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
NFs are generated on a case-by-case basis.
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
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
Basel, Clinical Trials Unit, CTU, dkf.unibas.ch
Bellinzona, Clinical Trials Unit, CTU-EOC, www.ctueoc.ch
Bern, Clinical Trials Unit, CTU, www.ctu.unibe.ch
Geneva, Clinical Research Center, CRC, crc.hug.ch
Lausanne, Clinical Research Center, CRC, www.chuv.ch
St. Gallen, Clinical Trials Unit, CTU, www.kssg.ch
Zürich, Clinical Trials Center, CTC, www.ctc.usz.ch
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)