The Trial Master File (TMF) Reference Model was presented to the annual meeting of the Drug Information Association (DIA) in Washington, DC in June. There has been a lot of confusion lately as different regulatory agencies have enforced clinical trial TMF requirements in different ways. The TMF Reference Model was developed by the DIA Document and Records Management TMF Reference Model Working Group and at least one major regulatory agency is taking a close look. The Reference Model utilizes Section 8 of the ICH GCP Guideline (E6) Essential Documents as the core “artifacts” for the TMF. They also have recommended artifacts. As sponsors move from paper to electronic and as TMFs become more complex, it is hoped that the reference model can help determine what documents are necessary to satisfy regulatory requirements for clinical trial documentation.
At the Avandia Advisory Committee meeting FDA discussed the TMF publicly for the first time that I am aware of with regards to a sponsor inspection. Anecdotally I know that FDA field investigators are now auditing the TMF. Sponsors and CROs need to review their TMF procedures and document control if they expect FDA to feel that data integrity is a component of their application. Hopefully, the Reference Model developed by DIA will help.
There is a LInkedIn group that discusses the reference model that can be found at:
UPDATE 30 April 2012:
Please join your industry colleagues in completing the 2012 TMF Reference Model Survey, and use results to inform your TMF best practices.
This fifteen minute survey is designed by members of the TMF Reference Model team to provide valuable insight into Trial Master File practices, both paper and electronic, to identify common problem areas, assess changes in practice and reveal opportunities for improvement. All respondents who complete the survey and provide contact information will be provided with the survey results.
Data collection closes June 1st; please join us today.
Two Important New GCP Documents:
There is a Draft Guidance on Electronic Source Documentation in Clinical Investigations. The comment period is for 90 day (April 4, 2011 ?)
There is a new Final Rule on required elements of Informed Consent. You can read the Federal Register Announcement here that includes FDA comments in the preamble. The exact change in 21 CFR Part 50 is:
“Sec. 50.25 Elements of informed consent.
* * * * *
(c) When seeking informed consent for applicable clinical trials,
as defined in 42 U.S.C. 282(j)(1)(A), the following statement shall be
provided to each clinical trial subject in informed consent documents
and processes. This will notify the clinical trial subject that
clinical trial information has been or will be submitted for inclusion
in the clinical trial registry databank under paragraph (j) of section
402 of the Public Health Service Act. The statement is: “A description
of this clinical trial will be available on
http:[sol][sol]www.ClinicalTrials.gov, as required by U.S. Law. This
Web site will not include information that can identify you. At most,
the Web site will include a summary of the results. You can search this
Web site at any time.”
Read the Final Guidance from the European Medicines Agency on Electronic Data Capture:
Update: Read the blogster in Applied Clinical Trials
ALSO: Please join me at: