This case highlights potential dilemmas encountered by postdoctoral fellows in a research setting. Does the promise of a U.S. standard of medical care undermine informed consent in foreign based studies? It also explores the issues of informed consent when U.S. supported medical research is taking place in a developing country.
From: Graduate Research Ethics: Cases and Commentaries - Volume 5, 2001
edited by Brian Schrag
Ellen, an American graduate student in medical research, is working on a research study in a small town in sub-Saharan Africa. As part of her duties, she is asked to make herself available during participant recruitment to clarify any questions that the recruitment personnel or the participants may have. On one of these occasions, Tefera, a nurse who is native to the area, is obtaining informed consent from a young pregnant woman named Sebena. Sebena was born and raised just outside the town where the research study is being conducted. Like most persons in this area, she is unable to read or write. Therefore Tefera is reading the informed consent form to her. Although Ellen does not speak the native dialect, she is familiar with the informed consent form. The form is a direct translation of the form originally written in English by her adviser, the principal investigator on the study. Both the original form in English and the official translation were approved by the university with which she and her adviser are affiliated and the local collaborating university.
The informed consent form includes information on the purpose of the study, a single-blinded, randomized intervention trial to test the efficacy of a new vaginal wash to be used during delivery to reduce the probability of transmission of a viral infection from mothers to babies during delivery. The form explains the risks and benefits of participation at length, including the anticipated minimal risk of the vaginal wash to either the mother or baby. The only anticipated risk includes a topical sensitivity reaction to the contents of the wash, which may include redness at the site of application and a slight feeling of mild burning, which can be relieved by rinsing the area with water.
The benefits are thought to outweigh the risks. All participants will benefit by receiving general obstetric and gynecologic examinations and treatment for other possible infections following the standard of medical care in the United States. The participants in the treatment arm of the study may also benefit from the hypothesized reduction in viral transmission from the use of the vaginal wash. Finally, the form explains that the information collected may provide efficient and affordable means of reducing mother-to-baby transmission of this viral infection.
As Tefera is reading the informed consent form, Sebena appears somewhat uncomfortable and apprehensive. Ellen thinks that her response may be related to the surroundings. They are sitting in an office that includes modern laboratory technology obviously unfamiliar to Sebena, whose attention often turns to empty vials sitting next to a microscope. The room is located in a new health care facility built through funds provided by the study to help support the research and to give something back to the community.
Ellen is also struck by Sebena's interaction with Tefera. Her nods and occasional brief responses sound more like someone receiving a set of instructions than an indication of understanding.
Ellen knows that Sebena is already familiar with the study, as her community elders had signed an agreement with the local collaborating university providing permission to conduct the study among members of the community. Perhaps all of her questions have been addressed through community discussions.
During the time it takes to complete the informed consent form, which is quite lengthy, Ellen begins to wonder whether Sebena truly understands the research study and her part in it. During her stay in this area, Ellen has learned a little about the community in which she is working including their understanding of health and disease and their traditional therapies for various ailments. These are all very different from Ellen's understanding of disease and treatment, and she wonders whether Sebena comprehends what a virus is, and how the vaginal wash may help to reduce viral transmission. Ellen also questions whether Sebena understands what randomization is and how this technique will affect her as a research participant. Ellen is distracted from her meditations by movement from across the room. Sebena is ready to place her mark on the informed consent form. She seems to be eager to do so. The form states that study subjects have the right to refuse to participate and that they may withdraw at any time, but Ellen begins to question whether Sebena truly has a choice in giving her consent. Do the benefits from this study, such as the medical treatment that she will receive, overwhelm any concerns she may feel regarding being in the study? Is she afraid of the repercussions of refusing to participate, given that her community has already agreed to the study?
Ellen is unsure how to address her discomfort with the informed consent process that she has just witnessed. She cannot speak with Sebena herself as she does not speak her language, and she begins to deliberate about what course of action she should take to address her concerns.
Posted 12 years and 6 months ago
Karen M. T. Muskavitch Boston College
This case is likely to prompt those who use it to reflect on all three ethical principles put forth in the Belmont Report1 - respect for persons, beneficence and justice - and to consider how well they are addressed in the research described. However, the focus of the case is on the first principle, treating people as autonomous agents, and its application in the process of informed consent.
The right of potential research subjects to choose for themselves in a free and informed manner is central to all of the guidelines that have been written for research involving human subjects such as the Nuremberg Code,2 the Declaration of Helsinki,3 the Belmont Report1 and the CIOMS International Ethical Guidelines for Biomedical Research Involving Human Subjects.4 These ethical guidelines have then been used as the basis for regulations and more applied guidelines that can be used to evaluate proposed research protocols.5 -7
Ellen's situation is particularly interesting because all the basic ethical requirements for international collaborative research of the type described seem to have been met. Yet Ellen, sitting in on subject recruitment, feels that all is not as it should or could be. Yes, approvals have been received from both the PI's American university and the local, collaborating university. These approvals presumably came from the universities' human subjects committees, duly constituted to be aware of the applicable regulations and of the local cultural norms. These committees have approved the consent process and forms that are being used and, as is recommended for such research7, the community elders have been consulted and have given their consent. The potential risks associated with the experimental treatment are quite minimal, and the researchers are providing benefits to the research subjects in the form of obstetric and gynecologic exams and treatments, and to the entire community by building a health care facility that will remain after the end of the study. In addition, this is not a case of Western researchers coming in to test a treatment that those in the subject pool could never afford. Rather, the experimental treatment that is being tested is one that could benefit this community and others just like it. Despite all of these facts, however, Ellen is uncomfortable.
The questions in this case go beyond simple compliance with regulations, as important as that is, to considering congruence with the spirit of central ethical principles such as respect for persons.
Informed consent includes three elements: "information, comprehension and voluntariness".1 It seems that Tefera is reading to Sebena all the relevant information about the research study, but Ellen has concerns about Sebena's ability to understand the information she is being given because of her cultural background. In addition, Ellen questions the voluntariness of Sebena's offer to put her mark on the consent form. Voluntariness requires that the consent be "free of coercion and undue influence".1 Is there an element of coercion? Is Sebena simply obeying the perceived authority of the nurse and the researchers, or the community elders ?8(pp. 68-69) Or do the benefits of the research constitute an undue influence? Does Sebena feel an obligation to consent to be a research subject because of what the researchers have done for her community, or because of the medical care they promise for her and her unborn child if she joins the study? Since she cannot talk directly to Sebena, it is impossible for Ellen to answer these questions immediately, but SebenaÀs body language tells Ellen that there is cause for concern.
In following up on her concerns, it is important for Ellen to be aware that applying Western ethical standards to other cultures is not as simple as it might initially seem. The idea of autonomy is based on a Western understanding of individualism. In other cultures, the community is central to oneÀs life, and the individual is much less important. Important decisions may be made by the community as a whole or its elders, rather than by the individuals directly involved. This locus of decision making can result in an ideological conflict for an ethically concerned researcher such as Ellen. On one hand, it seems a good thing to respect other cultures and avoid coming in as an outsider and challenging the traditional authority structure of these communities. However, there is also good in working to empower less well represented individuals in these communities and sharing with them a different world view in which they as individuals have inherent worth. This tension can be particularly acute if the less powerful individuals are women and the community elders are all male. Some of these concerns and tensions are discussed in an article by Dena Davis.9
What should Ellen do? First she needs to creatively consider the wide variety of options that may be available to her. In a discussion of this case, this is a point where brainstorming possible options could be very productive. Then the discussion can move to evaluation of the various courses of action suggested. Most would agree that Ellen should do something, and similarly that she should be wary of being too righteous or heavy handed in her approach. One good approach is to spend a lot of time asking questions.10 In this way she could learn more and perhaps cause others to acknowledge their own uncertainties and/or consider the questions Ellen raises.
If there really is a problem and Ellen can gain support from those with more authority in the study, then some changes could be made. Perhaps the vocabulary used in the consent process could be revised so that it is more consistent with common usage in the town. Any proposed changes would need to be approved by the appropriate IRBs,5,7 and it is important to avoid misunderstandings such as those that resulted from the use of the term "bad blood" in the Tuskegee study.8(pp. 71-73) Perhaps there could be a program of community education in current medical concepts such as disease, treatment and research. This strategy would be consistent with the understanding that informed consent is an ongoing process of communication between subject and researcher, not a one-time signature on a form. Perhaps the consent process for the individual women could be moved out of the clinic and into a more familiar setting. These are just a few suggestions.
A final note: Just as our awareness and understanding of ethical issues associated with international and cross-cultural research are developing, so are the associated guidelines and regulations.11 Therefore, what might be considered to be the best course of action now may not be evaluated in the same way several years later.
From: Graduate Research Ethics: Cases and Commentaries - Volume 5, 2001 edited by Brian Schrag
This case was designed to highlight some of the complexities involved in obtaining informed consent from human subjects participating in clinical trials. Since this case takes place in a resource-poor area of the world and among peoples with different cultural meanings of disease and treatment, other issues present themselves more acutely than when research is conducted in the United States (for example, the difficulty of communicating the nature of the study so that enough meaningful information is conveyed for the individual to make an informed decision whether to participate). Moreover, community permission was sought and obtained for this research. Therefore, the case also raises questions of seeking individual informed consent after, and in addition to, informed consent that has been received from the community as a whole. Finally, difficult issues arise when the research group is principally from the United States, although a collaborative relationship exists with the local university. In summary, this case is intended to review the current regulations regarding informed consent as established both in the United States and internationally, to enhance discussion regarding certain complications and dilemmas that may arise with respect to gaining individual consent, and finally to raise broader and more difficult questions about cross-cultural research.
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The informed consent process is a primary component of protecting the rights and welfare of individuals involved in research. This protection is grounded in the concept of the right to autonomy or self-determination, which is understood as an ethically necessary means of demonstrating genuine respect for human integrity and dignity. All of the influential international and national documents governing medical research involving human subjects begin from the ethical principle of respect for persons to justify the doctrine of informed consent, including the Nuremberg Code, The Declaration of Helsinki, International Ethical Guidelines for Biomedical Research Involving Human Subjects and the Belmont Report. The Belmont Report is typical in its description of the informed consent process as necessary to ensure respect for persons. It understands individuals as autonomous agents "capable of deliberation about personal goals and acting under the direction of such deliberation."
Respect for persons, according to the Belmont Report, is itself based on "two ethical convictions: first, that individuals should be treated as autonomous agents, and second, that persons with diminished autonomy are entitled to protection." This approach requires researchers to ensure that potential subjects voluntarily decide whether to participate in research and that they have enough information to make an informed choice. In this case, Ellen has questions regarding both requirements. Because of the earlier agreement that her community elders made with the research study, it is not clear that Sebena has provided consent freely and voluntarily. For example, in a large smallpox vaccination research study in five areas of West Africa, other researchers have documented that obedience to tribal leaders was the strongest factor that influenced the populations' receptivity to the program.
The full ramifications of community consent for Sebena's decision are unclear. One would need more information about the type of community she lives in, the nature of the power that a community decision has over her actions, and finally how the elders introduced and explained the study to her.
Notwithstanding the paucity of information, it is clear that one of Ellen's possible courses of action would be to find some way to communicate with Sebena and ascertain the voluntariness of her decision. Ellen has an obligation to herself to ensure that she behaves with integrity, to Sebena to protect her rights as a research subject, and to the project to ensure it upholds to the rules and regulations governing medical research with human subjects. It may be of interest to speculate on what Sebena may have related to Ellen, and the ethics of then pursuing some course of action. Nevertheless, the one wrong action in this situation is clear: for Ellen to do nothing to ensure that SebenaÀs participation is truly voluntary.
This situation also raises questions about the guideline that researchers must ensure that participants have enough information to make an informed choice. This issue, however, is somewhat more complicated given the nature of working in a resource-poor region of the world where a wide gap exists between types of knowledge, cultural values and beliefs. Communicating enough information may require something quite different for a patient in a middle-class clinic in a suburb of a large metropolitan city in the United States and a woman living in an isolated small town in sub-Saharan Africa. What is immediately apparent in this case is that the informed consent form, although it may have been adequate for the purposes of passing regulations in the United States, may be wholly inappropriate in the present circumstances.
Unfortunately, no clear guidelines exist for explaining complex terminology and concepts in clinical, virologic and research methodology. Even in the United States, it has been found that receiving more information on abstract concepts like randomization does not increase participants' understanding of the concept.
Moreover, some researchers have suggested deviating from the traditional form of informed consent forms to make them easier for participants to understand, e.g., putting some aspects in point form and including pictures. However, these techniques have not been demonstrated to increase understanding above the level achieved with the traditional forms. What we do know is that understanding increases when there is a collegial process of obtaining consent, including maintaining good communication with the participant.
It may be appropriate to provide more training for Tefera and to conduct the process in a less intimidating environment. It might also be helpful to involve the community in designing an appropriate informed consent form. It is clear that collaboration ought to occur in such a situation, particularly when other work is not providing clear guidelines about the best procedures for obtaining informed consent.
One way to ensure that the individual is truly capable of making an informed decision is to bring in another party. In this case, bringing in the community serves this purpose to some extent. The community elders provide another level of assurance that the research is ethical and beneficial to the community and its participants and that a reasonable decision is made that balances the risks versus the benefits of participating.
Nevertheless, as Ellen notices, community consent has a negative side: It may bias individuals' decision whether to participate. This issue may require some further discussion with the participant. It is likely that in this study, as in medical research in general, participation is kept strictly confidential. One option for Ellen would have been to review this requirement with Sebena so that she understood that her decision would be kept confidential and that the community and the elders would have no means of knowing what her choice was.
In addition to respect for persons, the Belmont Report discusses another major principle that is intended to guide medical research involving human subjects - beneficence. It is imperative that research minimizes risks and maximizes benefits. One of the risks of a research study - particularly a clinical trial - is the augmentation of a standard of care that individuals are entitled to when they are not participating in a study. In all clinical research studies in the United States, it is now a part of the process to ensure that subjects receive the same standard of care they would have received had they not been participating in a research study.
This commitment to ensuring that access to care is not compromised by participation in a clinical trial sometimes means that for certain groups of individuals the standard of care actually increases if they are research subjects. That is particularly the situation in the present case, where the researchers are providing a standard of care that is comparable to that given in the United States in a resource-poor area where such medical care is prohibitively expensive and where the needed technology and expertise are not available. Most scholars regard this situation as ethical conduct in international research.
On the other hand, many have argued that introducing a U. S. standard of care is inappropriate for both scientific and ethical reasons. Arguments that support this view rest on the premise that if the research is being undertaken to provide evidence for the practice in these areas, then the work needs to take account of the environment in which findings will be implemented. It is clear that even though a research study may find a beneficial effect of some intervention, that does not necessarily mean that the benefit will exist outside the conditions of the research study. Therefore it may not be appropriate to test interventions designed for care in the host community using standards of care that do not exist there. Finally, providing a level of care above that available in the host country also risks coercion. The host community may not turn it down even though they may have some serious questions about it. In this case, the researchers have built a new medical facility for the community and are training local practitioners in laboratory and clinical work that would not be accessible to them otherwise. At an individual level, this situation may also unduly influence Sebena decision to participate. These are complicated dilemmas to resolve but may be of interest to discuss given their significance to recent international dedication to provide support to resource-poor areas of the world, including research help.
The Belmont Report also discusses researchers' ethical obligation to conduct research in accordance with justice. This requirement most immediately applies to this case with two competing ethical obligations. The first is to ensure that the research subjects are not being asked to take on an unfair burden of the research. In this case the intervention is designed specifically for this community and is intended to benefit the research subjects and others in this community. Therefore this study does not specifically entail complicated deliberations with respect to this concept of ethical conduct of research.
On the other hand, research should also be undertaken to provide just distribution of new knowledge and techniques. Researchers have an obligation to ensure that no person is deprived of the opportunity to participate in research, and consequently to benefit from knowledge and understanding gained therefrom. To conduct research in accordance with the principle of justice, the medical research community has an obligation to study diseases that occur primarily in resource-poor areas of the world. This case would be an example of a research study that is being pursued in accordance with dictates of justice. That is not always the case, and historically the principle of justice has been disregarded with tragic human consequences.
The concept of autonomy is rooted in Western enlightenment thinking where one school of thought holds that individuals ought to be treated as ends in themselves and not simply as means. Concepts such as respect for persons, voluntary choice and informed consent are justified on the basis of this idea. Persons have the right to choose what happens to themselves, and this decision is free only if it is made with knowledge of the situation. (The alternative would be deceit.)
However, other ethical theories, including utilitarianism and feminism, understand autonomy differently. If one were to follow these theories in this situation, one might reach different conclusions with respect to what autonomy means in the context of informed consent. The paramount respect for individualism inherent in informed consent has been questioned recently regarding whether it is truly respectful of people of all cultures. Is it right for some societies to insist that their ethical standards are applied elsewhere? These are difficult philosophical questions, which rest to some extent on beliefs in relative as opposed to universal ethical principles. However, complexity does not preclude the need for thoughtful deliberation.