Standardization has become the norm across the clinical research spectrum. The industry has embraced data standards such as MEDRA, CDISC, and eCTD.  Electronic Health and Medical Records will continue to push the boundaries of data standards and interoperability.

The TMF Reference Model group has done an admirable job to bring a structured organization of content to both paper and electronic Trial Master Files.  By having a large number of participants (from Sponsors, CROs, Vendors, and Consulting Firms) the Reference Model Group has been able to ensure that the TMF content structure satisfies industry needs. Additionally, as various regulations and industry drivers appear, the group continues to improve upon the model (V3 is coming this summer). The large number of sponsors, CROs and vendors using the TMF Reference Model is a testament to the long overdue need for harmonization in this area.  The group continues to strive toward goals of near real-time inspection readiness and ICH/GCP compliance.  Providing a consistent view and navigation of a TMF should help reduce inspection time and risks.

However, there are some areas that still need to be addressed:

  • How to exchange documents and metadata from various systems of record within an organization?
  • How to exchange documents and metadata between sponsor and CRO eTMF systems?
  • How to manage the TMF documents through their full records retention life cycle in a consistent and reproducible manner?
  • How can we exchange documents and be sure that the sender and receiver are congruent about the document definition / purpose?
  • How do we reliably exchange audit trail and electronic signature data.

The current version of the reference model does not answer these questions, but thankfully progress is being made on two fronts:

  • Reference Model 3


As I mentioned earlier, the Reference Model Group is working on Version 3 of the model which will update/enhance the content structure while also focusing on defining a technical specification that will allow the various solutions to more seamlessly connect.

The Reference Model Group is not the only entity tackling these problems. Almost two years ago, the OASIS eTMF Technical Committee began working on an interoperable Electronic Trial Master File (eTMF) Specification that will define machine readable formats for clinical trial master file content interoperability and data exchange to include:

  • An eTMF content classification model comprised of a standards-based vocabulary and content classification ontology
  • A set of eTMF content classification rules and policies
  • An eTMF Data Model and format for the interoperable exchange of electronic trial master file information for the clinical trials domain, whereby eTMF content can be exchanged through either cloud or physical media and viewed online or offline in web browsers.

As we wait to see the results of both of these initiatives, it is important to look at the big picture. The TMF interoperability initiatives are following a similar path as other successful interoperability efforts.

The DIA EDM Reference Model began as a spreadsheet that drove the organization and naming of regulatory submission documents.  It was not until the CDISC standard was introduced that the work really brought benefit to the industry and regulatory agencies.  With a machine readable interoperable xml standard, sponsors were now able to submit global dossiers and metadata to Health Authorities.  Health Authorities were able to check the submission for consistency and reject submissions not meeting the specifications.


To move to the next level in eTMF management the interoperability standard needs to gain more traction.  This is not a battle between the TMF Reference Model group and the OASIS eTMF Technical Standard Group.  This is an opportunity for clinical and technical people to come together and share knowledge and expertise to bring quality and efficiency to the management of clinical trial documentation.  The only way for clinical trials to become more efficient is to allow our clinical systems to exchange documents and data using officially recognized standards.

The TMF Reference Model served as a valuable input for the OASIS standard.  In addition, a handful of people from the TMF Reference Model group reviewed each artifact in the OASIS eTMF standard.  The group had to work within the vocabulary constraints required to meet the NCI Thesaurus standard. Lastly, over 800 comments on the OASIS eTMF Standard were submitted during the public review and addressed by the Technical Committee working on the standard.

Interoperability: “Think Standard Inventory Means Technical Interoperability? Think Again.” – Empower the navigation and exchange of TMF components with technical interoperability standards.   Learn more about this topic at the 51st DIA Annual meeting in Washington, D.C.  on June 17, 2015 from 8:00 to 9:30 AM.  This session is part of the Track 07 Technology/Data/Records and Submissions.  The session is titled “Mapping the Future for Trial Master File: Advancing Standards by Harmonizing Clinical and Technical Strengths”.  Additional information will be presented by Donna W. Dorozinsky, President, DWD & Associates, Inc. and Eric Rubinson, Director, DD&R Business Operations, Actavis, Inc.  Meet the Paragon team at booth 2204 in the exhibit hall.

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