Understanding informed consent for participation in international health research

To participate in health research, there is a need for well-administered informed consent. Understanding of informed consent, especially in international health research, is influenced by the participants' understanding of information and the meaning attached to the information communicated to them regarding the purpose and procedure of the research. Incorrect information and the power differential between researcher and participants may lead to participants becoming victims of harmful research procedures. Meningitis epidemics in Kano in early 1996 led to a response from drug companies, especially Pfizer, as well as humanitarian workers from Médecins Sans Frontiers, which resulted in an unethical trial. Pfizer's drug trial during the epidemics has left a lasting controversy, which has yet to be resolved. This paper examines the key issues surrounding the controversy, discusses the context of informed decision-making, the ethical issues and implications of the incident, and concludes with some recommendations. Relevant texts, journals, Internet materials, newspaper articles and documentary materials on the conduct of the Pfizer's Trovan trial have been consulted. Four types of action (act intuitively, act rationally, act ignorantly, and act contextually – based on information provided) are identified as possible options for decision making. Participants most likely acted in ignorance due to poor understanding of the information contained in the verbal informed consent administered, thereby raising ethical issues. It is concluded that health research ethics committees have an important role to play nationally and locally in overseeing research, and in avoiding future occurrences.     

Prioritising African perspectives in psychiatric genomics research: Issues of translation and informed consent

Psychiatric genomics research with African populations comes with a range of practical challenges around translation of psychiatric genomics research concepts, procedures, and nosology. These challenges raise deep ethical issues particularly around legitimacy of informed consent, a core foundation of research ethics. Through a consideration of the constitutive function of language, the paper problematises like‐for‐like, designative translations which often involve the ‘indigenization’ of English terms or use of metaphors which misrepresent the risks and benefits of research. This paper argues that effective translation of psychiatric genomics research terminology in African contexts demands substantive engagement with African conceptual schemas and values. In developing attenuated forms of translational thinking, researchers may recognise the deeper motivational reasons behind participation in research, highlighting the possibility that such reasons may depart from the original meaning implied within informed consent forms. These translational issues might be ameliorated with a critical re‐examination of how researchers develop and present protocols to institutional ethics review boards.     

The adequacy of informed consent forms in genetic research in Oman: a pilot study

Genetic research presents ethical challenges to the achievement of valid informed consent, especially in developing countries with areas of low literacy. During the last several years, a number of genetic research proposals involving Omani nationals were submitted to the Department of Research and Studies, Ministry of Health, Oman. The objective of this paper is to report on the results of an internal quality assurance initiative to determine the extent of the information being provided in genetic research informed consent forms. In order to achieve this, we developed checklists to assess the inclusion of basic elements of informed consent as well as elements related to the collection and future storage of biological samples. Three of the authors independently evaluated and reached consensus on seven informed consent forms that were available for review. Of the seven consent forms, four had less than half of the basic elements of informed consent. None contained any information regarding whether genetic information relevant to health would be disclosed, whether participants may share in commercial products, the extent of confidentiality protections, and the inclusion of additional consent forms for future storage and use of tissue samples. Information regarding genetic risks and withdrawal of samples were rarely mentioned (1/7), whereas limits on future use of samples were mentioned in 3 of 7 consent forms. Ultimately, consent forms are not likely to address key issues regarding genetic research that have been recommended by research ethics guidelines. We recommend enhanced educational efforts to increase awareness, on the part of researchers, of information that should be included in consent forms.     

Informed consent in clinical research at a general hospital in Mexico: opinions of the investigators

In Mexico informed consent is a legal requirement that ensures that patients who are invited to participate in clinical trials are provided with all the information needed to decide whether to participate, or not, in a research protocol. To improve our understanding of the problems physicians in developing countries encounter, when obtaining informed consent (IC), we examined their opinion on the importance of IC in clinical research, the quantity and quality of the information provided to the participant, and the conditions in which the IC is obtained. Investigators considered that IC was useful to the patients, providing information that helped the patient to make a decision about his/her participation. Nevertheless, they felt that for some aspects of the research, like drug development in general, the use of placebos, and the randomization process, many of the patients were not capable of fully understanding the information provided, referring to the complexity of the information and illiteracy as the main reasons. Many investigators were not acquainted with some of the guidelines established in the Mexican General Law of Health,(1) 36% of them admitting to not having completed their IC letters. Most investigators gave only minutes to the patient to make a decision and 20% of ICs were obtained while the patient was hospitalized. Except for one investigator, all of them considered that specific training in medical ethics would be useful for the daily clinical work.     

The role and responsibilities of witnesses in the informed consent process

Various mechanisms to ensure the protection of subjects in human research have been suggested, including the presence of witnesses during the informed consent process. For our commentary on the use of witnesses and their potential role and responsibility during the consent process, we start by addressing current guidelines for human subjects research in four Latin American countries. By using examples from public health research, we highlight some of the practical difficulties of using witnessed consent, from becoming a meaningless ritual at one end of the spectrum to the research subject feeling intimidated or coerced to participate at the other. Apart from these practical difficulties, it is unclear what responsibility the witness could and should have. We argue that there are important ethical questions about the role of witnesses that have not been adequately addressed in national and international regulations. This work addresses these gaps and argues that more debate is required to define the role and responsibilities of witnesses in the consent process, their training requirements and whether a universal legal requirement for witnessed consent, regardless of the type of research, is desirable.     

Lay concepts in informed consent to biomedical research: the capacity to understand and appreciate risk

Persons generally must give their informed consent to participate in research. To provide informed consent persons must be given information regarding the study in simple, lay language. Consent must be voluntary, and persons giving consent must be legally competent to consent and possess the capacity to understand and appreciate the information. This paper examines the relationship between the obligation to disclose information regarding risks and the requirement that persons have the capacity to understand and appreciate the information. There has been insufficient attention to the extent to which persons must be able to understand and appreciate study information in order to have their consent deemed valid when the information is provided in simple, lay language. This paper argues that (1) the capacity to understand and appreciate information that should be deemed necessary to give valid consent should be defined by the capacity of the typical, cognitively normal adult and (2) the capacity of the typical, cognitively normal adult to understand and appreciate the concept of risk is limited. Therefore, (3) all things being equal, potential subjects must possess a limited capacity to understand and appreciate risk to be deemed competent to consent to research participation. (4) In some cases investigators ought to require that persons possess a greater than typical capacity to understand and appreciate risk.     

Informed consent for controlled human infection studies in low- and middle-income countries: Ethical challenges and proposed solutions

In controlled human infection studies (CHIs), participants are deliberately exposed to infectious agents in order to better understand the mechanism of infection or disease and test therapies or vaccines. While most CHIs have been conducted in high-income countries, CHIs have recently been expanding into low- and middle-income countries (LMICs). One potential ethical concern about this expansion is the challenge of obtaining the voluntary informed consent of participants, especially those who may not be literate or have limited education. In some CHIs in LMICs, researchers have attempted to address this potential concern by limiting access to literate or educated populations. In this paper, we argue that this practice is unjustified, as it does not increase the chances of obtaining valid informed consent and therefore unfairly excludes illiterate populations and populations with lower education. Instead, we recommend that investigators improve the informed consent process by drawing on existing data on obtaining informed consent in these populations and interventions aimed at improving their understanding. Based on a literature review, we provide concrete suggestions for how to follow this recommendation and ensure that populations with lower literacy or education are given a fair opportunity to protect their rights and interests in the informed consent process.     

Improving the Quality of Host Country Ethical Oversight of International Research: The Use of a Collaborative ‘Pre‐Review’ Mechanism for a Study of Fexinidazole for Human African Trypanosomiasis

Developing countries face numerous barriers to conducting effective and efficient ethics reviews of international collaborative research. In addition to potentially overlooking important scientific and ethical considerations, inadequate or insufficiently trained ethics committees may insist on unwarranted changes to protocols that can impair a study's scientific or ethical validity. Moreover, poorly functioning review systems can impose substantial delays on the commencement of research, which needlessly undermine the development of new interventions for urgent medical needs. In response to these concerns, the Drugs for Neglected Diseases Initiative (DNDi), an independent nonprofit organization founded by a coalition of public sector and international organizations, developed a mechanism to facilitate more effective and efficient host country ethics review for a study of the use of fexinidazole for the treatment of late stage African Trypanosomiasis (HAT). The project involved the implementation of a novel ‘pre‐review’ process of ethical oversight, conducted by an ad hoc committee of ethics committee representatives from African and European countries, in collaboration with internationally recognized scientific experts. This article examines the process and outcomes of this collaborative process.     

Informed consent and collaborative research: perspectives from the developing world

Introduction: Informed consent has been recognized as an important component of research protocols and procedures of disclosure and consent in collaborative research have been criticized, as they may not be in keeping with cultural norms of developing countries. This study, which is part of a larger project funded by the United States National Bioethics Advisory Commission, explores the opinions of developing country researchers regarding informed consent in collaborative research. Methods: A survey of developing country researchers, involved in human subject research, was conducted by distributing a questionnaire with 169 questions, which included questions relating to informed consent. In addition, six focus group discussions, eight in-depth interviews and 78 responses to open-ended questions in the questionnaire provided qualitative data. Results: 203 surveys were considered complete and were included in the analysis. Written consent was not used by nearly 40% of the researchers in their most recent studies. A large proportion of respondents recommended that human subject regulations should allow more flexibility in ways of documenting informed consent. 84% of researchers agreed that a mechanism to measure understanding should be incorporated in research studies as part of the process of informed consent. Discussion: This paper is an empirical step in highlighting the ethical issues concerning disclosure. Health researchers in developing countries are well aware of the importance of consent in health research, and equally value the significance of educating human subjects regarding study protocols and associated risks and benefits. However, respondents emphasize the need for modifying ethical regulations in collaborative research.     

The challenge of cross-cultural clinical trials research: case report from the Tibetan Autonomous Region, People's Republic of China

Efforts to conduct Western clinical research in non-Western medical settings with little or no familiarity with such methodologies are on the rise, but documented accounts of the ways that biomedical science requires negotiation and translation across cultures are not plentiful. This article adds to this literature through analysis of an NICHD-funded collaborative research effort in women's health carried out in the Tibetan Autonomous Region of the People's Republic of China. The research involved a feasibility study for an eventual clinical trial comparing Tibetan medicine with misoprostol for preventing postpartum hemorrhage in delivering women. It explores strategies of negotiation and translation in and around notions of the scientific method, informed consent procedures, randomization, blinding, placebo, and concepts of medical standardization.     

The Challenges of Research Informed Consent in Socio‐Economically Vulnerable Populations: A Viewpoint From the Democratic Republic of Congo

In medical research, the ethical principle of respect for persons is operationalized into the process of informed consent. The consent tools should be contextualized and adapted to the different socio‐cultural environment, especially when research crosses the traditional boundaries and reaches poor communities. We look at the challenges experienced in the malaria Quinact trial, conducted in the Democratic Republic of Congo, and describe some lessons learned, related to the definition of acceptable representative, the role of independent witness and the impact of socio‐economic vulnerability. To ensure children's protection, consent is required by the parents or, in their absence, by a legally mandated representative. In our setting, children's responsibility is often entrusted permanently or temporarily to relatives or friends without a tribunal mandate. Hence, a notion of ‘culturally acceptable representative’ under supervision of the local Ethics Committee may be more suitable. To ensure protection of illiterate subjects, an independent witness is required to confirm that the consent was freely given. However, in low‐literacy contexts, potential witnesses often don't have any previous relationship with patient and there may be power‐unbalance in their relationship, rather than genuine dialogue. In poor communities, trial participation may be seen as an opportunity to secure access to healthcare. Poverty may also lead to ‘competition’ to access the research‐related benefits, with a risk of disturbance at societal or household level. Adjusting consent procedures to sociocultural and socioeconomic realities is essential for fulfilling the underlying ethical principles. This requires a collaborative dialogue between researchers, regulators and ethics committees.     

South African Museums and the Creation of a New National Identity

Museums are important sites of national cultural production, collective memory making, and the construction of national narratives. Contemporary South Africa is a particularly interesting place to study these processes. With the demise of apartheid, South Africa faces the difficult challenge of creating a new national identity that incorporates an examination of past oppression yet leaves the way open for building a national identity that incorporates all its diverse groups. The museums reviewed below, the Robben Island Prison Museum, the District Six Museum in Capetown, and the Kwa Muhle local history museum in Durban all make important contributions to this process.     

Investigating assumptions of vulnerability: A case study of the exclusion of psychiatric inpatients as participants in genetic research in low‐ and middle‐income contexts

Psychiatric genetic research investigates the genetic basis of psychiatric disorders with the aim of more effectively understanding, treating, or, ultimately, preventing such disorders. Given the challenges of recruiting research participants into such studies, the potential for long‐term benefits of such research, and seemingly minimal risk, a strong claim could be made that all non‐acute psychiatric inpatients, including forensic and involuntary patients, should be included in such research, provided they have capacity to consent. There are tensions, however, regarding the ethics of recruiting psychiatric inpatients into such studies. In this paper our intention is to elucidate the source of these tensions from the perspective of research ethics committee interests and decision‐making. We begin by defining inpatient status and outline some of the assumptions surrounding the structures of inpatient care. We then introduce contemporary conceptions of vulnerability, including Florencia Luna’s account of vulnerability which we use as a framework for our analysis. While psychiatric inpatients could be subject to consent‐related vulnerabilities, we suggest that a particular kind of exploitation‐related vulnerability comes to the fore in the context of our case study. Moreover, a subset of these ethical concerns takes on particular weight in the context of genetic research in low‐ and middle‐income countries. At the same time, the automatic exclusion of inpatients from research elicits justice‐related vulnerabilities.     

Engaging Diverse Social and Cultural Worlds: Perspectives on Benefits in International Clinical Research From South African Communities

The issue of benefits in international clinical research is highly controversial. Against the background of wide recognition of the need to share benefits of research, the nature of benefits remains strongly contested. Little is known about the perspectives of research populations on this issue and the extent to which research ethics discourses and guidelines are salient to the expectations and aspirations existing on the ground. This exploratory study contributes to filling this void by examining perspectives of people in low‐income South African communities on benefits in international clinical research. Twenty‐four individuals with and without experience of being involved in clinical research participated in in‐depth interviews. Respondents felt that ancillary care should be provided to clinical research participants, while a clinical study conducted in particular community should bring better health to its members through post‐trial benefits. Respondents' perspectives were grounded in the perception that the ultimate goal of international clinical research is to improve local health. We argue that perspectives and understandings of the respondents are shaped by local moral traditions rather than clinical research specificities and require attention as valid moral claims. It is necessary to acknowledge such claims and cultural worlds from which they emerge, thus building the foundation for equal and embracing dialogue to bridge different perspectives and handle contradicting expectations.     

Physical growth in a transitional economy: the aftermath of South African apartheid

The economic transition in developing countries is not always the result of the change from a centrally-planned to a free-market economy, but may be found within an already existing free-market economy as a result of profound political change, as in South Africa. The release of Nelson Mandela in February 1990 heralded an end both to the political system of apartheid and to the concomitant social, political, and economic disenfranchisement of 30 million non-White people in South Africa. The first freely elected non-White government came to power in 1994 and initiated a number of social and economic reforms aimed at alleviating the worst consequences of apartheid. This paper examines the effect of post-apartheid economic and social transition on the growth and development of urban children. Over 4000 children born in Soweto and Johannesburg were enrolled in the Birth to Ten (BTT) birth-cohort study in 1990. Whilst these children were born with lower birth weights than in developed countries, they did grow strongly in infancy, particularly in weight, to reflect normal reference values for body mass index (BMI) by 1 year of age. While post-apartheid social and economic changes were expected to take some time to affect child growth and development, the rate of change has been slower than expected. Data from the BTT study demonstrate that the growth of White children continues to be superior to that of their non-White peers and differences that existed at birth and during infancy have not diminished during childhood and early adolescence. Whatever factors are changed at the national or community levels during economic (and social) transition in South Africa appear not yet to have resulted in improved child physical growth.     

Hydrochemical response during storm events in a South African mountain catchment: the influence of antecedent conditions

The influence of different antecedent conditions on hydrochemical response during storm events was investigated in a small, south-western Cape mountain catchment. Winter and summer storms (four in total) were sampled both before and after the catchment was deliberately burnt. During winter storms, discharge responded rapidly to rainfall, and direct runoff represented the major component of streamflow. Marked lags were observed between rainfall and discharge peaks during the summer storms, and streamflow was dominated by delayed interflow. Chloride, PO _inf4 ^sup3– -P and NO _inf3 ^sup– -N exhibited variable response to discharge according to seasonal variations in soil-moisture levels, whereas the response of HCO _inf3 ^sup– , H⁺ and NH _inf4 ^sup+ -N was not influenced by season. The movement of ions appears to be affected more by geochemical processes operating within the soil than by plant-uptake dynamics, as the prescribed burn appeared to have little effect on relationships between ionic concentration and discharge. The findings of the study highlight the complexity of relationships between solute concentration and discharge.     

The reporting of IRB review in journal articles presenting HIV research conducted in the developing world

Objectives: We investigated how often journal articles reporting on human HIV research in four developing world countries mention any institutional review boards (IRBs) or research ethics committees (RECs), and what factors are involved. Methods: We examined all such articles published in 2007 from India, Nigeria, Thailand and Uganda, and coded these for several ethical and other characteristics. Results: Of 221 articles meeting inclusion criteria, 32.1% did not mention IRB approval. Mention of IRB approval was associated with: biomedical (versus psychosocial) research (P = 0.001), more sponsor‐country authors (P = 0.003), sponsor‐country corresponding author (P = 0.047), mention of funding (P < 0.001), particular host‐country involved (P = 0.002), journals having sponsor‐country editors (P < 0.001), and journal stated compliance with International Committee of Medical Journal Editors (ICMJE) guidelines (P = 0.003). Logistic regression identified 3 significant factors: mention of funding, journal having sponsor‐country editors and research being biomedical. Conclusions: One‐third of articles still do not mention IRB approval. Mention varied by country, and was associated with biomedical research, and more sponsor country involvement. Recently, some journals have required mention of IRB approval, but allow authors to do so in cover letters to editors, not in the article itself. Instead, these data suggest, journals should require that articles document adherence to ethical standards.     

Entrepreneurship in South African township tourism: the impact of interracial social capital

Ethnic entrepreneurship scholarship has demonstrated the importance of social capital for “minority” entrepreneurs, but these studies presume that social capital is co-ethnic. I complicate this assumption by investigating entrepreneurial black women and interracial social capital in South African township tourism, a niche market within the nation’s growing tourism industry. Drawing from ethnographic fieldwork conducted in two black townships in Cape Town, I spotlight black women who have established home-based bed and breakfasts and formed connections with white Europeans and South Africans during their entrepreneurial journeys. Employing Bourdieu’s theory of capital, I discuss how these entrepreneurs develop ties with whites to acquire social, economic, cultural, and symbolic forms of capital that have been systemically denied to them as black South African women. The interracial transference of these resources underscores the deep inequalities between blacks and whites, but also the agency of marginalized entrepreneurs to attain assets within constricting social structures.