Feature Article
Ethics Around the World: International Projects and the BUMC IRB
December 2011 Issue
By Katherine Semrau, PhD, MPH
Assistant Professor, Center for Global Health & Development
BUMC IRB Board Member, Panel Blue
Authors has nothing to disclose with regards
to commercial support.
- Introduction
- Context
- Who is engaged in international research
- Determination as to whether a project is RESEARCH
- Training and Supervision of Field Research Staff
- Informed Consent
- Data Security
- Availability of the Investigators
- Conclusion
- Quiz
Over the past decade, research projects conducted in countries outside of the United States have dramatically increased. With such an increase in human subjects research, the BUMC IRB, as well as principal investigators and study personnel, must consider a complex series of contextual and ethical issues. While these issues are not absent in U.S.-based research, the course through the regulatory and ethical minefield is less clear when we venture overseas.
The U.S. Health and Human Services (HHS) Office of Human Research Protections (OHRP) ethical review standards must be maintained for international projects, but international research is also subject to local laws and local ethical review. OHRP uses the FWA (Federalwide Assurance) system to encourage consistency of human subjects’ protection around the world. OHRP-registered institutional review boards (IRBs) exist in most, but not all, countries where BU/BMC researchers work. Meeting the requirements imposed by two or more IRBs is always challenging, even more so when those IRBs are halfway around the world from each other. In this article, we present some of the challenges as well as the potential solutions related to conducting and getting BUMC IRB approval for international research.
In real estate, we hear the phrase, “Location, location, location.” This is especially true in international health research where context and culture matter. Understanding the guidelines from the local ethics review committee or institutional review board is the responsibility of the principal investigator and study team. These guidelines have to be integrated with the requirements of the BUMC IRB. Informing the BUMC IRB about any local requirements as part of the protocol submission can help expedite the processing of an international protocol. Many IRB staff or panel members have not worked professionally outside the U.S., so including relevant information about the country, the study population, health systems and standards of care can give a background for the analysts and panel members who are reviewing the study protocol. Detailing the local standard of care applicable to a control group can be particularly important.
As part of its review, IRBs are required to consider “local context”. In accordance with BUMC policies, in minimal risk international studies where there is not a member of the IRB who is familiar with the local site or culture, the IRB will identify a local context consultant (who is not a member of the research team) to provide relevant information about the local culture. For most studies involving greater than minimal risk, review by a “local IRB” from the country in which the research is taking place will be required. Even for those studies where there is not a local IRB involved, many times there are some local review requirements; for example, approval of the research project by the Ministry of Health.
Who is engaged in international research?
Because of the potential involvement of multiple people from multiple institutions in the research, a key question to consider will be, “Who is engaged in the research?” OHRP has a guidance on their website called ENGAGEMENT OF INSTITUTIONS IN HUMAN SUBJECTS RESEARCH. This guidance document is used by Investigators and the IRB to identify all persons working on the project who are engaged in the research.
Determination as to whether a project is RESEARCH
There has been a recent increase in requests for BUMC faculty to conduct program monitoring and program evaluations at international sites. Some of these projects will NOT meet the federal definition of human subjects research; while others will, by federal definition, involve research. It is often challenging for researchers and the IRB to make the distinction as to what constitutes “human subjects research” and what does not. OHRP has posted guidance on its website which is useful, but still leaves room for interpretation.
If the PI believes that the project is simply a quality assurance /monitoring project that does NOT involve any human subjects research activities, then he/she can submit an abbreviated IRB application for Exempt /Not Human Subjects Research (NHSR) review. If the IRB agrees that the project does NOT include any human subjects research activities, then the IRB will generate a NHSR letter and no further BUMC IRB review will be needed. If, however, the IRB determines that the project includes human subjects research activities, then the application will be returned to the investigator so it can be revised for full IRB review.
Even when a project does not meet the definition of human research, approval by government officials or local oversight bodies may be needed before research can be started. The PI is expected to be aware of these local approval requirements.
Training and Supervision of Field Research Staff
In preparing a field team for work in international settings, the training plan needs to minimally address: Research ethics, good clinical practice, data security/confidentiality and study specifics SOPs.
Ethics Training: All investigators and study staff anywhere who are engaged in human subjects research must provide documentation that they have received basic human subjects protection training. While investigators at BUMC have multiple options for obtaining this training, field investigators in remote locales may not have access to these options. In these situations, the BUMC IRB can approve an “alternative” method for human subjects protection training. These alternative training programs must address the same principles as the traditional BUMC-approved programs (e.g., the Belmont Principles, voluntariness of participation, informed consent, etc.), but may be presented in a locally relevant way. The BU Center for Global Health and Development has a PowerPoint slide set which has been used successfully by BU investigators as a starting point for teaching these principles.
Good Clinical Practice Training: In many cases, research done internationally will involve participation by “non-traditional” researchers such as birth attendants and local community members. Along with ethics training, these community researchers will require a significant amount of training on basic research procedures, such as: How to properly conduct research, how to accurately collect and record data, how to report adverse events and unanticipated problems, etc. Training in these areas will need to be combined with ongoing monitoring and supervision to ensure that the research is being done properly (e.g., all adverse events are being reported in a timely manner, all subjects meet the eligibility criteria, etc.).
Data Security and Privacy Training: In the U.S., it is common for investigators to receive data security training in the form of HIPAA training. While the U.S. HIPAA regulations do not usually apply to international research, it is necessary for international researchers to have an understanding of basic measures needed to protect subjects’ privacy and the confidentiality of their data.
Study-specific training: As with any research study, the staff must be trained regarding the specific details of the study. The additional challenge for international researchers may be the need for study- specific research documents, especially from multi-site studies, to be translated or further clarified for the local research staff.
When obtaining informed consent in international research, a key question will be, “Who can consent?” Here in Massachusetts and at BUMC, fairly standardized rules exist about obtaining consent for participation of minors, consent by substituted judgment (LAR), and obtaining consent for subjects who are “wards of the state.” For international research, the laws regarding such issues vary significantly from country to country and even from region to region. Listed below are a few examples of informed consent challenges that had to be resolved in the past. When issues like these occur, the BUMC IRB must work with the investigator and the local IRB to ensure that research remains compliant with the U.S. federal regulations, but is also respectful of local customs and local laws.
- Who can give informed consent in high risk drug studies for orphaned minors whose heads of households are other orphaned minors?
- How do you balance the rights of subjects to self-determination regarding participation in research with the local custom of the village chief making such decisions for his tribe?
- Is parental consent/permission required for pregnant adolescents to participate in pregnancy-related research?
In order for a truly informed consent process to occur, informed consent must be given to subjects in a language that is understandable to them. Since the subjects of international research frequently will not speak or read English, consent and assent forms will need to be translated into the local language(s).
At the recent meeting of the Consortium of University Programs in Global Health, Dr. Goma, Dean of the University of Zambia Medical School and a former official in the Ministry of Health, was asked if bioethics training is a constraint on IRBs in his country. He said, “No … ethical standards are the same as in the West and ethics training is readily available. The problem for developing country IRBs is contextualizing the procedures.” His particular concern was informed consent forms: “Some Informed Consent Forms are so complex that, when you try to translate them into the local language, they make no sense.”
Keeping this in mind, investigators who write consent forms for international research must be very cautious to ensure that forms are written as clearly and simply as possible. Consent forms that are short and simple with limited medical /technical jargon will be much easier to translate appropriately into local languages. The BUMC Clinical Research Resources Office provides valuable assistance in helping investigators simplify their consent forms.
Translation of informed consent documents can be a tricky issue because balancing the complex requirements of informed consent with the spirit of the consent is essential. Rather than requiring a word-for-word “back translation” of the English version of the consent, BUMC policy requires that the English version of the consent be translated by a qualified translator . After this is done, a second qualified person reviews the translation and “attests” to the fact that the translation is accurate and contains the required elements of consent.
Investigators should carefully consider when to get the consent forms translated. Consent forms should NOT be translated until the English versions have been approved by the BUMC IRB, because the IRB may require additional changes to the consent which would then also need to be translated. Ideally, consent forms should not be translated until they have been also reviewed by the local (international site) IRBs -- unless those IRBs need the translated versions for their reviews. Only when the final English version of the consent has been approved by all IRBs should translation take place. Once the translation has been done, then the translated consent forms with the attestation forms must be submitted to the BUMC IRB so that they can be validated. Click here for a suggested step-by-step process for obtaining approval for translated consent forms.
A number of unique data security issues can arise when conducting international research. Often investigators must transport large volumes of study data and study documents over long distances. If the research data is particularly sensitive in nature, then additional protections may be necessary to keep the data secure. Whether conducting domestic or international research, researchers are required to record study data using study IDs and a separate master code that links subjects’ identifiers to minimize the risk of breaches in data security. When traveling internationally, there is an increased risk for study documents to be confiscated or lost. Thus, it is even more important for study data to be coded and for investigators to store the master code separate from the study data. This means that the study data and master code should not be packed in the same suitcases, and probably should not be carried by the same person (especially if the research data is very sensitive and identification of the subjects could put them at risk).
Many investigators will use the Internet to send their research data back home. Again, these data need to be coded with the master codes transmitted separately so that if the communications are intercepted or misdirected, then subjects will not be put at risk of identification. Depending on the sensitivity of the data, it may need to be transmitted via a secure network.
Certain international research sites may present physical challenges for how data is secured and managed. There may not be locked facilities available to store the data; or, local “officials” who are not involved in the research may believe it is their right to search through research documents. Depending on the sensitivity of the data being collected, additional measures may need to be taken to ensure the confidentiality of the records. In the end, it is the study PI’s responsibility to be aware of any local regulations related to protection of subjects’ private information, as well as the release of subjects’ medical information outside the country.
Availability of the Investigators
One of the benefits, as well as the challenges, of international research is the travel. International researchers are frequently not at BUMC, but are at one of their research sites. Depending on the site location, there may be limited or no Internet access. During the course of BUMC IRB review, the IRB staff and Board members frequently have questions for the investigators. It is important that if the PI is frequently unavailable, that there is a local study staff member available who understands the research, is aware of the local issues, and who can communicate with the PI. Otherwise, delays in IRB approvals and renewals can occur while waiting for clarifications and additional information. International researchers must make sure their progress reports are submitted in a timely manner so that there is as much time as possible to resolve outstanding issues prior to study expiration in case the PI is immediately unavailable.
International health research can be rewarding and interesting, and can promote health in neglected environments. Ensuring human subjects’ protection is essential to the ethical conduct of a study in any part in the world. The BUMC IRB, principal investigators, and study personnel must consider the context and culture of the local environment--determining who is engaged with the research, and working hard to train field staff in human subjects’ protection.
Click here for a step-by-step instructions for obtaining IRB approval for translated consent forms
Special thanks to Frank Feeley, JD, Associate Chair, Academics; Associate Professor Department of International Health Center for Global Health and Development, Boston University School of Public Health for his assistance with this article .
Quiz
This Quiz applies to the next recertification period from July 1, 2013 to June 30, 2015, but we recommend that you take this quiz now so you can stay up-to-date.