This Course will discuss international research and the unique issues that it presents to researchers concerning the application of the Belmont Principles, cultural competency, and informed consent. We will discuss international guidelines for research, including the International Compilation of Human Research Standards, “Responsible Conduct in the Global Research Enterprise: A Policy Report,” and the “Casebook on Ethical issues in International Health Research.” The Office of Human Research Protection’s federal regulation dealing with international research will also be presented. The module will conclude with a brief quiz.
- Review considerations for ethical research with international populations
- Examine international guidelines for human subjects research
- Discuss cultural considerations for informed consent, recruitment and incentives in international research
This Module will discuss international research and the unique issues that it presents to researchers concerning the application of the Belmont Principles, cultural competency, and informed consent. We will discuss international guidelines for research, including the International Compilation of Human Research Standards, “Responsible Conduct in the Global Research Enterprise: A Policy Report,” and the “Casebook on Ethical issues in International Health Research.” The Office of Human Research Protection’s federal regulation dealing with international research will also be presented.
The OHRP guidelines state that policies and procedures to protect human subjects in foreign countries may differ from those that are in place within the United States. If the policies and procedures of the foreign country offer at least as much protection as those set out in the Code of Federal Regulations, then the foreign procedures may be substituted.
In recent years, there has been a significant increase in international research requiring Institutional Review Boards to review more international research (ref 83).
When international research is conducted in a developed nation, the researcher’s main concern is that nothing within the research violates that nation’s laws. Just as researchers conducting research within the United States need to insure the proposed research does not violate state or federal laws, international researchers need to make sure that their research does not violate any laws of the nation in which it is to be conducted.
International research becomes more of a challenge when that research is to be conducted in a developing nation. Because of the significant differences in U.S. society and the society of many developing nations, IRBs will examine proposed research very carefully. Coercion and the potential difference in power may be related to gender, culture, religion or caste. In addition, economic differences may create unique challenges for researchers proposing to use incentives. The IRB will pay particular attention to the application of the Belmont Principles, informed consent, and cultural considerations.
Review levels of review (IRB and location of research)
It is often required that a local IRB review the research. If the level of risk is high, a researcher might be required to have a consultant who is familiar with research in the local area. When the IRB reviews the international research proposal, they will look at the local regulations, social and political situations. Coercion can be very different in a foreign country. IRBs will also monitor international research once it is approved. It should be noted that many foreign IRBs do not have requirements for continuing review, as US IRBs do. (ref 83)
Ethical Research with International Populations
The Belmont Report of 1978 outlines three key principles of ethical research: respect for persons, beneficence, and justice. These three principles are used by all IRBs to guide the decisions they make regarding research and should be used by all researchers in the creation of their research, especially international research. (ref 4)
Nigerians await ‘botched drug trial’ settlement (ref 82)
Respect for persons encompasses at least two parts. The first is that all individuals should be treated as autonomous agents, meaning each individual can deliberate about personal choices and act upon those deliberations. The second is that those individuals who are of diminished autonomy must be protected. These individuals may be of diminished autonomy because of illness, mental disability, cognitive deficits, or immaturity. Individuals in developing nations may also have diminished autonomy because of power differentials within their society based upon social class, race, or gender (among other considerations). (ref 4)
Four conditions flow from respect for persons: voluntary consent, informed consent, protection of privacy and confidentiality, and the right to withdraw without penalty from a study. (ref 4)
Beneficence asks us to examine the risks and the benefits of the study. First, the study should not do harm. Second, benefits must be maximized while harm is minimized. Third, the risks are justified by the benefits of the study. (ref 4) This can be particularly difficult to do when conducting research in a developing nation. What may not be harmful in American society may be very harmful in another country. A woman who participates in a study dealing with women’s rights in the U.S. may not be placed at any more than minimal risk, whereas the same study, conducted in a nation where there is a considerable power differential between men and women might put subjects at considerable risk.
Justice is the third Belmont principle. This principle requires that the benefits and risks of research be evenly distributed through society. Specifically, this means that the disadvantaged must not bear the risks of research, while the advantaged reap the benefits—something that has happened all too often throughout the history of human subjects research since Nuremberg. (ref 4)
Justice can present particular challenges to researchers in developing nations. Many of these countries have a considerable history of colonialism and have suffered from hundreds of years of being exploited by developed nations. Researchers need to ask themselves if their own research is continuing this tradition.
Cultural competency consists of knowledge of the language of the target nation, the social and political structures of the nation. Researchers should also be aware of power differentials within the target country. Cultural competency is very important when conducting international research, especially considering the increase in international research in developing nations. It is very important to understand the local research context, both in terms of who the subjects are and the research environment. Researchers should never assume that they have cultural competency but should constantly strive to enhance their knowledge of the people and culture of the nation in which they plan to conduct international research. An IRB will require that the level of knowledge the researcher has be commensurate with the level of risk involved in the research. Any researcher who conducts international research will need to demonstrate to the IRB that they have this knowledge. (ref 83)
Informed consent, recruitment and incentives
Researchers need to carefully consider the appropriateness and local norms of informed consent when conducting international research. Regardless of where research is conducted, the expectation is that individuals must agree to participate in research freely and voluntarily, without undue coercion or pressure being put upon them to participate. But it can often be difficult to gauge what actions are “voluntary” in a foreign culture. In some countries, residents perceive an expectation by their governing leaders to participate in clinical trials or other types of research. The concept of voluntariness is one that we understand fairly broadly in western culture, however the same is not true in all countries and cultures. Allegations related to India drug trials, for example, suggest that research subjects did not believe they were free to decline participation. In very poor areas, a lack of voluntariness may stem from the promise of free treatments or medications. When parents or family members cannot afford to treat a condition, the promise of free treatment or medication may be coersive in that people might agree to something they otherwise would not, or they may agree to something without fully understanding the implications. Coersion or undue influence removes the voluntary nature of informed consent.
Consent must also be “informed,” which means research subjects know what they are agreeing to do and specifically that they know they’re participating in a research study and understand the risks and benefits of that participation. One of the most obvious violations of this in international research is lack of proper translation for the language of the potential participants. Informed consent is intended to be a process, not a form, yet concerns raised about international research trials suggest that not only was informed consent not properly documented in the language of the participants, often it was not obtained at all and frequently, research subjects were not aware they were participating in a research study until injury or harm had already occurred. For clinical trials where a placebo is used, participants must be clearly informed that some subjects will receive the treatment while others will receive no treatment or a placebo. This can be a difficult concept to translate or convey to those unfamiliar with such trials, which can leave international research subjects unaware that a life-saving treatment might not, in fact, be delivered as part of the research.
Individuals who participate in research should expect that the information that they share in the context of research will be kept private, that their personal information will not be shared and that they will be protected from damaging or embarrassing information that may be revealed during the context of research. In some cultures, the concept of privacy is very different than our Western expectations, and the conditions can make it very difficult to truly ensure privacy for participants. Simply being in a trial is often an indicator of a specific condition or illness, and unlike the privacy afforded by clinics in the US, the distribution or delivery of medications or treatments is often done in relatively public spaces in other parts of the world.
Finally, any individual who agrees to participate in research can decide to discontinue participation at any time, for any reason, without giving a reason and without any penalty. But if there is a power differential between the researcher and the subject, it can be difficult to gauge that subjects not only understand this right to discontinue participation but are willing to do so. (ref 4)
In the United States, the basic expectation is that signed informed consent documents will be part of the informed consent process for research studies. In some international research settings, a signed consent may not be culturally appropriate or possible. Literacy is often a significant issue with international research, particularly in less developed countries. Ethics boards might question whether an “X” in the signature line is really sufficient to demonstrate informed consent. Certainly, the process around the documentation of informed consent takes on increased significance where literacy is an issue, but in some cultures a written language simply does not exist or is only rarely used. Providing written informed consent and requesting a signature in such cultures would be meaningless and inappropriate. Some cultures have expectations that only the head of a family will sign anything; asking for an adult child or a female member of the household to sign any document could be very disrespectful of cultural norms and expectations. It is important to understand the cultural nuances of the proposed research location before making assumptions that signed informed consent is a requirement. Alternatives that still ensure true informed consent can be considered, but may also be inappropriate; for example, audio or video taping the consent process may be appropriate in some cultures where obtaining signed informed consent is not possible, but may raise additional concerns in others. Researchers should have a good understanding of the cultural norms and expectations before establishing an informed consent process, and should ensure that the process they use is appropriate, meaningful, and respectful.
Many of the same issues and concerns raised with informed consent also apply to recruitment when conducting international research. The two biggest risks with recruitment internationally are ensuring the privacy of potential research subjects, and avoiding coercion or undue influence in recruitment practices.
Recruitment strategies in international research can look very similar to strategies we see in the US, but can also tend to rely more on physicians and other experts, as well as on word of mouth. This is due in part to access issues in some less developed countries to other typical recruitment approaches, such as recruitment flyers and internet recruitment. Because of this, coercion and undue influence are serious concerns with recruitment. If a doctor or other respected leader in a community asks for volunteers, potential subjects might feel like they have to agree. This can also lead to subjects deferring to expert opinion on the risks and benefits of research, as opposed to seeking their own understanding and making a voluntary decision about research opportunities. Physician recruitment, in particular, can pose concerns, especially when there are not clear alternatives to participation in research, or when subjects are not made sufficiently aware that they are agreeing to something experimental. This can be somewhat mitigated by very good informed consent processes and by removing the physician from the informed consent process if he or she was involved in recruitment, but in cultures that place certain medical and governmental leaders in positions of primary authority it can be very difficult to fully manage this undue influence.
Privacy concerns, too, arise from the recruitment strategies often employed in international research. When residents are in close quarters, particularly in economically disadvantaged locations, researchers may rely on word of mouth to recruit additional participants once they have introduced a study to a community. Privacy laws differ internationally, leading to different norms and expectations about sharing private information in an effort to recruit more subjects. Some subjects may be paid or incentivized to bring in new subjects or give names of new subjects to researchers. While such strategies are often monitored by ethics review boards, subjects may believe a free treatment or medication can help others in their community and spread the word even if it’s not part of the official recruitment strategy. As with informed consent, researchers are responsible for being aware of cultural norms and expectations when developing their recruitment strategy in order to minimize privacy and coercion concerns.
IRBs in the US are watchful of incentives to participate in research mainly to ensure they don’t result in undue influence over subjects, leading them to agree to participate in something they otherwise would not. This concern is especially significant when potential subjects are low income or when incentives are particularly valuable, such as high monetary amounts or expensive treatments or medications.
In poverty-stricken international locations, the amount of money can be very, very small by US standards and still influence participation. Research has shown that female subjects in South Africa who reported being motivated to participate in research by monetary incentives equaling about $3 also reported regretting their participation. (Sikweyiya & Jewkes, 2013 (Qualitative Health Review). Often incentives take the form of expensive treatments or medications that subjects in research could not possibly otherwise afford. While this can also happen in the US, the lack of many commonly-available tests, treatments, and medications in some extremely poverty-stricken countries make subjects there especially succeptible to undue influence based on incentives. This is complicated by factors described above related to recruitment and informed consent in international research. Once again, a clear understanding of cultural norms and expectations can ensure that incentives are appropriate for research in that location and with the population being included in the research.
International Guidelines for Human Subjects Research
International Compilation of Human Research Standards
The Office for Human Research Protections U.S. Department of Health and Human Services has assembled laws, regulations and guidelines for human subjects research from countries all over the world. It is updated yearly and is an invaluable resource for any researcher who plans to conduct international research. This document is a good resource for any researcher who plans to conduct international research. (ref 84)
The document is broken down into the following seven areas: general human subjects research, drugs and devices, research injury, privacy and data protection, human biological materials, genetic, and embryos, stem cells, and cloning. For social and behavioral science researchers, the section dealing with general human subjects research is the most germane. (ref 84)
The InterAcademy Council (IAC) & The Global Network of Science Academies (IAP)
The IAC and the IAP authored “Responsible Conduct in the Global Research Enterprise: A Policy Report” in 2012. This report states that responsible research conduct is a part of excellent research. It addresses values, principles, and guidelines for the responsible conduct of research and lays out seven overlapping values in research which apply to the entirety of the research process: honesty, fairness, objectivity, reliability, skepticism, accountability, and openness. This document highlights that peer review and social responsibility in research plans is key. It also emphasizes that research cannot inflict harm or infringe upon the values of autonomy, freedom, dignity, nondiscrimination, and lack of exploitation. (ref 85)
World Health Organization
In 2009 the World Health Organization published the “Casebook on Ethical issues in International Health Research.” This casebook is designed to be used as an instructional tool to teach students and potential researchers. Chapter one presents a definition of research. Chapter two discusses issues within study design. It states: “International research carried out in developing or resource-poor countries requires that the research be sensitive to the social, cultural, political and economic context of the country and community in which the research will take place.” (p.25) Chapter three examines harm and benefit. Chapter four discusses voluntary informed consent. Chapter five looks at standard of care, which examines whether there should be one universal standard of care. Chapter six examines obligations to participants and to the community. There is little agreement regarding what researchers owe to the community in which they conduct research. Chapter seven deals with privacy and confidentiality and points out that placing a high value on privacy and confidentiality is not universal. Chapter eight looks at professional ethics of conflict of interest and scientific misconduct. (ref 86)
This Module discussed international research and the unique issues that it presents to researchers concerning the application of the Belmont Principles, cultural competency, and informed consent. We discussed international guidelines for research, including the International Compilation of Human Research Standards, “Responsible Conduct in the Global Research Enterprise: A Policy Report,” and the “Casebook on Ethical issues in International Health Research.” The Office of Human Research Protection’s federal regulation dealing with international research was also presented.