[R] Request for Assistance in R with NonMem

From: Michael White <mpdubb_at_gmail.com>
Date: Wed, 26 Nov 2008 13:46:30 -0500


Hi
I am having some problems running a covariate analysis with my colleage using R with the NonMem program we are using for a graduate school project. R and NonMem run fine without adding in the covariates, but the program is giving us a problem when the covariate analysis is added. We think the problem is with the R code to run the covariate data analysis. We have the control stream, R code (along with the error), and data attached. If anyone can help we would really appreciate it. Thank you very much.
Michael

R Code:
# load MItools from within R
library(MItools)

ProjectDir <- "~/EssentialsOpenCourseware/continuous_PKPD/Examples" NMcom <- "nm6osxg77big.pl"
cov <- c("AGE", "BW")

# run NONMEM using 3032.ctl
NONR(ProjectDir=ProjectDir,

     NMcom=NMcom,
     dvname="Test (mcg/L)",
     diag=1,
     covplt=1,
     b=3032,
     boot=0,
     nochecksum=TRUE,
     grp=c("FLAG")

)

ERROR MESSAGE:
ld warning: for symbol _cm41_ tentative definition of size 32 from /usr/local/nm6osxg77big/nm/nonmem.a(INITL.o) is is smaller than the real definition of size 28 from /usr/local/nm6osxg77big/nm/BLKDAT.o

/usr/local/nm6osxg77big/test/nm6osxg77big.pl is starting
/Users/mpdubb/EssentialsOpenCourseware/continuous_PKPD/Examples/3033/nonmem.exe
/usr/local/nm6osxg77big/test/nm6osxg77big.pl is complete
No TAD item for run 3033.
Error in as.vector(x, mode) : invalid 'mode' argument Run 3033 complete.
NONR complete.

CONTROL STREAM (in NONMEM):
$PROB RUN# 3033 EFFECT COMP POPULATION PK-PD MODEL 2
$INPUT C REPL ID ARM TIME AGE BW GNDR DV MDV FLAG AMT EVID

;FLAG 1 = PK, FLAG 2=PD,
;CMT 1=GUT, 2=CENTRAL
;DV =PK  ORDERED BY ID, TIME

$DATA ../projectRSD1.csv IGNORE=C
$SUBROUTINE ADVAN2 TRANS2 INFN=../MItoolsRunlogNM6.for
$ABB COMRES=8
$PK
FLA2=FLAG
TVKA=THETA(1)
TVCL=THETA(2)

TVV=THETA(3)
CL=TVCL*EXP(ETA(1))
V=TVV*EXP(ETA(2))
KA=TVKA*EXP(ETA(3))
S2=V
$ERROR
EMAX=THETA(4)*EXP(ETA(4))
EC50=THETA(5)*EXP(ETA(5))
N = THETA(6)*EXP(ETA(6))

EFF= (EMAX*F**N)/(EC50**N+F**N) + ERR(2) CONC= F + F*ERR(1)
Y = CONC*(2-FLAG) + EFF*(FLAG-1)
IPRED=Y
    "  LAST
    "  COM(1)=G(1,1)
    "  COM(2)=G(2,1)
    "  COM(3)=G(3,1)
    "  COM(4)=G(4,1)
    "  COM(5)=G(5,1)
    "  COM(6)=G(6,1)
    "  COM(7)=HH(1,1)
    "  COM(8)=HH(2,1)

$THETA
(0, 1.7) ;KA (0, 4.7) ;CL (0, 38) ;V (0.0, .5) ; EMAX (0.0, 100) ; EC50 (0.0, 1, 10) ; N

$OMEGA
0.04
0.04
0.04
0.04
0.04
0.04

$SIGMA

0.04
5
$ESTIMATION MAXEVAL=9999 NOABORT METHOD=0 POSTHOC PRINT=5
$COVARIANCE
$TABLE ID TIME AGE BW GNDR TVKA TVV TVCL ETA1 ETA2 ETA3
EVID NOPRINT ONEHEADER FILE=TABLE.PAR
$TABLE NOPRINT FILE=../3033.TAB ONEHEADER
ID TIME AGE BW GNDR KA V CL TVKA TVCL TVV FLAG FLA2 EVID EFF CONC IPRED FLAG
$TABLE NOPRINT ONEHEADER FILE=../3033par.TAB
ID TIME AGE BW GNDR KA V CL TVKA TVCL TVV EMAX EC50 ETA1 ETA2 ETA3 EVID
$TABLE ID TIME COM(1)=G11 COM(2)=G21

COM(3)=G31 COM(4)=G41 COM(5)=G51 COM(6)=G61 COM(7)=H11 COM(8)=H21 IPRED MDV NOPRINT ONEHEADER FILE=cwtab1.deriv



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