Ethics in Acute Care Research: A Global Perspective and Research Agenda Jon Mark Hirshon, MD, MPH, PhD, Bhakti Hansoti, MBChB, MPH, Mark Hauswald, MS, MD, Kinjal Sethuraman, MD, MPH, Nancy Louise Kerr, MD, MPH, David Scordino, MD, and Michelle H. Biros, MS, MD
Abstract The 2013 Academic Emergency Medicine consensus conference focused on global health and emergency care research. One conference breakout session discussed research ethics and developed a research agenda concerning global acute care research ethics. This article represents the proceedings from that session, particularly focusing on ethical issues related to protecting human subjects while conducting acute care research. Protecting human research subjects from unnecessary risk is an important component of conducting ethical research, regardless of the research site. There are widely accepted ethical principles related to human subjects research; however, the interpretation of these principles requires speciﬁc local knowledge and expertise to ensure that research is conducted ethically within the societal and cultural norms. There is an obligation to conduct research ethically while recognizing the roles and responsibilities of all participants. This article discusses the complexities of determining and applying socially and culturally appropriate ethical principles during the conduct of global acute care research. Using case studies, it focuses both on the procedural components of ethical research conducted outside of “Western” culture and on basic ethical principles that are applicable to all human subjects research. This article also proposes speciﬁc research topics to stimulate future thought and the study of ethics in these complex circumstances. ACADEMIC EMERGENCY MEDICINE 2013; 20:1251–1258 © 2013 by the Society for Academic Emergency Medicine
rotecting human research subjects from unnecessary risk is a critical component of conducting ethical research, both in the United States and globally. It is well known and documented that there have been intentional and unintentional abuses in human subjects research during the past 100 years, examples of which include unethical medical experiments on human prisoners during World War II and the Tuskegee syphilis experiment in the United States. There are widely accepted ethical principles related to
human subjects research, such as those contained within the Belmont Report and the Declaration of Helsinki; however, the interpretation of these principles requires speciﬁc local knowledge and expertise to ensure that research is conducted ethically within the societal and cultural norms. Obtaining ethical approval to conduct research often requires merging the requirements of a “Western” process, including institutional review board (IRB) regulatory approval from the investigator’s institution, with a
From the Department of Emergency Medicine, University of Maryland School of Medicine (JMH, KS), Baltimore, MD; the Department of Emergency Medicine, Johns Hopkins University (BH, DS), Baltimore, MD; the Department of Emergency Medicine, University of New Mexico (MH), Albuquerque, NM; the Department of Emergency Medicine, Hennepin County Medical Center (MHB), Minneapolis, MN; the Department of Obstetrics & Gynecology, University of New Mexico (NLK), Albuquerque, NM; and the Department of Emergency Medicine, University of Minnesota Medical School (MHB), Minneapolis, MN. Received July 19, 2013; revision received August 4, 2013; accepted August 4, 2013. This article reports on a breakout session of the May 2013 Academic Emergency Medicine consensus conference in Atlanta, GA: “Global Health and Emergency Care: A Research Agenda.” Breakout session participants: Michelle H. Biros, Simon Brown, Nadia Elkana, Marna Greenberg, Bhakti Hansoti, Mark Hauswald, Jon Mark Hirshon, Nancy Louise Kerr, Catlin McCord, Jolion McGreevy, Aasim Padela, Jennifer Reifel-Saltzberg, Megan Rybarczyk, Sangeeta Sakaria, J. Reifel Saltzberg, David Scordino, Kinjal Sethuraman, James E. Svenson, and Vicken Y. Totten. The authors have no relevant ﬁnancial information or potential conﬂicts of interest to disclose. Supervising Editor: David C. Cone, MD. Address for correspondence and reprints: Jon Mark Hirshon, MD, MPH, PhD; e-mail: [email protected]
© 2013 by the Society for Academic Emergency Medicine doi: 10.1111/acem.12271
ISSN 1069-6563 PII ISSN 1069-6563583
culturally sensitive, local approach appropriate for the speciﬁc research locale. The former is a highly formalized process based on a well-developed regulatory and legal framework designed to cover a multitude of ethical and regulatory concerns. The latter is often less clearly deﬁned and frequently less concerned with the Western regulatory framework. These approaches are rarely (if ever) in opposition, since fundamental ethical principles (respect, beneﬁcence, justice) are relatively universal. However, integrating the regulatory, legal, and cultural needs and expectations of the different perspectives can be both practically and ethically challenging, especially when placed within the context of a research activity, which may have limited resources, and that may place the research subjects in a potentially vulnerable position due to ﬁnancial and other inequities. There is an obligation to conduct research ethically while recognizing the roles and responsibilities of all participants. This article discusses the complexities of determining and applying socially and culturally appropriate ethical principles during the conduct of global acute care research. Using case studies, we focus on the procedural components of ethical research conducted outside of Western culture, as well as overarching ethical principles, applicable to all human subjects research. We also offer a research agenda and speciﬁc research challenges to stimulate future thought and study of research ethics in these complex circumstances. ETHICAL FRAMEWORK FOR ACUTE CARE RESEARCH Research Ethics Background Ethical regulations and standards in human subject research have developed over the past century based on historical moral and ethical principles, affected in large part by past abusive research activities. Over the past 60 years or so, there has been a myriad of guidance on the ethical conduct of research with humans (see Table 1 for deﬁnitions).1–5
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The Nuremberg Code (1947), which grew out of the verdict in the trial of the Nazi doctors, identiﬁes 10 principles of research ethics. The ﬁrst states that “The voluntary consent of the human subject is absolutely essential ….”6 The Nuremberg Code was an “attempt to formulate a universal natural law standard for human experimentation.”6,7 As a response to atrocities committed against unwilling victims of brutal human experiments, the Code focuses on the protection of human subjects and adopts as its core principle voluntary informed consent.7 The World Medical Association’s Declaration of Helsinki (1964)8 continued to promote the protection of human subjects; however, it relaxed the Nuremberg Code’s strict voluntary informed consent requirement to allow research to improve the care of patients who lack the capacity to consent (e.g., children, mentally disabled patients, and patients in extremis).8,9 The Declaration of Helsinki also added the requirement that independent research ethics committees review and approve proposed studies. The two most recent revisions (in 2000 and 2008), motivated in part by ethical concerns about research in low-income countries—including placebocontrolled HIV studies and trials of drugs intended for wealthy markets—strengthen protections for vulnerable subjects. The 2008 Declaration states, “Medical research involving a disadvantaged or vulnerable population or community is only justiﬁed if the research is responsive to the health needs and priorities of this population or community and if there is a reasonable likelihood that this population or community stands to beneﬁt from the results of the research.”8 The Declaration of Helsinki offers valuable guidance for researchers, but should be seen as a minimum standard and a work in progress, shaped not only by ethical debate but also by economic and political tensions.9 Researchers should evaluate potential research, not just in terms of the speciﬁc guidelines provided by the Declaration of Helsinki and other codes of ethics, but according to general ethical principles as well. One
Table 1 Human Subject Research Ethics Definitions Research ethics: A set of ethical norms and guidelines aimed at both protecting human subjects of medical research and promoting advances in medical knowledge that benefit society. Beneficence: “Help, or at least do no harm.”2 Provide benefit to research participants and the community—and, at the same time, minimize (prevent) harm (Belmont Report 19793). Clinical equipoise: “A state of genuine uncertainty on the part of the clinical investigator regarding the comparative therapeutic merits of each arm in a trial.”4 Deontology: Moral theory that emphasizes rules. Deontologists argue based on duties, or absolute imperatives, such as “do not kill” and “do not lie.” Justice: Treat people fairly. The principle of justice demands fair distribution of the benefits and burdens of research. Research participants should be chosen based on characteristics that are relevant to the scientific problem, not based upon their availability or diminished power to refuse; benefits derived from research (e.g., new treatments) should be provided to participants, who endured the burdens; and participants should not be disproportionately drawn from populations unlikely to benefit from the research.3,5 Respect for persons/autonomy: Promote self-determination. An autonomous, “self-governing,” person has the mental capacity and individual freedom to make voluntary, informed, and reasoned decisions. The principle of respect for persons entails 1) promoting autonomous decision-making and 2) protecting persons with diminished autonomy.3 Utilitarianism/consequentialism: Moral theory that judges action based on their consequences. Utilitarians aim to produce the greatest happiness for the greatest number. Virtue ethics: Moral theory that emphasizes the character and moral wisdom required to habitually identify and do what is good.
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commonly used set of principles is contained in the Belmont Report (1979),3 which like the Nuremberg Code and Declaration of Helsinki was a response to abuse—in this case of poor black patients from the southern United States in the Tuskegee syphilis experiment. The Belmont Report develops a universal moral framework for medical research. It consists of three abstract principles (respect for persons, beneﬁcence, and justice) that researchers translate into speciﬁc actions based on the actual context in which they conduct research.3,10 Philosophical Framing of Research Ethics The three principles in the Belmont Report are, from the perspective of principle-based ethics, part of the universal common morality: all moral people everywhere, regardless of their individual religious or philosophical perspective, agree that these principles are central to moral life.11 There is, however, less agreement about how to apply these principles. How do the principles translate into speciﬁc action? How is the application of principles shaped by context? And how should conﬂicts between principles be resolved? To answer these questions, some turn to religious and cultural traditions; others turn to moral theory. Two moral theories, deontology and utilitarianism, guided early developments in bioethics. A third moral theory, virtue ethics, has also contributed substantially to the ﬁeld. Deontology views morality in terms of duties, or absolute imperatives, such as “do not kill” and “do not lie.” Utilitarianism (consequentialism) seeks the greatest happiness for the greatest number, judging actions by their consequences. Virtue ethics focuses on the character of moral agents and the wisdom required to habitually be and do good. Different moral theories, especially deontology and utilitarianism, can lead to radically different ethical conclusions. A key example deals with the moral status of the autonomous person, who for a deontologist must never be treated as merely a means to an end, no matter what beneﬁcial consequences deﬁne the end. A utilitarian, on the other hand, could justify using an innocent person as a pure means (for example, as a subject in a dangerous research experiment) to save the lives of many others. The inﬂuence of deontology is clearly seen in the principle of respect for persons and utilitarianism in the principle of beneﬁcence, although each principle is shared by both moral theories. The principle of justice is less easily framed in terms of abstract moral theory.11 Many unanswered questions remain about how to protect vulnerable people and communities from exploitation, how to promote the welfare of the least advantaged, and how to develop fair policies that affect the distribution of health.11,12 Feminist and human rights perspectives draw attention to and attempt to resolve these questions. They have helped to broaden the scope of ethical concern beyond the historically narrow focus on the behavior and obligations of researchers to a more holistic examination of the social and institutional context of research, particularly those features that threaten vulnerable populations and perpetuate inequalities.13 Many of the key ideas in research ethics developed in response to past abuses of vulnerable people and com-
munities. Major documents in research ethics, such as the Nuremberg Code, Declaration of Helsinki, and the Belmont Report, are a collective step toward a universal standard for ethical research; however, many theoretical and practical questions remain about how to apply universal moral standards in speciﬁc cultural and economic contexts and how to resolve conﬂicts that arise between and among universal principles and cultural norms. Practical Framing of Research Ethics As an alternate conceptual framework, research ethics can be discussed from a more pragmatic and practical perspective. “Practical” research ethics include the ethical treatment of research participants, as deﬁned by the local culture and the ﬁeld behavior of the researchers (fulﬁlling all responsibilities for the research including prestudy and poststudy care, nonabandonment of research subjects at the conclusion of the study, etc.). Ethical conﬂict arises further when the investigator is faced with a practical need to apply the approved study design in a resource-poor setting where the local standard of care provides less care than the proposed study (e.g., less monitoring, less patient privacy, less comfortable surroundings). In such circumstances, the practical ethical (and moral) dilemma is whether to accept the standard of care as the control arm of the study or to try to improve the standard of care for all. “Procedural” research ethics involves seeking approval for human subjects’ research after fulﬁlling the requirements of an oversight body (i.e., an IRB). Oversight approval is based on understanding the local deﬁnition of ethics; in global acute care research, this may be different for the approving entity and the setting of the proposed research. The investigator has the obligation to understand the culture, the social norms, and the hierarchy of decision-making at the location where the research will be performed (engaging a local, knowledgeable champion can assist in this interpretation). Unless the oversight entity clearly understands the ethical context in which the research is to be performed, no decision made regarding the ethics of the proposed research can be truly informed. CASE STUDIES Three cases studies are presented to demonstrate the ethical complexities and challenges of acute care human subject research in global settings. Each case primarily focuses on one of the key ethical principles identiﬁed in the Belmont Report, but also raises issues related to all the principles. These vignettes are intentionally complex to mirror the difﬁculties of conducting research in reallife settings; these political and ﬁnancial complexities are acknowledged but not further explored. These cases raise many ethical questions that are philosophical (and likely unanswerable), but need to be considered within the moral framework of the sponsors, investigators, and subjects of international studies. These philosophical questions may, however, help to generate research questions that are worthy of study, with measurable answers that could be used to further the ethical conduct of global acute care research. We
propose both categories of questions, to instill integrity into our research practices and to provide a research agenda on the ethics of global acute care research. Case 1: Respect for Persons You are studying the epidemiology of opiate abuse in a Southeast Asian country through interviews at local community health centers and acute care facilities. Community leaders plan to use the data to improve resource allocation and decrease the burden of disease associated with opiate abuse. Of note, there is signiﬁcant social stigma associated with this problem in this community. The all-male village council, which consists of the local religious leader, the owner of the local hostel, the hereditary chief, and four village elders, has voted to “consent” for everyone in the community to enroll in the study. You are about to interview a 19-year-old female with a history of opiate abuse who presented to the local acute care center with altered mental status that improved with an opiate antagonist. The patient declines to participate in the study, but her husband arrives and, citing the consent of the village council, demands that she be enrolled so that she can more readily access drug abuse treatment resources. Issues Brought Up by Case 1. This case highlights a number of critical ethical concepts and tensions related to informed consent, particularly as it relates to autonomy and respect for the individual versus the role of the community or society in which the individual lives. Community consent may supplement, but should not supplant, individual voluntary informed consent.1 However, how is “voluntary” deﬁned in a setting where there are multiple societal and personal pressures placed on the potential research subject? Community consent works by allowing an identiﬁed and clearly delineated community to make a decision allowing for the opportunity to participate in research for the individuals in that community. Community consent, particularly in a research setting, contradicts prior ethical principles since it could, in part, relinquish control by the individual to the larger community. Of note, community consent is different from the concept of community consultation, which is used in the United States for exception from informed consent studies. Such studies examine a life-saving intervention in a time-sensitive, life-threatening situation where individual consent cannot be obtained because of the nature of the condition. Community consultation serves as a means of obtaining ideas, concerns, and questions regarding the research from the community when studies are proposed that will require an exception from informed consent. The results of this process are then reviewed and approved by an IRB. The community, as deﬁned by MacQueen et al.,14 is “a group of people with diverse characteristics who are linked by social ties, share common perspectives, and engage in joint action in geographical locations or settings.” It serves as a locus for decision-making. Consent in this environment is made by the group or its accepted representatives to account for the burdens that the community faces, which are different than the burdens faced by the individuals.15 Additionally, it allows
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for a consent process when the individual participants may not have the knowledge or ability to give a truly informed consent for participation. Alternatively, it is also a mechanism for approval when the community denies certain community members the right to give consent. Thus, it has both an intrinsic component related to (mental) capacity and an extrinsic component related to rights (social laws). Allowing community consent raises a number of ethical questions. For example, what is the appropriate balance between community beneﬁts versus individual autonomy, especially if the subject is vulnerable within the community? How does this balance change based on the deﬁned roles of individuals within a community, such as the different roles played by men and women in many cultures? Clearly, there is the potential for signiﬁcant tension or conﬂict, or even abuse, when a researcher from outside the community, with his or her own cultural perspective and norms, presents to conduct research. How can the risk/beneﬁt ratio of the research be maximized (beneﬁcence) between the community and the individual? When the consent is obtained from the community but the individual is the one placed at risk from the research, is equitable distribution of the burdens and beneﬁts of research participation (justice) met? Suggestions for Future Research From Case 1:. 1. How do researchers obtain “community consent” (i.e., permission from required community leaders to invite community members to enroll in studies) without creating or exacerbating coercive inﬂuences that potentially violate the research participant’s individual right to voluntary informed consent or refusal? How effective are the various consent methods? In what ways does community consent enhance (or diminish) individual consent? Does community consent improve the quality of the individual consent if individual capacity is limited? Alternatively, what happens if the limitation is due to societal role? How does community consent affect the most vulnerable groups, e.g., women, orphans and vulnerable children, sex workers, the extreme poor? What responsibility does the researcher have if the research subject completely defers to the community—i.e., how can researchers assess the voluntariness of this decision and the potential consequences to the individual? How can one determine if this deferral is being made voluntarily? Many of these questions are anthropologic in nature, but relevant to all researchers faced with some form of community consent. 2. What methods would improve individual informed consent in global acute care research? How do researchers handle challenges to the informed consent standard created by contextual factors such as language, education, culture, religion, gender relations, community governance, local assessment of risk, and understanding of disease causation and medical research? How do researchers disclose speciﬁc study information (e.g., diagnosis and risk, research design, possible posttrial beneﬁts, conﬂict of interest), and how do they measure understanding
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in communities and among individuals with limited knowledge and experience with Western science? Are there alternatives to standard tools used in the United States (such as informed consent forms requiring signature) that better address the needs, capabilities, and traditions of host communities and at the same time meet the substantive, although not necessarily the procedural, requirements of U.S. and international research ethics guidance? Is there cultural variation in the way that competence is understood that would inﬂuence the consent process in global acute care research? Could visual media, or alternate forms disclosing study information and facilitating informed consent, improve comprehension of personal and community beneﬁts and risks? What is the relative effectiveness of various methods? What characteristics of the participants and the community make particular methods more effective than others? How should the consent process be evaluated in an ongoing manner, and should consent monitoring be included in study designs?16 3. There are a multitude of other possible research questions that could be developed around the ideas of respect and consent. For example, would U.S. focus groups of immigrants from the country of study provide insight into community opinions? If so, how would this be done and would these groups be representative? What types of questions would they raise that the local IRB would not? Could an immigrant group (for example, one that understands the norms and traditions of both the sponsor and the host community) identify opportunities for enhanced partnerships between researchers (from both the sponsor and the host country) and the community? Another series of questions could be asked concerning the current knowledge and level of understanding of IRBs related to the concept of community consent in a global health setting. Are there different levels of acceptance and understanding concerning community consent by different IRBs? How would the decision of an IRB based on a Western regulatory framework differ from that of the local community consenting group? Can these differences be predicted beforehand and measured? Case 2: Beneﬁcence In a low-resource clinic in sub-Saharan Africa, you propose a clinical trial comparing the effectiveness of intravenous (IV) quinine versus intramuscular (IM) artemether in the treatment of acute malaria. Using an IM medication can be extremely advantageous in lowresource settings, where IV access is often difﬁcult. In addition, there is substantial mounting evidence of the increased prevalence of quinine-resistant malaria in sub-Saharan Africa. For the purpose of this study, the only change in the standard treatment is the medication used for malaria. Concurrent HIV diagnosis and treatment is not in the purview of the research protocol. However, considering the signiﬁcant clinical interactions between malaria and HIV, as well as the issues related to access to health care, diagnosis and clinical treatment of HIV is potentially intertwined with the research study.
Issues Brought Up by Case 2. Through the ethical principle of beneﬁcence, this case highlights the issue of ancillary care provision in clinical research. Simply put, the researcher is expected to maximize beneﬁts while minimizing the risks of research.17 The ethical principle of beneﬁcence states that there is a duty to beneﬁt participants or at least do no harm.18 However, maximizing participant beneﬁts may have substantial implications for the individual, the society, and the researcher. Consideration is required of not only risk/beneﬁt ratio for the individual but also the broader impact of the research. In this case, the individual participant would likely receive the greatest beneﬁt through HIV diagnosis and treatment. However, what if the local participants did not desire the added knowledge? What if HIV seropositivity would cause them to be vulnerable to group disapproval or even cause the research subjects to be ostracized? What are the implications for providing HIV testing on the ﬁnancial feasibility of the study? Also, would providing HIV-related resources undermine preexisting government programs? From the researcher’s perspective, by not providing concurrent HIV diagnosis and treatment, the costs of the study would be minimized and project success would likely be increased. Alternatively, for the researcher it may be important to ﬁnd out subjects’ HIV status, as this could be a signiﬁcant confounder in a clinical trial of malaria treatment. Thus, HIV diagnosis and care may be required to improve scientiﬁc validity of the research. From this perspective, provision of HIV services would not be considered ancillary care, but an important component of the research. Taken further, does beneﬁcence demand that researchers in low-resource settings be responsible for building the capacity of the local health care system? This concept is termed ancillary care provision.19 Ancillary care services are generally not required to ensure scientiﬁc validity or patient safety. Ancillary care services and capacity building of the local health care environment could be accomplished in several ways, such as raising awareness or building infrastructure or through long-term beneﬁts that occur as a result of the research.20 In this case, possible ancillary service options include: 1) provide no HIV treatment, 2) provide HIV diagnosis and referral to alternative sites for care, and 3) provide HIV diagnosis and treatment to all participants. Considering the beneﬁts at differing levels of effect (i.e., the individual, the researcher, and the community), ethical tensions within the principle of beneﬁcence are highlighted. Thus, with the potentially competing beneﬁts, which has the greatest priority? Ultimately, what are the implications for the research study, participants, and society for each option? Suggestions for Future Research From Case 2:. 1. What role should acute care researchers play in improving clinical and research capacity in lowresource communities? To what extent should capacity building be incorporated into research in low-resource settings, and what approaches make capacity building feasible and sustainable? A way to answer some of these questions, at least based on current understanding,
would be to conduct a consensus process that includes expert researchers and ethicists from both in the United States and in international settings regarding the role and sustainability of capacity building in global acute care research. 2. From a community and human subjects’ perspectives, what are the short-term and long-term effects of global emergency care research? Consider assessing the effects of “ﬂy-in/ﬂy-out” research activities: what are the long-term implications of a short-term research project? Assess the sustainability of the project, including how to create a more sustainable activity. How is the community deﬁned and how is the effect of the project on the community assessed? What is the responsibility of the research to assure sustainability? How would these questions change in the setting of research in disaster response and a humanitarian crisis? 3. How can researchers and communities work together to ensure that the research and any associated capacity building best address the needs of the community and provide the most beneﬁt? As an example, one could survey community leaders and members, both before and after a study, concerning the effect of the research on the individual and community. Alternatively one could systematically examine improvements in knowledge, health and research infrastructure, and public policy as a result of existing clinical trial networks. Case 3: Justice An unnamed government has sponsored research to evaluate a blood substitute for use in wartime trauma occurring in remote humid tropical settings. Although the product looks good in the lab, this study would be the ﬁrst human use of the product. The project is top secret, and the product would not be marketed or released for general use. The investigating country is not currently involved in any tropical warfare, but does secretly supply medical supplies to a rebel group involved in a civil war. The researchers have had extensive discussions with many of the members and leaders of the rebel group about this study, and the rebels have agreed to be research participants. The discussion has included consideration of potential personal beneﬁt for a participant if the product is successful, but has also indicated that the potential for success is not known because the blood substitute has never been tested in humans before. It is also noted that the product would be administered to traumatized persons in extremis and who do not speak the language of the investigators. Issues Brought Up by Case 3. This is a complex case that touches on a number of ethical issues. The sponsored researchers are asking a group dependent on donated medical supplies to give consent for a study of an investigational agent with no established safety proﬁle. The obvious power differential between the rebels and the investigating agency could be viewed as coercive, with failure to comply possibly associated with the penalty of the loss of donated medical supplies. The risk/beneﬁt of research involvement is unknown, but it is stated that there is a potential for direct beneﬁt for
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the enrolled individual; however, suggesting the potential for beneﬁt may not be reasonable when the safety proﬁle of the intervention is not known. If the study is successful, the investigational agent will only be available to the sponsoring country and no longer to the rebel group. Justice in research refers to the equitable distribution of the burdens and beneﬁts of research participation. The rebels in this case would incur the risks but would not receive the beneﬁts of the research (i.e., access to the blood substitute if proven effective). Many ethicists consider research beneﬁts to include posttrial access to research products.21–23 With this interpretation, conﬂicts arise regarding justice in research when the product of successful research is not available to the society in which the research was performed—the society that has been exposed to potential risk during the research process. If the end product of research will not beneﬁt all people, including those who have borne the burden of research, some believe that the concept of justice in research is not, in the strictest sense, met. For global acute care research, perhaps a more relevant issue for the traditional concept of justice is the deﬁnition of beneﬁt. Is access to the end product of research the only potential beneﬁt to research participation? Even in the best-conducted clinical trials within the developed world, new interventions may take years to be put into clinical practice. Posttrial access to a new product in the developing world may be further hampered by poorly functioning health care systems, and there is no way to assure that the products will ever reach those who are most in need.24 There may be other beneﬁts besides or in addition to the results of the research.25 In the case described above, it is unlikely that adequate medical infrastructure exists for the beneﬁt of the local society. However, justice in research requires the establishment of priorities related to the local society to balance the overall risk-to-beneﬁt ratio. The risk-to-beneﬁt assessment of the trial must be considered within the social context of where the research will occur.26,27 While the ultimate speciﬁc end product of the research may prove ineffective and never be available, this research may provide better local understanding of the importance of stopping acute traumatic hemorrhage, the need to triage injured individuals based on those most likely to beneﬁt from available resources, and the need for an organized manner to access emergent care. There may also be a potential medical beneﬁt to the individual person in extremis as no other treatment (experimental or otherwise) may be available. Another issue raised by this case concerns the exploitation of a vulnerable group, rebel soldiers dependent on medical supplies from the sponsoring country. Participation in research becomes exploitative when the terms of the agreement are not fair.28 Reducing the potential for exploitation is a critical challenge in global acute care research. Exploitation in global research occurs for a number of reasons, including poverty, social pressure, limited health services, conﬂation of research and clinical treatment, and lack of local regulatory agencies to provide human subjects protection.26 Reducing the potential for exploitation requires honest
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assessment by the sponsor and investigators to assure that the research design, subject recruitment, and beneﬁts of the research will have social value and that the aspirations and self-interest of the researchers do not interfere with this assessment. Suggestions for Future Research From Case 3: 1. How does the process of obtaining IRB/ethics approval in the United States compare to the process in other countries? There is an opportunity to research the attitudes of (U.S.) IRBs concerning research in other countries to inform and streamline the research review process. How can the linkage between local community input and the Western IRBs be improved? In addition to improved review processes, how can the safe conduct of research be improved? 2. How can coercion for an individual or community to participate in research be measured? When does it rise to a level of concern? How can a community’s ability to do adequate risk assessment, in the face of extremely limited health services, be assessed? How does the research community deﬁne what a reasonable person would want within a speciﬁc culture or research project? How can researchers and regulators protect vulnerable populations from exploitation? 3. Much of research ethics, even in the global health setting, relies on Western IRB doctrines to guide the practical and procedural application of core ethical principles. However, these ethical principles may guide research priorities in different directions depending on the local cultural context. What is the effect of these divergent priorities and activities? The global acute care research community should develop feasible methods to determine unanticipated consequences of research activities and ﬁndings. As one means of initially accomplishing this, interviews with other researchers in the area of the study may provide guidance to the limitations that must be enforced within the emergency research study or methods by which unexpected ﬁndings can be dealt with.29 A systematic review of both the scientiﬁc and the gray literature would help inform this question. SUMMARY The ethics consensus group for global health and emergency care has reviewed ethical concepts in research and reasserted the importance of ethical conduct in acute care research in global settings. Most researchers from the developed world are well versed in the basic ethical principles and the practicalities of research within their own universities, states, and countries. However, when research is conducted transnationally and cross-culturally, universal ethical principles may be interpreted and assessed differently from traditional understanding in the developed world. We presented three cases to illuminate the concepts of autonomy, beneﬁcence, and justice and to raise questions that are in need of clariﬁcation and thus further study. A research agenda and speciﬁc research questions have
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