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
  • A description of corrective measures to prevent reoccurrence
  • A confirmation that corrective action(s) have resolved the problem, or what procedures were implement if the issue could not be solved
  • Applicable dates and signatures

 

NFs are generated on a case-by-case basis. The content explains why things were done and the way they were done. NF provide important information to monitors during monitoring visits, during communication with SP-INV, and potential audits and regulatory inspections (e.g. Swissmedic).

NF should not be misused to avoid a protocol amendments. Repeated protocol deviation require an amendment.

More

 

NF 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 quality)
  • 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. The management of NFs requires that:

  • A issue or deviation is explained and corrective actions are described
  • Relevant study staff is trained to prevent deviation reoccurrence
  • The NF is written and printed on institutional paper with letterhead
  • An index is maintained that summarised all NFs according to topic, and where they can be located (e.g. filed in TMF and/or ISF)
  • Serious deviations are reported to EC and RA (e.g. Swissmedic), as applicable

 

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 the responsibility and must use common sense, pragmatism and study experience.

For more information refer to Documents in this Trial Guide

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 (access liable to costs) – see in particular section

  • Risk management: Principles and guidelines
Abbreviations
  • CTU – Clinical Trials Unit
  • eCRF – electronic Case Report Form
  • EC – Ethics Committee
  • ICH GCP – International Council for Harmonisation Good Clinical Practice
  • ISF – Investigator Site File
  • ISO – International Organization for Standardization
  • NF – Note-to-File
  • RA – Regulatory Authorities
  • Site-INV – Site-Investigator
  • SP-INV – Sponsor-Investigator
  • TMF – Trial Master File
Conduct ↦ Quality and Risk ↦ Deviation Documentation ↦ Note to File
Study
Basic

Provides some background knowledge and basic definitions

Basic Protocol
Basic Statistics
Basic Monitoring
Basic Drug or Device
Concept

Starts with a study idea

Ends after having assessed and evaluated study feasibility

Concept Protocol
Concept Statistics
Concept Drug or Device
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
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 Quality and Risk
Set-Up Drug or Device
Conduct

Starts with participant recruitment

Ends after the last participant has completed the last study visit

Conduct Protocol
Conduct Statistics
Conduct Drug or Device
Completion

Starts with last study visit completed

Ends after study publication and archiving

Completion Protocol
Completion Statistics
Completion Drug or Device
Current Path (click to copy): Conduct ↦ Quality and Risk ↦ Deviation Documentation ↦ Note to File

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