The trial master file (TMF) is a growing priority for companies and for regulatory agencies. Knowing the who, what, where, when, and why of the TMF requires having a big-picture perspective.
To retain that oversight, companies often turn to a study owner – also referred to as TMF managers or TMF leads – to connect all stakeholders and make sure everyone is aware of what has been agreed to.
Who is the study owner?
As the subject matter expert for the TMF, it is the study owner who is best situated to answer TMF-related questions as diverse as those likely to come from the study manager, study team, and functional line document owners.
At a high level, the study owner’s responsibilities include:
- Developing TMF plans
- Setting up, maintaining, and closing out of the TMF
- Reviewing and improving KPIs
- Overseeing the quality review process
- Remediating periodic or ad-hoc quality reviews
- Managing TMF health
- Supporting audits and inspections
- Serving as TMF expert and trainer
To be successful in the role, the study owner needs to be knowledgeable about the regulations. They need to keep up with changes to the regulations and apply any new requirements to their day-to-day work as well as train the team.
The study owner is also expected to not only prepare and share key performance indicators (KPIs), but also to understand how they are built and how they affect the TMF as a whole. Importantly, the study owner should also be proficient with electronic systems.
A champion for the TMF
Since the TMF touches multiple functions and departments – regulatory, pharmacovigilance, vendors and contract research organizations (CROs), and study teams – the study owner must be adept at engaging with all stakeholders. The TMF is typically not a top priority for these departments, so it is up to the study owner to influence all stakeholders and keep them engaged in order to be inspection ready at any time.
So, on top of having deep TMF knowledge and technical skills, the study owner needs to be the TMF champion, bringing people along, and convincing them to do what is needed despite their many other commitments.
Working to a set of key performance indicators (KPIs) won’t suffice. Rather, the study owner should engage with the study teams to emphasize the importance of the TMF and make sure they file the necessary documents to achieve TMF completeness. They can achieve that by closely monitoring emerging issues and providing constructive feedback.
Additionally, study owners should identify any trends and, based on those, implement improvements.
They also need to identify problems that arise and understand why they occur. For example, if a quality KPI is below expectations, they should determine the underlying cause. If it turns out that a single user repeatedly makes the same mistake, take the time to retrain that person.
If the timelines KPI was not met, the study owner should discuss the reasons for the delay with study team. Some reasons might be understandable, such as the team was focused on an inspection for another study for the past month; some might need further analysis, such as a vendor not adhering to an agreed timeline for quality control; and some may need immediate action, such as clinical research associates not uploading any documents in last two to three months.
If the issue affects completeness, with a lot of documents being missing, the study owner should review to determine whether all expected documents are correctly defined. When certain milestones are expected, software solutions will typically populate a basic list of what these are. The study owner should review these and amend as needed based on the study build, different repositories used (e.g. regulatory documents might be held elsewhere), and other key criteria.
In all instances, the TMF should become the standing agenda item during the study team meetings, and the study owner should present KPIs to the team and work with them to improve these KPIs as needed.
Interpreting data and supporting teams
While metrics and KPIs provide useful insights, the real value the study owner brings is the ability to proactively analyze TMF data to determine the issues impacting accuracy, timeliness and completeness. If there are issues around timeliness, data might show problems with reporting requirements and simply amending those may address the issue.
It may be that problems with document quality control are coming from the same source, which could indicate one person is perhaps not properly trained or is new to the team. The study owner needs to be able to identify the problem, whether it’s just a simple fix or if there are repeated issues, consider mitigation strategies such as training or retraining particular team members.
Sometimes there are more serious issues with the TMF, and the study owner needs to be able to deliver bad news without discouraging the study team members. For example, if the TMF health is in bad shape, the study owner needs to succinctly and clearly communicate the problems to the team and guide them to devise a plan on how best to improve TMF documentation.
It’s therefore important that the study owner has full visibility into the TMF for particular studies, including KPIs and any background information as to why issues are occurring and steps to address these.
At the same time, the study owner needs to understand that study teams have many other priorities or may not have an immediate answer. Working patiently with those team members to assess the problem and work out a solution is key.
It’s about showing the study teams they have full support and someone who will be there for them through inspections, while communicating effectively with them. After all, the study owner is the TMF champion and so it’s up to them to connect the dots. Building a rapport and trust with study teams will allow the study owner to support the TMF across its lifecycle. While not all companies have the role of a study owner, they can, and do, play an important role in a study’s overall success.
About the author:
Justyna Alsztyniuk is lead customer success manager at PharmaLex, responsible for advising customers about solutions that would best serve their eTMF needs and helping them achieve their goals. In her role within the customer success team, she draws on her experience at both large and small pharmaceutical companies.
