116  Introduction to NONMEM Version VI

Authors

Stuart L. Beal

Edited by Thomas Ludden and Alison Boeckmann

Published

June 1, 2023

GloboMax
ICON plc.
Blue Bell, PA.

Copyright by the Regents of the University of California
2008, 2013, 2023
All rights reserved

The appearance of the June 2023 edition conincides with the appearance of NONMEM 7.6.0. It revises the March 2013 edition which coincided with the appearance of NONMEM 7.3. For the May 2023 edition, a few statements have been updated from the March 2013 version. Also, the most relevant information to this Introduction to NONMEM Version VI has been incorporated into Guides IV, V, VI, and VIII, and it should be unnecessary to consult Guide VI for understanding or technical help in using NONMEM. This document as of May 2023 is of mostly of historical interest, outlining the changes from NONMEM V to NONMEM VI.

The March 2013 edition in turn revised the Introduction to NONMEM Version VI (2008), which accompanies NONMEM VI 2.0. For the March 2013 version, the Guide was reformatted, with no changes made to the content. All Version VI 1.0 bugs identified as of the date of this document have been fixed. Version VI 2.0 is upwards compatible with 1.0, 1.1, 1.2 and 1.3.

1 Changes to October 2006 document (which accompanied NONMEM VI 1.0)

  • 1.5a. Changes to SIZES
  • 1.6a. Updated version of NONMEM Users Guide III
  • 1.6b. Changes to SETUP and CDSETUP6.BAT
  • 1.6c. Changes to NMFE6 and NMFE6.BAT
  • 1.6d. Html with hyperlinks
  • 1.6e. nmsee6.for - New version of nmsee
  • 2.1.4. Stieltjes Method is fully implemented
  • 2.1.4a. Further Notes on Stieltjes
  • 2.1.9a. Implementing PRIOR routines
  • 2.1.12a. Elements of ROCM50 may be used in abbreviated code
  • 2.1.14. Default Boundary Test is User-selectable
  • 2.2.9. Increase in the number of records
  • 2.2.10. Increase in the maximum number of function evaluations
  • 2.2.11. Table: PRED, RES, and WRES with NOAPPEND; more items
  • 2.2.12. Table and Scatter: more PRED-defined labels
  • 3.5. PREDPP: New Feature: Initial Steady State
  • 3.6. PREDPP: New in SIZES: MAXFCN
  • 4.1.24. NM-TRAN datafiles: LAST20=50
  • 4.1.25. NM-TRAN input files: 160 characters per line
  • 4.1.26. NM-TRAN datafiles: Ill-formed files
  • 4.1.27. NM-TRAN datafiles: Blank lines in files (BLANKOK)
  • 4.1.28. NM-TRAN datafiles: Filenames
  • 4.1.29. NM-TRAN datafiles: Tab and ^M
  • 4.1.30. $DATA record: RECORDS option
  • 4.1.31. $PRIOR record
  • 4.1.32. $ESTIM record: NOOMEGABOUNDTEST option
  • 4.1.33. $ESTIM record: MAXEVAL option
  • 4.1.34. $TABLE and $SCATTER: G and H elements
  • 4.1.35. Abbreviated code: PHI
  • 4.1.36. Abbreviated code: ROCM50
  • 4.2.4. $MODEL and $PK: I_SS option (Initial Steady State)
  • 5.4 New Reference: Wang, Y. (Wang 2007)

2 Overview of Version VI

This document provides an introduction to NONMEM Version VI, indicating the new features and basic changes from Version V. Perhaps the most important aspects of Version VI, however, are:

  1. All Version V bugs identified as of the date of this document have been fixed,
  2. Numerous small improvements to Version V have been made, such as messages,
  3. The stability and speed of Version V computations have been significantly improved, and depending on the model, size of the data set and estimation method, the user should notice this.
  4. Version VI is essentially upwards compatible with Version V. The formatting of the report file, however, is a little different, and there are some minor changes noted below in sections 2.2.5 and 4.1.2 and 4.1.15 and 4.1.23. Model specification files created by version V cannot be used with version VI and vice versa. There is no single-precision version of NONMEM VI.
  5. There is now a single INCLUDE file named SIZES. This file contains all the constants previously contained in NSIZES, PSIZES, TSIZES and LSIZES. SIZES contains a new variable, MAXIDS, the maximum number of individuals in a data set. The default value is 1000.
  • Changes to SIZES.
    • MAXFCN has been moved from PREDPP code to SIZES and has been given a larger value. See I.3.6 below.
    • The following have larger values: LVR2, LNP4, LSW1, MAXIDS, PIR, DIMTMP, DIMCNS, DINEW, DIMRV, DIMPKS. (See the SIZES Help Item)
  1. NONMEM Users Guides I–VIII and NONMEM V Supplement are provided as .pdf files on the NONMEM VI CD. With the exception of Guide II, these .pdf files are searchable. Guides I–II, IV–VII and Guide VIII, have been updated to incorporate features NONMEM VI. Changes for 2.0 are marked with “|” in the right margin.
  • NONMEM Users Guide III (Installation) has been updated for NONMEM VI 2.0.
  • Installation utilities SETUP (Unix) and CDSETUP6.BAT have been changed. SETUP now performs the complete installation on a Unix system. E.g., it makes the NONMEM VI 2.0 directory, copies tar files from the cdrom, and extracts all files from them. Previously, these steps had to be performed by the user. Thus, SETUP can be used much like CDSETUP6.BAT. Both SETUP and CDSETUP6.BAT have a new argument, “recompile (y/n)”, and will detect if the SIZES file is newer than the binary files. If SIZES is modified after NONMEM has been installed, or if post-installation changes or patches are made, SETUP (or CDSETUP6) may be run with recompile set to y, and all binaries will be recompiled. (Previously, the user had to remove old binary files in order to recompile.)
  • NONMEM execution tools NMFE6 (Unix) and NMFE6.BAT have been changed. NM-TRAN messages (e.g., warnings and other informational messages) are now saved in a file FMSG, and are copied to the NONMEM report file as well as being written to the console.
  • HTML with hyperlinks.
    • With NONMEM VI 1.0, there is a directory html on the NONMEM distribution medium containing html versions of the NONMEM help items.
    • With NONMEM VI 2.0, the HTML files also include hyperlinks between help items, and between help items and the NONMEM Users Guide pdf files, including the present guide.
  • nmsee6.for
    • There is a new version of nmsee, nmsee6.for. It is very similar to nmsee5.for, but with a few new options and prefixes. It is now described in on-line help and Guide VIII. All files may be obtained via ftp from https://nonmem.iconplc.com/nonmem/nmsee6. Note that this utility is provided for the convenience of the user but is not supported by Icon Development Solutions.

NONMEM has three major parts: NONMEM, PREDPP, and NM-TRAN. Strictly speaking, “Version V” refers to the version of NONMEM, where the releases of these parts are V, IV, and III, respectively, and “Version VI” refers to the version of NONMEM, where the releases of these parts are VI, V, and IV, respectively.

Brief descriptions of new features and basic changes from NONMEM Version V that relate to the NONMEM program itself are found in section 2; those that relate to PREDPP are found in section 3; those that relate to NM-TRAN are found in section 4.

Detailed descriptions may be found in the Help items (NONMEM Users Guide VIII). The Help items should also be consulted for some new useful examples. Improvements have been made to many of the older items, in particular NMPRD5 (auto-correlation). Some terminology has been changed in a few help items. What were previously referred to as “scaled, transformed parameters” or STP are now designated as “unconstrained parameters” or UCP.