[R] Request for Assistance in R with NonMem

[Michael White]

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