Trial By Fire: A TMF Training Case Study

How LMK’s TMF University inspired one new hire to overcome her trial by fire and become part of a new generation of TMF professionals.

The life sciences industry faces a serious problem—a widespread trial master file (TMF) skills gap. There are simply not enough skilled TMF professionals to support the explosive growth and complexity of clinical research. The result of this skills gap is the rising incidence of TMF-related inspection findings that have the potential to delay patient access to lifesaving treatments. Despite the critical importance of addressing this TMF skills gap, most sponsor organizations and contract research organizations (CROs) lack structured TMF training beyond the minimum skills required to log in to the eTMF. As one new hire learned, however, a fresh approach to TMF training can transform the prevailing narrative. This case study is her story.

The Challenge: Jumping on a Moving Treadmill

I remember my first day working in clinical research. I recently graduated from college, having completed an undergraduate biology degree and a few summers ofinternships working in a doctor’s office. It was not a strong job market, so I was extremely thankful to be mentored by a family friend who worked in the pharmaceutical industry. She taught me a handful ofbuzzwords, which was just enough to secure an interview at a CRO for a clinical trial associate (CTA) role.

I was ecstatic when I got the job offer. When I shared the news with my friend, however, she warned me that CTA turnover was high. My job, I learned, was to call trial sites (who wouldn’t want to talk to me) and file their documents. My challenge, according to my friend, was tosurvive just long enough to get my big break as a clinical research associate. I wondered if my excitement for this first real job was misplaced. Perhaps I shouldn’t have applied at all.

On my first day on the job, I filled out my paperwork with a dozen other new CTAs. Rather quickly, I was alone at my desk, reading and acknowledging a mountain of SOPs. Meanwhile, around me were unfolding snippets of phone calls with trial sites, discussions about the day-to-day, and most notably, a lot of complaining about the TMF. Those talking most emphatically about the TMF were carrying folders crammed full of papers. They also seemed very stressed.

Before day one I knew just a little bit about the TMF. I knew it was where the documents of a clinical trial were filed. My friend had even directed me to read ICH GCP,  which I vaguely understood to be the regulations my company needed to follow. GCP was also mentioned in passing and during my onboarding, but nobody really told me how it related to my job. After four days of reading SOPs and mindlessly clicking through compliance training, I completed my assigned e-training to get my eTMF login.

That afternoon, I was assigned my first study team, which was where the trouble started.

Almost immediately, I was inundated with regulatory documents I had never seen before from colleagues I had never met. The TMF for the study, my study, was much larger and more complicated than I expected. I opened the TMF reference model for the first time and was instantly overwhelmed. When I looked at my TMF, it didn’t match what I had already learned. In fact, from what I could tell, my TMF was already a mess.

I soon realized my job was more complicated than simply filing documents where they needed to go. These documents were interrelated in complex ways. I needed to understand these relationships to know where my regulatory documents needed to be filed in the TMF and,more importantly, to determine what regulatory documents I was missing.

I had a thousand questions, but my study team didn’t have time to answer them. When they did reply, they usedacronyms I didn’t understand. The other CTAs on my team were kind and helpful when they could be, but many were as overwhelmed as I was, and all were just as busy. I felt like I had jumped on a moving treadmill and was seconds away from falling off.

I now grasped my mentor’s cautionary words from when I told her about my offer. The clinical research learning curve is dangerously steep. I was undergoing my clinical research trial by fire. There wasn’t anyone who wouldteach me about clinical research or the TMF. Either I learned on my own or I’d be part of the CTA turnover statistic by the end of the month.

The Solution: LMK’s TMF University Empowers All Learners

During my second week, I got an email. The entire department of CTAs had been signed up for TMF University. Although many of the experienced CTAs were bristling at the prospect of more assigned training—especially training that lasted a few weeks and had homework—I was secretly relieved. The backlog of regulatory documents was growing in my inbox. While I had made some progress on my own and was beginning to speak the clinical research “language,” it seemed that my study team’s expectations were increasing faster than my ability was growing. I knew I had a lot more to learn about the TMF.

What is TMF University? When I received my email invitation, I didn’t know either, but I had a short description in my inbox:

LMK’s TMF University is the first and only internationally recognized and accredited certification program for working TMF professionals. TMF University allows TMF professionals of all backgrounds to access real-time and asynchronous,remote TMF-learning courses tailored to meet learners at their level of expertise. Each course is competency-based and supported by real-world case studies using high-quality simulated regulatory documents. Topics span from TMF fundamentals, such as the basics of document QC and indexing, to the advanced, including TMF regulation and TMF metrics and reporting.

I might finally get some TMF help, but what if I failed this course too? After all, maybe this training course would be as cryptic and high-level as the others.

Of course, now writing this case study for LMK Clinical Research Consulting, I know a lot more. TMF Universityoffers multiple starting levels, and learners can achievetwo different qualifications: Qualified TMF Associate and Qualified TMF Manager. TMF University is designed to meet TMF experts and novices at their levels of proficiency. I’m a Qualified TMF Manager now, but at the time, my employer had decided to commit all permanent CTAs to achieve the Qualified TMF Associate qualification.

The Implementation: Competency-Based, Real-World Training

The first TMF University module I took was “Introduction to the TMF.” I recall being shocked at how enthusiastic the instructor seemed about the TMFcompared to my colleagues. I was equally surprised when a clear roadmap of the course, including defined learning outcomes and assessment criteria, was laid out before me in the first few slides.

The instructor told us we would learn the basics, leaving us with a strong foundation of TMF understanding. By the end of the course, I would be able to explain:

• The difference between the TMF and ISF
• The purpose of ICH GCP compliance and how the TMF supports it
• The importance of the TMF to my company and the sponsors of my clinical trials
While it seemed like a daunting list, these were all skills I knew I needed to learn to succeed at my job. The instructor had my attention. Up until my first few minutes of TMF University, the importance of the TMF revolved solely around my ability to keep my job. But now, the grand ideas that had led me to apply for my first job in clinical research slowly returned to the forefront. The connection between my role and the patients at the trial sites was becoming clearer.

During that first module, we discussed our preconceived notions of the TMF in detail. We dissected the key differences between the TMF and ISF, considered how they were divided in our current business processes, and reinforced how they must come together to tell a unified story. We went through the important lines of ICH GCP that are the basis of the TMF. We talked about the basic definition of an essential document and the purpose it must fulfill.

By the end of the module, I knew the twenty essential documents needed in the TMF before a trial began. I knew what the TMF Reference Model was, and I could file all the simulated essential documents in the right location. After each session, I was able to slowly chip away at my TMF filing backlog.

More than keeping my head above water, I was starting to understand why I was doing what I was doing during my day-to-day responsibilities as a CTA. I was also beginning to understand how my role fit within the functional lines of a CRO and the bigger conduct of a clinical trial. I felt much more hopeful about my future as a CTA.Somewhere, below the surface, a seed of confidence was planted.

I was also stunned that my company would trust a relatively inexperienced employee (like me) with the TMF. The TMF seemed much more important than I had been led to believe.

The Outcome: Building the Next Generation of TMF Professionals

TMF University had a major impact on the morale of my CTA team and noticeably improved TMF quality. For new CTAs like me, gaining the initial foundation of TMF knowledge was an invaluable first step towardunderstanding the business processes assigned to my role. It was one thing to learn about the 1572, but it was another to walk through the 1572 box-by-box with LMK’s instructor and map how it altered the expected document checklist for my trial site.

For the more experienced CTAs, I believe TMF University provided important reinforcement of core skills and the opportunity to pursue more advanced skills in a supportive environment. The most profound effect of TMF University, though, was a revitalization of TMF culture. The message of enrolling all of us in TMF University was clear: the TMF is important—important enough that we are willing to invest time and resources in your knowledge as a TMF professional. TMF health became a shared goal instead of a lingering burden.

As you might have suspected, today I am a TMF Consultant at LMK Clinical Research Consulting. The path between CTA and TMF Consultant involved many years, roles, employers, and TMF education. My first employer’s early investment in my skills through TMF University made all the difference. Armed with a solid foundation of TMF knowledge and skills, I incrementally grew into my first CTA role and developed the confidence and proficiency necessary to prospectively and positively shape the narrative within the TMF. I impressed my supervisors with my performance and was able to effectively demonstrate my clinical operations knowledge and skills to potential employers.

Looking back, although I was a young and inexperienced CTA, I had stumbled onto an early seed of truth. There was, and continues to be, a mismatch between the priority placed on TMF health and its critical importance in the outcome of a clinical trial and clinical development program. Many promising treatments fail not because of the validity of their science but because of the inability to navigate their regulatory pathway.

Consider that more than 50% of drugs fail in phase II of their clinical program. While safety and efficacy concerns are the primary indicated reasons for these failures, the direct and indirect consequences of failure to close the TMF and resulting delays to important milestones are significant. Some sources cite costs associated with delays in excess of eight million dollars a day in certain situations.

Despite the paramount importance and high stakes of TMF health, TMF experts have suffered from the harmful notion that TMF management is clerical work and that all TMF professionals are simply document reviewers. But this couldn’t be further from the truth. 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. The only solution to close this TMF skills gap is to invest in the growth of TMF professionals through modern and dynamic TMF education. While working with the TMFmay have once been an entry-level or administrative role, today it is a skilled discipline and is deserving of the same organizational investment and devotion to excellence as any other discipline in the life sciences industry.

As an occasional TMF University Instructor, it is now my turn to give back by helping others gain the confidence and skills necessary to achieve TMF success. Each time I address a new cohort of learners, I think back to my own trial by fire. I know that by helping even the most novice of learners overcome their early TMF misconceptions and fears, I am equipping the next generation of skilled TMF professionals to implement—and perhaps even create—the next great TMF innovation. I am proud that TMF University and LMK Clinical Research Consulting aretaking a powerful step toward eliminating the TMF skills gap and realizing the transformative promise of eTMF technology. All of which, of course, is in service of our industry’s shared goal: to unite patients speedily and safely with our most promising and innovative treatments.