...Marc Schwartz said the following on 2004-12-18 01:19:
As you are likely aware, other statistically relevant issues are contained in various ICH guidance documents regarding GCP considerations and principles for clinical trials:
http://www.ich.org/[EMAIL PROTECTED]&@_TEMPLATE=272
ICH E9 states that (p. 27):
"The computer software used for data management and statistical analysis should be reliable, and documentation of appropriate software testing procedures should be available."
Some commercial software vendors (SAS, Insightful, and StatSoft) offer white papers stating that their software can work within an 21 CFR Part 11 compliant system.
http://www.sas.com/industry/pharma/develop/papers.html
http://www.insightful.com/industry/pharm/21cfr_part11_Final.pdf
http://www.statsoft.com/support/whitepapers/pdf/STATISTICA_CFR.pdf
Some commercial vendors (SAS and Insightful) also offers tools for validation of the installation and operation of the software. SAS has
http://support.sas.com/documentation/installcenter/common/91/ts1m3/qualification_tools_guide.pdf
and S-PLUS has validate().
As a statistical consultant working within the pharamceutical industry, I think that our clients find the white papers being some kind of quality seal. It signals that someone has actually thought about the issues involved, written a document about it, and even stated that it can be done. Of course, there's a lot of FUD going on here. But if our lives can be made simpler by producing similar white papers and QA tools, why not?
(But for some people, only SAS will do:
Last week we were audited on behalf of a client. One of the specific issues discussed were validation and the Part 11 compliance of S-PLUS. In this specific trial, data are to be transferred from Oracle Clinical -> SAS -> SPLUS, and they auditors were really worried about the first and last link of that chain. Finally, they suggested using only SAS... And in this particular case, Part 11 is really a non-issue since physical records exists (i.e. case report forms) and all final S-PLUS output and code will also be stored physically (i.e. print-outs) -- no need for electronic signatures here!)
There is also a general guidance document for computer systems used in clinical trials here:
http://www.fda.gov/ora/compliance_ref/bimo/ffinalcct.htm
Though it is to be superseded by a draft document here:
http://www.fda.gov/cder/guidance/6032dft.htm
From the introduction (p. 2):
"This document provides guidance about computerized systems that are used to create, modify, maintain, archive, retrieve, or transmit clinical data required to be maintained and/or submitted to the Food and Drug Administration (FDA)"
The `retrieve' part is certainly applicable.
Henric
That is not clear. And since FDA allows submissions using Excel, with not even an audit trail, and with known major statistical computing errors in Excel, I am fairly certain that it is not applicable or at the least is not enforced in any meaningful way.
--
Frank E Harrell Jr Professor and Chair School of Medicine
Department of Biostatistics Vanderbilt University______________________________________________ [EMAIL PROTECTED] mailing list https://stat.ethz.ch/mailman/listinfo/r-help PLEASE do read the posting guide! http://www.R-project.org/posting-guide.html
