# RE: BAYES method and initial estimate bounds

From: Bob Leary <Bob.Leary>
Date: Tue, 22 Dec 2015 20:56:48 +0000

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

________________________________
From: owner-nmusers
of Bauer, Robert [Robert.Bauer
Sent: Tuesday, December 22, 2015 1:40 PM
To: Bill Gillespie
Cc: nmusers
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
Robert.Bauer
www.iconplc.com<http://www.iconplc.com>

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

Hi Bob,

Thanks for the reply. On investigating further I see this happens when NONM=
EM 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 <Robert.Bauer
ailto:Robert.Bauer
Bill:
I just tested this on a simple script (see below), and the boundaries are i=
mposed 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
\$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>
Robert.Bauer
www.iconplc.com<http://www.iconplc.com>

From: owner-nmusers
ilto:owner-nmusers
Behalf Of Bill Gillespie
Sent: Tuesday, December 22, 2015 8:14 AM
To: nmusers
Subject: [NMusers] BAYES method and initial estimate bounds

Hi all,

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

I initially thought they might work in conjunction with the prior specifica=
tions 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 tr=
ipped even when THETA(1) is bounded between -10 and 10 in the \$THETA state=
ment.

Happy Holidays,
Bill

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Received on Tue Dec 22 2015 - 15:56:48 EST

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