RE: PPC
Your bootstrap runs may terminate because of "parameter estimates near
to the boundary" due to a new feature in NONMEM VI, the "default
boundary test". See the help manual entry for $ESTIMATION:
THETABOUNDTEST, OMEGABOUNDTEST, SIGMABOUNDTEST
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With NONMEM VI, the estimation step sometimes terminates with the
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message
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PARAMETER ESTIMATE IS NEAR ITS DEFAULT BOUNDARY.
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These options request that the "default boundary test" be per-
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formed for THETA, OMEGA, and SIGMA, respectively. THETABOUNDTEST
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may also be coded TBT or TBOUNDTEST; OMEGABOUNDTEST may also be
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coded OBT or OBOUNDTEST; SIGMABOUNDTEST may also be coded SBT or
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SBOUNDTEST. These options are the defaults.
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NOTHETABOUNDTEST, NOOMEGABOUNDTEST, NOSIGMABOUNDTEST
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Instructs NONMEM to omit the "default boundary test" for this
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type of variable, i.e., to behave like NONMEM V in this regard.
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Any option listed above may be preceded by "NO". The THETA,
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OMEGA, and SIGMA choices are independent of each other. E.g., it
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is possible to specify NOOBT (to prevent the "default OMEGA boun-
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dary test") and permit both the "default THETA boundary test" and
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"default SIGMA boundary test".
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Try turning turning off "default boundary test".
William J. Bachman, Ph.D.
Director, Pharmacometrics R&D
Icon Development Solutions
6031 University Blvd., Suite 300
Ellicott City, MD 21043
Office 410-696-3002
Cell 301-467-8635
Quoted reply history
________________________________
From: [EMAIL PROTECTED] [mailto:[EMAIL PROTECTED]
On Behalf Of andreas lindauer
Sent: Thursday, July 31, 2008 7:27 AM
To: [email protected]
Subject: RE: [NMusers] PPC
Hello NMUSERS,
Let me just add one more thought on the bootstrap discussion. Sometimes
when doing a bootstrap it happens that the runs terminate because of
parameter estimates near to the boundary (e.g. values for OMEGA close to
0). When this happens in a considerable number of runs, lets say in 10%
of the runs, how would you then calculate the CI for that parameter?
Because the bootstrap parameter distribution derived from all runs -
irrespective of their termination status - would then be bimodal with
one mode close to the boundary.
Best regards, Andreas.
____________________________
Andreas Lindauer
University of Bonn
Department of Clinical Pharmacy
An der Immenburg 4
D-53121 Bonn
phone:+49 228 73 5781
fax: +49 228 73 9757