Essential Records and the Site File

Part of Clinical Research Coordinator (CRC) Training: Study Start-Up at the Site.

About 6 minutes. Free, in your language, no account needed.

Why this matters

A trial can only be judged from its records. If an inspector cannot reconstruct what happened at your site from what you kept, then for regulatory purposes it did not happen the way you say it did.

This lesson is about the collection of documents your site must hold. It is unglamorous and it is one of the highest-risk areas at any site.

The term changed: essential records

ICH E6(R2) used the phrase "essential documents". ICH E6(R3) uses "essential records", and the change is meaningful. Records include data and relevant metadata, such as the audit trail in an electronic system, not just signed paper.

E6(R3) Appendix C lists the essential records and sets the rules for handling them. Two features of Appendix C surprise experienced staff.

The list is risk-proportionate. Appendix C frames its table conditionally: if these records are produced, they are essential and should be retained. A record your trial never generated is not missing. What your site must be able to do is explain why it does not exist.

"Trial master file" and "investigator site file" are names, not requirements. Appendix C says the essential records should be held in repositories by the sponsor and by the investigator or institution, and that these repositories may be referred to as a trial master file, or in the site's case an investigator site file. The requirement is the records and the repository, not the label.

What your site holds

The site's collection, commonly called the investigator site file or regulatory binder, normally includes:

Investigator and staff records

• Signed and dated curricula vitae for the investigator and key staff.
• Current professional licenses or registrations where the role requires one.
• Good Clinical Practice and protocol training records.
• The delegation of authority log.
• Financial disclosure forms where required.

Ethics committee records

• The initial approval, and approvals of every amendment and consent form version.
• Continuing review approvals.
• Correspondence, acknowledgments and any conditions attached to approval.
• The committee's membership list, where the sponsor requires it.

Sponsor-provided records

• The protocol and every amendment, with superseded versions clearly marked.
• The Investigator's Brochure and its updates.
• Laboratory, pharmacy, imaging and other study manuals.
• Safety letters and periodic safety reports, with evidence the investigator reviewed them.

Site-specific records

• The signed clinical trial agreement.
• Laboratory accreditation and current normal reference ranges.
• Equipment calibration and maintenance records.
• Site standard operating procedures, where filed.

Operational records

• Screening and enrollment logs.
• The participant identification list linking codes to names, held securely at the site.
• Investigational product accountability and temperature records.
• Monitoring visit records and correspondence.

The rules Appendix C sets

A few requirements are worth knowing precisely.

• Version control and attribution. Records should be identifiable and version controlled where appropriate, and should show authors, reviewers and approvers as appropriate, with date and signature where necessary.
• A record of where records are. The sponsor and the investigator or institution should each maintain a record of where essential records are located, including source records.
• Readability and access. Records must remain complete, readable and readily available, and be directly accessible on request by regulatory authorities, monitors and auditors. Any alteration to an essential record must be traceable.
• Certified copies. A copy may permanently replace an original only if it meets the definition of a certified copy: verified by a dated signature, or generated through a validated process, to hold the same information as the original, including relevant metadata. An unverified scan is not a certified copy, so you may not scan and shred on that basis alone.

How long to keep them

ICH E6(R3) states no retention period in years. Section 3.16.3 requires the sponsor to inform the investigator, institution and relevant service providers in writing of the retention requirements, and to notify them in writing when records are no longer needed. Section 2.12.12 requires the site to retain essential records for the period required by applicable regulation, or until the sponsor says they are no longer needed, whichever is longer.

So the answer to "how long do we keep this?" is never a number you remember from another study. It is the written instruction from this sponsor, filed where the next person will find it.

Section 2.12.13 also requires the site to tell the sponsor who is responsible for maintaining the records during the retention period. Name a person and a role, not just a cupboard.

Keeping it current

The file is not built once. Four habits keep it usable.

1. Use a table of contents, and keep it accurate.
2. File as you go. A pile of loose documents "to be filed" is the normal state of a site heading for a finding.
3. Track expiry dates: licenses, training, laboratory accreditation, ethics approvals.
4. Review the file at every monitoring visit, not only at start-up and close-out.

In practice

At Northside Clinic, Nadia is asked by an auditor for the approval covering consent form version 3.0, which was used between March and September.

She finds the approval letter, the version-control table showing the dates the version was in use, and the training record showing the staff were trained on it before it was used. It takes four minutes.

The auditor then asks whether the site still holds the paper originals of the signed consent forms, since scans exist in the electronic system. Nadia checks the sponsor's written instruction rather than guessing. The scans were generated through the institution's validated process and meet the certified copy definition, but the sponsor's instruction is to retain the paper as well. The paper stays.

Finally the auditor asks how long the site will keep everything. Nadia produces the sponsor's written retention instruction and the name of the institution's records manager responsible for the archive.

Every one of those answers existed before the auditor asked. That is what a maintained file is.

Key takeaways

• ICH E6(R3) uses the term "essential records" and includes data and relevant metadata, not only signed documents.
• Appendix C is risk-proportionate: a record a trial never produced is not missing, but the site must be able to explain why it does not exist.
• "Trial master file" and "investigator site file" are permitted names for the repositories, not the guideline's requirement in themselves.
• A copy may replace an original only if it is a certified copy, verified by dated signature or generated through a validated process, including relevant metadata.
• E6(R3) sets no retention period in years; the sponsor must state the requirement in writing, and the site retains records for that period or until told otherwise, whichever is longer.