Review of Site File documentation at closure for pre-directive trials

[MonitorH]

GCP 8.1 states that "a final close-out of a trial can only be done when the monitor has reviewed both investigator/institution and sponsor files and confirmed that all necessary documents are in the appropriate files."

What is appropriate for long-running trials which may have been set up prior to the EU directive and are only being closed now, where comprehensive records of all site documents may not have been instituted and maintained in the past?

[rammellconsult]

I think a pragmatic, risk-based approach is appropriate. I would suggest that a review of the files by the monitor is still appropropriate but use judgement in terms of what might be expected for studies that are very old.

It is important to remember though that although the clinical trial directive 2001/83/EC is relatively recent, ICH GCP itself has been in existence with an expectation that it is followed since 1996 (18 years). Going back even further, the basic principles of good clinical practice - including the maintenance of appropriate records - was also documented in the CPMP Note for Guidance 111/3976/88 wich was published in 1988 and adopted in 1990. So the requirement to maintain adequate trial records has been a specific regulatory requirement for at least 24 years. Trials would have to be VERY long-running to pre-date these requirements but I'm guessing there may be some that fit into this category.