Special policies and procedures cover research activities conducted at sites located in foreign countries or culturally different domestic sites. This is particularly important when the domestic research is being conducted in an environment comprised largely of subjects who differ markedly from those in the greater Pittsburgh area because of differences in ethnicity or national origin (e.g., Hispanics, Russian Immigrants), religion (e.g., Old Order Mennonites or Amish), and/or customs and values (e.g., Native Americans).
These are activities conducted at sites that do not fall under the authority of the University of Pittsburgh IRB, and are not owned or operated by the University of Pittsburgh, UPMC, or affiliated institutions. More than one IRB may be responsible for these off-site research activities. Note that the Pittsburgh VA Medical Center and the CMU Brain Imaging Research Center are not considered to be off-site, and are not covered by these policies.
Special provisions reflect the regulatory mandate that IRBs must have sufficient knowledge of the local research context to ensure that (a) selection of subjects is equitable, (b) subject privacy is protected and confidentiality of data is maintained, (c) informed consent is sought in a language that is understandable to the subject and under conditions that minimize the possibility of undue influence, and (d) appropriate safeguards exist to protect the rights and welfare of vulnerable subjects [45 CFR 46.111(a)(3), (a)(4), (a)(7), (b), and 46.116]. The following policies pertain not only to non-exempt research conducted at sites outside of the U.S., but also to off-site research conducted within the U.S.
For any research activity conducted at a non-local domestic or international institution or site, the following must be addressed in the IRB protocol by the Pitt/UPMC investigator:
- name of the site
- the anticipated scope of the research activities to be conducted at the non-local institution or site;
- the types of subject populations likely to be involved and the languages spoken by them;
- the size and complexity of the institution or site where the research is being conducted;
- description of cultural norms and local laws which differ from the greater Pittsburgh area relevant to the research activities to be conducted;
- the methods for ensuring equitable selection of subjects;
- the methods for protecting subjects’ privacy;
- the methods for maintaining the confidentiality of the research data;
- the methods for minimizing the possibility of coercion or undue influence in seeking consent;
- the safeguards to protect the rights and welfare of vulnerable subjects;
- the FederalWide Assurance number assigned to the site if applicable;
- description of any licenses, permits, or other permissions necessary for the procedures to be performed at that site;
- either a letter of authorization to conduct the research at the facility or a signed statement of work.
If the site is engaged in research, the investigator must provide the qualifications of the principal investigator and co-investigators at each site, as well as the resources available to the research team at the specific location(s) where the research will be conducted, including but not limited to facility resources such as the testing and safety equipment available.. The site principal investigator is expected to maintain appropriate professional credentials and licensing privileges.
For research activities that involve more than minimal risk:
The research protocol must be accompanied by a letter from the chair of the local IRB or equivalent entity specifying that the local IRB or equivalent entity has determined that:
- The study complies with local laws and customs;
- The local facilities/resources are adequate;
- The local investigator and key personnel are appropriately qualified to conduct the study;
- Whether a local representative from the research site is required to participate during the University of Pittsburgh IRB review.
When the research activities involve greater than minimal risk to subjects and the investigators are interacting or intervening with subjects at the non-local site, the IRB has the following responsibilities:
Meeting minutes must document that the IRB has obtained appropriate information about the local research context through one or more of the following means:
- Personal knowledge of the local research context on the part of one or more IRB members, such knowledge having been obtained through extended, direct experience with the non-local research site, its subject populations, and its surrounding community;
- Participation by one or more appropriate consultants in the IRB Committee discussion of the research study, either physically or via teleconferencing;
- Prior written review of the proposed research by one or more appropriate consultants, with consultants available either in person or via teleconference to address questions, when needed, raised during the Committee meeting.
To ensure that these elements are included in the minutes, the research review coordinator will utilize the non-local research form.
The IRB must also include all of the following in the IRB records for this project:
- Written notification that the research study has been approved by an IRB or other human subject protections entity located at the site where the research is to be conducted;
- A letter from the chair of the non-local IRB/entity indicating that they will not require that a representative of their IRB/entity participate in the University of Pittsburgh IRB review of the research study.
Additional Requirements When Research is Conducted Outside of the United States
International Research Module
US investigators and their research team members who interact with research subjects or have access to their identifiable data must complete the CITI “International Research” course.
Engagement in Research
When human subject research is conducted outside of the United States, additional matters must be addressed. If the foreign site will be engaged in human subject research and if the research is federally funded in whole or in part, the foreign site must file an International FWA. The International FWA number should be provided in the protocol. Investigators may direct the foreign site to this OHRP site to obtain the necessary paperwork: http://www.hhs.gov/ohrp/register-irbs-and-obtain-fwas/fwas/file-a-new-fwa/
Good Clinical Practice
If investigational drugs or devices will be used at the foreign site, the foreign site must agree to abide by the FDA Guidance on Good Clinical Practice (“GCP Guidance”), which was developed as part of the work of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). The Guidance is available at: http://www.fda.gov/downloads/Drugs/.../Guidances/ucm073122.pdf
- GCP Guidance provides a consistent set of definitions and requirements for record-keeping, adverse event reporting and all other aspects of clinical trial conduct.
- Any agreement with the foreign site should expressly reference the GCP Guidance, and the University investigator must be comfortable that the foreign site is equipped to meet GCP Guidance standards.
Shipment of Investigational Drugs or Devices
If the investigational drugs or devices will be shipped from the University to the foreign site, the investigators must obtain written permission from the manufacturer and meet any necessary import requirements from the receiving country. Investigators should obtain written documentation from the foreign site stipulating that all necessary approvals for use of an investigational drug or device under the local laws have been obtained.
Post approval monitoring may be imposed when necessary. As with domestic projects, investigators are obligated to report subject complaints, unanticipated problems involving risk to subjects or others and other reports of potential non-compliance to the IRB. Research subjects are provided with the University of Pittsburgh international telephone number as part of the informed consent. Complaints by research subjects participating in transnational research will be handled in compliance with Chapter 17.