Reuse of samples: ethical issues encountered by two institutional ethics review committees in Kenya

There is growing concern about the reuse and exploitation of biological materials (human tissues) for use in research worldwide. Most discussions about samples have taken place in developed countries, where genetic manipulation techniques have greatly advanced in recent years. There is very little discussion in developing countries, although collaborative research with institutions from developed countries is on the increase. The study sought to identify and describe ethical issues arising in the storage, reuse and exportation of samples in a developing country. Research protocols presented to two Ethics Review Committees in Kenya during a period of two years were reviewed. A record was made of the protocol title, sample collected, request for storage, reuse or exportation and whether or not subject consent was sought. The findings indicated that about 25% out of the 388 protocols sought permission for reuse and only half of those actually informed subjects of the contemplated re-use. Less than 20% requested storage and again, about half of them sought consent from subjects. There is an indication that investigators do not see the need to seek consent for storage, reuse and exportation of samples. It is proposed that these issues should be addressed through policy interventions at both the national and global levels.     

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.     

TRAINING NEEDS ASSESSMENT IN RESEARCH ETHICS EVALUATION AMONG RESEARCH ETHICS COMMITTEE MEMBERS IN THREE AFRICAN COUNTRIES: CAMEROON,MALI AND TANZANIA

Background: As actors with the key responsibility for the protection of human research participants, Research Ethics Committees (RECs) need to be competent and well‐resourced in order to fulfil their roles. Despite recent programs designed to strengthen RECs in Africa, much more needs to be accomplished before these committees can function optimally. Objective: To assess training needs for biomedical research ethics evaluation among targeted countries. Methods: Members of RECs operating in three targeted African countries were surveyed between August and November 2007. Before implementing the survey, ethical approvals were obtained from RECs in Switzerland, Cameroon, Mali and Tanzania. Data were collected using a semi‐structured questionnaire in English and in French. Results: A total of 74 respondents participated in the study. The participation rate was 68%. Seventy one percent of respondents reported having received some training in research ethics evaluation. This training was given by national institutions (31%) and international institutions (69%). Researchers and REC members were ranked as the top target audiences to be trained. Of 32 topics, the top five training priorities were: basic ethical principles, coverage of applicable laws and regulations, how to conduct ethics review, evaluating informed consent processes and the role of the REC. Conclusion: Although the majority of REC members in the targeted African countries had received training in ethics, they expressed a need for additional training. The results of this survey have been used to design a training program in research ethics evaluation that meets this need.     

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.     

The perspectives of researchers on obtaining informed consent in developing countries

Background: The doctrine of informed consent (IC) exists to protect individuals from exploitation or harm. This study into IC was carried out to investigate how different researchers perceived the process whereby researchers obtained consent. It also examined researchers’ perspectives on what constituted IC, and how different settings influenced the process. Methods: The study recorded in‐depth interviews with 12 lecturers and five doctoral students, who had carried out research in developing countries, at a leading school of public health in the United Kingdom. A purposive, snowballing approach was used to identify interviewees. Results: Although the concept and application of the doctrine of IC should have been the same, irrespective of where the research was carried out, the process of obtaining it had to be different. The setting had to be taken into consideration and the autonomy of the subject had to be respected at all times. In areas of high illiteracy, and where understanding of the subject was likely to be a problem, there was an added responsibility placed on the researcher to devise innovative ways of carrying out the study, taking into consideration the peculiarities of the environment. Conclusion: The ethical issues for IC were the same, irrespective of where the research was conducted. However, because the backgrounds, setting, and knowledge of populations differed, there was the need to be similarly sensitive in obtaining consent. The problems of obtaining genuine IC were not limited to developing countries.     

STAKEHOLDER PERSPECTIVES ON ETHICAL CHALLENGES IN HIV VACCINE TRIALS IN SOUTH AFRICA

There is little published literature on the ethical concerns of stakeholders in HIV vaccine trials. This study explored the ethical challenges identified by various stakeholders, through an open-ended, in-depth approach. While the few previous studies have been largely quantitative, respondents in this study had the opportunity to spontaneously identify the issues that they perceived to be of priority concern in the South African context. Stakeholders spontaneously identified the following as ethical priorities: informed consent, social harms, collaborative relationships between research stakeholders, the participation of children and adolescents, access to treatment for participants who become infected with HIV, physical harms, fair participant and community selection, confidentiality, benefits, and payment.
While there is some speculation that research in developing countries poses special ethical challenges, overall no issues were identified that have not been anticipated in international guidance, literature and popular frameworks. However, the South African context affords a distinctive gloss to these expected issues; for example, respondents were concerned that the predominant selection of black participants may perpetuate racist practices of apartheid. Stakeholders should be aware of contextual factors impacting on the implementation of ethical principles. We make a series of recommendations for South African trials, including amendments to the ethical-legal framework and research policies, and, for further research.     

Research Ethics: Beyond the Guidelines

There is international recognition of the need for sustainable research ethics committees to provide ethical review of human subjects research in developing countries, but many developing countries do not have such committees (often called 'IRBs'). Theoretical and practical uncertainties encountered by an IRB on the Caribbean island of Grenada offer insight into ethical review of research in developing countries. Theoretical uncertainties include questions about whether means of ensuring confidentiality and obtaining informed consent will be effective in local settings, and whether deviations from Western norms are justifiable. International guidelines are helpful in addressing these concerns, but are subject to interpretation. Guidelines are less helpful in practical areas like selecting members or chairs. They do not address what sort of procedures and paperwork will work in a developing country, or IRBs' relationships to governments that have no mandate for them. Experiences presented here show that IRBs in developing countries can sustainably adhere to international standards. Sustainability requires knowledge, personal commitment, and an official mandate to uphold international standards. Capacity building must therefore focus on educational programs to make developing country leaders knowledgeable about the value of international guidelines to their nations. Such knowledge is needed before people will become motivated to promote, implement, and uphold the guidelines. People in developing countries must help design bridges to help their nations put international standards into practice. The structure of such bridges may, of necessity, vary in different settings.     

Ethics committees. Research ethics: beyond the guidelines

There is international recognition of the need for sustainable research ethics committees to provide ethical review of human subjects research in developing countries, but many developing countries do not have such committees (often called 'IRBs'). Theoretical and practical uncertainties encountered by an IRB on the Caribbean island of Grenada offer insight into ethical review of research in developing countries. Theoretical uncertainties include questions about whether means of ensuring confidentiality and obtaining informed consent will be effective in local settings, and whether deviations from Western norms are justifiable. International guidelines are helpful in addressing these concerns, but are subject to interpretation. Guidelines are less helpful in practical areas like selecting members or chairs. They do not address what sort of procedures and paperwork will work in a developing country, or IRBs' relationships to governments that have no mandate for them. Experiences presented here show that IRBs in developing countries can sustainably adhere to international standards. Sustainability requires knowledge, personal commitment, and an official mandate to uphold international standards. Capacity building must therefore focus on educational programs to make developing country leaders knowledgeable about the value of international guidelines to their nations. Such knowledge is needed before people will become motivated to promote, implement, and uphold their guidelines. People in developing countries must help design bridges to help their nations put international standards into practice. The structure of such bridges may, of necessity, very in different settings.     

Assessment of the ethical review process in Sudan

The ethical review process is an important component of contemporary health research worldwide. Sudan started an ethical review process rather late in comparison with other countries. In this study, we evaluate the structure and functions of existing ethics review committees. We also explore the knowledge and attitudes of Sudanese researchers toward the ethical review process and their experience with existing ethics review committees. There are four ethics review committees in the country; these committees have no institutional regulations to govern their functions. Furthermore, Sudan also lacks national guidelines. Ethical reviews are carried out primarily for studies seeking international funding and are almost always governed by the funding agencies' requirements. Nearly half of respondents (46.3%) knew about the existence of research ethics committees in Sudan. Researchers reported a variety of experiences with the ethical review process; most of them were unable to define 'ethics committee'.     

Informed Consent in Health Research: Challenges and Barriers in Low‐and Middle‐Income Countries with Specific Reference to Nepal

Obtaining ‘informed consent’ from every individual participant involved in health research is a mandatory ethical practice. Informed consent is a process whereby potential participants are genuinely informed about their role, risk and rights before they are enrolled in the study. Thus, ethics committees in most countries require ‘informed consent form’ as part of an ethics application which is reviewed before granting research ethics approval. Despite a significant increase in health research activity in low‐and middle‐income countries (LMICs) in recent years, only limited work has been done to address ethical concerns. Most ethics committees in LMICs lack the authority and/or the capacity to monitor research in the field. This is important since not all research, particularly in LMICs region, complies with ethical principles, sometimes this is inadvertently or due to a lack of awareness of their importance in assuring proper research governance. With several examples from Nepal, this paper reflects on the steps required to obtain informed consents and highlights some of the major challenges and barriers to seeking informed consent from research participants. At the end of this paper, we also offer some recommendations around how can we can promote and implement optimal informed consent taking process. We believe that paper is useful for researchers and members of ethical review boards in highlighting key issues around informed consent.     

Alternatives of Informed Consent for Storage and Use of Human Biological Material for Research Purposes: Brazilian Regulation

Informed consent is recognized as a primary ethical requirement to conduct research involving humans. In the investigations with the use of human biological material, informed consent (IC) assumes a differentiated condition on account of the many future possibilities. This work presents suitable alternatives for IC regarding the storage and use of human biological material in research, according to new Brazilian regulations. Both norms – Resolution 441/11 of the National Health Council, approved on 12 May 2011, and Ordinance 2.201 (NATIONAL GUIDELINES FOR BIOREPOSITORIES AND BIOBANKS OF HUMAN BIOLOGICAL MATERIAL FOR RESEARCH PURPOSE) of the Brazil Ministry of Health, approved on 14 September 2011 – state that the consent of subjects for the collection, storage and use of samples stored in Biobanks is necessarily established by means of a Free and Informed Consent Form (ICF). In order to obtain individual and formal statements, this form should contain the following two mutually exclusive options: an explanation about the use of the stored material in each research study, and the need for new consent or the waiver thereof when the material is used for a new study. On the other hand, ICF suitable for Biorepositories must be exclusive and related to specific research. Although Brazilian and international regulations identify the main aspects to be included in the IC, efforts are still necessary to improve the consent process, so that the document will become a bond of trust between subject and researcher.     

Opinions of researchers based in the UK on recruiting subjects from developing countries into randomized controlled trials

Background: Explaining technical terms in consent forms prior to seeking informed consent to recruit into trials can be challenging in developing countries, and more so when the studies are randomized controlled trials. This study was carried out to examine the opinions of researchers on ways of dealing with these challenges in developing countries. Methods: Recorded in‐depth interviews with 12 lecturers and five doctoral students, who had carried out research in developing countries, at a leading school of public health in the United Kingdom. A purposive, snowballing approach was used to identify interviewees. Results: Researchers were divided on the feasibility of explaining technical trials in illiterate populations; the majority of them held the view that local analogies could be used to explain these technical terms. Others were of the opinion that this could not be done since it was too difficult to explain technical trials, such as randomized controlled trials, even to people in developed countries. Conclusion: Researchers acknowledged the difficulty in explaining randomized controlled trials but it was also their perception that this was an important part of the ethics of the work of scientific research involving human subjects. These difficulties notwithstanding, efforts should be made to ensure that subjects have sufficient understanding to consent, taking into account the fact that peculiar situations in developing countries might compound this difficulty.     

Presuming patient autonomy in the face of therapeutic misconception

Therapeutic misconception involves the failure of subjects either to understand or to incorporate into their own expectations the distinctions in nature and purpose of personally responsive therapeutic care, and the generic relationship between subject and investigator which is constrained by research protocols. Researchers cannot disregard this phenomenon if they are to ensure that subjects engage in research on the basis of genuine informed consent. However, our presumption of patient autonomy must be sustained unless we have compelling evidence of serious misunderstanding. This article argues that the mere expression of aspects of therapeutic misconception should not necessarily displace the presumption of subject autonomy or undermine ethical inclusion in research for at least three reasons. First, some interpretations of the empirical data do not suggest misunderstanding. Second, assessment of misestimation and optimism are delicate and value‐laden, and turn quickly from questions of autonomy to questions of judgment. Third, incomplete understanding may yet be sufficient to allow a subject to engage in a substantially autonomous decision‐making process. Our point is not to dismiss the possibility of genuine therapeutic misconception, but to question its frequency and fatality to the consent process.     

Challenges faced by research ethics committees in El Salvador: results from a focus group study

Objective:  To identify perceived barriers to capacity building for local research ethics oversight in El Salvador, and to set an agenda for international collaborative capacity building.
Methods:  Focus groups were formed in El Salvador which included 17 local clinical investigators and members of newly formed research ethics committees. Information about the proposed research was presented to participants during an international bioethics colloquium sponsored and organized by the St. Jude Children's Research Hospital in collaboration with the National Ethics Committee of El Salvador and the University of El Salvador. Interviews with the focus group participants were qualitatively analyzed.
Results:  Participants expressed the need to tailor the informed consent process and documentation to the local culture; for example, allowing family members to participate in decision-making, and employing shorter consent forms. Participants indicated that economic barriers often impede efforts in local capacity building. Participants valued international collaboration for mutual capacity building in research ethics oversight.
Conclusions:  Research ethics committees in El Salvador possess a basic knowledge of locally relevant ethical principles, though they need more training to optimize the application of bioethical principles and models to their particular contexts. Challenges increase the value of collaborative exchanges with ethics committee members in the United States. Further research on facilitating communication between host country and sponsor country ethics committees can maximize local research ethics expertise, and thus raise the standard of protecting human participants involved in international research.     

Trends in health research ethics in the Philippines during the American Colonial Period (1898‐1946)

Research involving human participants has been conducted in the Philippines since the beginning of the Spanish colonial period. Such studies are expected to adhere to internationally accepted ethical guidelines. This paper discusses trends in clinical research ethics in the Philippines during the American colonial period (1898‐1946). Specifically, studies were assessed on: 1) their observance of ethical protocols, including review; 2) identification of inclusion and exclusion criteria in the selection of participants; 3) use of vulnerable subjects; and 4) practice of the informed consent process. Only the informed consent process had a significant logistic correlation with progression of years. Recruitment of vulnerable groups was common during this period; children and prisoners were the most common participants. Trends in medical ethics in the Philippines reflected those in the United States prior to the publication of the Nuremberg Code, which served as a milestone in the protection of human welfare in clinical research.     

Informed consent in human experimentation before the Nuremberg code.

The issue of ethics with respect to medical experimentation in Germany during the 1930s and 1940s was crucial at the Nuremberg trials and related trials of doctors and public health officials. Those involved in horrible crimes attempted to excuse themselves by arguing that there were no explicit rules governing medical research on human beings in Germany during the period and that research practices in Germany were not different from those in allied countries. In this context the Nuremberg code of 1947 is generally regarded as the first document to set out ethical regulations in human experimentation based on informed consent. New research, however, indicates that ethical issues of informed consent in guidelines for human experimentation were recognised as early as the nineteenth century. These guidelines shed light on the still contentious issue of when the concepts of autonomy, informed consent, and therapeutic and non-therapeutic research first emerged. This issue assumes renewed importance in the context of current attempts to assess liability and responsibility for the abuse of people in various experiments conducted since the second world war in the United States, Canada, Russia, and other nations.     

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.     

Ethical issues surrounding controlled human infection challenge studies in endemic low-and middle-income countries

Controlled human infection challenge studies (CHIs) involve intentionally exposing research participants to, and/or thereby infecting them with, micro-organisms. There have been increased calls for more CHIs to be conducted in low- and middle-income countries (LMICs) where many relevant diseases are endemic. This article is based on a research project that identified and analyzed ethical and regulatory issues related to endemic LMIC CHIs via (a) a review of relevant literature and (b) qualitative interviews involving 45 scientists and ethicists with relevant expertise. In this article we argue that though there is an especially strong case for conducting CHIs in endemic (LMIC) settings, certain ethical issues related to the design and conduct of such studies (in such settings) nonetheless warrant particularly careful attention. We focus on ethical implications of endemic LMIC CHIs regarding (a) potential direct benefits for participants, (b) risks to participants, (c) third-party risks, (d) informed consent, (e) payment of participants, and (f) community engagement. We conclude that there is a strong ethical rationale to conduct (well-designed) CHIs in endemic LMICs, that certain ethical issues warrant particularly careful consideration, and that ethical analyses of endemic LMIC CHIs can inform current debates in research ethics more broadly.     

Ethical and epistemological insights: a case study of participatory action research with young people

Debates over how to determine age of consent for youth to participate in research feature prominently in the practice of researchers, research ethics boards (REBs), and community decision makers working with youth. In particular, tensions can arise over how the ethical principles of beneficence, autonomy, and justice are interpreted and applied in research involving young people. We discuss our experiences obtaining ethical approval to conduct a participatory action research project involving youth and the differences of opinion we encountered regarding underage youth's capability to make informed consent. We suggest that researchers, REBs, and community decision makers all share a responsibility to conduct proactive outreach to youth participants, so that they are adequately informed of their rights related to research.