These memos are often sloppy, contradictory, confusing, or alarming (I once monitored at a site where the PI had written the following memo “Although employees and family members of Dr. XXXX and this facility were enrolled in the trial XXXX, they were in no way unduly influenced or coerced to participate.” Ummm, wow, this was part of the study record and you can’t retract it under any circumstances). Memos to File have to be reviewed and reconciled between the Site Master File and the TMF. Frankly, there are better ways to capture the information i.e. training logs, protocol deviation forms, monitoring reports, etc. so why do many monitors insist that the site generate a million NTF? I actually ask my coordinators to take it easy on the memos and to avoid writing them unless absolutely necessary or at least after serious consideration.
Some Memos to File are global correspondence from the sponsor or CRO and are necessary to address operational issue or questions (expanded specimen shipping instructions, imaging vendor holiday operation hours, clarification on processes, tracking, substitution of lab kits, etc.) these are beyond the scope of my discussion here.
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A Note to File may be well-intended but can also provide an
interested party or inspector with a roadmap to a finding – yikes! |
On-site, a series of NTFs all with the same date, in preparation for an inspection, or as a corrective action from an audit are a huge red-flag for me as a monitor. Just document along the way, during trial operations, and avoid lengthy notes to file. Personally, when I see file notes, I get a bit suspicious and inspired to dig deeper to make sure I am being given the whole story. I propose that many NTF raise additional concern rather than actually addressing deficiencies.
Don’t misunderstand, I would propose that a NTF can be a good tool to supplement the clinical conduct record but please try to minimize how often these are used and ensure that they are accurate and contemporaneous. For example, a NTF can be helpful when you are explaining gaps in documentation or inconsistencies, “B. Hill received rater training on 11-Jan-2011 but the certificate is unavailable, please refer to the training log. “ I would tend to use a Memo to discuss trial-related gaps rather than subject-related documentation issues. A simple post-dated progress note in the subject’s source can address any ICH/GCP concerns instead.
I’ve used Memos to File to organize Site Master File binders “The pharmacy temperature log for this study is located in Suite 1027 and updated twice daily. Please refer to the original logs.” and also in the sponsor level TMF to address gaps or clarify, “CRF approvals are filed in section 7.1.2.” “Translation certifications are filed at TMF level 3.6.”
A Memo to File can also be very helpful to reconstruct a record of conduct or to explain corrections that are made to documents that might raise questions. For example, if an Informed Consent Form had a mistake (the wrong date was written, a signature was not obtained, an incorrect version was used, etc) it may be helpful for the study staff to generate a NTF to explain when the error was realized and what corrective actions were taken to come back into compliance. If the subject forgot to date then the subject could be asked to date at the next visit and the SC could write a note explaining why a later date was used. The corrective action could be additional site training and a procedure to review the consent form by a second person at the time of consent; this revision to the procedure would be helpful to capture in a NTF.
I am assuming this will be a controversial topic because monitors tend to be very passionate about whether these notes are a hindrance or a help; please leave a comment with your thoughts. There is no regulatory requirement to produce Memos to File but I think in some cases sponsors and sites can benefit from them at times…they are, however, more powerful when used in moderation. Oh, and if you produce a NTF please sign and date it, accurately.
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