By Gina Daniels, Human Research Quality Manager, OHRA/CRRO
Guidance for Writing a Note-to-File
A Note-to-File (NTF) is a clear and concise note added to research records/source documents that identifies a discrepancy, error, or omission in study documentation; or clarifies a policy or process.
When meeting with investigators or their study team members, the BMC/BU Medical Campus Quality Assurance (QA) reviewers are sometimes asked to clarify when it is acceptable to use notes-to-file, and what information should be included in them.
The purpose of this article is to answer those questions.
There are no specific regulations or guidances to help investigators know when an NTF is appropriate in a given situation and how to write such a note. However, there are some clues in the regulations that provide guidance. The federal regulation on case histories 21 CFR 312.62(b) , requires investigators to “prepare and maintain adequate and accurate case histories that record all observations and other data pertinent to the investigation on each individual . . . Case histories include the case report forms and supporting data including, for example, signed and dated consent forms and medical records including, for example, progress notes of the physician, the individual's hospital chart(s), and the nurses' notes.”
If a study team member, study monitor, or a QA reviewer finds that the records are inadequate and inaccurate, then it is generally recommended to prepare an NTF to explain what happened and, if appropriate, what corrections were made to address the problem.
When is it appropriate to write a NTF?
Here is an example: You discover that a study subject recorded the wrong date on an informed consent form they signed, and will not be returning for another study visit. To address the error, you would like to write a NTF. Writing a note in this situation is appropriate and will provide current and future study staff (as well as QA reviewers and auditors) with the information necessary to understand what occurred and why.
When writing NTFs, study staff should take into consideration the underlying reason for the note. Creating NTFs does not solve the problem that a deviation occurred. Inappropriate NTFs could cause more problems than the ones they mean to correct. For example, a NTF explaining why it is ok to enroll a subject who doesn’t meet eligibility criteria is not sufficient in and of itself. In the case where an NTF is created to explain a deviation, the deviation should be logged on the protocol deviation log, and reported to the IRB as necessary. Additional documentation of other steps that have been taken may also be necessary. For instance, if the purpose of the NTF is to explain why a subject was enrolled who was a year older than the exclusion criteria allowed, then the study records should also include a prospectively obtained (and approved) IRB protocol exception request; or, if the event is discovered after it happened, a record that a Reportable Events and New Information (RENI) form was submitted.
What information should be included in the NTF?
An adequate NTF meets the same criteria as other source documents: it is timely, legible if handwritten, and signed/dated by the person who prepared it. When addressing a discrepancy/error/omission, it should explain the cause of the problem, corrective actions taken, and steps put in place to prevent the issue from occurring again. NTFs should be stored in the regulatory or participant files, along with the document it is meant to clarify. NTFs should be full documents, not simply a handwritten post-it note (as these can be easily lost).
NTFs can be a useful tool for providing supplemental information to the study research records, but must only be used when necessary. Overreliance on their use may be viewed as a "red flag" that potential issues are not being prevented or that previously identified issues are continuing to occur. In fact, the FDA has cited investigators for using too many “memos-to-file.”
Remember, an NTF is not a universal remedy that can be used to retroactively fix problems in your study. If you find that you are generating many NTFs, the study team should consider whether there has been appropriate training for study personnel on study procedures and documentation. The team should also consider whether the protocol is clear enough or if it should be modified.
A Note-to-File template is now available on the CRRO website to help you prepare your NTFs. If you have any questions concerning the use of Notes-to-File, you can reach out to Gina Daniels at gdaniels@bu.edu.
The CRRO is supported by the Boston University Clinical Translational Science Institute (CTSI) and the Office of Human Research Affairs.