International Research

Introduction

When conducting international research, additional review and documentation is required from both the international site and the Pitt IRB. It is imperative that you start the process early and request a consultation with the IRB staff during the initial planning stages.  If the PI is a student, we highly recommend that both the faculty mentor and student PI meet with the IRB staff consultant.

When is IRB review required?

All human subjects research conducted by University of Pittsburgh faculty, staff, or students, regardless of funding source or the location at which the research will be conducted, requires submission to the Pitt IRB.

What additional regulatory reviews are needed?

When research is conducted outside the United States, investigators must comply both with the U.S. regulations and with the local policies and regulations governing the international research sites. It is important to do your homework early and, if possible, enlist a local collaborator to help you address that site’s requirements and assist in identifying who to contact and what is required to obtain ethics reviews and permissions to conduct research at that international site.

Definitions

Minimal risk: the probability and magnitude of physical or psychological harm anticipated in the research are not greater in and of themselves than those ordinarily encountered in daily life, or in routine medical, dental, or psychological examinations.

Greater than minimal risk: the research involves more than minimal risk to subjects.

Cultural appropriateness: Sensitivity and awareness of how other ethnic, racial, and/or linguistic groups differ from one's own. Sensitivity can be manifested through knowledge of different languages or manners of speech, norms, and mores, religious beliefs and practices, family structures and dynamics, community decision-making patterns, and class consciousness and socioeconomic realities.

Federal Wide Assurance (FWA): an assurance of compliance with the U.S. federal regulations for the protection of human subjects in research. It is approved by the Office for Human Research Protections (OHRP) for all human subjects research conducted or supported by the U.S. Department of Health and Human Services (HHS).

Ethics committee: a committee that has been formally designated to approve, monitor and review biomedical and behavioral research involving humans. May also be referred to as an Institutional Review Board (IRB), an Independent Ethics Committee (IEC), an Ethical Review Board ERB) or Research Ethics Board (REB).

What is required for Minimal Risk studies?

Depending on the international site, local ethics committee review may not be required. It is the responsibility of the PI to contact the appropriate entity who will make that determination and obtain written documentation that review is not required. However, even if local ethics committee review is not required, additional documentation will be required to assess the cultural appropriateness of the proposed research and activities to be performed.

Two documents are required for studies where international regulations do not require local ethics review
  1. Memo of Cultural Appropriateness
    1. Authored by an individual completely independent of your study who is highly familiar with the culture of the region where the research will be conducted
    2. Required elements:
      1. Reference the title of the study displayed in the IRB application
      2. Describe the expertise of the individual preparing the letter to address the local cultural and social norms
      3. Confirm they understand the intent of the research and activities to be performed
      4. Confirm the planned study does not conflict with local and cultural norms
      5. Document is signed and dated
  2. Documentation that the local regulations do not require a local ethics review
    1. Providing direct references to the local regulations that state ethics review is not required; or
    2. Acknowledgement of Unregulated Research Activities letter confirming that local ethics review is not required
    3. Required elements:
      1. Provided on the official letterhead of the signatory
      2. Document is signed and dated
      3. Clearly state the planned research does not require local regulatory oversight
      4. Confirm the Regulatory Official understands the intent of the research and activities to be performed
      5. Reference the title of the study displayed in the IRB application
Required document for studies where international regulations do require local ethics review
  1. Letter of Approval from an Ethics Committee
    1. Required elements:
      1. Reference the title of the study displayed in the IRB application
      2. Clearly state the research study was designated Minimal Risk by the committee
      3. Clearly state the planned research was reviewed and approved
      4. Document is signed and dated
      5. Provided on the official letterhead of the signatory

What is required for Greater than Minimal Risk studies?

Studies that are designated as greater than minimal risk require a formal ethics review within the country where the research will be conducted.  Not all countries have an ethics review committee and the oversight may be addressed by the Department of Ministries or other governmental entities.  This is why it is important to collaborate with local individuals early in the planning process so they can assist you in identifying the proper mechanism to obtain the approval.

  1. Letter of Approval from an Ethics Committee
    1. Required elements:
      1. Reference the title of the study displayed in the IRB application
      2. Clearly state the planned research was reviewed and approved
      3. Document is signed and dated
      4. Provided on the official letterhead of the signatory

When are site permissions required?

When research is conducted at any site other than Pitt or UPMC facilities, an authorized individual from the proposed research site must provide written permission that the research can be conducted.

  1. Site permission letter from authorized individual
    1. Required elements:
      1. Reference the title of the study displayed in the IRB application
      2. The document is signed and dated
      3. Confirm the authorized individual understands the intent of the research and activities to be performed

Why is it important to have a local collaborator and knowledge of the local culture?

Investigators are strongly encouraged to collaborate with an individual or organization with expertise in the region. This collaboration will greatly assist in identifying appropriate research sites, navigating the local regulations and policies, understanding culture, local infrastructure, overcoming language barriers & increasing community partnership.

Based upon study location and risk level, the IRB may require a local site collaborator.

What are the additional requirements for enrolling non-English speaking participants?

When enrolling non-English speaking research subjects, investigators must have a plan to manage communications with participants during all phases of study participation. Given that participants may have questions or concerns at any time, Investigators must be prepared to manage communication beyond the consent process and data collection.

The initial Pitt IRB submission should only include the English version of documents that will be used with research subjects, (recruitment materials, consent documents, data collection materials, etc.). Once the materials are approved both by the Pitt IRB and foreign Ethics Committee, the approved documents should be submitted to a translator. Once translated, a Modification must be submitted to and approved by the Pitt IRB to provide the final English language documents, final translated documents, back translations (if required) and a signed translator certification form. The documents may not be used until this Modification is approved.

For more detailed guidance, please see: Non-English Speaking Participants.

What additional information must I provide in my IRB application if I want to compensate participants in foreign countries?

If the laws and regulations of the foreign country permit research participants to receive monetary compensation for their time, item 6.2 of the OSIRIS application must describe the planned amount of compensation in both US and foreign currency. To prevent undue influence from inappropriately high levels of compensation, information regarding the average daily wage in the country must also be provided. 

Note: The University has additional policies and procedures, not overseen by the IRB, dictating how participant payments in foreign countries are implemented. For more information on the topic of compensation outside of the U.S. visit the University of Pittsburgh Global Operations website.

Why is it important to start the process early?

Now that you have a good understanding of the required review and documentation process, you can see that research in some areas of the world can require a significant timeline to accomplish.  Investigators’ most common mistake when implementing international research is not allowing a realistic amount of time for protocol development and regulatory reviews.

When developing project timelines, Investigators should consider issues such as the stability of local government and infrastructure, time differences between countries, availability of communication technology in the foreign location, responsiveness of foreign offices, cultural differences within professional organizations and how frequently regulatory bodies convene.

Specific travel plans and the purchasing of plane tickets should not occur until all of the required reviews and approvals have been obtained.

Can I submit to the Pitt IRB before I have ethics approval from my international site?

You are permitted to submit to the Pitt IRB before foreign ethics approval is granted. In these cases, the Pitt IRB approval letter will state no research activities may begin until a Modification is submitted to and approved by the Pitt IRB, providing documentation of foreign ethics approval.

How far in advance should I submit my international application to the Pitt IRB?

Minimal Risk applications should be submitted to the Pitt IRB a minimum of 2 months prior to Investigator approval deadlines. Submission 3 months prior is highly encouraged.

For Greater Than Minimal Risk applications the location and topic of the research may require the Pitt IRB to employ a foreign consultant with the appropriate expertise to assist in the ethical review. Locating and enlisting the assistance of consultants may make the review process take significantly longer. So, it is crucial to allow a sufficient time for IRB review.

Do foreign research regulations greatly differ from those of the U.S.?

There is a high level of variability in the procedural details across international research regulations. However, the majority of foreign regulations are based upon the foundational ethical guidelines provided within the International Conference of Harmonization (ICH) and the Council for International Organizations of Medical Sciences (CIOMS).

Where can I locate information on foreign research regulations for the specific country where I plan to conduct research?

Investigators can begin to educate themselves about applicable foreign research regulations, by specific country, using the resources below:

How can I locate a Foreign Ethics Committee to provide review and approval of my study?
 

U.S. Federally funded research studies

Research studies supported by U.S. Federal funds are required to undergo foreign IRB review by an Ethics committee that holds a Federal Wide Assurance (FWA). 

Investigators of U.S. Federally funded research studies can search the OHRP “Database for Registered IORGs and IRBs, Approved FWAs and for Documents Received by OHRP in the Last 60 days” to locate foreign IRBs that hold an FWA:

Non-U.S. Federally funded research studies

Investigators of  Non-Federally funded research studies can search the OHRP “Database for Registered IORGs and IRBs, Approved FWAs and for Documents Received by OHRP in the Last 60 days” to locate a foreign oversight body:

 

Summary of Required Documents by Review Type

Additional University Policies Related to Conducting University Business Outside of the U.S.

When affiliates of the University of Pittsburgh are engaged in international projects there are additional University Policies and procedures that must be followed. For a summary of all University policies relating to international projects, please visit the University of Pittsburgh Global Operations website.

What information must I provide in my IRB application regarding the local site and culture?

It is imperative that investigators be fully informed about the local site and cultural context before submitting to the Pitt IRB. Below is the information you will be required to provide in your OSIRIS application regarding local sites and culture.

2.19  Will this research be conducted in (a) a foreign country and/or (b) at a site (e.g., Navajo Nation) where the cultural background of the   subject population differs substantially from that of Pittsburgh and its surrounding communities?

[It is the responsibility of the PI to ensure that copies of training records, licenses, certificates are maintained in the study regulatory binder which are subject to audit by the Research Conduct and Compliance Office (RCCO). In addition, the PI is also responsible for ensuring all members of the research team engaged in human subject research outside the United States must also complete the International Research course available on the CITI training website.]

2.19.1  Address the following for each of the foreign/culturally different sites where this research will be conducted:

  • Name of site
  • Name of authorized individual (e.g., IRB Chair) from the local IRB or other human subject protections entity that is responsible for the review and approval of the project; upload approval letter with an English translation, if applicable
  • Name and qualifications of the site collaborator responsible for the conduct of the research (e.g., site PI)
  • The anticipated number of subjects that will be enrolled at that site
  • If Federally funded, provide the Federal Wide Assurance number (FWA) assigned to the site

2.19.1.1 Provide a description of the context of cultural norms and local laws and highlight differences between U.S. culture in all areas relevant to your study, including, at a minimum:

  • Age of majority of participants to be enrolled
  • If study includes minors or decisionally impaired subjects, summarize laws on guardianship
  • If your study involves any invasive medical procedures (including blood draws), provide assurance that the individuals undertaking those procedures for research purposes are appropriately credentialed.
  • If your study involves the administration of a drug, device, or biologic for research purposes, describe the process for shipping, labeling, storing and dispensing, and indicate how these are consistent with all relevant local (and U.S.) laws, including those requiring import/export permits.
  • If your study involves collection of biologic specimens, describe the process for shipping, labeling, storing and using such samples.  Identify any special local consent requirements, and any special permits that may be required by local laws.

2.19.1.2  Describe any aspects of the local cultural, political or economic climate that might increase the risks of harm for either local participants or researchers. Describe the steps you will take to minimize these risks. UPitt Faculty, Staff, and Students must access the Travel Registry page. Go to my.pitt.edu and the link is displayed under My Resources.

2.19.2  Will all individuals being recruited to participate in this research study be able to read and comprehend English?

2.19.2.1  If translated documents are used, upload a Translator Certification Form certifying the accuracy of the translation

2.19.3  Will all of the research procedures described in this IRB application be conducted at the foreign/culturally different sites?

2.19.4  To what extent do the local site requirements to protect subject confidentiality and privacy differ from U.S. standards. If applicable, explain how those will be addressed by this research team

2.19.5  If the researcher is a student, describe how the student will communicate with the advisor during the conduct of the research and how the advisor will oversee the research

Additional Resources

Checklist for Exempt Research
Checklist for Non-Exempt Minimal Risk Research
Checklist for Greater than Minimal Risk Research