Regulatory Science Symposium: “Keys to a Clinical Trial: Management and Operations” Session 3 - Ensuring Documentation and Regulatory Compliance in the Evolving Landscape of Clinical Trials (2024)

Competencies: Pharmacy, Regulatory Science, Clinical Trials, GCP, Clinical Trials, Regulatory and Quality Sciences, Policies and Procedures, Clinical Trial Workforce

Course Syllabus/Topics:

1. Agenda
2. Good Clinical Practices
1. Clinical Trial Documentation and Compliance
1. Must capture all events happening outside of the norm, and all schedule activities are documented in the case of audits.
2. If you didn’t document it…. it didn’t happen!
3. Reference model for “trial master files” available - to be used by sponsors and sites
3. Key Reading: Good Clinical Practices (GCP)
1. Goal of documentation to reconstruct clinical trial and how it was conducted
2. Emphasis on documentation and how it should be stored.
4. Essential Documents and Records
1. Essential Documents are those that individually and collectively permit evaluation of the conduct of a trial and the quality of the data produced.
1. Referred to as “inspectable files.”
2. ICH E6(R2/3) Good Clinical Practices – Essential Documents and Records
1. ICH E6 lists the minimum inventory of essential documents
2. ICH E6(R3) replaces the word “document” with “record” to account for the move away from paper documents.
3. Records should be identifiable, and version controlled, and should include authors, reviewers and approvers as appropriate, along with date and signature (electronic or wet ink) where necessary.
4. Arrangements should be made for transfer of access or management of essential records throughout the trial and retention following completion in the event of transferred or delegates activities by sponsor or investigator/institution.
5. Essential records should be maintained in or referred to from repositories, such as in the trial master file (TMF) or investigator site file (ISF).
5. US Financial Disclosure in Clinical Trials
1. FDA Form 3455 - for financial disclosures pertinent to the clinical trial
6. ICH Essential Documents
1. Form ICH e6 (R3) provides a lot of guidelines related to essential documents
1. Appendix C Table 1
2. During the trial the following source documents are also essential documents and must be located at the site
1. Signed consent forms
2. Screening/enrollment logs
3. Case report forms
4. Adverse Event/Serious Adverse Event forms and documentation
5. Drug accountability
7. Case Report Forms (CRFs)
1. Records all protocol required information.
2. Investigator should ensure accuracy, completeness, and timelines of data reported to sponsor in CRFs and in all required reports.
3. data reported should be consistent with the source documents (discrepancies should be explained)
8. Monitoring Case Report Forms
1. Checking accuracy and completeness of CRF entries, source documents, and other trial-related records against each other.
9. Source Documents/Records
1. Defined in ICH E6(R2)/GCPs as “original documents, data and records.”
2. ICH E6(R3): Assess whether systems, if identified as containing source records for the trial, are fit for purpose or whether issues can be appropriately mitigated
10. Trial Master Files (TMF)/eTMF
1. Established at beginning of the trial
2. Provide structure on how sites are maintained
3. Referenced in ICH E6 GCPs under “Essential Documents”
4. No specific US FDA reference other than GCPs but it is the industry standard for clinical trial documentation
5. Defines document types, called “artifacts,” which one would expect to find in a TMF, at both Sponsor and Investigator Site. Organized by Zones, then grouped together.
6. More on the TMF Reference Model can be found at https://tmfrefmodel.com
11. TMF vs ISF
1. Site TMF = Investigator Study File (ISF)
2. Open source and free from Veeva (not an endorsement)
12. Good Documentation Practices
1. Essential part of all Quality Managements systems
2. Consists of correct, complete, current and consistent information that meets regulatory and industry requirements
13. Conclusions
1. Good documentation can help ensure data integrity and regulatory compliance
2. Data integrity and regulatory compliance are the goal of good clinical trial management
3. Honor participants of the trial
4. They protect trial participants and advance medical product research, development and innovation
5. Allows research to be translatable
14. Questions and Comments
    

Acknowledgements
Accompanying text created by:
Roxy Terteryan, RKS Project Administrator, SC CTSI (atertery@usc.edu)
Nikhita Datar, Student Worker