The Memo to File or Note to File (NTF) is Overused

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.

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.



You may also like...from The Lead CRA archives:

• Site Master File: Correspondence March 2011
• Routine Monitoring Visits March 2008
• Close-Out Visits July 2008

Perfect Clinical Trial Source Documents

As a CRA, I regularly visit the sites to review the study conduct, encourage study participant recruitment, evaluate the ongoing suitability of the investigative site, provide protocol specific training, track investigative supplies, and to review source documents.  Source documents are the roadmap and clinical record to let me (or anyone who is reviewing) know what happened, when, how, and by whom.  When I look through source documents I am checking that they follow the principle of ALCOA:

• A-attributable, who wrote this?
• L-legible, can I read this?
• C-contemporaneous, was this recorded at the time of trial conduct or later?
• O-original, is this unaltered or copied?
• A-accurate, is this a correct reflection of the conduct?

The burden for documentation in a clinical trial is actually much higher than the burden for documentation in a standard clinical record or office/physician visit.  When you see your doctor for a flu he might write 3-4 lines in your chart documenting the visit.  If you were a clinical trial participant, the doctor or the clinical trial staff would likely need to collect and record a lot of specific information to satisfy the data collection requirements of the trial.

It is never acceptable to use
correction fluid in source documents.

The first time the pen touches the paper to record observations in a trial, this generates "source documents".  If the nurse writes your blood pressure on her hand, her hand is a source document. If you stand on the scale and your weight is recorded on a post-it, that is a source document.  One of the most important rules of GCP is that the Principal Investigator (PI) is ultimately responsible to ensure that all source documents are maintained in their original form and that any alterations or corrections are indicated in a compliant fashion (changes should be striken through with a single line (so as not to obscure the orignal entry); correction fluid should never be used! The revision should be initialed and dated so there is a record of who made the change and when. An explanation of the change is optional but best practice).  The PI should instruct his staff not to write on their hands or sticky notes, to make observations using indelible ink (not pencil since that can be erased!) and to always observe the ALCOA principle when generating or modifying source documents.

Some sponsors actually provide source documents to the investigators to assist them to record all the required data during the study visits.  The source templates will typically have a blank header to record the subject identifying information and to indicate the date of the visit. Quality source will also include signature or initial blocks on each page so that the person(s) completing the forms can be identified later. If source documents are complete and accurate, the clinical trial data can be copied over and provided to the sponsor on Case Report Forms for analysis. I'll provide an introduction to data capture/EDC and analysis in a future blog topic.

During source document review I always find items that are incomplete (left blank), inaccurate (such as blood pressures that are inconsistent with life, headers that indicate a different patient entirely, birth-dates that don't match the age, units or counts that aren't possible), or otherwise erroneous source.  I use small colored post-it notes (stickies) to flag my findings and ask the PI or the study nurse to review and update the source with notation.  I never "fix" the source myself.  If the source errors are very wide in scope, I will note it in my monitoring report and I may also ask the investigator to generate a signed and dated Note to File on the site letterhead explaining what happened with the source documents and the corrections completed during our visit.  Experienced study coordinators and investigators will not be surprised or frustrated when I request source corrections or clarifications.  Also, discovering errors in the source does not upset me at all, this is part of my job and I am partnering with the site to help them keep their documentation totally complete and an accurate reflection of what was done.

Source documents are created during the patient visit and should not be fabricated a few days before a monitoring visit.

Do I want to see perfect source at my visits?  Actually, absolutely not.  Original source documents will be working documents and I am expecting source documents to be a bit tattered, thumbed through with bent corners, covered in the occasional stain, marked with revisions, and otherwise imperfect.  Perfect source or typed source makes me especially suspicious and can be an indicator of fraudulent or sloppy record keeping.  I hope this discussion is helpful to you and that you will know what to look for when reviewing source documents at your monitoring visits.


You may also like...from The Lead CRA archives:

• Investigational Product Accountability June 2010
• Correspondence March 2011 
• Sponsor Furnished Source April 2011
• Routine Monitoring Visits March 2008