Monitoring Visit Follow-Up Letters

You’ll send a confirmation letter (or email if your SOPs allows it) prior to every monitoring visit, be it a pre-study qualification visit, a site initiation visit, routine monitoring visit, close-out visit, etc.  Then you’ll need to document your visit findings in a monitoring report.  Finally, you will send the principal investigator a follow-up letter summarizing the visit and discussing any critical findings or action items.

Create Your Monitoring Visit Follow-Up Letter

As a rule, I try to keep the follow-up letter to no more than two pages.  It is best practice to have the letter completed, reviewed, and sent within 7 days of the visit.  I write the letter to the Principal Investigator (PI) but Cc in the coordinator and trial TMF and/or the regulatory person, my Lead CRA or Project Manager, etc. as appropriate per my SOP.

your Lead CRA or the Sponsor may want
to approve the letter or provide a study-specific
template so check with your Lead before you send it

I dedicate the first sentence to listing the personnel who were present at the visit and thanking the study staff for their time and attention during the visit.  Be sure to include the dates of the visit as the letter will be filed in the Site Master File and the dates should match the Monitoring Visit sign-in log dates.  This is a good point to discuss any staff changes or recommended re-training.  Next I typically document the progress of study enrollment and then proceed to summarize the status of the Site Master File review, source data verification, and Case Report Form completion.

A Summary, Not a Novel

I break up the content where possible by using in-text tables or bulleted lists to note the following items as appropriate per the trial monitoring plan and SOP:

• Informed Consent tracking details
• Summary of patients/Case Report Forms reviewed
• Site Master File or Source Documentation deficiencies/inconsistencies or Safety Findings
• Protocol Deviations or Critical Findings (and appropriate recommended corrective actions as discussed with my regulatory contact, PM, or Lead CRA)
• Supply Issues: lab kits, Investigational Medicinal Product, source documents, etc.
• Action Items: resolved since last visit, new pending and wherever possible

No Surprises

My most important tip for follow-up letters is, “no surprises”.  During your time on-site you should be meeting with the PI and discussing the status and progress of the visit.  You should be summarizing your findings and discussing any issues so they can assist you to resolve everything while you are on-site.  If there are deviations or safety issues that need to be reported to the IRB, you can remind the Investigator of their responsibility to do so.  You can also provide re-training on the protocol or study procedures during your meeting on-site.

The Follow-Up letter should be
a recap of your discussion, not a news flash.

In regards to action items, it is best practice to resolve everything before you leave the site to the extent possible.  I have extended monitoring visits to an additional day with approval from my Lead when there were items I would be able to complete with an extra half a day or so rather than leave pending.

If you are unable to meet with the PI during the visit, document this in your follow up letter and include a reminder that you are available by phone to speak with the PI.

Follow-Up Letter Template

I’m not planning to post a template.  Please don’t email me for a template as you can easily make your own using the guidance from this post that is study-specific for your trial’s needs.

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

• Meeting with the PI August 2011
• Routine Monitoring Visits March 2008
• Close-Out Visits July 2008

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

Site Master File: Correspondence

The Site Master File (SMF) or Regulatory Binder contains all of the essential documents to provide a record of study conduct. The SMF when reviewed with the clinical charts and archived study materials allows sponsors, auditors, regulators, and all other interested parties to reflect back on a clinical trial and understand how things were conducted, when, and by whom. The Regulatory Binder is created at the beginning of a study, updated as needed throughout, reconciled with the sponsor's Trial Master File (TMF) along the way during routine monitoring visits, and then archived at the end of the study.

The SMF is usually a big chunky (broken) three ring binder (or series of many binders) stuffed to the gills, bulging at the seams, and typically just a little bit intimidating.

Most sponsors maintain documents electronically but our industry is very much still a world of paper and at a site level, most study documentation is physical original or copied papers. For a list of the required items in a regulatory binder for a US trial please refer to ICH E6 Guidance Document on Good Clinical Practice (E6), Section 8 “Essential Documents for the Conduct of a Clinical Trial.” (protocol, Investigator's Brochure, trial logs, lab documentation, IP documents, correspondence, etc.).

Today I am going to review the Correspondence section of the SMF and in a separate post provide some tips for monitoring this item. As a general rule, monitors do not enjoy reviewing the SMF; I would propose that the Correspondence section is one of the most detested sections and often skipped. I have seen correspondence that spans multiple volumes for longer trials and have personally lived the nightmare of organizing these on more occasions than I can count. Some people insist on filing every little stitch of paper but I encourage you to review the regulations, your company SOPs, and to file sparingly. Only file items that truly support the record of conduct and that tell the story of what happened, when, and by whom.

What needs to be filed in Correspondence?

Important emails/threads (As I discuss in a different post – not every email!), Note to File (sponsor/vendor generated), Official study memos, newsletters, Investigator Recruitment Plans, etc.

If found in Correspondence, File Elsewhere:

• Monitoring Visit Confirmation and Follow-Up letters (file these with the monitoring log or in their own tab for ease in reconciliation)
• Budget/Contract, generally anything with $$$ listed
• Duplicates (just shred the copy)
• Audit reports
• Training Files, agendas, and slide decks
• IND Safety Reports
• Investigational Product Documentation (packing lists, confirmation of receipt, destruction or return documents)
• Packing slips (study supplies, lab supplies, etc.)
• Subject identifying information (check-stubs for study participants, copies of IDs, medical records that have not been de-identified, etc.)
• Notes to File (site generated) If subject-specific file with the chart, If more global in nature, just give them their own tab (ensure copies are retrieved and submitted to the TMF)

How should correspondence be organized?

Please file correspondence in reverse chronological order; old stuff at the back, new stuff on top, sorted by date.

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

• Efficiency Tips for Tackling the Correspondence Tab March 2011
• Routine Monitoring Visits March 2008
• Email Management April 2011