What is it? Why is it important?

A note-to-file (NF) is a useful way to document an issue or discrepancy in the conduct of a study. It also allows one to document the action taken to correct it.

A NF contains:

  • A factual description of the problem or issue
  • A route cause analysis
  • Definition of corrective measures to prevent reoccurrence
  • Documentation that the corrective action has resolved the problem or how it will be addressed, if it cannot be directly solved
  • Applicable dates and signatures

More

NFs are generated on a case-by-case basis.

The content explains why things were done the way they were done, providing important information to monitor and SP-INV.

Its use should be limited to major errors (e.g. protocol deviations). Minor errors are usually corrected and documented elsewhere (e.g. eCRF entry corrections such as a change in recorded participant weight).

Who authors the NF depends whether the event or issue relates to:

  • Site performance: the respective site delegated person writes the note
  • Site-INV responsibilities: the Site-INV writes and signs the note (e.g. participant safety, data integrity)
  • Actions taken by SP-INV or monitor: the SP-INV or delegated person writes and signs the note

What do I need to do?

A NF is initiated and authored by the individual or organisation responsible for its content.

  • Explain problem or deviation and include corrective actions taken
  • Train applicable staff in order to prevent reoccurrence
  • Print NF on institutional paper with letterhead
  • Maintain an index summarising all NFs according to topic, and where they can be located (e.g. filed in TMF and ISF)
  • Report serious deviations to the EC/RA, as applicable

For more information refer to Documents in this Trial Guide

More

Errors or deviations can be classified according to level of seriousness. Unfortunately, there are no official guidelines that provide help on how to classify deviations.

When deciding on seriousness, the SP-INV and Site-INV carry this responsibility and must use common sense, pragmatism and study experience.

NF should not be misused to avoid protocol amendments. If a protocol deviation is done repeatedly a protocol amendment should be initiated.

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 guideline

  • 5.0 Quality management

ISO 31000 – see in particular section

  • Risk management: Principles and guidelines (access liable to costs)
Abbreviations
  • CTU – Clinical Trials Unit
  • eCRF – electronic Case Report Form
  • EC/RA – Ethics Committee / Regulatory Authorities
  • ISF – Investigator Site File
  • NF – Note-to-File
  • Site-INV – Site-Investigator
  • SP-INV – Sponsor-Investigator
  • TMF – Trial Master File
Conduct ↦ Quality and Risk ↦ Note to File ↦ Note to 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): Conduct ↦ Quality and Risk ↦ Note to File ↦ Note to File

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