RE: Mixture model at the IOV level?

From: "Piotrovskij, Vladimir [JanBe]" <VPIOTROV@janbe.jnj.com> Subject: RE: Mixture model at the IOV level? Date: Fri, 18 May 2001 14:15:12 +0200 One more example. If the drug is given orally it is not uncommon that ALAG can be seen in some patients and not seen in others. One way to model this is using the mixture, e.g.: ... SUBP = MIXEST SP1 = 0 SP2 = 0 IF (MIXNUM.EQ.1) SP1 = 1 IF (MIXNUM.EQ.2) SP2 = 1 ALAG1 = (SP1*THETA(1) + SP2*THETA(2))*EXP(ETA(1)) ... $MIX NSPOP = 3 P(1) = THETA(3) P(2) = 1-P(1) $THETA 0 FIX (0 1) Suppose now there are two occasions with the same drug. One can imagine a situation when in some patients ALAG is observable at one occasion and not observable at another occasion. In other patients ALAG is not observable at any occasion. One more possibility: at both occasions ALAG is observable. This situation can be modelled as follows: ... SUBP = MIXEST SP1 = 0 SP2 = 0 SP3 = 0 SP4 = 0 IF (MIXNUM.EQ.1) SP1 = 1 IF (MIXNUM.EQ.2) SP2 = 1 IF (MIXNUM.EQ.3) SP3 = 1 IF (MIXNUM.EQ.4) SP4 = 1 ALG1 = (SP1*THETA(1) + SP2*THETA(2)) * EXP(ETA(1)) ALG2 = (SP3*THETA(3) + SP4*THETA(4)) * EXP(ETA(2)) ALAG1 = (2-OCC)*ALG1 * EXP(ETA(3)) + (OCC-1)*ALG2 * EXP(ETA(4)) ; OCC is 1 or 2 ... $MIX NSPOP = 4 P(1) = THETA(5) P(2) = THETA(6) P(3) = THETA(7) P(4) = 1-P(1)-P(2)-P(3) $THETA (0 FIX) ; 1 (0 .5 1) ; 2 (0 FIX) ; 3 (0 1 2) ; 4 (0 .2 .3) ; 5 (0 .1 .2) ; 6 (0 .3 .4) ; 7 Finding proper boundaries for THETA(5) to THETA(7) can be a problem... Best regards, Vladimir ------------------------------------------------------------------------ Vladimir Piotrovsky, Ph.D. Research Fellow Global Clinical Pharmacokinetics and Clinical Pharmacology (ext. 5463) Janssen Research Foundation B-2340 Beerse Belgium Email: vpiotrov@janbe.jnj.com