From the CRRO
By Russell Gontar, Manager of Quality Assurance
Using Notes-to-File in Research
When meeting with investigators or their study team members, I am sometimes asked to clarify when it is acceptable to use memos to file, or as they are more commonly known, "notes-to-file" (NTFs). In many instances, the impetus to write an NTF is initiated in response to a discrepancy or a "loose end" in the research records/source documents that is discovered after the record was generated. Study sponsors or their designated study monitors often instruct study staff to write NTFs when a mistake is noted in the source documents, the document is incomplete or there was some other unusual circumstance that is not clearly described in the study records. For example, you may discover (after the fact) that a study subject recorded the wrong date on an informed consent form they signed, and now wish to write the NTF to address the error. Writing such a note in this situation is appropriate and will provide current and future study staff (as well as auditors or inspectors) with the information necessary to understand what occurred and why.
While 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, there are some clues within the regulations that provide guidance. Federal regulation 21 CFR 312.62(b)
"Case Histories" requires investigators to "prepare and maintain adequate and accurate case histories". Once an NTF is generated, these notes become part of the permanent study record. To be considered “adequate,” NTFs should meet the same criteria as other source documents. At the very least, the note should describe the specific issue it is intended to address and include the date it was written and the name of the individual who wrote it. If appropriate, corrective actions should be detailed. NTFs should be legible if handwritten and securely filed with the study records ("stickies" should be avoided).
When writing NTFs, study staff should take into consideration the underlying reason for the note. If it is being written to provide a simple clarification, then that is fine. However, additional documentation of the other steps that have been taken may also be necessary. If, for example, 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 submitted protocol deviation report.
NTFs can be a useful tool for providing supplemental information to the study research records, but must be used judiciously. 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”: http://www.fda.gov/ICECI/ EnforcementActions/WarningLetters/2007/ucm076552.htm
Remember, an NTF is not a universal remedy that can be used to retroactively fix problems in your study. Whenever writing a NTF becomes a necessity, investigators and their study team members are best served by using the situation as an opportunity identify the reasons for the NTF in the first place, and to further refine their study procedures to prevent the same problem from reoccurring.