International Research

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 VAapproved 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 Directors
Responsibilities

• Approving the PIs 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 ResearchInvestigators
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/RD

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 VAs liability
• Plan for oversight of research, including by any
  foreign country or entity
• Frequency content of monitoring reports
• VA IRB RD 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 RD 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 childrens
  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
• RD Committee minutes

27
CRADO Waivers for International Research
Research Involving Children

• For more information contact
• Lynn Cates
• lynn.cates_at_va.gov
• 202-254-0282
• Brenda Cuccherini
• brenda.cuccherini_at_va.gov
• 202-254-0277