NONMEM Users Network Archive

Hosted by Cognigen


From: Bachman, William <William.Bachman>
Date: Thu, 31 Jul 2008 09:02:11 -0400

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:

      With NONMEM VI, the estimation step sometimes terminates with the
      These options request that the "default boundary test" be per-
      formed for THETA, OMEGA, and SIGMA, respectively. THETABOUNDTEST
      may also be coded TBT or TBOUNDTEST; OMEGABOUNDTEST may also be
      coded OBT or OBOUNDTEST; SIGMABOUNDTEST may also be coded SBT or
      SBOUNDTEST. These options are the defaults.

      Instructs NONMEM to omit the "default boundary test" for this
      type of variable, i.e., to behave like NONMEM V in this regard.
      Any option listed above may be preceded by "NO". The THETA,
      OMEGA, and SIGMA choices are independent of each other. E.g., it
      is possible to specify NOOBT (to prevent the "default OMEGA boun-
      dary test") and permit both the "default THETA boundary test" and
      "default SIGMA boundary test".

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


From: owner-nmusers
On Behalf Of andreas lindauer
Sent: Thursday, July 31, 2008 7:27 AM
To: nmusers
Subject: RE: [NMusers] PPC



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

ICON plc made the following annotations.
This e-mail transmission may contain confidential or legally privileged i=
that is intended only for the individual or entity named in the e-mail ad=
dress. If you
are not the intended recipient, you are hereby notified that any disclosu=
re, copying,
distribution, or reliance upon the contents of this e-mail is strictly pr=
ohibited. If
you have received this e-mail transmission in error, please reply to the =
sender, so that
ICON plc can arrange for proper delivery, and then please delete the mess=
Thank You,
ICON plc
South County Business Park
Dublin 18
Registered number: 145835

***Please note that starting Monday July 14th ICON has standardized on th=
e domain name***

Received on Thu Jul 31 2008 - 09:02:11 EDT

The NONMEM Users Network is maintained by ICON plc. Requests to subscribe to the network should be sent to:

Once subscribed, you may contribute to the discussion by emailing: