Re: Question about handling BLOQ data with mixture model

On Fri, May 25, 2012 at 1:07 PM, [email protected] < [email protected]> wrote: > Sum of probabilities should sum to 1. More standard way would be to use > > P(1) = 1/(1+THETA(8)+THETA(9)) > > P(2) = THETA(8)/(1+THETA(8)+THETA(9)) > > P(3) = THETA(9)/(1+THETA(8)+THETA(9)) > > where THETA(8) and THETA(9) are any positive numbers > Regards > Leonid > > Original Message: > ----------------- > From: Martin Bergstrand [email protected] > Date: Fri, 25 May 2012 22:59:45 +0700 > To: [email protected], [email protected] > Subject: RE: [NMusers] Question about handling BLOQ data with mixture model > > > Dear Yaping, > > > > I can see that you need to make any particular consideration because you > are applying a mixture model. CUMD is dependent on IPRED that in its turn > is > dependent on the assigned mixture. That should be enough. > > > > However, I spot what must be an error in your way of defining your mixture > probabilities. As it is now you total probability does not sum up to 1. Why > don't you parameterize it his way: > > > > $MIX > > NSPOP=3 > > P(1) = THETA(8)/100 > > P(2) = (1-THETA(8)/100)*THETA(9)/100 > > P(3) = 1-THETA(8)/100 -THETA(9)/100 > > > > $THETA (0, 3.78, 100) ; PMIX1 > > $THETA (80, 91, 100) ; PMIX2/(1-PMIX1) > > > > I have kept the division of THETAs by 100 since I assume that you want > estimates in %. However the division with 1000 did not make any sense to me > despite the correctly assigned THETA boundaries? > > > > Finally a word of caution, be careful with the use of NONMEM reserved > variables such as T (integrated time in $DES) and F (default model > prediction with some ADVANS). In my experience things can go wrong when you > use them outside the way it was intended, conflicts can occur. > > > > Kind regards, > > > > Martin Bergstrand, PhD > > Pharmacometrics Research Group > > Dept of Pharmaceutical Biosciences > > Uppsala University > > Sweden > > [email protected] > > > > Visiting scientist: > > Mahidol-Oxford Tropical Medicine Research Unit, > > Bangkok, Thailand > > > > > > From: [email protected] [mailto:[email protected]] > On > Behalf Of Yaping Zhang > Sent: den 25 maj 2012 02:04 > To: [email protected] > Subject: [NMusers] Question about handling BLOQ data with mixture model > > > > Hello NMUsers, > > > > I am trying to analyze BLOQ data using the M3 method (Stuart Beal, Ways to > Fit a PK Model with Some Data Below the Quantification Limit, 2001). The > model I have is a mixture model to describe PD response of three > subpopulations. The complete control stream is pasted below. > > > > I have implemented just the mixture model (no BLOQ) and just the BLOQ error > model (no mixture) and it works fine with nonmem 6. But the run crashed > immediately using nonmem 6 if including both BLOQ and the mixture model. > > > > I am wondering if I need to account for the mixture in the section of the > code below when putting a mixture model together with the BLOQ error model > > IF (BLOQ.EQ.1) THEN > > F_FLAG=1 > > Y =CUMD + something based on MIXNUM? > > ENDIF > > > > Any ideas are gratefully received! > > > > Many thanks, > > Yaping > > > > > > $PROB AMN107A2303 > > > > $INPUT NUM=DROP STUD=DROP SUBJ=DROP ID AGE0=DROP SEX=DROP RACE=DROP > > DART=DROP ARM ACTT=DROP POP PPK=DROP COUN=DROP > > SOK OTIM=DROP TIME TVIS=DROP > > AMT=DROP DOSE=DROP SCHD=DROP AUC=DROP CMIN=DROP > > ODV=DROP MDV DV BLOQ STY=DROP EVDT=DROP > > > > $DATA ../data/AMN2303_ENEST.csv ; currently modified with matlab and saved > with oocalc > > > > IGNORE=@ > > IGNORE=(MDV.EQ.1) > > IGNORE=(ID.EQ.66, ID.EQ.92, ID.EQ.335, ID.EQ.346, ID.EQ.348, ID.EQ.416, > ID.EQ.496, ID.EQ.527, ID.EQ.762, ID.EQ.790) > > > > $PRED > > mu =THETA(1)*EXP(ETA(1)) > > AA =THETA(2)*EXP(ETA(2)) > > alpha =THETA(3)*EXP(ETA(3)) > > BB =THETA(4)*EXP(ETA(4)) > > beta =THETA(5)*EXP(ETA(5)) > > InCC =THETA(6)+ETA(6) > > gamma =THETA(7)*EXP(ETA(7)) > > > > T = TIME > > IF (TIME.LE.0) T = 0 > > > > EST=MIXEST > > IF (MIXNUM.EQ.1) F =AA*EXP(mu*T/8766) > > IF (MIXNUM.EQ.2) F =AA*EXP(alpha*T/8766)+BB*EXP(beta*T/8766) > > IF (MIXNUM.EQ.3) F > =AA*EXP(alpha*T/8766)+BB*EXP(beta*T/8766)+EXP(InCC)*EXP(gamma*T/8766) > > > > PROP=THETA(10) > > W=SQRT(PROP*PROP) > > > > IPRED=-2.8 > > IF(F.GT.0)IPRED =LOG10(F) > > LLOQ=-2.5 > > DUM=(LLOQ-IPRED)/W > > CUMD=PHI(DUM) > > > > IF (BLOQ.EQ.0) THEN > > F_FLAG=0 > > Y =IPRED+W*ERR(1) > > ENDIF > > > > IF (BLOQ.EQ.1) THEN > > F_FLAG=1 > > Y =CUMD > > ENDIF > > > > $MIX > > NSPOP=3 > > P(1)=THETA(8)/100 > > P(2)=(1-THETA(8)/100)*THETA(9)/1000 > > P(3)=(1-THETA(8)/100)*(1-THETA(9)/1000) > > > > $THETA (-10,-0.57,0) ; mu THETA(1) > > $THETA (0.0001,50.7,100) ; AA THETA(2) > > $THETA (-100,-14.2,0) ; alpha THETA(3) > > $THETA (0.0001,0.196,10) ; BB THETA(4) > > $THETA (-10,-0.678,0) ; beta THETA(5) > > $THETA (-100,-6.92,0) ; InCC THETA(6) > > $THETA (0, 2.15) ; gamma THETA(7) > > $THETA (0, 3.78, 100) ; THETA(8) > > $THETA (800, 910, 1000) ; THETA(9) > > $THETA (0.001,0.104, 5) ; ERR THETA(10) > > > > $OMEGA 0.001 FIX ; mu > > $OMEGA 0.767 ; AA > > $OMEGA 0.236 ; alpha > > $OMEGA 3.58 ; BB > > $OMEGA 0.148 ; beta > > $OMEGA 5 ; CC > > $OMEGA 0.858 ; gamma > > > > $SIGMA 1 FIX > > > > $EST METHOD=1 LAPLACIAN NOABORT MAXEVAL=9990 PRINT=1 MSFO=run012.nmmsf > SIG=2 > > > > $COV > > > > $TABLE ID TIME DV MDV IPRED EST > > FILE=run012.nmfit NOPRINT ONEHEADER > > > > $TABLE ID ETA1 ETA2 ETA3 ETA4 ETA5 ETA6 ETA7 mu AA alpha BB beta InCC gamma > > NOAPPEND FIRSTONLY FILE=run012.nmpar NOPRINT ONEHEADER > > > > > -------------------------------------------------------------------- > mail2web LIVE – Free email based on Microsoft® Exchange technology - > http://link.mail2web.com/LIVE > > >