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Saturday, April 4, 2009

Close-Out Visits this Quarter

I've been performing close-out visits for a variety of studies lately and I am ramping up on a new study. Sorry I haven't been able to post sooner, but in this economy I am happy to have a great job that is keeping me busy with such interesting and varied assignments.

I have been closing other people's sites on studies I didn't even work on so one of my more time-consuming responsibilities has been a full regulatory binder review. Typically for sites I manage over time, I know what is in the binder and can verify that the documentation contents at the study site match the contents at the sponsor's Trial Master File (TMF) exactly (since I work for a large organized CRO we also have a fantastic suite of applications and reports to help us with this reconciliation process). The reports and previous monitoring reports help me identify what documents need to be updated and I email the list to the coordinator several weeks before the visit. Since I need to retrieve a copy of any updated documents for the TMF I just ask the coordinator to slip a second copy for me in a folder or email me an electronic version and this has dramatically reduced the time I would spend taking apart their binder and hovering over the copy machine. Some sponsors want the site to keep originals of all study logs and some sponsors want the site to keep copies so they get the original. Some sponsors consider a signed CV to be good for 2 years whereas some require annual updates. Some sponsors want an updated 1572 and/or Financial Disclosure Forms at the end of the study and some sponsors don't ask for this at all. There are few hard and fast rules for documentation (aside from the ICH/GCP guidelines in section ICH E6, Section 8.4) so I have to understand the study specific requirements in advance of the visit (these are communicated in team meetings and documented in the study monitoring plan) to know which documents to retrieve.

Another area that has required a lot of time and attention is the return of the Investigational Product (IP). To assist me with the drug return I have requested reports from the inventory management system several weeks in advance of the visit and submitted them to the pharmacist or Study Coordinator. I ask them to organize the medication numerically by lot/kit # into used and unused lots and to check that all drug receipt and dispensing forms are accurate and complete and that the quantities match the CRFs. I follow-up over the next several days via phone or email and ensure they have completed the task. Typically they print the inventory reports and highlight them or make comments when there is a discrepancy. I always have them fax me any notes and copies of all the drug logs so I can review them. I can prepare the bulk of all my drug return documentation before I even arrive at this site and that saves a lot of time during the visit.

The last item that has been a real time-synch is reviewing the safety binder to ensure that every safety alert was acknowledged by the Principal Investigator (PI), submitted to the Institutional Review Board (IRB), acknowledged by the IRB, and that all that documentation is filed in the binder and submitted to the TMF. Luckily, I have been able to do work prior to the visit to help this task go as smoothly as possible (one study I closed out had over 5000 safety alerts so that could easily have been several days work whereas another study only had 42 and I knocked out the review task in about an hour). As you know, this review of safety letters should have been occurring all through conduct and regular monitoring visit but unfortunately, when it is not your site, you're really forced to re-review every bit of documentation unless the previous monitoring report(s) can confirm the documentation is current. For each site I closed I sent a safety letter tracker. It was just an excel spreadsheet where each alert was listed by date in the order in which it was sent to the site with a brief description that included the event #, event name, event onset date, patient initials, and a column specifying whether the event was an intial report or follow-up report. Finally, I added three blank columns to the end of the spreadsheet with the titles 'Date Ack. by PI' , 'Sent to IRB Y/N', 'Date of IRB Ack.' In each case, I required the study staff to complete the tracker and email it back to me prior to the visit. By using this technique we easily discovered missing documentation in advance fo the visit. I was able to forward blank copies to the site to prepare before the visit and we had time to obtain sign-offs and do the necessary IRB submissions. It was helpful to be sure pending safety letters didn't delay official notification to the IRB of study closure.

In summation, close-out visits at my own sites go pretty quickly and are fairly routine whereas there is a lot more work involved with closing out someone else's sites. To make the visits easier I worked with the site staff several weeks before the visit to address the documentation gaps in the regulatory binder, review all the IP documentation, and to ensure that all safety letters had been properly acknowledged by both the PI and the IRB. By thoroughly preparing in these 3 time-consuming areas, I had plenty of time while on site to accomplish all of my close-out responsibilities (click here to learn more about COVs in my blog post from last year). One other huge plus is that I knew what to expect once I arrived on the site, had developed a rapport with the staff, had prepared organized checklists, and then I left the sites with minor or no pending action items whatsoever. This all contributed to being able to easily and quickly finalize my close-out visit reports. I hope my experience helps you better prepare when you are asked to close-out someone else's site (or even your own). Do your homework before the visit and it should go like clockwork.

1 comment:

PRT said...

Great article. I have a bunch of close out visit in the following months in the same situation as yourself. The study was not my responsibility until now and these tips will help a lot.

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