A Trial Master File (TMF) should be set up at the beginning of a trial. The essential documents that make up the file should be kept in a secure but accessible manner. A well-kept TMF can help with efficient trial management and can facilitate the reconstruction of the conduct of the trial during the audit/inspection process.
The TMF should be held at the coordinating site (usually the Chief Investigator’s office or Coordinating Centre) and for multi-site trials, copies of relevant documents should be kept at each participating site in an Investigator Site File (ISF). Most sponsors will provide guidance on the content and set up of the TMF/ISF based on their local policies/procedures.
The TMF/ISF should be maintained throughout the course of the trial and it should be clear who has been given the task of maintaining it, for example by indicting this role on the Delegation Log (pdf, 27.25 KB).
European Commission Detailed Guidance on the Content of the Trial Master File and Archiving (PDF, 279 KB)* outlines documents which should be kept as part of a Clinical Trial of an Investigational Medicinal Product (CTIMP). Some documents must be in place before a trial is opened, some are generated as the trial progresses and others are added to the file only at the end (e.g. analysis codes and DMC closed reports and minutes). In addition to the guidance above, researchers may also be required to file any trial documentation specific to local policies/procedures.
*In certain trials, some of the documents listed may not be available or applicable. The MHRA Risk-adapted Approaches to the Management of Clinical Trials of Investigational Medicinal Products has been published to help sponsors define a risk-based approach. See page17 for possible adaptation relating to study documentation and filing.
For non-CTIMP research, it would be good practice to file any document that meets the definition of an essential document. Sponsors and host organisations may provide specific guidance on content of files in their policies/procedures.
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- Trial Planning & Design
- Within the scope of the Clinical Trial Regulations?
- Risk Assessment
- Protocol Development
- GCP & Serious Breach Reporting
- Trial Management & Monitoring
- Trial Documentation
- Trial Supplies
- R&D Consultation
- Funding Proposal
- Peer Review
- Funding Secured
- Trial Master File
- Unique Trial Number
- EudraCT Number
- Confirm Sponsor
- Feasibility & Investigator Selection
- Contracts & Agreements
- Final Protocol
- CI Checklist Before Seeking Approval
- CTA Submission
- Ethics Submission
- R&D Submission
- Permissions & Approvals Obtained
- Final Trial Management Documentation
- Trial is Abandoned
- Trial Begins
- Informed Consent
- Safety Reporting
- Progress Reporting
- Ongoing Management & Monitoring
- MHRA Inspection
- Addition of New Sites & Investigators
- Substantial Amendments
- Urgent Safety Measures
- Temporary Halt or Early Termination
- Trial does not Recommence
- End of Trial Declaration
- Statistical Data Analysis
- Clinical Trial Summary Report
- Dissemination of Results
Key to Symbols
Demonstrates processes that can be done in parallel
Demonstrates that not all processes will apply to all trials
|Standard Process||Legal Requirement||Good Practice|
|Specific for trials within Directive's scope|
|Relevant to all trials|