1.5 Requirements for Research Conducted with International Sites

1.0 Purpose

The purpose of this policy is to describe the Organization’s requirements for research conducted with international sites. For the purposes of this policy, “Research conducted with International Sites” (international research) is defined as (1) research conducted by a faculty member, staff, student, or other representative of the Organization at an international site, or (2) research conducted by external investigators under the direction of a faculty member, staff, student, or other representative of the Organization, or (3) research where an investigator receives identifiable private information or identifiable biospecimens from an international site.

2.0 Policy

It is the policy of the Organization that:

• 2.1. The PI assumes responsibility for the safe and proper conduct of the research in full compliance with all applicable U.S. regulations, country specific laws and regulations, local IRB (IEC, REB, REC) requirements and UNMC HRPP policies.

• 2.2. Non-exempt research conducted with an international site by the Organization’s faculty, staff, students, or other representative of the Organization, must be reviewed and approved by both the UNMC IRB, and by any local IRB at the international site which has review and oversight jurisdiction over the research. If there is no local IRB, an exception may be granted by the Institutional Official upon recommendation by the IRB Executive Chair.

• 2.3. Exempt research conducted at an international site by the Organization’s faculty, staff, students, or other representative of the Organization, requires review and approval by both the ORA, and by any local IRB or official which has review and oversight jurisdiction. If there is no local IRB or official which has review and oversight jurisdiction, an exception may be granted by the IRB Executive Chair/designee.

• 2.4. When reviewing research conducted entirely or in part in other countries, the IRB must have appropriate knowledge concerning the laws, regulations, guidance, and customs in that country either through the direct expertise by a member or by the use of consultants.

  Note: The IRB may utilize as a resource the latest edition of the “OHRP International Compilation of Human Research Standards” as well as the information provided by the investigator in Addendum T of the IRB application.

• 2.5. When conducting or participating in international research conducted entirely or in part in other countries, the investigator must have appropriate knowledge concerning the laws, regulations, guidance, and customs in that country either through the direct expertise or by the use of consultants.

• 2.6. Protections of human subjects at the international site must be at least equivalent to HHS regulations at 45 CFR 46

• 2.7. International research involving prisoners is not permitted.

3.0 Investigator Responsibilities

• 3.1. Non-Exempt International Research
  • 3.1.1. In order for the Organization’s faculty, students, staff, or other representatives to conduct non-exempt research with an international site, the following must be submitted to the IRB for review:
    • 3.1.1.1. The appropriate IRB application
    • 3.1.1.2. Addendum T: International Research
    • 3.1.1.3. A copy of the approval letter from the local IRB as required.
    • 3.1.1.4. A copy of the ICF approved by the local IRB which has been translated into English.
    • 3.1.1.5. A copy of the ICF approved by the local IRB in the native language.
    • 3.1.1.6. An agreement between the international site and the investigator and/or institution which specifies the responsibilities of the local IRB/REB which includes, but is not limited to, the following:
      • 3.1.1.6.1. Continuing review will be performed no less often than annually.
      • 3.1.1.6.2. Post approval monitoring as appropriate will be conducted at the site.
      • 3.1.1.6.3. Reports of complaints, serious or continuing noncompliance, protocol deviations, and unanticipated problems involving risk to the subject or others will be forwarded to the UNMC IRB.
      • 3.1.1.6.4. Reports of other serious problems in the conduct of the research will be forwarded to the UNMC IRB.
• 3.2. Exempt International Research
  • 3.2.1. In order for the Organization’s faculty, staff, students, staff, and other representatives to conduct exempt research with an international site, the following must be submitted to the ORA for review:
    • 3.2.1.1. The appropriate IRB application
    • 3.2.1.2. Addendum T: International Research
    • 3.2.1.3. A copy of the approval letter from the local IRB or authorized official
    • 3.2.1.4. A copy of the ICF approved by the local IRB (if a consent form is required) which has been translated into English.
    • 3.2.1.5. A copy of the ICF approved by the local IRB (if a consent form is required) in the native language.
• 3.3. When any international research involves the shipment of human biological materials, hazardous materials, or dangerous goods, the PI must comply with UNMC Hazardous Material/Dangerous Goods Shipping Plan. For more information contact the UNMC Biosafety Officer or the UNMC/Nebraska Medicine Department of Environmental Health & Safety, or the UNO Office of Research and Creative Activity (ORCA).
• 3.4. The PI must comply with UNMC policy 8005 (Export Control Policy) or with UNO Export Control policy. For more information contact the UNMC Export Control Office, the UNMC Chief Compliance Officer, or the UNO Office of Research and Creative Activity (ORCA).
• 3.5. The PI is responsible for ensuring all appropriate host country permissions to conduct research are in place (including as appropriate, institutional, governmental or ministerial, IRB or EC, local or tribal).

4.0 ORA Responsibilities

• 4.1. Non-Exempt International Research

  • 4.1.1. In addition to the criteria for approval under 45 CFR 46.111, when conducting its review, the IRB will consider whether:
    • 4.1.2.1. The PI and research personnel are qualified to conduct research in the specified country, including knowledge of relevant laws, regulations, guidance, and customs.
    • 4.1.2.2. The consent process and consent documents are appropriate for the languages of the subjects and communication with the subject population, and whether appropriate arrangements are considered to communicate with the subjects throughout the research.
    • 4.1.2.3. The PI has in place an adequate process for handling:
      • 4.1.2.3.1. Modifications to the research. The IRB and investigators should consider as many contingencies as possible when research is reviewed and approved.
      • 4.1.2.3.2. Complaints, noncompliance, protocol deviations, and unanticipated problems involving risk to subject or others.
      • 4.1.2.3.3. Post-approval monitoring of the research.
    • 4.1.2.4. There is an adequate mechanism for communication between the IRB and the PI and research personnel when they at the international site.
  • 4.1.3. The UNMC IRB will review the protocol in accordance with HRPP policies 2.2 (Full IRB Review) and HRPP 2.3 (Expedited Review).
  • 4.1.4. Written documentation of informed consent may be waived by the IRB if the subjects or legally authorized representatives are members of a distinct cultural group or community in which signing forms is not the norm, provided that the research presents no more than minimal risk of harm to subjects and there is an appropriate alternative mechanism for documenting informed consent was obtained (45 CFR 46.117(c)(1)(iii)).
  • 4.1.5. If a conflict arises between country specific laws/regulations and applicable US regulations, the IRB will consult with legal counsel (per HRPP policy 1.11 HRPP Access to Legal Counsel), other legal consultants, OHRP, and FDA as necessary.

• 4.2. Exempt International Research

  • 4.2.1. The ORA will review the protocol in accordance with HRPP policy 2.6 (Exempt Research).
  • 4.2.2. As appropriate, the ORA will consider whether:
    • 4.2.2.1. The PI and research personnel are qualified to conduct research in the specified country, including knowledge of relevant laws, regulations, guidance, and customs.
    • 4.1.2.2. If informed consent is required, the consent process and consent documents are appropriate for the languages of the subjects and communication with the subject population, and whether appropriate arrangements are considered to communicate with the subjects throughout the research.
    • 4.1.2.3. The PI has in place an adequate process for handling complaints, noncompliance, protocol deviations, and unanticipated problems involving risk to subject or others.
    • 4.1.2.4. There is an adequate mechanism for communication between the IRB and the PI and research personnel when they are at the international site.

• 4.3. If a conflict arises between country specific laws/regulations and applicable US regulations, the IRB will consult with legal counsel (per HRPP policy 1.11 HRPP Access to Legal Counsel), other legal consultants, OHRP, and FDA as necessary.

DOCUMENT HISTORY:

 Written: 1/13/2016 (Approved: 1/13/2016) - original author not recorded

 Revised: 2/9/2018 - revision not documented

 Revised: 12/8/2022 – revised title to stress international research includes work with international sites in addition to work at those sites; added specific definition to include research where an investigator receives or sends human biological or data from or to an international site; corrected reference to UNMC policy shipping of Hazardous Materials; corrected reference to Department of Environmental Health & Safety; added UNO policies; deleted requirement for formal reliance agreement (section 5.1.1.6); deleted references to sections effective after the revision of the Common Rule; revised section 2.3 so that exception may be granted by the Executive Chair rather than IO. {Approved Chris Kratochvil (Institutional Official), Bruce Gordon (Assistant Vice Chancellor for Regulatory Affairs, Executive Chair)}

 Board notified: 12/12/2022

 Revised 5/9/2023 – Revised definition of international research to remove sending human biological material or data; reformatted to separate investigator responsibilities and IRB/ORA responsibilities; clarified ORA responsibilities when considering exempt international research. {Approved Russell McCulloh (Institutional Official), Bruce Gordon (Assistant Vice Chancellor for Regulatory Affairs, Executive Chair)}