Re: Question about handling BLOQ data with mixture model

From: Andy Stein andy.stein Date: Fri, 25 May 2012 14:45:07 -0400 To: LGibiansky il.com Subject: Re: [NMusers] Question about handling BLOQ data with mixture model I wanted to follow up on the comments to Yaping's email. First, the three probabilities below from the original code do in fact sum to 1. P(1)=THETA(8)/100 P(2)=(1-THETA(8)/100)*THETA(9)/1000 P(3)=(1-THETA(8)/100)*(1-THETA(9)/1000) Note that: P(2) + P(3) = 1-THETA(8)/100 And thus P(1) + P(2) + P(3) = 1 Also, the model worked completely fine when the BLOQ part of the code was left out and only the mixture was modeled. That is what led us to think that the combination of BLOQ with a Mixture was causing the problem. Andy On Fri, May 25, 2012 at 1:07 PM, LGibiansky LGibiansky > Sum of probabilities should sum to 1. More standard way would be to us e > > 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 martin.bergstrand > Date: Fri, 25 May 2012 22:59:45 +0700 > To: yapingz2011 > 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 yo u > are applying a mixture model. CUMD is dependent on IPRED that in its t urn > is > dependent on the assigned mixture. That should be enough. > > > > However, I spot what must be an error in your way of defining your mixtu re > 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 whe n 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 > > martin.bergstrand > > > > Visiting scientist: > > Mahidol-Oxford Tropical Medicine Research Unit, > > Bangkok, Thailand > > > > > > From: owner-nmusers com] > On > Behalf Of Yaping Zhang > Sent: den 25 maj 2012 02:04 > To: nmusers > 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). T he > 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 crash ed > 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 th e > code below when putting a mixture model together with the BLOQ error mod el > > 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 *EXP(mu*T/8766) > > IF (MIXNUM.EQ.2) F *EXP(alpha*T/8766)+BB*EXP(beta*T/8766) > > IF (MIXNUM.EQ.3) F > *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 MAXEVAL90 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 > > > -------------------------------------------------------------------- mail2web LIVE Free email based on Microsoft Exchange technology - http://link.mail2web.com/LIVE