1.34+154 is often on many systems used to indicate an improbably large floating 
point number that is likely an error of some sort. It is the sqrt of the 
largest representable real*8 value, 1.797+308


________________________________
From: [email protected] [[email protected]] on behalf of 
Bauer, Robert [[email protected]]
Sent: Tuesday, December 22, 2015 1:40 PM
To: Bill Gillespie
Cc: [email protected]
Subject: RE: [NMusers] BAYES method and initial estimate bounds

Bill:
Yes, and when that happens, the execution path is difficult to anticipate.

Robert J. Bauer, Ph.D.
Vice President, Pharmacometrics R&D
ICON Early Phase
Office: (215) 616-6428
Mobile: (925) 286-0769
[email protected]<mailto:[email protected]>
www.iconplc.com<http://www.iconplc.com>

From: Bill Gillespie [mailto:[email protected]]
Sent: Tuesday, December 22, 2015 11:25 AM
To: Bauer, Robert
Cc: [email protected]
Subject: Re: [NMusers] BAYES method and initial estimate bounds

Hi Bob,

Thanks for the reply. On investigating further I see this happens when NONMEM 
reports a THETA value of 1.34+154 in the PRDERR file. Would I be correct in 
thinking that is the result of a floating point error somewhere in the sampling 
process?

Thanks,
Bill

On Tue, Dec 22, 2015 at 12:40 PM, Bauer, Robert 
<[email protected]<mailto:[email protected]>> wrote:
Bill:
I just tested this on a simple script (see below), and the boundaries are 
imposed in BAYES analysis for me.

$PROB RUN# Example 1 (from samp5l)
$INPUT C SET ID JID TIME  DV=CONC AMT=DOSE RATE EVID MDV CMT CLX V1X QX V2X 
SDIX SDSX
$DATA example1.csv IGNORE=C
$SUBROUTINES ADVAN3 TRANS4
$PK
MU_1=THETA(1)
MU_2=THETA(2)
MU_3=THETA(3)
MU_4=THETA(4)
IF (THETA(1)<1.63.OR.THETA(1)>1.8) WRITE(50,*) THETA(1)
CL=DEXP(THETA(1)+ETA(1))
V1=DEXP(THETA(2)+ETA(2))
Q=DEXP(MU_3+ETA(3))
V2=DEXP(MU_4+ETA(4))
S1=V1
$ERROR
Y = F + F*EPS(1)
$THETA (1.63, 1.67,1.8) 2.0 2.0 2.0
$OMEGA BLOCK(4) VALUES(0.15,0.01)
$SIGMA  (0.6 )
$PRIOR NWPRI
$THETAP (2.0 FIX) (2.0 FIX) (2.0 FIX) (2.0 FIX)
$THETAPV BLOCK(4) FIX VALUES(10000,0.0)
$OMEGAP BLOCK(4) FIX VALUES(0.2,0.0)
$OMEGAPD (4 FIX)
$EST METHOD=BAYES INTERACTION NITER=1000 PRINT=100 CTYPE=3
$COV MATRIX=R PRINT=E UNCONDITIONAL

Robert J. Bauer, Ph.D.
Vice President, Pharmacometrics R&D
ICON Early Phase
Office: (215) 616-6428<tel:%28215%29%20616-6428>
Mobile: (925) 286-0769<tel:%28925%29%20286-0769>
[email protected]<mailto:[email protected]>
www.iconplc.com<http://www.iconplc.com>

From: [email protected]<mailto:[email protected]> 
[mailto:[email protected]<mailto:[email protected]>] On 
Behalf Of Bill Gillespie
Sent: Tuesday, December 22, 2015 8:14 AM
To: [email protected]<mailto:[email protected]>
Subject: [NMusers] BAYES method and initial estimate bounds

Hi all,

If bounds are specified in the $THETA statements for initial estimates, what, 
if any, effect do they have when the BAYES method is used?

I initially thought they might work in conjunction with the prior 
specifications to implement truncated priors. However that does not seem to be 
true because statements like "IF(ABS(THETA(1)) > 10) EXIT 1 14" sometimes get 
tripped even when THETA(1) is  bounded between -10 and 10 in the $THETA 
statement.

Happy Holidays,
Bill


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