This month’s intriguing question…
Does a Note-to-File forgive all of your sins?
During audits, we come across many Notes-to-File in all kinds of documentation. Sometimes the Trial Master File or the Investigator Site File are packed with Notes-to-File. Very often, these Notes-to-File date from the days before the audit, when the monitor made a last review of the files.
Therefore, it may be relevant to clarify the real use and purpose of such Notes-to-File.
A Note-to-File only has a clarification function. Sometimes a document can be misinterpreted and with a Note-to-File the real meaning of a document or a situation can be clarified. When writing a Note-to-File, keep it simple and try to imagine how a third person will understand what you want to explain. Sometimes Notes-to-File complicate things more than if they did not exist.
Responsibility and Timing:
As it is important during an audit to note who explains certain activities to you, it is as important to note who has written and signed the Note-to-File. Moreover the timing is important based on the date on the Note-to-File. Anyone who signs a Note-to-File takes the responsibility for the content of that Note-to-File. A Note-to-File tells the auditor a lot about responsibilities and involvement in a study. When, for e.g. explanations regarding the decision on the recruitment of patients in a clinical study, can be written by a study coordinator, nurse or other study personnel but when the Note-to-File is not endorsed by the investigator with the date and his signature, one can wonder whether this information is reliable. When the QA person signs notes to file in a TMF, one can ask questions about the QA’s independence of the operational team.
A major mistake is to replace protocol changes or corrections, that should have been subject of an amendment, with a Note-to-File.
No audit observation because of a Note-to-File ?
There is a strong misunderstanding regarding Notes-to-File. It is thought that all issues, that are reported in a Note-to-File, cannot be subject to an observation; this is a wrong supposition. The auditor will look at the timing of the Note-to-File. If issues should have been addressed previously, the fact that they have not been addressed at the right moment may be an observation. Moreover, a Note-to-File may clarify a situation but if no corrective or preventive action has been taken, only part of the issue has been addressed.