TMF Reference Model V4: A Data-Driven, Digital Approach to TMF

In the world of clinical research, clarity and consistency are paramount. CDISC (Clinical Data Interchange Standards Consortium) excels in this by uniting a global network of experts to develop and enhance data standards of the highest calibre. One key tool is the TMF Reference Model (TMF RM), which is a great resource when standardising the taxonomy and metadata of Trial Master Files (TMFs).

What is the TMF Reference Model?

The TMF Reference Model offers a structured approach to defining TMF content through standardised nomenclature. It comprises of all of the essential documents that collectively enable the evaluation of trial conduct and the quality of data produced. Essentially, it serves as a blueprint for organising and managing clinical trial documentation.

Key Takeaways from Recent CDISC TMF Survey

CDISC annually surveys a diverse range of stakeholders—including sponsors, CROs (Contract Research Organisations), vendors, sites, and consultants to gauge the adoption and implementation of the TMF RM globally. Here are some noteworthy insights from the latest survey:

Adoption Rates: From 52% to 92%

The adoption of the TMF Reference Model has surged dramatically, with implementation rates soaring from 52% to 92% among pharma and life sciences organisations. This dramatic increase reflects the model’s growing global recognition and its value in managing clinical trial documentation. Another pull factor for the TMF RM is the community of industry experts whose extensive experience in clinical trial management has been crucial in refining and promoting the model.

Customisation: 74% Tailor the Model

Customisation of the TMF Reference Model (TMF RM) is extremely high, with 74% of organisations adapting the model to suit their specific needs. While this flexibility allows organisations to define their own sub artefacts there is the possibility that measures may be introduced in V4 to restrict deviation from the model.

Shift to Digital from 8% to 65%

The shift towards digital solutions is a major trend, with the use of fully electronic Trial Master Files (TMFs) and Investigator Site Files (ISFs) soaring from just 8% to 65%. This big move to digital emphasises the growing need to move to digital, though making such a major change poses challenges for many organisations.

User adoption is one of the critical challenges when transitioning from paper to digital eTMF and ISF systems, as it requires not only technical implementation but also operational shifts from a workforce who are more accustomed to paper-based document management and archiving. Effective education, training and change management is essential to ensure that all practitioners are not only comfortable using the new tools, but understand the processes that support their use and adoption.

Additionally, the collaboration between departments such as IT, quality assurance, and clinical operations ensures that the clinical data is being managed effectively, adhering not only to organisational policy, but also regulations and guidelines e.g EU CTR, FDA CFR 21 Part 11.

Recent inspections reveal key issues

The survey also highlighted recent inspection findings which were of key concern, including completeness, timeliness, and CRO/site oversight.

Completeness issues were identified in 65% of inspections, emphasising the need for thorough and accurate documentation good practice and processes.

Timeliness concerns, noted in 61% of inspections, point to the importance of up-to-date records to maintain trial integrity.

Problems with CRO and site oversight, observed in 44% of inspections, indicate a need for improved monitoring and management of these entities to ensure they adhere to protocols and standards.

Introducing TMF Reference Model V4

The TMF Reference Model has been due for an update since Version 3 was released in 2015. The increasing volume of data collected by life sciences organisations, accelerated by the Covid-19 pandemic—which spurred more decentralised studies and the adoption of digital technology across the clinical trial landscape —has made this update crucial. Additionally, the transition towards digital solutions has highlighted the need for a revised model that supports contemporary challenges and technological advancements. This is also reflected in recent updates included within the EU’s guidelines on the use of computerised systems in clinical trials and ICH E6 R3.

On September 17, 2024, CDISC unveiled their highly anticipated roadmap for Version 4 of the TMF Reference Model. While the project faces complex challenges and a demanding timeline, the promising news is that V4 could be available to the public within 18-24 months. This ambitious update is spearheaded by the CDISC/TMF team, a group of industry experts from sponsors, vendors, and consultants, each contributing valuable insights towards achieving a “Data-Driven, Digital Approach to TMF.”

Updates surrounding the TMF Reference Model will be provided during the CDISC Conference in late October and also during the Q4 General Meeting in early December.

Arkivum is delighted to be both sponsoring and speaking at the conference, and we’re looking forward to engaging with stakeholders and the wider community at the event.