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.     

Distinct Pathogenic Genes Causing Intellectual Disability and Autism Exhibit a Common Neuronal Network Hyperactivity Phenotype

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From protectionism to inclusion: A New Zealand perspective on health‐related research involving adults incapable of giving informed consent

The revision of the Council of International Organizations of Medical Sciences (CIOMS) International ethical guidelines for health‐related research (2016) heralds a paradigm shift from the ‘protectionist’ policies that emerged following historical research atrocities of the 20th century, towards a more nuanced and inclusive approach to research participation. Adopting this modified approach will enable countries to secure the benefits of research for individuals and for society as a whole, while at the same time minimizing the potential for exploitation and research‐related harms. This article considers the potential impact of Guideline 16 of the CIOMS 2016 from a New Zealand perspective, with respect to research involving adults with impaired capacity and who are incapable of giving informed consent. While the CIOMS 2016 apply a ‘minimal risk’ threshold to guide research involving adults who lack capacity to consent, New Zealand law currently adopts a ‘best interests’ standard which significantly restricts the scope of permissible research that may be performed in this context. This article argues that the CIOMS 2016 should influence change to New Zealand’s legal framework for ethical review of research. CIOMS 2016 provides useful guidance for the necessary standards and processes to enable the responsible and ethical inclusion of adults with impaired capacity in research.     

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.     

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.     

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.     

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.     

Ethical Issues in Adolescents' Sexual and Reproductive Health Research in Nigeria

There is increasing interest in the need to address the ethical dilemmas related to the engagement of adolescents in sexual and reproductive health (SRH) research. Research projects, including those that address issues related to STIs and HIV, adverse pregnancy outcomes, violence, and mental health, must be designed and implemented to address the needs of adolescents. Decisions on when an individual has adequate capacity to give consent for research most commonly use age as a surrogate rather than directly assessing capacity to understand the issues and make an informed decision on whether to participate in research or not. There is a perception that adolescents participating in research are more likely to be coerced and may therefore not fully comprehend the risk they may be taking when engaging in research. This paper examines the various ethical issues that may impact stakeholders' decision making when considering engaging adolescents in SRH research in Nigeria. It makes a case for lowering the age of consent for adolescents. While some experts believe it is possible to extrapolate relevant information from adult research, studies on ethical aspects of adolescents' participation in research are still needed, especially in the field of sexual and reproductive health where there are often differences in knowledge, attitudes and practices compared to adults. The particular challenges of applying the fundamental principles of research ethics to adolescent research, especially research about sex and sexuality, will only become clear if more studies are conducted.     

Using,risking, and consent: Why risking harm to bystanders is morally different from risking harm to research subjects

Subjects in studies on humans are used as a means of conducting the research and achieving whatever good would justify putting them at risk. Accordingly, consent must normally be obtained before subjects are exposed to any substantial risks to their welfare. Bystanders are also often put at risk, but they are not used as a means. Accordingly—or so I argue—consent is more often unnecessary before bystanders are exposed to similar substantial risks to their welfare.     

‘Bioethical Realism’: A Framework for Implementing Universal Research Ethics

Implementation of existing ethical guidelines for international collaborative medical and health research is still largely controversial in sub‐Saharan Africa for two major reasons: One, they are seen as foreign and allegedly inconsistent with what has been described as an ‘African worldview’, hence, demand for their strict implementations reeks of ‘bioethical imperialism’. Two, they have other discernible inadequacies – lack of sufficient detail, apparent as well as real ambiguities, vagueness and contradictions. Similar charges exist(ed) in other non‐Western societies. Consequently, these guidelines have been correctly judged as an inadequate response to the complex and ever shifting dilemmas met by researchers and research regulators in the field. This paper proposes a framework for effective implementation of existing guidelines without much worry about bioethical imperialism and other inadequacies. This framework is proposed using an analogy of Legal Realism, specifically its key assertions on how, in reality, judicial systems operate using general legal rules to settle specific cases. Legal realists assert that in judicial decision‐making, general legal rules do not totally dictate court decisions in specific cases. This analogy is used to coin a new term, ‘Bioethical Realism.’ The framework suggests that local Research Ethics Committees ought to be construed as analogues of judicial courts with the resulting implications. Consequently, just like legal rules are general rules that do not always dictate court decisions, similarly international bioethical guidelines are general ethical rules that should not always dictate local RECs’ decisions and such decisions (ought to) enjoy considerable immunity from outsiders.     

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.     

Emergency Preservation and Resuscitation Trial: A Philosophical Justification for Non‐Voluntary Enrollment

In a current clinical trial for Emergency Preservation and Resuscitation (EPR), Dr. Samuel Tisherman of the University of Maryland aims to induce therapeutic hypothermia in order to ‘buy time’ for operating on victims of severe exsanguination. While recent publicity has framed this controversial procedure as ‘killing a patient to save his life’, the US Army and Acute Care Research appear to support the study on the grounds that such patients already face low chances of survival. Given that enrollment in the trial must be non‐voluntary, the study has received an exemption from federal standards for obtaining informed consent. How exactly, if at all, is non‐voluntary enrollment morally justifiable? In this essay, I appeal to the notable work of Hans Jonas in an effort to defend the EPR trial's use of non‐voluntary enrollment. It is often thought and, as I show, it may appear that Jonas has called for the end of experimental medical practice. Still, I derive from Jonas a principle of double‐effect upon which physicians may be seen as morally permitted to pursue innovations in emergency medicine but only as a byproduct of pursuing therapeutic success. With this position, I argue that the EPR trial can be granted a stronger philosophical justification than simply waiving the requirement of obtaining informed consent. The double‐effect justification would obtain, perhaps regardless of the success of such innovative procedures as therapeutic hypothermia.     

Conducting Research with Human Subjects in International Settings: Ethical Considerations

Biomedical research in international settings is undergoing expansive growth andmay potentially result in far-reaching benefits, such as direction of researchresources toward solving basic health care needs of world populations. However,key ethical concerns surround this expansion and must be carefully considered byinternational researchers. International research is impacted by differences inlanguage, culture, regulatory structures, financial resources, and possiblyethical standards. Local community leadership involvement in the planning stagesof research is imperative. Especially in resource-poor countries, the researchagenda must be designed to address local needs and provide local benefit.Capacity strengthening efforts, aimed at improving institutional support forethical conduct of human subjects research, must continue to be supported bywealthier nations.     

Blending Genetics and Sociocultural Historical Inquiry: Ethics, Culture,and Human Subjects Protection in International Cross Cultural Research

In this paper, we examine the implementation and difficulties when conductinggenetics research in a rural, traditional West African culture within the frameof the United States’ grounded research ethics. Research challenges arehighlighted by Western researchers following U.S. Institutional Review Board(IRB) guidelines and practices in a non-Western country. IRB concepts areculture bound in Western ideals that may not have synchronicity andcompatibility with non-Western cultures. Differences in sociocultural norms,traditions, language, and geography were influencing factors that can affectapplication of IRB principles. Suggestions for change are offered, which willpotentially aid researchers considering application of IRB requirements whenconducting research in non-Westernized, non-industrialized countries.     

Health‐related Research Ethics and Social Value: Antibiotic Resistance Intervention Research and Pragmatic Risks

We consider the implications for the ethical evaluation of research programs of two fundamental changes in the revised research ethical guideline of the Council for International Organizations of Medical Sciences. The first is the extension of scope that follows from exchanging “biomedical” for “health‐related” research, and the second is the new evaluative basis of “social value,” which implies new ethical requirements of research. We use the example of antibiotic resistance interventions to explore the need to consider the instances of what we term the pragmatic risks of such interventions to evaluate the social value of certain kinds of health‐related research. These (pragmatic) risks severely threaten the social value of interventions in every area where human and social responses significantly impact on their effectiveness. Thus, the social value of health‐related research needed to demonstrate its effectiveness depends on the extent and successful management of such risks. Research designed to take into account the management of pragmatic risks also gives rise to similar types of risks, and the potential for social value in light of those risks needs to be considered in ethical reviews based on the new guidelines. We argue that, to handle this new expanded task, the international system of research ethical review addressed by the guidelines needs institutional development.