Clinical Research Responsibilities for NIDCR-Funded Investigators

1. NIDCR CROMS Clinical Research Operations and Management Support Rho, Inc., Federal Division National Institute of Dental and Craniofacial Research National Institutes of Health Clinical Research Responsibilities for NIDCR-Funded Investigators V4.0 2013-02-28

2. Disclaimer • Note that this is a general slide presentation designed for a broad audience of clinical researchers. • Accordingly, some sections may not apply to your protocol. • Information that may not be applicable for all studies is indicated via blue italics.

3. Disclaimer • Examples include references to: • Investigational Product (IP), the Investigator’s Brochure (IB), or a study pharmacist • Safety reporting and adverse events • Randomization and unblinding procedures • Regulatory authorities • Clinical treatment (for a behavioral or study or a registry)

4. Basis for Research Roles and Responsibilities • Good Clinical Practice (GCP) Guidelines (ICH-E6) • Widely accepted international research standards • Title 45 Code of Federal Regulations (CFR) Part 46 • Applies to federally funded research • Federal regulations to protect human subjects • Subpart A: The Common Rule • IRB roles and responsibilities/Informed Consent

5. NIDCR Study Types • Clinical Trials involving a biomedical or behavioral intervention • Clinical Research Studies, including: • Observational • Specimen Collection • Epidemiology or Surveillance studies

6. Objectives To review keyroles and responsibilities of investigators and staff engaged in NIDCR-funded research • Human Subject Protection • Administrative and Regulatory Responsibilities • Research Planning and Considerations • Documentation and Record Keeping

7. Human Subject Protection:IRBs and the Informed Consent Process

8. The Institutional Review Board or Ethics Committee • Required for human subjects research supported by DHHS • Must register IRB with OHRP/File FWA • Applications can be submitted online • Commitment to comply with 45 CFR Part 46

9. IRB Requirements • Membership, functions, and operations • Initial and continuing review of research • Criteria for approval of research • Decisions regarding termination/suspension of study due to harm or noncompliance • Documentation and record keeping

10. IRB and Investigator Interactions • Know your IRB’s review schedule and process • Obtain/document IRB approval prior to initiating research • Obtain/document IRB approval prior to implementing any protocol amendments (administrative or otherwise) • Notify IRB regarding adverse events (AEs) and unanticipated problems (UPs) as required • Obtain and document IRB acknowledgement of study completion

11. The Consent Process • Obtain without coercion or undue influence • Language understood by subjects • Cannot contain language waiving subject’s legal rights • Cannot release institution from liability for negligence • Answer questions/allow time for consideration • Subjects must receive signed/dated copy of the consent document

12. Elements of Consent Document • Statement that the study involves research • Statement that participation is voluntary • Information about purpose, duration, and procedures • Number of subjects involved in the study • Description of risks, benefits, and alternatives • Information about compensation/care for injury • Statement regarding confidentiality of records

13. Elements of Consent Document (continued) • Description of possible unforeseen risks • Circumstances for termination without subject consent • Consequences of withdrawing from the study • Additional costs that may result from participation • Statement that new research findings will be shared • Contact information for questions/concerns

14. Special Provisions for Vulnerable Populations • Title 45 CFR Part 46; Subparts B, C, and D • Subpart B: Additional protections for pregnant women, human fetuses, and neonates • Subpart C: Additional protections for prisoners • Subpart D: Additional protections for children

15. Administrative and Regulatory Responsibilities

16. Administrative and Regulatory Responsibilities Investigators who are responsible for study conduct should: • Have appropriate education, experience, and training • Maintain current CV and credentials • Thoroughly understand and comply with the protocol • Comply with applicable regulations/GCP guidelines • Follow your institution’s HIPAA requirement policies • Permit monitoring by sponsors and their representatives

17. Administrative and Regulatory Responsibilities (continued) • Provide and document protocol, GCP/regulatory training • Maintain a delegation of responsibilities log • Maintain training records/log • Maintain screening and enrollment logs • Maintain subject code list • Maintain monitoring visit log • Create and maintain an investigator binder to store documentation and records

18. Research Planning and Considerations

19. Research Study Planning When designing and developing a study protocol, consider: • Time needed for the development of: • the protocol and consent document • additional documents such as the Manual of Procedures and Case Report Forms/Data Collection Tools • Recruitment and enrollment strategies for study population • Necessary time commitments for all investigators

20. Research Study Planning (continued) • Adequate ancillary staff support • Proper training of research staff • Available facilities and space • Time required for review of these items by NIDCR and the IRB

21. Protocol Adherence • Document investigators’ agreement to follow the protocol • NIDCR protocol template has sign-off page • Adhere to the IRB-approved protocol/protocol amendments • Only deviate from the protocol to avoid immediate hazards to subjects • Document and report all protocol deviations to the IRB

22. Adverse Event (AE) Reporting • Review protocol for reporting requirements • Notify subjects of care needed and provide referral • Actively monitor, ensure care for, and document AEs • Follow to resolution • Report AEs to the IRB/Safety Committee and comply with any specific guidance

23. Unanticipated Problem (UP) Reporting • Review protocol for reporting requirements • Train study team members on UP definition • Report UPs to the IRB/other oversight bodies specified by the protocol, and comply with any specific guidance • Actively monitor, ensure care for, and document UPs • Follow to resolution

24. Documentation and Record Keeping

25. Adequate Documentation, Record Keeping, and Retention • Permits evaluation of the conduct of a study • Permits evaluation of data collected • Demonstrates GCP and compliance with applicable regulatory requirements • Facilitates study management and oversight • Allows for monitoring and evaluation of practices

26. Documentation:Types of Essential Documents • IRB-approved protocols, consents, advertisements • IRB correspondence/approval letters • CVs/credentials for investigators • Staff training logs/records • Delegation of Responsibilities log • Screening/enrollment logs • Subject ID code lists • Signed consent documents and data collection forms • Monitoring visit log/visit reports

27. Monitoring • The Clinical Site Monitoring Plan will include: • Site Assessment • Site Initiation Meeting • Interim Monitoring Visits • Close-out Visit • Other monitoring may include: • Core lab • Data Coordinating Center / Data Management Center

28. Data Collection and Management • Describe how data will be collected and maintained • Development of a Data Management Plan • Development of a source document management process • Develop Case Report Forms (CRFs) or appropriate data collection tools • Maintain source documentation • Record data on study forms in a timely manner • Examples include interview forms, questionnaires, data collection forms, research chart (paper or electronic format)

29. Data Collection and Management(continued) • Ensure data is accurate, complete and legible • Data corrections should not obscure original entries • Implement data quality control procedures

30. Specimens • Includes (but is not limited to) collection, labeling, processing, storage, shipment, and tracking of specimens • Handling in accordance with the requirements of the protocol, MOP, IRB, and applicable regulations • Tracking of final disposition of samples at end of study

31. In Summary • 45 CFR 46 & ICH E6 GCP Provides Guidance and Standards for: • Rights, safety, and well-being of subjects • Roles and Responsibilities of Investigators and Research Staff • Study conduct and protocol management • Safety reporting • Documentation and Record Keeping

32. Questions?

33. Resources

34. NIDCR Resources Forms • NIDCR Investigator of Record Agreement • Delegation of Responsibilities Log • Training Log • Site Screening and Enrollment Log • Subject Code List • Adverse Event Forms • Monitoring Visit Log

35. NIDCR Resources (Continued) Training Presentations • Investigator Responsibilities (ICH & GCP) These resources and other tools are available through NIDCR’s Toolkit for Clinical Researchers: http://nidcr.nih.gov/research/toolkit