The TMF Trifecta: Finding Balance in an Era of Constant Change

Representatives from TransPerfect Life Sciences and LMK Clinical Research Consulting recently participated in the Fierce Trial Master File Summit from May 2 to May 4 in New Orleans, Louisiana. While in past conferences, the focus of discussion has been eTMF technology, this most recent conference marked an unexpected paradigm shift toward people- and process-related TMF solutions.

For years, TMF thought leaders, including LMK’s founder and TMF trailblazer Sholeh Ehdaivand, have described the TMF in terms of an operational framework of people, process, and technology. These three elements, which LMK calls the TMF Trifecta, represent the real-time interplay of the TMF stakeholders, the actions those stakeholders take, and the technology necessary for them to carry out their role successfully and efficiently. Through the lens of the TMF Trifecta, TMF decision-makers have a conceptual framework with which they can address even their most difficult TMF challenges. But what comprises the three elements of the TMF Trifecta? What components of the TMF Trifecta were on the minds of TMF Summit speakers, especially now, as we enter this new, highly interconnected, and rapidly evolving era of TMF operations?

People

When considering the people component of a TMF, topics including hiring, professional development, training, leadership, relationship building, and in-housing come to the forefront. All these topics stem from a greater imperative to understand and address the needs, challenges, priorities, and goals of TMF professionals. Training, however, especially in light of ongoing skills shortages and competition in the hiring market, was a major topic of discussion by the speakers at this year’s TMF Summit.

LMK’s Ben Rodgers, Manager of TMF Education & Employee Development, presented LMK and TransPerfect’s vision of the future of training for TMF professionals. During his session, Rodgers dispelled the harmful notion that TMF professionals are simply document reviewers. According to Rodgers, all of today’s TMF professionals must have advanced skills in project management and clinical operations oversight to achieve the ever-increasing expectations of regulators. Such skills are also necessary to overcome widespread TMF hurdles such as inadequate functional area collaboration, incomplete expected document lists, and lack of TMF contemporaneousness.

Rodger’s sentiments were echoed by Gillian Gittens, Director, eClinical Strategy & Solutions at TransPerfect Life Sciences, whose TMF Summit workshop stressed the importance of continuous learning by TMF managers to achieve and maintain subject matter expertise in the fundamentals of TMF operations and management. TMF managers are responsible for setting the expectations of completeness, timeliness, and quality based on current regulations and industry best practices for the TMFs they oversee. According to Gittens, expertise in the underlying fundamentals of the TMF is critical for the selection of meaningful and appropriate TMF KPIs and the achievement of total inspection readiness. Moreover, TMF managers who are confident in the fundamentals of the TMF are also able to better support a culture of mentorship and collaboration that empowers less-experienced TMF professionals to succeed throughout their training as they grow into their role’s responsibilities.

Overall, the growing need for highly skilled TMF professionals means that all life sciences organizations must have a roadmap to close the skills gaps in all levels of their TMF departments. To be effective, Rodgers noted that this TMF training roadmap must address the “Why?” of learners, going far beyond the industry-favored approach of “read and acknowledge.” Ensuring TMF professionals understand the regulatory basis for document quality and TMF indexing, for example, encourages buy-in and enables the holistic clinical trial perspective necessary to effectively manage TMF processes and use the TMF as a trial oversight tool. Implementing relevant and ongoing training that provides the opportunity for quality feedback is the clearest path to developing the new class of TMF professionals necessary to meet the needs of the future.

Process

Once a team of highly skilled TMF professionals is assembled, processes must be developed to ensure that stakeholder roles are well-defined, tasks are completed consistently, and performance can be measured quantitatively—all of which is made possible through harmonization and standardization. Given the recent announcement that the TMF Reference Model Group has officially affiliated with CDISC, standardization and harmonization was a major focus of many presenters and panel discussions.

CDISC, or the Clinical Data Interchange Standards Consortium, is a standards development organization that aims to “enable information system interoperability to improve medical research and related areas of healthcare.” Many CDISC standards are now incorporated into FDA guidance and required by the FDA as part of electronic format regulatory submissions and data analysis. As discussed in a recent blog post by TransPerfect, the purpose of the TMF Reference Model collaboration with CDISC was to achieve similar benefits for the eTMF that previous standards implementations have brought to other domains of the life sciences industry: mainly, improved efficiency, interoperability, and data reusability.

In the opening panel session of the TMF Summit, representatives from CDISC and the TMF Reference Model Steering Committee expressed that the affiliation represents a strategic, long-term investment to secure the continued relevancy and future potential of the TMF Reference Model. Through the affiliation with CDISC, the TMF Reference Model will have greater reach, greater legitimacy, and an opportunity to become a recognized standard by regulatory agencies, including the FDA. Furthermore, leveraging the processes and infrastructure already in place at CDISC will allow the TMF Reference Model Steering Committee to take on worthy initiatives, including expanding the model with richer metadata, producing training materials, authoring detailed guidance, and mapping to other models and standards. Finally, the affiliation also underscores that any technological improvement, including industry adoption of the eTMF, will only remain relevant if supported by well-designed, consensus-driven standards and processes.

Technology

Until recently, the technology element of the TMF Trifecta, specifically eTMF technology, has dominated discussion about the future of the TMF. This emphasis on technology coincided with the massive industry effort to adopt eTMF technology and migrate existing paper TMFs into the eTMF—a landmark accomplishment that has improved many aspects of clinical operations for the better.

Experienced TMF professionals observed, however, that many of the digital transformation promises of eTMF adoption have either faded from discussion or been pushed into the future. eTMF technology, as noted above, has also expanded the scope and type of trial conduct information captured in the eTMF, leading to increased regulatory expectations and new types of TMF quality problems. These quality problems, including the ongoing industry struggle with contemporaneousness and certified copies, for example, showcase how new TMF technology is not guaranteed to bring about digital transformation without full consideration of how that technology will integrate into existing processes and full understanding of how TMF stakeholders choose to use the tools made available to them.

At this year’s TMF Summit, in contrast, TMF technology was primarily discussed in terms of how it can aid the other TMF Trifecta elements—people and process—through advanced automation and AI. Speakers shared positive use cases of automatic document indexing, metadata extraction, and redaction. AI was also leveraged to improve inspection readiness through automated metric generation, intelligent dashboards, and automatic integration of data from other systems (for example IRB systems, translation systems, and CTMS systems) to better inform QC activities. These new developments in automation and AI suggest that eTMF solutions providers and TMF decision-makers have looked past the drive for broad eTMF adoption and overfitting features in favor of automation and analysis tools. These AI tools are rooted in serving users and their processes, most notably by freeing TMF stakeholders from repetitive tasks so that they can take greater ownership of trial oversight. This process- and people-focused approach to AI represents a significant step toward achieving the full digital transformation imagined when eTMF technology was first introduced to the life sciences.

Three Elements in Balance

All three elements of the TMF Trifecta, people, process, and technology, must be in balance to achieve TMF success—if any one of the elements is absent or unbalanced, a TMF will struggle or even fail. In this way, it is fitting that industry focus has been revitalized for the people and process elements of the TMF Trifecta, especially now that the acute challenges of the COVID-19 pandemic have subsided and the clinical operations community looks to establish a new normal.

In many ways, the TMF Trifecta also embodies TransPerfect Life Sciences and LMK’s Complete TMF Solution, which supports the people, processes, and technology of your TMF through four essential domains: TMF education, deep TMF expertise, powerful technology solutions, and scalable system-agnostic services. Uniting these domains into one values-driven organization offers our clients a simple, flexible, efficient, and collaborative model of TMF health that restores balance to all the elements of your TMF Trifecta.