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.     

RESEARCH ON PRISONERS – A COMPARISON BETWEEN THE IOM COMMITTEE RECOMMENDATIONS (2006) AND EUROPEAN REGULATIONS

The Institute of Medicine (IOM) Committee on Ethical Considerations for Revisions to DHHS Regulations for Protection of Prisoners Involved in Research published its report in 2006. It was charged with developing an ethical framework for the conduct of research with prisoners and identifying the safeguards and conditions necessary to ensure that research with prisoners is conducted ethically. The recommendations contained in the IOM report differ from current European regulations in several ways, some being more restrictive and some less so. For example, the IOM report suggests limiting the percentage of prisoners that should be involved in a biomedical study to 50%, a limit that does not exist in Europe. However, the report does not specifically advise against research without a direct benefit to an individual prisoner: the European regulations are more restrictive than the IOM committee recommendations in this respect. The definition of minimal risk varies, as well as the proposed role of the minimal risk requirement and of the principle of subsidiarity (research that can only be done effectively in prisons). The IOM report proposes a number of thoughtful suggestions, which it would be beneficial to implement everywhere, such as registers of research on prisoners. The European regulations offer pragmatic solutions to several thorny issues. In summary, the IOM committee report represents an admirable effort to tackle the present inconsistencies and deficiencies of federal regulations in the US on research on prisoners (45 CFR 46 Subpart C). Nonetheless, before acting on the recommendations, US regulators might consider revisiting international guidelines such as those published by the Council for International Organizations of Medical Science (CIOMS) and the Declaration of Helsinki.     

Biomedical Big Data: New Models of Control Over Access,Use and Governance

Empirical evidence suggests that while people hold the capacity to control their data in high regard, they increasingly experience a loss of control over their data in the online world. The capacity to exert control over the generation and flow of personal information is a fundamental premise to important values such as autonomy, privacy, and trust. In healthcare and clinical research this capacity is generally achieved indirectly, by agreeing to specific conditions of informational exposure. Such conditions can be openly stated in informed consent documents or be implicit in the norms of confidentiality that govern the relationships of patients and healthcare professionals. However, with medicine becoming a data-intense enterprise, informed consent and medical confidentiality, as mechanisms of control, are put under pressure. In this paper we explore emerging models of informational control in data-intense healthcare and clinical research, which can compensate for the limitations of currently available instruments. More specifically, we discuss three approaches that hold promise in increasing individual control: the emergence of data portability rights as means to control data access, new mechanisms of informed consent as tools to control data use, and finally, new participatory governance schemes that allow individuals to control their data through direct involvement in data governance. We conclude by suggesting that, despite the impression that biomedical big data diminish individual control, the synergistic effect of new data management models can in fact improve it.     

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.     

Reassessing insurers' access to genetic information: genetic privacy, ignorance, and injustice

Many countries have imposed strict regulations on the genetic information to which insurers have access. Commentators have warned against the emerging body of legislation for different reasons. This paper demonstrates that, when confronted with the argument that genetic information should be available to insurers for health insurance underwriting purposes, one should avoid appeals to rights of genetic privacy and genetic ignorance. The principle of equality of opportunity may nevertheless warrant restrictions. A choice-based account of this principle implies that it is unfair to hold people responsible for the consequences of the genetic lottery, since we have no choice in selecting our genotype or the expression of it. However appealing, this view does not take us all the way to an adequate justification of inaccessibility of genetic information. A contractarian account, suggesting that health is a condition of opportunity and that healthcare is an essential good, seems more promising. I conclude that if or when predictive medical tests (such as genetic tests) are developed with significant actuarial value, individuals have less reason to accept as fair institutions that limit access to healthcare on the grounds of risk status. Given the assumption that a division of risk pools in accordance with a rough estimate of people's level of (genetic) risk will occur, fairness and justice favour universal health insurance based on solidarity.     

Best Practice Updates for Informed Consent and Patient Education in Weight Loss Surgery

To update evidence‐based best practice guidelines for obtaining informed consent from weight loss surgery (WLS) patients, with an emphasis on appropriate content and communications approaches that might enhance patient understanding of the information, we performed a systematic search of English‐language literature published between April 2004 and May 2007 in MEDLINE and the Cochrane database. Keywords included WLS and informed consent, comprehension, health literacy, and patient education; and WLS and outcomes, risk, patient safety management, and effectiveness. Recommendations are based on the most current literature and the consensus of the expert panel; they were graded according to systems used in established evidence‐based models. We identified over 120 titles, 38 of which were reviewed in detail. Evidence suggests that WLS outcomes, including long‐term rates of relapse, vary by procedure. For some weight loss surgeries, long‐term outcomes may not be known. Risks also vary by patient and provider characteristics. Informed consent should incorporate realistic projections of the short‐ and long‐term risks, benefits, and consequences of surgery, as well as alternatives to WLS. For consent to be informed, the education process should continue until the patient demonstrates comprehension of all relevant material and concepts. Confirmation of comprehension can protect patients engaged in the process of consent for WLS. Future research should focus on the outcomes and consequences of WLS, and different approaches that facilitate patient understanding of, and decision making about, WLS.     

Ethical Issues of Using CRISPR Technologies for Research on Military Enhancement

This paper presents an overview of the key ethical questions of performing gene editing research on military service members. The recent technological advance in gene editing capabilities provided by CRISPR/Cas9 and their path towards first-in-human trials has reinvigorated the debate on human enhancement for non-medical purposes. Human performance optimization has long been a priority of military research in order to close the gap between the advancement of warfare and the limitations of human actors. In spite of this focus on temporary performance improvement, biomedical enhancement is an extension of these endeavours and the ethical issues of such research should be considered. In this paper, we explore possible applications of CRISPR to military human gene editing research and how it could be specifically applied towards protection of service members against biological or chemical weapons. We analyse three normative areas including risk–benefit analysis, informed consent, and inequality of access as it relates to CRISPR applications for military research to help inform and provide considerations for military institutional review boards and policymakers.     

Consent and confidentiality in the light of recent demands for data sharing

Many attempts have been made to formalize ethical requirements for research. Among the most prominent mechanisms are informed consent requirements and data protection regimes. These mechanisms, however, sometimes appear as obstacles to research. In this opinion paper, we critically discuss conventional approaches to research ethics that emphasize consent and data protection. Several recent debates have highlighted other important ethical issues and underlined the need for greater openness in order to uphold the integrity of health‐related research. Some of these measures, such as the sharing of individual‐level data, pose problems for standard understandings of consent and privacy. Here, we argue that these interpretations tend to be overdemanding: They do not really protect research subjects and they hinder the research process. Accordingly, we suggest another way of framing these requirements. Individual consent must be situated alongside the wider distribution of knowledge created when the actions, commitments, and procedures of researchers and their institutions are opened to scrutiny. And instead of simply emphasizing privacy or data protection, we should understand confidentiality as a principle that facilitates the sharing of information while upholding important safeguards. Consent and confidentiality belong to a broader set of safeguards and procedures to uphold the integrity of the research process.     

Out-of-Pocket Payments,Health Care Access and Utilisation in South-Eastern Nigeria: A Gender Perspective

Out-of-pocket (OOP) payments have severe consequences for health care access and utilisation and are especially catastrophic for the poor. Although women comprise the majority of the poor in Nigeria and globally, the implications of OOP payments for health care access from a gender perspective have received little attention. This study seeks to fill this gap by using a combination of quantitative and qualitative analysis to investigate the gendered impact of OOPs on healthcare utilisation in south-eastern Nigeria. 411 households were surveyed and six single-sex Focus Group Discussions conducted. This study confirmed the socioeconomic and demographic vulnerability of female-headed households (FHHs), which contributed to gender-based inter-household differences in healthcare access, cost burden, choices of healthcare providers, methods of funding healthcare and coping strategies. FHHs had higher cost burdens from seeking care and untreated morbidity than male-headed households (MHHs) with affordability as a reason for not seeking care. There is also a high utilisation of patent medicine vendors (PMVs) by both households (PMVs are drug vendors that are unregulated, likely to offer very low-quality treatment and do not have trained personnel). OOP payment was predominantly the means of healthcare payment for both households, and households spoke of the difficulties associated with repaying health-related debt with implications for the medical poverty trap. It is recommended that the removal of user fees, introduction of prepayment schemes, and regulating PMVs be considered to improve access and provide protection against debt for FHHs and MHHs. The vulnerability of widows is of special concern and efforts to improve their healthcare access and broader efforts to empower should be encouraged for them and other poor households.     

Ethical and regulatory issues arising from proteomic research and technology

Over the last two decades, medical research has begun to make extensive use of products of human origin in therapeutics, oncology, and most recently, in genetic diseases. This has raised many ethical issues involving patient rights, including issues of consent. Besides informed consent, researchers should address several topics when designing studies using human tissues. Reward for the patient should be kept minimal. Sample transfer should be organized along non-profit lines, at least in Europe. Sampling procedures should be at no risk for human volunteers, and at minimal risk for patients. Biosafety aspects should be addressed, in particular when international collaborations are intended or when collaboration is existing between academia and industry. Regulations on importation and exportation of human tissues should be observed. Data acquisition and storage should be addressed in accordance with national data protection regulations, in particular when using computerized databases. If follow-up information is to be taken, the authorization for such information should be requested. The right for patient's information (or for no information) on the research results should also be addressed. The issues of validation and patenting should be also solved, usually by informing the patient that he/she will have no commercial rights on potential research results. The patient should be told if the samples are transferred to another research laboratory or private company. Samples and related data should be destroyed on request at any time point during the course of the study. If possible, traceability of the donor should be ensured.     

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.     

WHICH BENEFITS OF RESEARCH PARTICIPATION COUNT AS ‘DIRECT’?

It is widely held that individuals who are unable to provide informed consent should be enrolled in clinical research only when the risks are low, or the research offers them the prospect of direct benefit. There is now a rich literature on when the risks of clinical research are low enough to enroll individuals who cannot consent. Much less attention has focused on which benefits of research participation count as ‘direct’, and the few existing accounts disagree over how this crucial concept should be defined. This disagreement raises concern over whether those who cannot consent, including children and adults with severe dementia, are being adequately protected. The present paper attempts to address this concern by considering first what additional protections are needed for these vulnerable individuals. This analysis suggests that the extant definitions of direct benefits either provide insufficient protection for research subjects or pose excessive obstacles to appropriate research. This analysis also points to a modified definition of direct benefits with the potential to avoid these two extremes, protecting individuals who cannot consent without blocking appropriate research.     

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.     

Does benefit justify research with children?

The inclusion of children in research gives rise to a difficult ethical question: What justifies children's research participation and exposure to research risks when they cannot provide informed consent? This question arises out of the tension between the moral requirement to obtain a subject's informed consent for research participation, on the one hand, and the limited capacity of most children to provide informed consent, on the other. Most agree that children's participation in clinical research can be justified. But the ethical justification for exposing children to research risks in the absence of consent remains unclear. One prevalent group of arguments aims to justify children's risk exposure by appealing to the concept of benefit. I call these ‘benefit arguments’. Prominent versions of this argument defend the idea that broadening our understanding of the notion of benefit to include non‐medical benefits (such as the benefit of a moral education) helps to justify children's research participation. I argue that existing benefit arguments are not persuasive and raise problems with the strategy of appealing to broader notions of benefit to justify children's exposure to research risk.     

Evaluation of progress toward universal health coverage in Myanmar: A national and subnational analysis

BackgroundUniversal health coverage (UHC) encompasses 2 main components: access to essential healthcare services and protection from financial hardship when using healthcare. This study examines Myanmar’s efforts to achieve UHC on a national and subnational level. It is a primer of studying the concept of UHC on a subnational level, and it also establishes a baseline for assessing future progress toward reaching UHC in Myanmar.Methods and findingsThe study uses the Demographic and Health Survey (2015) and the Myanmar Living Conditions Survey (MLCS; 2017) and adapts a previously developed UHC index to provide insights into the main barriers preventing the country’s progress toward UHC. We find a negative correlation between the UHC index and the state/region poverty levels. The equity of access analysis reveals significant pro-rich inequity in access to all essential healthcare services. Socioeconomic status and limited availability of healthcare infrastructure are the main driving forces behind the unequal access to interventions that are crucial to achieving UHC by 2030. Finally, financial risk protection analysis shows that the poor are less likely to use healthcare services, and, once they do, they are at a greater risk of suffering financial catastrophe. Limitations of this study revolve around its correlational, rather than causal, nature.ConclusionsWe suggest a 2-pronged approach to help Myanmar achieve UHC: Government and state authorities should reduce the financial burden of seeking healthcare, and, coupled with this, significant investment in and expansion of health infrastructure and the health workforce should be made, particularly in the poorer and more remote states.

Zlatko Nikoloski and colleagues provide analytical insight into Myanmar’s efforts to achieve universal health coverage on a national and sub-national level.     

Justifying Community Benefit Requirements in International Research

It is widely agreed that foreign sponsors of research in low‐ and middle‐income countries (LMICs) are morally required to ensure that their research benefits the broader host community. There is no agreement, however, about how much benefit or what type of benefit research sponsors must provide, nor is there agreement about what group of people is entitled to benefit. To settle these questions, it is necessary to examine why research sponsors have an obligation to benefit the broader host community, not only their subjects. Justifying this claim is not straightforward. There are three justifications for an obligation to benefit host communities that each apply to some research, but not to all. Each requires a different amount of benefit, and each requires benefit to be directed toward a different group. If research involves significant net risk to LMIC subjects, research must provide adequate benefit to people in LMICs to avoid an unjustified appeal to subjects’ altruism. If research places significant burdens on public resources, research must provide fair compensation to the community whose public resources are burdened. If research is for profit, research sponsors must contribute adequately to the upkeep of public goods from which they benefit in order to avoid the wrong of free‐riding, even if their use of these public goods is not burdensome.     

Open exchange of scientific knowledge and European copyright: The case of biodiversity information

Background. The 7^th Framework Programme for Research and Technological Development is helping the European Union to prepare for an integrative system for intelligent management of biodiversity knowledge. The infrastructure that is envisaged and that will be further developed within the Programme “Horizon 2020” aims to provide open and free access to taxonomic information to anyone with a requirement for biodiversity data, without the need for individual consent of other persons or institutions. Open and free access to information will foster the re-use and improve the quality of data, will accelerate research, and will promote new types of research. Progress towards the goal of free and open access to content is hampered by numerous technical, economic, sociological, legal, and other factors. The present article addresses barriers to the open exchange of biodiversity knowledge that arise from European laws, in particular European legislation on copyright and database protection rights.We present a legal point of view as to what will be needed to bring distributed information together and facilitate its re-use by data mining, integration into semantic knowledge systems, and similar techniques. We address exceptions and limitations of copyright or database protection within Europe, and we point to the importance of data use agreements. We illustrate how exceptions and limitations have been transformed into national legislations within some European states to create inconsistencies that impede access to biodiversity information.Conclusions. The legal situation within the EU is unsatisfactory because there are inconsistencies among states that hamper the deployment of an open biodiversity knowledge management system. Scientists within the EU who work with copyright protected works or with protected databases have to be aware of regulations that vary from country to country. This is a major stumbling block to international collaboration and is an impediment to the open exchange of biodiversity knowledge. Such differences should be removed by unifying exceptions and limitations for research purposes in a binding, Europe-wide regulation.     

The Ethics of Elective (Non-Therapeutic) Ventilation

Elective ventilation (EV) is ventilation applied, not in the interest of patients, but in order to secure transplantable organs. It carries with it a small risk that patients who would otherwise have died will survive in a persistent vegetative state. Is EV ever justifiable? We argue: (1) The only thing which can justify exposing patients to risk not taken for their benefit is their consent, and we cannot rely on implied consent or third party consent in the case of EV. Thus, absent explicit consent of patients, EV is not justifiable. (2) It is not clear that explicit consent should be sought, or where it is offered honoured, given the potential EV has for deterring organ donors and causing stress to staff and families.     

Best practices for the use and exchange of invertebrate biological control genetic resources relevant for food and agriculture

The Nagoya Protocol is a supplementary agreement to the Convention on Biological Diversity that provides a framework for the effective implementation of the fair and equitable sharing of benefits arising out of the utilization of genetic resources, including invertebrate biological control agents. The Protocol came into force on 12 October 2014, and requires signatories and countries acceding to the Protocol to develop a legal framework to ensure access to genetic resources, benefit-sharing and compliance. The biological control community of practice needs to comply with access and benefit sharing regulations arising under the Protocol. The IOBC Global Commission on Biological Control and Access and Benefit Sharing has prepared this best practices guide for the use and exchange of invertebrate biological control genetic resources for the biological control community of practice to demonstrate due diligence in responding to access and benefit sharing requirements, and to reassure the international community that biological control is a very successful and environmentally safe pest management method based on the use of biological diversity. We propose that components of best practice include: collaborations to facilitate information exchange about what invertebrate biological control agents are available and where they may be obtained; knowledge sharing through freely available databases that document successes (and failures); cooperative research to develop capacity in source countries; and transfer of production technology to provide opportunities for small-scale economic activity. We also provide a model concept agreement that can be used for scientific research and non-commercial release into nature where access and benefit sharing regulations exist, and a model policy for provision of invertebrate biological control agents to other parties where access and benefit sharing regulations are not restrictive or do not exist.