Collaborative sponsor-contract research organization (CRO) relationships can be the key to ensuring outsourced clinical trial activities run smoothly. One area where strong partnerships are of paramount importance is the Trial Master File (TMF). While regulatory responsibility for oversight lies with the trial sponsor to demonstrate GCP (Good Clinical Practice) during a clinical study, CROs play a critical part when they assume a role in the conduct of the study.
In a February 2023 FierceBiotech webinar, “Improving Sponsor Oversight of the Trial Master File at Chiesi: A Case Study,” pharmaceutical company Chiesi and CRO CROMSOURCE shared best practices from their decades-long partnership integral to ensuring inspection-ready TMFs.
A brief summary is below; for the full story view the on-demand webinar here.
Choosing the right TMF solution: in-house or outsource
As one of the first companies to implement the TMF Reference Model in 2011, Chiesi recognized the importance of training its CRO on the Reference Model, capturing their feedback on what was working and what wasn’t.
As the Trial Master File moved from paper to electronic (eTMF), it soon became apparent that using a CRO’s systems was becoming more complicated. Each CRO had their own system and for people working in different study teams, it meant chopping and changing between different eTMF systems. It also meant the company was losing the metadata and other important information from the system. Chiesi implemented an eTMF solution and required its CROs to use that eTMF – a trend which more and more sponsors are adopting.
Defining roles and responsibilities
Alignment with regards to the study setup and the roles and responsibilities of all parties involved is critical. While the overall structure for managing the TMF is the same from one study to the next, the study requirements and people involved are different. Specific documents track each person’s roles and responsibilities to ensure clarity around who is doing what, how and when the work is being carried out, and what is expected. There is also an ongoing feedback loop to capture what is working and what isn’t.
Having this clarity from the setup phase and setting expectations simplifies oversight and clarifies required activities throughout the study.
The importance of training
To ensure CROs are managing the client’s TMF appropriately, proper training is imperative. This should cover not only the system itself, but also functionalities and how the system is set up.
Training should be specific to each role. For example, the project director of a study is focused on oversight and needs to know how to properly monitor the team to assess status and review how the team is managing the TMF. On the other hand, the user uploading documents would need training specific to their task.
Training should not be a one-and-done activity. Rather it should be ongoing, for at least the first month after the release of the system, to ensure any issues in the transition from theory to practice are addressed, questions are answered, and any new problems are tackled.
In addition, it is important the CROs are trained on the sponsor’s standard operating procedures (SOPs) to understand how documents should be managed in the system, what needs to be generated, and where they should be filed. Prepare a checklist for the TMF at the outset of the study so everyone involved knows what documents are needed and what are not, and how these documents should be associated.
These steps ensure training is carried out with people, process and technology in mind.
Healthy oversight
Sponsors are also implementing TMF “Health Checks” to have a global overview of different functions involved and to have accountability for the overall TMF, provided by an independent, expert perspective. This process helps ensure the TMF is inspection-ready in terms of quality, completeness, and timeliness.
As part of the health check, periodic study reports provide oversight into what is happening with the study. The report is discussed with all parties to understand what is missing, any delays, or other problems. It might be that site documentation is missing because the site is not responding for various reasons. This provides country-level and site-level insight into any issues.
At the end of the health check, a remediation plan (if needed) is put in place where issues that need to be resolved are itemized, including realistic deadlines for follow-up and completion before the next health check.
A health check at the start of a study can help to address issues immediately. Equally, it is important to include those heavily involved in the study to ensure the right documentation is included and queries and requests are quickly and accurately addressed.
Key metrics for an inspection-ready TMF
From the sponsor perspective, there are two primary metrics for good oversight. These are first, the availability of documents and, second, ensuring the documents are ready at the correct time and properly filed. To ensure these metrics are in place during the setup phase, before the first patient visit, the documents required for each milestone are defined in the TMF. This is a key step to ensuring inspection-readiness.
In addition to document completeness and timeliness of uploading those documents, it’s also important to keep track of any issues detected within documents. With this in mind, the CRO should conduct quality checks on content outside the TMF and ensure corrections are made before the document is uploaded.
Partners throughout
Working collaboratively on documentation, roles and responsibilities and oversight from study setup can help to mitigate any issues that arise during the study. While sponsors and CROs each has their own responsibilities, expectations need to be set and issues need to be discussed openly. Communication is key.
As the global authority in Trial Master File best practices, Phlexglobal helps trial sponsors and CROs worldwide improve TMF quality and oversight. To learn more, visit https://www.phlexglobal.com/tmf-services or contact us today.