W-35: The Importance of Measuring TMF Health for Continuous Inspection Readiness

Poster Presenter

Dawn M Niccum

Director, Quality Assurance
Inseption Group
United States

Objectives

This poster will detail the work of the Metrics Champion Consortium (MCC)’s TMF Working Group to develop meaningful metrics to track the quality and completeness of the Trial Master File.

Method

The working group, consisting of pharmaceutical and biotech industry representatives, shared best practices and developed a common core set up metrics to address the current regulatory expectations regarding the completeness, quality, and timeliness of artifacts included in the Trial Master File.

Results

According to ICH GCP E6, essential documents permit the evaluation of the trial and the adherence to Good Clinical Practice. The Trial Master File (TMF) should be established at the beginning of the trial and provide a contemporaneous record of the conduct of the trial. The Metrics Champion Consortium (MCC) has established a working group to develop metrics to assess the health of the TMF. The team has developed standard metrics to monitor the health of the TMF by measuring quality, timeliness and completeness at defined Milestones and Events. These metrics will apply whether the documents are stored in an electronic content management system or in paper with an index for the documents. The categories of measurements will be hierarchal with the stages of content being Study, Country, and Site. The stages of a trial being measured will have TMF Checkpoints defined at Startup, Conduct and Closeout study segments. Once the stages and checkpoints have been defined, Events and Milestones are bring established Each Event/Milestone will be assessed against the MCC TMF Artifacts Mapping Tool (based on the TMF Reference Model) where the artifacts expected at each Event/Milestone will be identified. The presence of the artifacts will reflect the health of the TMF at that Event/Milestone. As the terminology used across industry may vary, a Wiki (i.e list of terms and their definitions) was developed in conjunction with the working group efforts. Milestones and Events were also defined to assure consistent interpretation.

Conclusion

Metrics document the control of the TMF by sponsors over the course of the trial. Increasing regulatory critical inspection findings note instances where the provision of the TMF is not readily available or accessible or incomplete to such an extent that it cannot form the basis of the inspection. Critical findings can be the basis for the rejected of a Marketing Application or other legal actions. Metrics help ensure that the TMF is inspection ready throughout the course of the clinical trial.