What is it? Why is it important?

The Trial Master File (TMF) and the Investigator Site File (ISF) are repositories used to file study documents (e.g. essential-, quality documents).

As a document repository:

  • SP-INV documents are filed in the TMF, while site documents are filed in the ISF
  • Documents are filed both prior, during and after study completion
  • Filing can either include hardcopies, electronic copies, original documents or a mix
  • A TMF/ISF index system greatly facilities the document management of the study
  • The TMF/ISF are important resources during audits and inspections

TMF/ISF files are important documents that bear witness to the conduct of the study. They confirm the study’s compliance with the study protocol, ICH-GCP, including regulatory requirements. Incomplete filing bears the risk of non-compliance, jeopardising participant safety and the quality of study data.

More

The ISF binder is checked during:

  • Study monitoring both at the beginning, during and after the completion of the study
  • SP-INV audits

Both TMF and ISF binders are checked during

  • Regulatory inspection (e.g. Swissmedic)

Upon study completion TMF/ISF folders must be archived for a required number of years (e.g. based on legal requirements or specifications in the study protocol). This will allow applicable authorities to re-visit the study should that become necessary.

What do I need to do?

As a SP-INV of a planned study:

  • Establish and start to file study relevent documents in the TMF already while planning your study
  • Include a binder directory
  • In a multicentre study, set-up and provide each study site with an ISF
  • During monitoring check TMF and ISF folders at study site(s) to ensure that document filing is complete and current

As a SP-INV and Site -INV

  • Keep TMF/ISF binders in a place only accessible to study staff
  • Update both TMF/ISF whenever applicable documents become available
  • Ensure that an essential document-tracking list is set-up and up to date

More

  • The SP-INV and Site-INV are responsible to maintain a record stating the location(s) of all essential study documents
  • Irrespective of media used, the storage system:
    • Should allow for the correct document identification, location and retrieval
    • Must ensure that documents are protected against accidental disclosure, change or deletion
  • The set-up of a study relevant DMS is here the key
  • Once the study is terminated archiving procedures must ensure that documents remain readable during the entire archiving period

Where can I get help?

Your local CTU can support you with experienced staff regarding this topic

References

ICH GCP E6(R2) – see in particular guidelines

  • 4.9 Records and Reports
  • 5.5 Record Keeping
  • 8 Essential Documents for the Conduct of a Clinical Trial
Abbreviations
  • CTU – Clinical Trials Unit
  • ICH-GCP - International Council for Harmonisation - Good Clinical Practice
  • DMS – Data Management System
  • ISF – Investigator Site File
  • Site-INV – Site Investigator
  • SP-INV – Sponsor Investigator
  • TMF – Trial Master File
Set-Up ↦ Documents ↦ Required Documents ↦ Master and Site File
Study
Basic

Provides some background knowledge and basic definitions

Basic Protocol
Basic Statistics
Basic Monitoring
Basic Drug or Device
Basic Biobanking
Concept

Starts with a study idea

Ends after having assessed and evaluated study feasibility

Concept Protocol
Concept Statistics
Concept Drug or Device
Concept Biobanking
Development

Starts with confidence that the study is feasible

Ends after having received ethics and regulatory approval

Development Protocol
Development Statistics
Development Drug or Device
Development Biobanking
Set-Up

Starts with ethics and regulatory approval

Ends after successful study initiation

Set-Up Protocol
Set-Up Ethics and Laws
Set-Up Statistics
Set-Up Drug or Device
Set-Up Biobanking
Conduct

Starts with participant recruitment

Ends after the last participant has completed the last study visit

Conduct Protocol
Conduct Statistics
Conduct Drug or Device
Conduct Biobanking
Completion

Starts with last study visit completed

Ends after study publication and archiving

Completion Protocol
Completion Statistics
Completion Drug or Device
Completion Biobanking
Current Path (click to copy): Set-Up ↦ Documents ↦ Required Documents ↦ Master and Site File

Please note: the Easy-GCS tool is currently under construction.