Guest Commentary: A discussion on the trial master file (TMF) Reference Model presented to this summer’s annual meeting of the Drug Information Association (DIA). As clinical trials have evolved, regulatory authorities and GxP professionals have discussed the need for clear definitions and examples of the documents necessary for effective clinical trials. DIA began an effort to try and determine what would work in a globalized clinical trial environment. The result is the TMF Reference Model. While it is a work in progress, the TMF Reference Model has helped many clinical trial professionals determine how to record the data necessary to support a regulatory submission. This Guest Commentary by Karen Redding helps explain the concept of the TMF Reference Model.
Guest Commentary by Karen Redding
What is the TMF Reference Model?
The TMF Reference Model (TMF RM) is a single, unified interpretation of the regulations in the form of a list of TMF artifacts which would be accepted by all clinical trial stakeholders and which can be adopted or adapted by any company, institution or organization. It does not provide guidance in terms of the process by which the artifact is created or collected. It extends beyond regulatory guidance, such as ICH E6 section 8, which addresses only a sub-set of documents required in a TMF.
Who is sponsoring the reference model?The initiative to create a TMF RM is supported by the Document and Records Management SIAC of the Drug Information Association (DIA). The TMF RM team consists of more than 130 representatives from 91 bio-pharmaceutical companies, contract research organizations (CROs), consultancies, technical vendors, industry groups, healthcare, academia, non-profit / NGO and regulatory agencies.
What is the structure of the reference model?
The TMF RM consists of standardized taxonomy and metadata and outlines the clear definition and organization of TMF content using consistent nomenclature. It is emphasized that this model is a reference and should not be considered mandatory, but rather as an opportunity for harmonization and alignment across the industry. The TMF RM can be adapted to an electronic or paper based TMF and by design does not endorse, nor require, any specific technology for application. The document types defined in the model are called artifacts. Version 1 .0 was released on 4th June 2010.
What are the key questions we are trying to answer in the upcoming meetings?
Collectively, the members of the TMF RM experience the same challenges, and many of these directly result in sub-groups being set up to provide a collective opinion. Current questions include:
1. How much does TMF management actually cost a company, how can we measure it, and how can we improve efficiencies?
2. What requirements need to be met to allow for a paperless environment, can we destroy scanned paper, can we retain documents in electronic form only?
3. Many studies are contracted to CROs, how much documentation needs to be maintained by the Sponsor to show oversight, and how is this oversight defined?
How do you get more information on the reference model? Is there a non-commercial website?The TMF RM group meets by teleconference every 3 weeks to discuss issues such as those above. Various sub-committees exist such as the Communications, Metrics, Paper Management and Review team, and these groups meet separately to discuss the specific aspects assigned to them. Many documents are published in the DIA Web Office. In addition, there is a LinkedIn group and a blog. You are invited to follow TMF RM activities on LinkedIn by joining the TMF Reference Model group.
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 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.”
There is a Draft Guidance on Electronic Source Documentation in Clinical Investigations. The comment period is for 90 day (April 4, 2011 ?)
UPDATE: My favorite industry magazine, Applied Clinical Trials, now has a LinkedIn Group:
Applied Clinical Trials LinkedIn
++++ In News From GxP Perspectives++++
ALSO: Read the updated article on the Form FDA 1572 in:
ALSO: Please join me on LinkedIn at: