What’s New in E6 R3? Essential Records

Last, but not least, we feature the E6 R3 changes to the Essential Records section.  This section has been moved from the last section in R2 to an appendix in R3, but this move is not intended as a demotion.  If we think back to the structural changes we covered in our first blog post on this topic, future plans for R3 involve production of “annexes” to provide guidelines for different types of clinical trials.  Annex 1, which makes up the bulk of GCP, is devoted to trials that support product registration.  Future annexes may address decentralized trials, real-world trials, academic research, or other as-yet-undreamed-of approaches. The three appendices – investigational brochures, protocols, and essential documents – are intended to apply to Annex 1 and all future annexes.

Accordingly, this section has been reworked to front-load document management principles that apply to all types of trials.  Instead of the lists of documents required to be collected before, during, and after a trial in site and sponsor files, we have two relatively short lists.  The first lists essential records for all trials (registrational and otherwise); the second, “potential essential records,” the “essentiality” of which (their term, not ours) depends on whether the document meets one of 27 criteria defined in section C.3.1.

The upshot for clinical trials?  Not much has changed. Most “potential” essential records are essentially essential when the 27 criteria are applied. The following documents have been added to the old R2 list, bringing GCP in line with typical best practice:

• Data Monitoring Committee agreements, procedures, meeting minutes, submissions
• Trial-specific training records’
• Site delegation log
• Documentation of collection, processing, shipment, and storage of body fluids/tissue samples
• Documentation of IMP storage at investigator’s site
• Centralized monitoring reports
• Data cleaning and finalization documentation (query resolution, SAE reconciliation, QC reports, coding completion, output data sets)
• Statistical documentation
• Trial-specific plans
• Records of protocol and GCP deviations and CAPAs

We don’t think these revisions are intended to impact how clinical study teams collect Trial Master File documents, but we fear that the truncated “essential” list will cause confusion and perhaps lead more inexperienced teams to cut down on the records they file.