9)373-7599x6730 fax:373-7556 http://www.phm.auckland.ac.nz/Staff/NHolford/nholford.htm