Re: Mixture model simulation
should it be IF(MIXEST.EQ.2) Z=0 for the fitting run?
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Leonid Gibiansky, Ph.D.
President, QuantPharm LLC
web: www.quantpharm.com
e-mail: LGibiansky at quantpharm.com
tel: (301) 767 5566
Quoted reply history
On 5/7/2013 11:31 AM, Paul Hutson wrote:
> Dear Users:
> I note the Jan 26, 2013 response to Nick Holford's query about results
> from the use of the $MIX mixture model for simulation. I have created a
> data set of N=100 subjects using R to randomly distribute their
> covariates, both continuous and categorical. I then ran the following
> sim with SUBPOP=1 to generate their corresponding DV values using the
> following code:
> ; SIMULATION CTL
> $PROBLEM SIM 2COMP
> $INPUT ID TIME AMT DV WT HT BMI BSA GFR AGE SEX TOB EVID
> $DATA MethodSim1.CSV IGNORE=#
> $SUBROUTINES ADVAN4 TRANS4
> $SIMULATION (12345) SUBPROBLEMS=1 ONLYSIMULATION
>
> $MIX
> NSPOP=2
> P(1)=THETA(7)
> P(2)=1.0-THETA(7)
>
> $PK
> KA=THETA(1)* EXP(ETA(1)); ETA removed in subsequent fitting of data
> CL1=THETA(2)*((WT/70)**0.75) ; non-renal clearance of subpop1
> CL2=THETA(3)*((WT/70)**0.75); non-renal clearance of subpop1
> CLr=(GFR*60/1000)*0.5 ; renal clearance
>
> Z=1
> IF(MIXNUM.EQ.2) Z=0
> CL=(Z*(CL1 + CLr) + (1.0-Z)*(CL2 + CLr))* EXP(ETA(2))
> V2 = THETA(4)*(WT/70)*EXP(ETA(3))
>
> Q = THETA(5)*(WT/70)**0.75
> V3 =THETA(6)*(WT/70)
> S2=V2
>
> $ERROR
> IPRE = F
> W1=F
> DEL = 0
> IF(IPRE.LT.0.001) DEL = 1
> IRES = DV-IPRE; NEGATIVE TREND IS OVERESTIMATING IPRED WRT DV
> IWRE = IRES/(W1+DEL)
> Y=F*(1+ERR(1))
>
> $THETA (2); KAS
> $THETA (0.1); CL1
> $THETA (5); CL2
> $THETA (5); VC
> $THETA (12); Q
> $THETA (40); VP
> $THETA (0.4); FZ
>
> $OMEGA 0 FIXED; IEKA
> $OMEGA 0 FIXED; IECL
> $OMEGA 0 FIXED; IEV2
>
> $SIGMA 0.03;
>
> $TABLE ID TIME AMT DV WT HT BMI BSA GFR AGE SEX TOB EVID NOPRINT
> NOHEADER NOAPPEND FILE=SimData.txt
>
> However, when I come back and attempt to model the simulated data set,
> my ETA1 on CL (note difference from the simulation ctl above) still
> shows a bimodal distribution. With the incorporation of the $MIXture
> model , I would expect a unimodal distribution of ETA_CL entered on 0.
> Can the community please advise?
>
> ;FITTED CTL
> $MIX
> NSPOP=2
> P(1)=THETA(7)
> P(2)=1.0-THETA(7)
>
> $PK
> KA=THETA(1)
> CL1=THETA(2)*((WT/70)**0.75)
> CL2=THETA(3)*((WT/70)**0.75)
> RS=THETA(8)
> CLr=(GFR*60/1000)*RS
> Z=1
> IF(MIXNUM.EQ.2) Z=0
> CL=((Z*CL1 + CLr) + ((1.0-Z)*CL2 + CLr))*EXP(ETA(1))
> V2 = THETA(4)*(WT/70)*EXP(ETA(2)
> Q = THETA(5)*(WT/70)**0.75
> V3 =THETA(6)*(WT/70)
>
> Thanks
> Paul