International Research & Research Involving Children

1. International Research &Research Involving Children K. Lynn Cates, MD Assistant Chief Research & Development Officer Office of Research & Development Department of Veterans Affairs

2. International Research • All subjects must be provided appropriate protections in accord with those given to subjects in the U.S. • Research must reflect understanding and respect for the community, the group, the culture, and the environment

3. International Research • VHA Directive 2005-050, “Requirements for Conducting VA-Approved International Research Involving Human Subjects, Human Biological Specimens, or Human Data,” Nov. 4, 2005 • “…requires permission be granted by the Chief Research and Development Officer (CRADO), or designee, prior to initiating or conducting Department of Veterans Affairs (VA)-approved international research involving human subjects, human biological specimens, or human data.”

4. International ResearchDefinition of “International Research” • “…any VA-approved human subjects research conducted at international sites (not within the United States (U.S.), its territories, or Commonwealths) or any VA–approved research using either human biological specimens or human data originating from international sites.”

5. International ResearchMulti-site Studies • Covered only if • VA is the sponsor • VA functions as the coordinating center • VA subcontracts to a foreign site • The PI for the total project is a VA investigator

6. International ResearchMedical Center Director’s Responsibilities • Approving the PI’s request for permission to conduct international research before it is sent to the CRADO for action • Providing a memorandum to the CRADO indicating he/she approves the study • Ensuring permission has been obtained from the CRADO before the PI initiates the project

7. International ResearchInvestigator’s Responsibilities • Conducting research in compliance with all applicable VHA and other Federal regulations and policies • Obtaining permission from the CRADO • Reporting all unexpected or adverse events

8. International ResearchRequests for CRADO Permission • Cooperative Studies Program (CSP) • ORD Director of Clinical Science Research & Development will request permission after the CSP review process • VA Merit Review funding • PI to submit required information with proposal • Research projects NOT submitted for VA Merit Review funding • PI to submit required information through ACOS/R&D

9. International ResearchRequired Information - Proposal • Rationale for conducting research at an international site(s) including • Why it cannot be conducted in U.S. • If partnership, rationale for partnership & benefits to the VA and U.S. veteran population

10. International ResearchRequired Information - Proposal • Information on Human Studies • Risks to subjects • Human subjects involvement & characteristics • Sources of materials • Potential risks • Adequacy of protection from risks • Recruitment & informed consent • Protection against risk • Potential benefit of proposed research to subject & others • Importance of knowledge to be gained

11. International ResearchRequired Information - Proposal • Qualifications of investigators to conduct this research

12. International ResearchRequired Information - Other • Financial arrangements • Funding source • Payment to subjects • Financial arrangements involving research sites & local investigators • Discussion of each site • Foreign investigator • Location • Facility where research will be conducted

13. International ResearchRequired Information - Other • Ethical principles governing research in each location • Research assurances at international site(s) • Copy of approvals required by foreign country & institution • Information on how U.S. VA IRB of record & foreign IRB decisions will be communicated & reconciled

14. International ResearchRequired Information - Other • Information on VA’s liability • Plan for oversight of research, including by any foreign country or entity • Frequency & content of monitoring reports • VA IRB & R&D Committee minutes • All IRB-approved informed consent forms • If children involved, CRADO waiver

15. International ResearchRequired Information – Just-in-Time • May be submitted during just-in-time process • Foreign approvals • VA IRB minutes • VA R&D Committee minutes • All IRB-approved informed consent forms

16. International ResearchONLY Human Biological Specimens or Data Derived from Persons • Prior list of requirements • Identify sources of research material • From individually identifiable living human subjects as specimens, records, or data • About deceased individuals or material that is de-identified

17. International ResearchONLY Human Biological Specimens or Data Derived from Persons • If material obtained for research purposes • Copy of approval by research ethics committee • Copy of consent under which it was collected • If material will be, or has been, collected for non-research purposes • Reason for collection • Applicable ethics review committee approvals to use material for research purposes • Copy of research ethics committee approval • Copy of consent under which material was collected (in English & information on language used)

18. Research Involving Children

19. Research Involving Children • VA is authorized to care for veterans and to conduct research that supports the mission of VHA and enhances the quality of health care delivery to veterans • Most VA facilities do not care for children • Most VA staff and IRB members do not have sufficient expertise in pediatrics and pediatric research to ensure the safety of children participating in research

20. Research Involving Children “…research involving children must not be conducted by VA investigators while on official duty or at VA or approved off-site facilities unless a waiver has been granted by the Chief Research and Development Officer.” VHA Handbook 1200.5, Appendix D, 7

21. Research Involving Children “If the waiver is granted, the research must be in accordance with applicable Federal regulations pertaining to children as research subjects (see 45 CFR Part 46, Subpart D…).” VHA Handbook 1200.5, Appendix D, 7

22. Research Involving ChildrenDefinition of “Child” Any person who has not attained the legal age for consent to treatments or procedures involved in the research under the applicable laws of the jurisdiction in which the research will be conducted

23. Research Involving ChildrenRequirements for Requesting a Waiver • VHA Directive 2001-028, “Research Involving Children,” April 27, 2001 Expired April 30, 2006, but still relevant

24. Research Involving ChildrenCriteria for a Waiver • The study must • Represent no greater than minimal risk • Meet all requirements in 45 CFR 46, Subpart D, “Additional DHHS Protections for Children Involved as Subjects in Research” • The IRB reviewing the study must have • Appropriate membership to represent children’s interests and pediatric expertise • Specific policies and procedures regarding children in research

25. Research Involving ChildrenCriteria for a Waiver • The medical center Director must certify that the facility is able to respond to pediatric emergencies • If a contractor and/or a non-VA employee conducts the research, the facility must make certain that the individual, or entity performing the research, has procured appropriate liability insurance

26. Research Involving ChildrenORD Requirements to Consider Waiver • Letter from medical center Director – must include relevance to veterans • Study protocol • Informed consent form • Assent document • IRB minutes • Should reflect discussion regarding level of risk, the consent and assent forms, the investigators’ qualifications to conduct research involving children, and any additional safeguards incorporated into the protocol • R&D Committee minutes

27. CRADO Waivers for International Research & Research Involving Children For more information contact Lynn Cates lynn.cates@va.gov 202-254-0282 Brenda Cuccherini brenda.cuccherini@va.gov 202-254-0277