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 GCP Inspection Working Group have produced a ‘Guideline on GCP compliance in relation to trial master file (paper and/or electronic) for content, management, archiving, audit and inspection of clinical trials’ (March 2017), to assist sponsors and investigators to comply with the requirements of the Clinical Trials Regulation (EU) No 536/2014. In addition, the MHRA FAQs for Trial Master Files (TMF) and Archiving provide further guidance on their expectations when scanning paper documents for electronic archive.
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 indicating this role on the Delegation Log (pdf, 27.25 KB).
The European Commission has published Recommendation on the Content of a Trial Master File and Archiving* and is primarily based on ICH GCP E6 (R2) Section 8. 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 page 17 for possible adaptation relating to study documentation and filing. This approach is supported by ICH GCP E6 (R2) which now includes the following statement, ‘Essential documents for the trial should be supplemented or may be reduced where justified (in advance of trial initiation) based on the importance and relevance of the specific documents to the trial.’
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.