From: "Tzeng, Tsang-Bin" Tsang-Bin.Tzeng@astrazeneca.com Subject: [NMusers] NM mixture model with three subgroups Date: Sun, 18 Dec 2005 09:22:47 -0500 Anyone has experience to extend the NONMEM mixture model in clearance from a two-subgroup (bimodality, as shown below) one to a three-subgroup one. We are currently working on a drug with polymorphism in metabolism (a primary elimination pathway) and three subgroups (ultrafast, extensive, and slow metabolism) have been identified either from previous work or from the histogram plot of the current data. Thanks! ; MIXTURE MODEL EST = MIXEST POP1 = 0 POP2 = 0 IF (MIXNUM.EQ.1) THEN POP1 = 1 ELSE POP2 = 1 ENDIF CL = POP1*CL1 +POP2*CL2 $MIX P(1) =THETA(8) P(2) =1-THETA(8) NSPOP = 2 Sincerely yours, Tsang-Bin Tzeng, Ph.D. AstraZeneca Pharmaceuticals (302) 885-9954 _______________________________________________________ From: "Riley, Steve" Steve.Riley@pfizer.com Subject: RE: [NMusers] NM mixture model with three subgroups Date: Mon, 19 Dec 2005 09:23:48 -0500 Tsang-Bin, I would code the problem as follows: ; MIXTURE MODEL EST = MIXEST IF (MIXNUM.EQ.1) THEN CL = CL1 ELSE IF (MIXNUM.EQ.2) THEN CL = CL2 ELSE CL = CL3 ENDIF $MIX P(1) = THETA(8)/(1 + THETA(8) + THETA(9)) P(2) = THETA(9)/(1 + THETA(8) + THETA(9)) P(3) = 1/(1 + THETA(8) + THETA(9)) NSPOP = 3 Steve _______________________________________________________ From: "Tzeng, Tsang-Bin" Tsang-Bin.Tzeng@astrazeneca.com Subject: RE: [NMusers] NM mixture model with three subgroups Date: Mon, 19 Dec 2005 09:54:36 -0500 Dear Joern, Sam, Mouksassi, and Steve: Thanks very much for these wonderful helps and tips! They are more than what we originally anticipated. I shall share with you if we are lucky enough to come out with something from this modeling exercise using your suggestions. Sincerely yours, Tsang-Bin Tzeng, Ph.D. AstraZeneca Pharmaceuticals (302) 885-9954 _______________________________________________________ From: brendan.m.johnson@gsk.com Subject: Re: [NMusers] NM mixture model with three subgroups Date: Mon, 19 Dec 2005 11:27:15 -0500 Hi Tsang-Bin, I recently had need for a 3 subpopulation model, and used the following $MIX ;TRIMODAL: NSPOP=3 EXTH10=EXP(THETA(10)) LGT1=EXTH10/(1+EXTH10) P(1)=LGT1 EXTH11=EXP(THETA(11)) LGT2=EXTH11/(1+EXTH11) P(2)=LGT2*(1-P(1)) P(3)=1-P(1)-P(2) you can then apply your conditional statements in a similar fashion to the 2 population model Brendan _______________________________________ Brendan Johnson, Ph.D. Clinical Pharmacokinetics/Modeling & Simulation GlaxoSmithKline Ph: +1 919 483 0672 _______________________________________________________