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| BAYES EXAMPLE 2 |
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This is example2.ctl from the NONMEM 7 distribution medium. It, along
with the data file, can be found in the examples directory.
;Model Desc: Two Compartment model with Clearance and
; central volume modeled with covariates age and gender
;Project Name: nm7examples
;Project ID: NO PROJECT DESCRIPTION
$PROB RUN# example2 (from sampc)
$INPUT C SET ID JID TIME DV=CONC AMT=DOSE RATE EVID MDV CMT GNDR AGE
$DATA example2.csv IGNORE=C
$SUBROUTINES ADVAN3 TRANS4
$PK
; LCLM=log transformed clearance, male
LCLM=THETA(1)
;LCLF=log transformed clearance, female.
LCLF=THETA(2)
; CLAM=CL age slope, male
CLAM=THETA(3)
; CLAF=CL age slope, female
CLAF=THETA(4)
; LV1M=log transformed V1, male
LV1M=THETA(5)
; LV1F=log transformed V1, female
LV1F=THETA(6)
; V1AM=V1 age slope, male
V1AM=THETA(7)
; V1AF=V1 age slope, female
V1AF=THETA(8)
; LAGE=log transformed age
LAGE=DLOG(AGE)
;Mean of ETA1, the inter-subject deviation of Clearance,
; is ultimately modeled as linear function of THETA(1) to THETA(4).
; Relating thetas to Mus by linear functions is not essential for
; ITS, IMP, or IMPMAP methods, but is very helpful for MCMC methods
; such as SAEM and BAYES.
MU_1=(1.0-GNDR)*(LCLM+LAGE*CLAM) + GNDR*(LCLF+LAGE*CLAF)
; Mean of ETA2, the inter-subject deviation of V1,
; is ultimately modeled as linear function of THETA(5) to THETA(8)
MU_2=(1.0-GNDR)*(LV1M+LAGE*V1AM) + GNDR*(LV1F+LAGE*V1AF)
MU_3=THETA(9)
MU_4=THETA(10)
CL=DEXP(MU_1+ETA(1))
V1=DEXP(MU_2+ETA(2))
Q=DEXP(MU_3+ETA(3))
V2=DEXP(MU_4+ETA(4))
S1=V1
$ERROR
CALLFL=0
; Option to model the residual error coefficient in THETA(11),
; rather than in SIGMA.
SDSL=THETA(11)
W=F*SDSL
Y = F + W*EPS(1)
IPRED=F
IWRES=(DV-F)/W
;Initial THETAs
$THETA
( 0.7 ) ;[LCLM]
( 0.7 ) ;[LCLF]
( 2 ) ;[CLAM]
( 2.0);[CLAF]
( 0.7 ) ;[LV1M]
( 0.7 ) ;[LV1F]
( 2.0 ) ;[V1AM]
( 2.0 ) ;[V1AF]
( 0.7 ) ;[MU_3]
( 0.7 );[MU_4]
( 0.3 ) ;[SDSL]
;Initial OMEGAs
$OMEGA BLOCK(4)
0.5 ;[p]
0.001 ;[f]
0.5 ;[p]
0.001 ;[f]
0.001 ;[f]
0.5 ;[p]
0.001 ;[f]
0.001 ;[f]
0.001 ;[f]
0.5 ;[p]
; SIGMA is 1.0 fixed, serves as unscaled variance for EPS(1).
; THETA(11) takes up the residual error scaling.
$SIGMA
(1.0 FIXED)
;Prior information is important for MCMC Bayesian analysis,
; not necessary for maximization methods
; In this example, only the OMEGAs have a prior distribution,
; the THETAS do not.
; For Bayesian methods, it is most important for at least the
; OMEGAs to have a prior, even an uninformative one,
; to stabilize the analysis. Only if the number of subjects
; exceeds the OMEGA dimension number by at least 100,
; then you may get away without priors on OMEGA for BAYES analysis.
$PRIOR NWPRI
; Prior OMEGA matrix
$OMEGAP BLOCK(4) FIX VALUES(0.01,0.0)
; Degrees of freedom to OMEGA prior matrix:
$OMEGAPD 4 FIX
; The first analysis is iterative two-stage.
; Note that the GRD specification is THETA(11) is a
; Sigma-like parameter. This will allow NONMEM to make
; efficient gradient evaluations for THETA(11), which is useful
; for later IMP,IMPMAP, and SAEM methods, but has no impact on
; ITS and BAYES methods.
$EST METHOD=ITS INTERACTION FILE=example2.ext NITER=1000 NSIG=2
PRINT=5 NOABORT SIGL=8 NOPRIOR=1 CTYPE=3 GRD=TS(11)
; Results of ITS serve as initial parameters for the IMP method.
$EST METHOD=IMP INTERACTION EONLY=0 MAPITER=0 NITER=100 ISAMPLE=300
PRINT=1 SIGL=8
; The results of IMP are used as the initial values for the SAEM method.
$EST METHOD=SAEM NBURN=3000 NITER=2000 PRINT=10 ISAMPLE=2
CTYPE=3 CITER=10 CALPHA=0.05
; After the SAEM method, obtain good estimates of the marginal density
; (objective function),
; along with good estimates of the standard errors.
$EST METHOD=IMP INTERACTION EONLY=1 NITER=5 ISAMPLE=3000
PRINT=1 SIGL=8 SEED=123334
CTYPE=3 CITER=10 CALPHA=0.05
; The Bayesian analysis is performed.
$EST METHOD=BAYES INTERACTION FILE=example2.TXT NBURN=10000
NITER=3000 PRINT=100 NOPRIOR=0
CTYPE=3 CITER=10 CALPHA=0.05
; Just for old-times sake, lets see what the traditional
; FOCE method will give us.
; And, remember to introduce a new FILE, so its results wont
; append to our Bayesian FILE.
$EST METHOD=COND INTERACTION MAXEVAL=9999 FILE=example2.ext NSIG=2
SIGL=14 PRINT=5 NOABORT NOPRIOR=1
$COV MATRIX=R UNCONDITIONAL
REFERENCES: Guide Introduction_7
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