Regulatory Binder: Maintaining Essential Study Documentation 11/12/2018 Regulatory Binder: Maintaining Essential Study Documentation

Regulatory Binder Based on ICH-GCP defined Essential Documents and OHRA’s Recordkeeping/Retention requirements ICH-GCP: International Conference on Harmonization – Good Clinical Practice Best Practice Standard Provides a template for maintaining and organizing documentation to ensure compliance with federal regulations, institutional policies, and good clinical practice Alternatives are acceptable. You can create your own way of organizing the required documentation in a way that works best for you and your study team. BE CONSISTENT!

Electronic Regulatory Binder (eBinder) The eBinders, developed in REDCap and Box.com, facilitate proper study management through electronic storage of study/regulatory documents and study management tools/logs. Instructions for institution-specific regulatory requirements, best practice recommendations, and GCP/Federal regulations are contained within each regulatory binder

Electronic Regulatory Binder (eBinder) The eBinders allows you to: Quickly download a custom template or utilize QIP’s template to customize your own binder to fit your study needs. Maintain regulatory documents for one or multiple studies. Securely share its contents with local and international study team members. How to access the binders: https://www.hsph.harvard.edu/ohra/quality-improvement-program-qip/study-management-tools/regulatory-binder/ Contains instructions for accessing our eBinder templates in REDCap and Box.com. Contact Stanley Estime to obtain access to the Box Template or if you have difficulty accessing REDCap’s eBinder.

Regulatory Binder Sections All Studies Study Specific Licensure Investigator Brochure/ Device Manual/ Package Insert Laboratory Documentation Drug/Device NIH Sponsor DSMB External/Local Ethical Review Protocol CVs for all study staff Logs IRB Documentation Consent and Recruitment Materials Data Collection Materials Training Data Protection

Essential Documents (all studies) Section Purpose Considerations / Recommendations Protocol Demonstrates investigator and/or sponsor agreement to the study aims, research design, research site(s), and all procedures, particularly those that involve human subjects. Ensure that the version number/date reflects the current, approved Research Protocol approved by the IRB. CVs and licensures Documents the qualifications and expertise of study staff to perform delegated tasks. CVs and licenses should be updated every 2 years to confirm that the information is current and accurate. CVs should be signed and dated Maintain licensure for staff conducting clinical study- related procedures

Essential Documents (all studies) Section Purpose Considerations / Recommendations Logs Assists with the collection of data that is required by or reported to the IRB or other regulatory authorities (e.g., Enrollment Log, Delegation of Responsibility Log). Information in QIP log templates can be customized to fit a specific study. IRB Documentation Demonstrates that the IRB has reviewed and approved the initial project and all modifications prior to the initiation of study procedures. Confirms that continuing review has been performed (as applicable) and that reportable new information has been communicated to the IRB. To simplify recordkeeping and avoid creating duplicate files, IRB documentation should be maintained in ESTR. Include a signed and dated note-to-file in the Regulatory Binder detailing the location of the documentation.

Essential Documents (all studies) Section Purpose Considerations / Recommendations Informed Consent Recruitment Material Documents that information given to participants supports their ability to give voluntary informed consent. Ensure that the most recently approved consent form and recruitment documents are used in the field. The most recently approved consent form and recruitment documents can always be accessed in ESTR. Data Collection Maintains original copies of all forms used to collect study data (e.g., case report forms, questionnaires, surveys). Only blank copies of forms should be kept in the Regulatory Binder. The most recently approved data collection forms can always be accessed in ESTR.

Essential Documents (all studies) Section Purpose Considerations / Recommendations Training Documents adequate human subjects training as well as any other study-specific training for all IRB approved study personnel. All study staff approved by the HLMA IRB must complete CITI human subjects training requirements every 3 years. Additional institution, department, or study-specific training requirements and time frames may vary (e.g., data security, laboratory safety). Data Protection Maintains documentation of data protection procedures not included in the Research Protocol, as well as specific records that may not be included in ESTR. For all documents maintained in ESTR, include a signed and dated note-to-file in the Regulatory Binder detailing the location of the documentation.

Participant Files Maintain participant files securely and separate from the Regulatory Binder Include original signed consent documents Depending on confidentiality provisions outlined in the Research Protocol, signed consent forms may be kept separate from the participant’s research data File completed data collection forms and source data Communication with participants As above, depending on confidentiality provisions outlined in the Research Protocol, communication that includes identifiers may be kept with signed consent documents and separate from research data

Single IRB and Multi-site Research 11/12/2018 Single IRB and Multi-site Research Include all institutional determinations and reliance agreements (SmartIRB or IRB Authorization Agreement and Institutional acknowledgments) in an External/Local Ethical Review file Regulatory documentation should reflect any reliance agreements The Overseeing IRB’s researchers should document up to date training and activities for all study staff that fall under the reviewing IRB’s oversight. Most reliance agreements allow for the reviewing institution to conduct an audit, for cause, of the ceding institution’s study documentation Regulatory documentation should still be kept at each institution to at least maintain site specific information. The protocol will determine how Participant Files should be maintained at each site.

Tips for Successful Record Keeping 11/12/2018 Tips for Successful Record Keeping Customize the Regulatory Binder to meet the specific criteria for your study Maintain binders in a secure location (e.g., locked file cabinet, password protected computer) Document and update materials in the Regulatory Binder in real time File hard copy documents in reverse chronological order (most recent on top)

Tips for Successful Record Keeping 11/12/2018 Tips for Successful Record Keeping Avoid maintaining duplicate records, particularly IRB documents (e.g., in ESTR, electronically on a shared drive, and hard copy in a paper-based Regulatory Binder) Review documentation routinely QIP recommends using the Investigator Self-Assessment as a guide when reviewing regulatory documentation Address and resolve documentation issues immediately upon discovery

Note-to-File A Note-to-File can reconcile many issues 11/12/2018 Note-to-File A Note-to-File can reconcile many issues When in doubt, write a note! Use to explain apparent discrepancies Use to identify location of files that are maintained outside of the Regulatory Binder (e.g., in electronic format on a shared drive or in ESTR) Each note-to-file should include the study number, PI name, date, and the initials of the person writing the note-to-file

Record Retention OHRA Policy: Maintain documentation for at least 7 years from study closure date The Regulatory Binder and study documents, including participant files, must be maintained securely and readily available to auditors Check with your sponsor to ensure compliance with their record retention policy

Resources OHRA web site Quality Improvement Program (QIP) web site 11/12/2018 Resources OHRA web site https://www.hsph.harvard.edu/ohra/ Quality Improvement Program (QIP) web site https://www.hsph.harvard.edu/ohra/qip/ QIP Study Management Tools - including Regulatory Binder tabs, Investigator Self-Assessment, and Note-to-File template https://www.hsph.harvard.edu/ohra/qip/study-management-tools/

OHRA Quality Improvement Program (QIP) Alyssa Speier, MS, CIP Associate Director, Office of Regulatory Affairs and Research Compliance aspeier@hsph.harvard.edu 617 432-2140 Lisa Gabel, CIP Senior QA/QI Specialist lgabel@hsph.harvard.edu 617 432-5842 Scott Meyers, CIP QA/QI Specialist scmeyers@hsph.harvard.edu 617 432-2143