At the heart of clinical trial documentation lies the Trial Master File (TMF), a comprehensive repository of essential documents and data pertaining to the trial. Let’s discuss this essential component of clinical trials.
Table of Contents
- What is the electronic Trial Master File (eTMF)?
- What Constitutes a Trial Master File?
- Documents Required in a Trial Master File
- Investigator Site File vs Trial Master File
- Managing Trial Master File Data
- Benefits of Using eTMF Software
What is an electronic trial master file?
An electronic trial master file is a digitized version of the traditional trial master file. It serves as a centralized, secure platform for storing and managing all trial-related documents and data electronically. Unlike its paper counterpart, an eTMF offers enhanced accessibility, version control, and efficiency in document management processes. eTMF is considered essential to meet Good Clinical Practice (GCP), which is required by multiple regulatory agencies including the EMA and MHRA.
Using electronic methods can accelerate clinical study timelines by streamlining data / correspondence collection, project management, and audit and inspection readiness, as well as significantly reducing manual workflows and tracking.
What constitutes a trial master file?
Every clinical trial must have a TMF. The TMF provides a record of all aspects of the clinical trial lifecycle, the process that was followed, and the resulting data showing efficacy. It provides evidence of compliance for regulatory agencies, investigators and auditors. Its primary purpose is to facilitate regulatory compliance, audit readiness, and the ability to reconstruct the trial from inception to completion. This includes protocols, informed consent forms, regulatory approvals, monitoring reports, and more.
Documents required in a trial master file
The requirements for the trial master file are set by several key regulations, including ICH Good Clinical Practice (or GCP), the FDA 21 CFR Part 312, and FDA 21 CFR Part 11 (or Part 11).
- ICH E6 (R2) Good Clinical Practice (GCP) is the international standard for human clinical trials. GCP outlines what data and documents need to be collected & stored for audit and inspection. Section 8 outlines which documents are ‘essential’.
- FDA 21 CFR Part 312 outlines the roles, responsibilities, and documentation required for investigational new drugs (INDs), a primary type of drug application.
- FDA 21 CFR Part 11 sets the standards for electronic records and signatures. If you are using any electronic system to store documents, be that a purpose-built eTMF system or a basic file sharing system like SharePoint or Box, it must meet Part 11 requirements.
Per these regulations, the eTMF should contain study-level, country-level, and site-level documents. These documents should be collected at multiple points during the study—from start-up through study close.
The structure of the TMF is defined by the TMF Reference Model per CDISC. The sections, or Zones, are outlined as follows:
- Trial Management
- Central Trial Documents
- Regulatory
- IRB, IEC and other Approvals
- Site Management
- IP and Trial Supplies
- Safety Reporting
- Central and Local Testing
- Third Parties
- Data Management
- Statistics
A sample of the key documents that need to be included per ICH E6 (R2) include:
- Investigator Brochure (IB)
- Signed Protocols, Amendments and CRF
- Informed Consent Forms (ICF & HIPAA Authorizations)
- Patient Recruitment Documentation
- Insurance Statement
- Signed Agreements between investigators, institutions, sponsors, CROs, etc
- Institutional Review Board (IRB) Approvals and Correspondence
- Investigator CVs
- Investigational Product (IP)
- Financial Disclosure Form (FDF)
- Training Logs
- Monitoring Logs
- Signature Logs
- Signature Sheets (SS)
- Statement of Investigator (FDA Form 1572)
To view the full list of essential documents, refer directly to the ICH E6 R2 documentation.
Investigator Site File vs Trial Master File
The Investigator Site File, now referred to as the Site File by regulators, shares many documents with the Sponsor’s TMF. The Site File is maintained by the investigators and contains site-specific documents, regulatory documents, and protocol information, as does the Sponsor TMF. Investigators are responsible for certain documents, while Sponsors are responsible for others. The TMF Reference Model delineates which elements of the TMF should be managed by the Sponsor vs the Investigator, as well as which documents are shared between parties. Given the overlap, maintaining clear communication, a delineation of responsibilities, and a shared structure for documents can significantly reduce confusion and version control issues. Using an electronic trial master file system that both parties can access can improve data integrity, collaboration, and streamline project timelines.
Managing Trial Master File Data
Effective data management in TMFs involves meticulous attention to detail and adherence to regulatory guidelines. This includes the incorporation of revised documentation, stringent access controls, robust data security measures, and redundant data storage to safeguard against loss or corruption.
Proper data management of the TMF is the subject of numerous whitepapers, webinars, conferences, and more! To learn more about best practices for TMF management, reach out to our team or visit our resources page.
Benefits of Using eTMF Software
The adoption of eTMF software offers a multitude of advantages for sponsors, CROs, and other stakeholders involved in clinical trials. From streamlining document workflows to facilitating real-time collaboration and ensuring regulatory compliance, eTMF software significantly enhances operational efficiency and data integrity throughout the trial lifecycle. Moreover, utilizing eTMF from the outset minimizes the need for labor-intensive processes such as digitizing and validating paper documents, thus optimizing resource allocation and accelerating time-to-market for investigational therapies.
Many sponsors choose to use their CRO’s eTMF system, or leverage a patchwork of file sharing solutions rather than implement their own eTMF. However, implementing a digital eTMF in-house can streamline operations and improve compliance.
Wondering if an eTMF system would be right for you? Check out this article on When and Why to Implement an eTMF. If you're starting evaluations, read through our guide on how to select your eTMF system.
Conclusion
In conclusion, understanding the intricacies of trial master files is fundamental for ensuring the successful execution and oversight of clinical trials. Whether in its traditional or electronic form, the TMF serves as a cornerstone of regulatory compliance, data integrity, and ultimately, the advancement of medical science.
