As a result of lacking documentation, missing data, or noted discrepancies, research professionals may turn to the use of a memo or note to file (NTF) to record and explain issues throughout a clinical trial.
We’ve all heard and advocated that “if it wasn’t documented, it wasn’t done”, but is a note to file the best way to remedy absent or deficient documentation?
What Is A Note To File In Clinical Research?
A note to file cannot replace actual documentation, but it can serve as an approach to record details and an explanation of the missing information.
While notes to file are commonly used as a method to comply with regulatory requirements, neither the ICH Guideline for Good Clinical Practice nor the FDA 21 CFR articles provide any guidance or instruction to utilize NTFs. In other words, using a note to file is not a regulatory requirement.
Likewise, notes to file do not prevent Warning Letters issued by the FDA during trial inspections. On the contrary, the FDA has cited a sponsor for failure “to take any action except to generate numerous memos to file after all the subjects completed the study.” In a separate citation to a clinical site, the FDA notes that the investigator failed to maintain adequate and accurate case histories, of which a discrepancy was recorded on an NTF. Therefore, a note to file alone cannot resolve documentation issues in clinical trials.
However, when utilized appropriately and purposefully, a note to file can serve as a helpful tool.
How To Write A Note To File
Here are four best practices to follow when considering a note to file in clinical research:
1. Do your due diligence
A note to file becomes a permanent part of the Regulatory Binder and Trial Master File (TMF). Before creating one, ensure you have done extensive due diligence, as a note to file points directly to areas of noncompliance. Is there someone else who can be contacted to resolve the issue? Can a research record or clinic note be directly corrected instead? Could a post-dated progress note be added to a subject’s record? A note to file should not be created until you’ve made every effort to locate missing documentation or considered if the issue can be documented elsewhere.
2. Be comprehensive
The purpose of documentation in clinical trials is to tell a complete story, and a note to file should contribute to that completeness by explaining any gaps. Don't have a note-to-file template handy? Just make sure your includes these items:
- The study protocol title
- An explanation and definition of the issue
- The reason or root cause for the issue
- When the error was realized and any due diligence you performed
- What subjects or study personnel were affected
- Your corrective and preventive action (CAPA) plan
- Signatures and dates from individuals who created the note to file
- Attachments or an explanation of the location of supporting documents, if applicable
Taking the time to include all essential information will make it easier for others to understand what happened as they review your note to file later.
3. Be timely
A stack of NTFs with the same date, which were created in preparation for an inspection or as a corrective action from a monitoring visit, can create red flags for FDA inspections. The FDA may also reprimand sites for the non-contemporaneous filing of NTFs. As part of the FDA and ICH GCP guidance, documentation should be attributable, legible, contemporaneous, original, accurate, and complete (ALCOA-C).
4. Implement a corrective and preventive action (CAPA) plan
Simply documenting a discrepancy or missing documentation in a note to file is not sufficient. Once a noncompliance issue is identified, a CAPA plan should be implemented to solve the issue and prevent reoccurrence. A common finding by the FDA has included the inadequate implementation of CAPA plans. A CAPA plan should be used to explain how nonconformities were corrected, what measures were implemented to limit risks for subjects, and the structure for securing compliance in future research activities. This may include process improvement updates, retraining of study staff or new quality control procedures.
A Final Note About That Note To File
A note to file cannot serve as a substitute for good source documentation in clinical trials. It should answer questions, not create questions. A better solution to the use of notes to file is to provide the training and tools needed by a clinical site to ensure study staff understand the protocol, Good Clinical Practice, and regulatory requirements.
IMARC offers comprehensive, convenient in-person or online training to ensure clinical research compliance fundamentals are a part of your best practices. Let us know how we can help!
When have notes to file helped you on a clinical trial? Share your examples and thoughts with us!