The ICH GCP Guidelines define Essential Documents as those documents which individually and collectively permit evaluation of the conduct of a trial and the quality of data produced. These documents serve to demonstrate compliance with standards of Good Clinical Practice and with all applicable regulatory requirements. Filing essential documents in a timely manner can greatly assist in the successful management of a clinical trial.
The Regulatory Binder is often the first document reviewed during audits and inspections. Not all the essential documents are available at the start of the study. Documents can be grouped into those that are generated before study initiation, those that are generated during trial conduct and those that are generated after study completion.
Not all documents have to be filed in one single binder. The Regulatory Binder may sometimes consist of several binders that are stored in the same or different locations. It is important to know where all these documents are located to be able to pull them out when needed in a timely manner. The Regulatory Binder is referred to synonymously as the Study Files, Investigator Files or Investigator Binder.
Organizing Your Regulatory Binder
Instructions: Create tabs for each section listed below and place the appropriate documents in each corresponding section in a binder. Be sure to label the outside of the binder (cover and spine) with the protocol number, PI name, and study site. Use multiple binders or master binders to maintain documentation if needed.
Anytime information is kept in a master binder, place a note to file (in the section of the Binder) referencing the location of the separate binder.
1. Site Visit (Monitoring) Log
This provides documentation at the site that the study was monitored and the frequency of monitoring. The monitor and designated site staff both sign the log to verify the date the monitor was present. For consecutive days, each day is entered separately.
2. Delegation of Authority (Responsibilities) Log
This log documents responsibilites assigned to research team members and their dates of involvement in the project. It helps ensure the appropriate delegation of study related tasks.
3. Site Personnel Signature Log
This documents the names and provides handwriting samples of all personnel involved in the conduct of the study
4. Study Personnel Education
All personnel involved in research with human subjects are required to complete the following:
Human Subject Protection Training
When adding personnel to the study, they must complete all of the above and their addition must be IRB approved prior to participating in the study.
4.1 Training Log
This is a record of training provided, e.g. protocol training or other study-specific training of staff. This should include a site initiation visit (SIV) attendance log.
5. CVs/Financial Disclosures/Investigator Statements
This section should include:
Curricula Vitae, licenses, and certifications for all study staff
Disclosure information, including each Study Specific Disclosure form submitted to the IRB.
FDA Form 1572 (if applicable): Date and sign all versions
FDA Form 1571 (if applicable): for Investigator initiated INDs
Signed investigator agreement (if applicable): for device studies
6. Public Registration of Research Studies (PRS) (If applicable)
All research studies that are applicable clinical trial must be registered at www.clinicaltrials.gov as per the International Committee of Medical Journal Editors (ICMJE), the FDA Amendment Act of 2007, and institutional policy.
Contact the Georgetown PRS Administrator, Patricia Mazar at email@example.com to set up a PRS user account.
Note: For commercially funded, multi-center studies, public registration is typically handled by the study sponsor or CRO.
Place the registration receipt in this section for initial registration and for any updates.
This section should include a log of subjects who were screened (and reason for screen failure) and enrolled. Some studies allow for re-screening of subjects.
This log tracks all enrolled subjects’ visits, reason for early termination and keeps visits scheduled as per protocol.
9. Subject Identification Code List
This is a confidential list of the names of all the subjects that provides a link between their identity and their study code to allow the Investigator to reveal the identity of any subject, if necessary.
10. Consent Forms
This section should include consent form document(s) (all IRB approved and stamped versions) stored in reverse chronological order with the current approved version first.
Place most currently approved consent form in a plastic sleeve
Note: Any changes to the consent form must be submitted to and approved by the IRB prior to use. Submit consent amendments through eRIC.
Guidance for consent of Non-English speaking subjects can be found here.
10.1 HIPAA Forms
(Authorization, Waiver, and/or Research Preparation Purposes)
This section includes all IRB approved and stamped versions of any of the HIPAA forms (as applicable).
This section should include the protocol (and protocol signature page) and all amendments (and amendment signature page or pages), stored in reverse chronological order with the current approved version first.
Note: Any changes to the protocol must be submitted to and approved by the IRB prior to implementation. Submit amendments through eRIC.
12. IRB Federal Wide Assurance Letter
This section should contain the most current IRB assurance letter
13. IRB Approval(s) /Communication
This section should include copies of the original IRB application/submission, IRB approval letters (contingent and final approval), and all correspondence with the IRB (including emails).
It includes IRB Membership Rosters, Continuing Review Submissions, protocol modifications and DSMB reports and close-out (final study) reports.
Contact the IRB for a copy of any missing documents.
14. Investigational Product Information (as applicable)
Investigator’s Brochure (IB)
This section must include all versions of the IB (may be maintained separately with note in section explaining location of IB) and receipt forms.
Evidence of IRB submission and review of all versions must be maintained.
For FDA approved agents, file a copy of the package insert.
Fo device studies this section should have a device information sheet/manual.
15. Study Termination
If your research study is being terminated or if the PI is leaving and the study will no longer be continued, inform the IRB through eRIC.
16. Protocol Deviations/Protocol Exceptions
This section should include correspondence relevant to the issue and copies of the documents stored in reverse chronological order with the most current documents first.
Please note that some Sponsor approved waivers may need to be approved by the IRB prior to implementation.
GU IRB Manual-Policy on Reporting Protocol Deviations
CAPA Template (Corrective Action and Prevention Plan)
17. Adverse Events and Unanticipated Problems
This section should include correspondence, copies and acknowledgements of reports for internal AEs and unanticipated problems reported to the IRB and Sponsor and regulatory authorities as applicable.
AE/SAE Log: Adverse events encompass both physical and psychological harms. They can occur in the context of medical, behavioral and social research.
Unanticipated Problem Log: Click here for examples of unanticipated problems that do not involve adverse events.
GU IRB Manual-Policy on Reporting Adverse Events and Unanticipated Problems
Submit reportable events through eRIC.
18. IND Safety Reports
This section should include correspondence (including IRB acknowledgement) and copies of Safety Reports for external AEs reported to the IRB.
19. Advertising/Educational Materials (if applicable)
This section should include: Any IRB approved advertisements, recruitment flyers, written educational, or other materials provided to study participants, stored in reverse chronological order with the most current documents first.
Note: For marketing materials used to recruit through mass media (e.g. newspaper, TV, radio, some internet postings, & etc.) you must contact the Georgetown University Medical Center Communications Office to ensure logo/branding is appropriate.
20. Sample Tracking and Shipping (if applicable)
This section should include a master log that allows tracking of research specimen sample collection, shipment (or transport), and storage, and packing and shipping training certification (from Saf-T-Pak or other approved equivalent program).
Shippers or receipts can be placed in this section or in individual subject files.
Note: All biological materials must be handled, stored, and shipped in compliance with FAA and IATA regulations as well as GUMC policies on hazardous materials.
21. Temperature Logs for Refrigerator/Freezer
Temperature logs document compliance with Protocol /Study Procedures requirements and GCP.
22. Investigational/Test Article
This section includes:
Shipment records (usually requires site signature of receipt and Sponsor notification of receipt)
Site Accountability Records (inventory of overall supply of drug/device, promps reordering of supply)
Subject Drug Accountability Records/Device Log (documents the date and quantity of drug/device dispensed to subject and return of drug/device from subject
Blind Break Instructions (instructions for revealing the identity of the treatment, if blinded)
Interactive Voice Response System Instructions (IVRS), if applicable
**Maintain drug accountability in the Research Pharmacy over the course of the study; at the trial completion file all records here.
23. Local Lab Certificates/Reference Ranges
For every lab listed on FDA Form 1572, place a copy of (maintain current certifications for duration of study):
Lab certificate(s) and reference ranges (for the duration of study)
Lab director’s CV
Note: The above is not required for research labs that perform testing where results will not be shared with subjects or their treatment providers.
For studies that use MedStar/Georgetown University Hospital Laboratories, click HERE
Please document and maintain all relevant, significant communication from the sponsor, the CRO or monitor in this section. Study related Newsletters may be placed in this section.
25. Blank Set of Case Report Forms
26. Notes To File (NTF)
These may include site generated and/or sponsor generated notes to file. Sponsor generated NTF may be global or site specific.
27. Other Documents
Other necessary approvals (e.g. Radiation Safety Committee)
Place other important study documents in this section. This can include: Certificates of Confidentiality, literature or publications, correspondence from the FDA or NIH, and other general correspondence.
28. Additional Tools
We’d like to hear from you. If you have suggestions, comments, or questions about this regulatory binder, please contact Bronwyn Murray at firstname.lastname@example.org or at 202-687-1350.