NONMEM is not compliant with CFR Part 11, i.e., it provides no traceability, a feature critical to regulatory submissions. PLT Tools is designed to ensure complete traceability of a NONMEM analysis other than creation of the dataset.
Features include:
All files created by NONMEM - FDATA, outputfiles and tables - are preserved completely unchanged.
Every file created as part of the analysis is named with an identical 13-character, 12-digit timestamp issued when the run is initiated. The format of the timestamp is YYMMDD-HHMMSS (2-digit year, 2-digit month, 2-digit day, 2-digit hour, 2-digit minute, 2-digit second).
NONMEM's nmsee utility is used to created an abbreviated version of the NONMEM output (Summary.TIMESTAMP.pdf).
All files are filed in an organized and consistent file structure created by PLT Tools.
PLT Tools creates a number of other files containing a file header, including the timestamp described above, a text version of that timestamp, text indicating when the run was started and ended, and the name of the computer and user. An example of the file header appears below:
Timestamp: 071108-145352
Analysis performed on plessthan2 by fisher
Run started at 2007-11-08 14:53:52
Run completed at 2007-11-08 15:16:51
FILES CREATED BY PLT Tools DURING EACH RUN (TIMESTAMP refers to the 13-character timestamp described above):
TABLES (the file delimiter can be either a comma, semicolon, or tab; csv shown here):
AllRecords.TIMESTAMP.csv: A NONMEM table in which the FIRSTONLY option has not been selected is modified: its first line ("Table #1") is deleted and all spaces are replaced with a delimiter. The file opens properly formatted in Excel.
FirstRecords.TIMESTAMP.csv: A NONMEM table in which the FIRSTONLY option has been selected is modified: its first line ("Table #1") is deleted and all spaces are replaced with a delimiter. The file opens properly formatted in Excel.
Halflives.TIMESTAMP.csv: If the analysis involves a 1-, 2, or 3-compartment pharmacokinetic model, the user can request creation of a containing post hoc estimates for half-lives, fractional coefficients, and Vss.
Input.TIMESTAMP.csv:The FDATA file in which all spaces are replaced with delimiters.
TEXT FILES:
Control.TIMESTAMP.txt: The unprocessed Control Stream preceded by the fileheader. This faciliates re-use of a Control Stream at a later date. In addition, it facilitates comparison of control streams.
PDF:
BriefSummary.TIMESTAMP.pdf: A 1-2 page summary of critical elements of NONMEM output (download example).
Results.TIMESTAMP.pdf: The NONMEM outputfile preceded by the file header (download example).
Summary.TIMESTAMP.pdf: The summary text file described above is saved in a PDF format (download example).
Graphics.TIMESTAMP.pdf: Graphics prepared from NONMEM's tables (download example).
FILE MANAGEMENT: In addition to the filed versions of the files, certain files (AllRecords.TIMESTAMP.csv, BriefSummary.TIMESTAMP.pdf, FirstRecords.TIMESTAMP.csv, Graphics.TIMESTAMP.pdf, Results.TIMESTAMP.pdf, and Summary.TIMESTAMP.pdf) are copied to a local directory (MostRecentRun-Copies) from which they can be discarded once reviewed.
DISCLAIMER: Although these steps should permit complete traceability of a NONMEM analysis, the user remains responsible for assuring Part 11 compliance.