Re: Problem in Simulation
I tried to commenting out that perticular observation point as Dr. Bonate
suggested and it gave me same error for next observation point. Even after
removing that perticular ID, i got the same error for ID 77. I tried as Jean
mentioned to put some IF statement for DADT(1), as below
Before: DADT(1) = -KTR*A(1) + KTR*A(1)*(1-DRUG)*((CIRC0/A(5))**GAM)
New Statement:
FAB= CIRC0/A(5)
IF(A(5).LE.0) FAB=CIRC0/0.0001
DADT(1) = -KTR*A(1) + KTR*A(1)*(1-DRUG)*((FAB)**GAM)
and this worked. Now i have a concern that, does this IF statement affects
physiological relevance of this process. As Neutrophil counts never goes to
zero, and in this model it does. So is it appropriate to use this statement or
I need to try some other options? (???)
Mayank Patel
B.S, M.S (Industrial Pharmacy)
Ph.D in Pharmaceutics (cont'd.)
Long Island University, NY, USA
Quoted reply history
________________________________
From: Luann Phillips <[email protected]>
To: "Bonate, Peter" <[email protected]>
Cc: mayank patel <[email protected]>; "[email protected]"
<[email protected]>
Sent: Monday, 4 June 2012 1:12 PM
Subject: Re: [NMusers] Problem in Simulation
Mayank,
((CIRC0/A(5))**GAM should be the problem.
CIRC0 approaching zero
or
A(5) becoming extremely large relative to current value of CIRC0 so that
(CIRC0/A(5)) is equivalent to a machine zero.
You may want to put in code to resample eta when you get an unusually small or
large eta value for CIRC0.
---
With respect to transit compartments, it is my understanding that
KTR= N/MTT where N=number of compartments
or
KTR = (N+1)/MTT when you start numbering transit compartments with n=0 so N is
1 less than the number of transit compartments
Luann Phillips
Director PK/PD
Cognigen Corporation
Bonate, Peter wrote:
> The problem looks like this part of the code:
>
> ((CIRC0/A(5))**GAM
>
> Either CIRCO0 or A(5) is equal to zero.
>
> Try this
>
> ((CIRC0/A(5) + .000001)**GAM
>
>
> pete
>
> Peter L. Bonate, PhD
> Senior Director
> Global Head - Pharmacokinetics, Modeling, and Simulation
> Global Clinical Pharmacology & Exploratory Development
>
> NOTICE OF NEW ADDRESS EFFECTIVE 29 MAY 2012:
> 1 Astellas Way, 2N.292
> Northbrook, Il 60062
> phone: 224-205-5855
> fax: 224-205-5914
> email: [email protected]
>
>
> A bumper sticker I recently saw - "Calculus - The Agony and dx/dt"
>
> -----Original Message-----
> From: [email protected] [mailto:[email protected]] On
> Behalf Of mayank patel
> Sent: Monday, June 04, 2012 10:13 AM
> To: [email protected]
> Subject: [NMusers] Problem in Simulation
>
> Dear NMUSERS,
> I am trying to simulate ANC using Transit compartment Neutrapenia model. I am
> simulating for different schedule. I have used this for another drug and it
> worked fine. But rightnow it gives me error as below. If someone can guide me
> regarding this problem, it would be helpful.
> PROBLEM NO.: 1 SUBPROBLEM NO.: 1 0PRED EXIT CODE = 10
> INDIVIDUAL NO. 61 ID= 6.10000000000000E+01 (WITHIN-INDIVIDUAL) DATA
> REC NO. 207 THETA= 5.45E+00 1.35E+02 1.74E-01 2.14E-01 0.00E+00 DES
> SUBROUTINE: ERROR IN COMPUTATION
> ATTEMPT TO COMPUTE BASE**POWER WITH BASE<0. MESSAGE ISSUED FROM SIMULATION
>STEP==== END TIME ==== Fri 06/01/2012 02:09 PM
>
> Please find below control stream. If anyone can take a look and advice on
> that it would be helpful.
>
> $PROB ANC Predictions
> $INPUT C=DROP ID EVID CMT AMT RATE DV TRET TIME DAYS $DATA
> all_schedules_grid.csv IGN=C $SUBS ADVAN8 TOL=5 $MODEL
> COMP=(STEM) ;1
> COMP=(TRANSIT1) ;2
> COMP=(TRANSIT2) ;3
> COMP=(TRANSIT3) ;4
> COMP=(TRANSIT4) ;5
> COMP=(Central) ;6
> COMP=(Peri) ;7
> $PK
> "FIRST" USE PRCOM_INT,ONLY:IMAX
> " MAIN
> " IMAX=9900000000
> CL = 1.14
> V1 = 6
> K12 = 0.14
> K21 = 0.06
> K10 = CL/V1
> CIRC0 = THETA(1)*EXP(ETA(1))
> MTT = THETA(2)*EXP(ETA(2))
> KTR = 4/MTT
> GAM = THETA(3)
> SLOPE = THETA(4)*EXP(ETA(3))
> A_0(1) = CIRC0
> A_0(2) = CIRC0
> A_0(3) = CIRC0
> A_0(4) = CIRC0
> A_0(5) = CIRC0
>
> $DES
> EDRUG = 0
> CP=A(6)/V1
> IF(TRET.EQ.1.OR.TRET.EQ.3) EDRUG = SLOPE*CP
> DRUG = EDRUG
> DADT(1) = -KTR*A(1) + KTR*A(1)*(1-DRUG)*((CIRC0/A(5))**GAM)
> DADT(2) = -KTR*A(2) + KTR*A(1)
> DADT(3) = -KTR*A(3) + KTR*A(2)
> DADT(4) = -KTR*A(4) + KTR*A(3)
> DADT(5) = -KTR*A(5) + KTR*A(4) ; CIRCULATING CELLS
> DADT(6) = -K10*A(6) -K12*A(6) +K21*A(7)
> DADT(7) = -K21*A(7) +K12*A(6)
> $ERROR
> IPRED = 0.0001
> IF(A(5).GT.0) IPRED = A(5)
> W = THETA(5)*IPRED
> IRES = DV - IPRED
> IWRES = IRES/W
> Y = IPRED+W*EPS(1) REP=IREP
> AA9 = A(6)/V1
> $THETA 5.45 FIX ;1 BASE
> $THETA 135 FIX ;2 MTT (h)
> $THETA 0.174 FIX ;3 POWER
> $THETA 0.2141 FIX ;4 SLOPE
> $THETA 0 FIX; (.554 ) ;7 Res err
> $OMEGA 0.168 FIX ;1 IIV CIRC0
> $OMEGA 0.0256 FIX ;2 IIV MTT
> $OMEGA 0.36 FIX ;3 IIV SLOPE
> $SIGMA 0 FIX ;1 FIX
> $SIM (889215690) ONLYSIM SUBPROBLEM = 5
> $TABLE REP ID TIME TRET DAYS CP EVID IPRED CIRC0 MTT GAM SLOPE NOPRINT
> NOHEADER FILE=ResultANC.tab
>
> Schedule file:
> C 24.7143mg_1on-0off
> C ID Evid CMT AMT RATE DV TRET TIME DAYS
> 1 0 5 0 0 . 3 0 0
> 1 1 6 24.71 24.71 . 3 0 0
> 1 0 5 0 0 . 3 12 0.5
> 1 0 5 0 0 . 3 24 1
> 1 1 6 24.71 24.71 . 3 24 1
> 1 0 5 0 0 . 3 36 1.5
>
> Mayank PatelPh.D Student,
> Long Island University, NY
>
>
>