Standard errors below 0.1%?
From: "Nele Plock" nplock@zedat.fu-berlin.de
Subject: [NMusers] Standard errors below 0.1%?
Date: Wed, 03 Aug 2005 09:41:48 +0200
Dear all,
I have been trying to implement a model for data with both iv and oral dosing. The
control stream is attached below. By using a model with first order absorption I
could get the covariance step to run. However, using a model with zero order absorption
led to a big drop in OF, although the runs terminate due to rounding errors. When I
change the TOLERANCE from 5 to 4 the run is successful and the covariance step as well.
What is weird though is that the highest standard error is estimated to be 0.1%, all
others are even below that value.
Now my questions are as follows:
What exactly does the change in TOL do that leads to a successful run?
Has anybody ever seen standard errors that low? What could be the reason, because
frankly speaking I dont trust those values at all?
Any help would be appreciated!
Nele
;PROJECT: test
;STUDY: iv/po multiple dose
;RUN: 048
;KINETICIST: N. Plock
;NOTES: 2-COMP. MODEL, COMBINED ERROR MODEL
;NOTES: IIV ON K10, V1, V2, D1, CL, zero order absorption, FOCE INT method
$PROBLEM iv/po
$INPUT ID TIME TILD AMT RATE ADMA CMT DV FLMA EVID VIST OCC DAY AGE SEX HT
CID=DROP TYPE=DROP FUPL FLAG
$DATA ivpo_220705_ID01-33 IGNORE=#
$SUBROUTINES ADVAN6 TRANS1 TOL4
$MODEL
NCOMPS=4
COMP=(CENTRAL, DEFOBS)
COMP=(PERIP1)
COMP=(DELAY)
COMP=(ELIM)
$PK
TVK10=THETA(1)
K10=TVK10*EXP(ETA(1))
TVV1=THETA(2)
V1=TVV1*EXP(ETA(2))
TVQ=THETA(3)
Q=TVQ
TVV2=THETA(4)
V2=TVV2*EXP(ETA(3))
TVD1=THETA(5)
D1=TVD1*EXP(ETA(4))
ALAG1=0
IF (ID.EQ.3.AND.OCC.GT.1) ALAG1=THETA(6)
IF (ID.EQ.6.AND.OCC.GT.1) ALAG1=THETA(6)
IF (ID.EQ.9.AND.OCC.GT.1) ALAG1=THETA(6)
TVEC50=THETA(7)
EC50=TVEC50
TVEMAX=THETA(8)
EMAX=TVEMAX
TVKIC=THETA(9)
KIC=TVKIC
TVCL=THETA(10)
CL=TVCL*EXP(ETA(5))
S1=V1
K14=CL/V1
K12=Q/V1
K21=Q/V2
$DES
CLIN=A(1)/V1
DADT(1)=-A(1)*K12+A(2)*K21-A(1)*K10*(1-EMAX*A(3)/(A(3)+EC50))-K14*A(1)
DADT(2) = A(1)*K12 -A(2)*K21
DADT(3) = KIC*(CLIN-A(3))
CL2=K10*(1-EMAX*A(3)/(A(3)+EC50))*V1
$ERROR
IPRED=F
DEL=0
IF (IPRED.EQ.0) DEL=0.0001
W=F
IRES=DV-IPRED
IWRES=IRES/(W+DEL)
Y=IPRED+W*EPS(1)+EPS(2)
;---------------------------------------INITIAL ESTIMATES-----------------------------------
$THETA (0.05,0.14) ; 1 K10
$THETA (0.1,21.2) ; 2 V1
$THETA (0.1,76) ; 3 Q
$THETA (0.1,30) ; 4 V2
$THETA (0.001,1) ; 5 D1
$THETA 1.23 FIX ; 6 ALAG1
$THETA (0.1,0.15) ; 7 EC50
$THETA 1 FIX ; 8 EMAX
$THETA (0.001,0.005) ; 9 KIC
$THETA (0.1,7.5) ; 10 CL
$OMEGA 5 ; 1 IIV_K10
$OMEGA 0.15 ; 2 IIV_V1
$OMEGA 0.1 ; 3 IIV_V2
$OMEGA 0.4 ; 4 IIV_D1
$OMEGA 0.3 ; 5 IIV_CL
$SIGMA 0.01 ; prop.error
$SIGMA 0.1 ; add. error
$ESTIMATION PRINT=5 METHOD=1 INTERACTION MSFO=msf MAXEVAL=9999 NOABORT
$COV
$TABLE ID TIME IPRED IWRES ONEHEADER NOPRINT FILE=sdtab
$TABLE ID ETA1 ETA2 ETA3 ETA4 ETA5 K10 V1 Q K14 V2 D1 ALAG1 EC50 EMAX KIC CL
CL2 Q FLAG ONEHEADER NOPRINT FILE=patab