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.
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| 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.
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