The Trial Master File is a window into the study through all phases of drug development. The TMF is comprised of the records that tell the story of your study. It gives evidence that the trial was conducted in alliance with standards of Good Clinical Practice (GCP). This story becomes the cornerstone of inspection readiness. The purpose of a regulatory inspection is to confirm that the study was conducted in compliance with GCP, confirm the integrity of the data, and ensure human subject protection.
How do we use the power of the TMF to influence the story of the study?
TMF – The Story of Your Clinical Trial
As the story of your study, the TMF is a narrative account of its sequence of events that includes chapters and verse with subplots and intermingled shorter stories. The question becomes, how do we know that we have a complete and accurate account of the story of the study.
Routine completeness review of the TMF is part of CRO TMF management and sponsor oversight. These reviews occur at set timepoints or milestones throughout the life of the study. They ensure that completeness gaps are identified and remediated in a timely manner. Whether the milestone is Site Initiation Visits, or an amendment, we do reviews of the TMF to ensure that the TMF is complete based on that part of the study. The question becomes what else can we learn from completeness reviews? For example, if we are missing protocol training for a set of sites, is this because the training was not collected, it was not performed, or it was not documented? If we identify that training was performed, but not documented, then we can implement a process to ensure that all sites are documenting training in a consistent manner going forward. Fixing a problem such as this allows you to impact the outcome of the story. If these gaps are not identified until the end of the study, then the story will tell something very different.
Another type of document that tells a big part of the study is the communications. Communications are always a challenge. Today sponsors document a large portion of their decisions via email. We want to file communications that contribute to the story of the study. Communications related study management, protocol instructions, safety information, or key decisions should be filed in the TMF. A communication that is not relevant to the study story is generally not filed in the TMF. It is important that the sponsor understands the stories that these communications are telling because these are often reviewed by an inspector during a health authority inspection.
A critical component to managing the study is clinical monitoring. The Clinical Monitoring Plan drives monitoring activities. However, if the monitoring is not conducted in alignment with this plan, there can be compliance ramifications. It is important that we understand monitoring expectations and then we ensure that they are aligned with actual monitoring activities. For example, if the monitoring plan states that IP Accountability documentation will be collected at each visit, but instead the monitors are waiting until the end of the study to collect this, we can suspect a couple of things. It could be that the monitors have not been trained on the Monitoring Plan. It could also be that there was a change in practice, but the Plan was never updated. Either way, routine review of the TMF would identify this. This will provide an opportunity to adjust the action to the Plan or edit the Plan to match the action. Either way, this improves the overall story of the monitoring.
Reviewing a TMF can tell us many things about the study. The key to review is to take action on findings. It is critical that queries issued as part of completeness review are resolved in a timely manner. This allows time to correct quality issues that may have been identified. Not only is it good oversight, but it is a great opportunity to influence the outcome of the story in a positive way.
Our team of TMF managers, project leads, and specialists can be a short-term solution to resourcing needs or a long-term solution for your study team. We develop TMF plans and conduct ongoing risk-based completeness reviews, working with all parties to ensure you have an inspection-ready TMF.
Contact Just in Time GCP now to talk about your TMF management service needs.