BENEFITS TO RESEARCH SUBJECTS IN INTERNATIONAL TRIALS: DO THEY REDUCE EXPLOITATION OR INCREASE UNDUE INDUCEMENT?

There is an alleged tension between undue inducement and exploitation in research trials. This paper considers claims that increasing the benefits to research subjects enrolled in international, externally‐sponsored clinical trials should be avoided on the grounds that it may result in the undue inducement of research subjects. It proceeds from the premise that there are good grounds for thinking that, at least some, international research sponsors exploit trial participants because they do not provide the research population with a fair share of the benefits of research. This provides a prima facie argument for increasing the benefits for research participants. Concern over undue inducement is a legitimate moral concern; however, if this concern is to prevent research populations from receiving their fair share of benefits from research there must be sufficient evidence that these benefits will unduly influence patients’ decision‐making regarding trial participation. This article contributes to the debate about exploitation versus undue inducement by introducing an analysis of the available empirical research into research participants’ motivations and the influence of payments on research subjects’ behaviour and risk assessment. Admittedly, the available research in this field is limited, but the research that has been conducted suggests that financial rewards do not distort research subjects’ behaviour or blind them to the risks involved with research. Therefore, I conclude that research sponsors should prioritise the prevention of exploitation in international research by providing greater benefits to research participants.     

Developing Clinical Research Relationship: Views from Within

The nature of the relationship between clinical investigator and research participant continues to be contested. The related discussions have largely focused on the doctor‐researcher dichotomy thought to permeate the work of a clinical investigator with research participants, whom in turn occupy two corresponding roles: patient and subject. This paper contributes to current debates on the topic by providing a voice to research participants, whose perspectives have been largely invisible. It draws on 42 in‐depth interviews conducted in Ghana and South Africa with respondents at different stages of involvement in clinical research, ranging from no experience in clinical research to enrollment in several clinical trials. The perspectives of all respondents were largely congruent and rooted in the common view that clinical research contributed to the improvement of local health. They went beyond the researcher/participant versus doctor/patient dichotomy, long established in research ethics, and preferred to view participants and investigators as partners working together to find ways to address local health needs. The conceptualization of investigator‐participant relations as a partnership reinforced expectations of care, transparency and accountability, which were viewed as necessary expressions of mutuality and respect within equal collaborations. It is important to engage with these views in order to avoid antagonizing societal expectations and to build up long‐term public trust, crucial for the continuous operation of clinical research.     

Covert moral bioenhancement,public health,and autonomy

In a recent article in this journal, Parker Crutchfield argues that if moral bioenhancement ought to be compulsory, as some authors claim, then it ought to be covert, i.e., performed without the knowledge of the population that is being morally enhanced. Crutchfield argues that since the aim of compulsory moral bioenhancement is to prevent ultimate harm to the population, compulsory moral bioenhancement is best categorized as a public health issue, and should therefore be governed by the norms and values that apply in public health settings. In this article, I argue for two related claims. First, I question the extent to which compulsory moral enhancement should be considered a public health issue that ought to be governed by the norms and values that apply in public health settings. Second, I argue that Crutchfield's argument that covert moral bioenhancement would better respect people's autonomy than an overt program overlooks two important autonomy‐based reasons that, in fact, favor an overt moral enhancement program over a covert one.     

It is better to be ignorant of our moral enhancement: A reply to Zambrano

In a recent issue of Bioethics, I argued that compulsory moral bioenhancement should be administered covertly. Alexander Zambrano has criticized this argument on two fronts. First, contrary to my claim, Zambrano claims that the prevention of ultimate harm by covert moral bioenhancement fails to meet conditions for permissible liberty-restricting public health interventions. Second, contrary to my claim, Zambrano claims that covert moral bioenhancement undermines autonomy to a greater degree than does overt moral bioenhancement. In this paper, I rebut both of these arguments, then finish by noting important avenues of research that Zambrano’s arguments motivate.     

A Framework to Link International Clinical Research to the Promotion of Justice in Global Health

How international research might contribute to justice in global health has not been substantively addressed by bioethics. Theories of justice from political philosophy establish obligations for parties from high‐income countries owed to parties from low and middle‐income countries. We have developed a new framework that is based on Jennifer Ruger's health capability paradigm to strengthen the link between international clinical research and justice in global health. The ‘research for health justice’ framework provides direction on three aspects of international clinical research: the research target, research capacity strengthening, and post‐trial benefits. It identifies the obligations of justice owed by national governments, research funders, research sponsors, and investigators to trial participants and host communities. These obligations vary from those currently articulated in international research ethics guidelines. Ethical requirements of a different kind are needed if international clinical research is to advance global health equity.     

LINKING INTERNATIONAL RESEARCH TO GLOBAL HEALTH EQUITY: THE LIMITED CONTRIBUTION OF BIOETHICS

Health research has been identified as a vehicle for advancing global justice in health. However, in bioethics, issues of global justice are mainly discussed within an ongoing debate on the conditions under which international clinical research is permissible. As a result, current ethical guidance predominantly links one type of international research (biomedical) to advancing one aspect of health equity (access to new treatments). International guidelines largely fail to connect international research to promoting broader aspects of health equity – namely, healthier social environments and stronger health systems. Bioethical frameworks such as the human development approach do consider how international clinical research is connected to the social determinants of health but, again, do so to address the question of when international clinical research is permissible. It is suggested that the narrow focus of this debate is shaped by high‐income countries' economic strategies. The article further argues that the debate's focus obscures a stronger imperative to consider how other types of international research might advance justice in global health. Bioethics should consider the need for non‐clinical health research and its contribution to advancing global justice.     

What Are Fair Study Benefits in International Health Research? Consulting Community Members in Kenya

Background

Planning study benefits and payments for participants in international health research in low- income settings can be a difficult and controversial process, with particular challenges in balancing risks of undue inducement and exploitation and understanding how researchers should take account of background inequities. At an international health research programme in Kenya, this study aimed to map local residents'' informed and reasoned views on the effects of different levels of study benefits and payments to inform local policy and wider debates in international research.

Methods and Findings

Using a relatively novel two-stage process community consultation approach, five participatory workshops involving 90 local residents from diverse constituencies were followed by 15 small group discussions, with components of information-sharing, deliberation and reflection to situate normative reasoning within debates. Framework Analysis drew inductively and deductively on voice- recorded discussions and field notes supported by Nvivo 10 software, and the international research ethics literature. Community members'' views on study benefits and payments were diverse, with complex contextual influences and interplay between risks of giving ‘too many’ and ‘too few’ benefits, including the role of cash. While recognising important risks for free choice, research relationships and community values in giving ‘too many’, the greatest concerns were risks of unfairness in giving ‘too few’ benefits, given difficulties in assessing indirect costs of participation and the serious consequences for families of underestimation, related to perceptions of researchers'' responsibilities.

Conclusions

Providing benefits and payments to participants in international research in low-income settings is an essential means by which researchers meet individual-level and structural forms of ethical responsibilities, but understanding how this can be achieved requires a careful account of social realities and local judgment. Concerns about undue inducement in low-income communities may often be misplaced; we argue that greater attention should be placed on avoiding unfairness, particularly for the most-poor.     

The Social Value of Knowledge and International Clinical Research

In light of the growth in the conduct of international clinical research in developing populations, this paper seeks to explore what is owed to developing world communities who host international clinical research. Although existing paradigms for assigning and assessing benefits to host communities offer valuable insight, I criticize their failure to distinguish between those benefits which can justify the conduct of research in a developing world setting and those which cannot. I argue that the justification for human subjects research is fundamentally grounded in the social value of knowledge, and that this value is context‐dependent in a manner which should inform our ethical evaluation of the conduct of research in specific settings. I propose a new framework for the assessment of research benefits assigned to developing world host communities, a natural implication of which is to limit the types of research projects which may permissibly be conducted in developing world settings.     

Quarantine,isolation and the duty of easy rescue in public health

We address the issue of whether, why and under what conditions, quarantine and isolation are morally justified, with a particular focus on measures implemented in the developing world. We argue that the benefits of quarantine and isolation justify some level of coercion or compulsion by the state, but that the state should be able to provide the strongest justification possible for implementing such measures. While a constrained form of consequentialism might provide a justification for such public health interventions, we argue that a stronger justification is provided by a principle of State Enforced Easy Rescue: a state may permissibly compel individuals to engage in activities that entail a small cost to them but a large benefit to others, because individuals have a moral duty of easy rescue to engage in those activities. The principle of State Enforced Easy Rescue gives rise to an Obligation Enforcement Requirement: the state should create the conditions such that submitting to coercive or compulsive measures becomes a fundamental moral duty of individuals, i.e. a duty of easy rescue. When the state can create such conditions, it has the strongest justification possible for implementing coercive or compulsive measures, because individuals have a moral duty to temporarily relinquish the rights that such measures would infringe. Our argument has significant implications for how public health emergencies in the developing world should be tackled. Where isolation and quarantine measures are necessary, states or the international community have a moral obligation to provide certain benefits to those quarantined or isolated.     

The potential influence of Internet-based social networking on the conduct of clinical research studies

The rapid growth of internet usage has led to an explosion of social networking sites for discussion of health issues. This provides a forum for subjects to communicate with one another during the course of the studies. Previous studies have raised concerns about the quality of health information on social networking sites, although none have evaluated content related to ongoing clinical trials. We reviewed material posted in virtual communities by self-identified clinical trial participants. We identified material posted in online health forums that could introduce bias into clinical research studies; we believe that this issue warrants further study and discussion. Physicians and others who conduct clinical trials should be aware of this issue. Study investigators and research teams should also talk to their study subjects about where and how they are obtaining information in order to prevent behaviors and correct misinformation that could put a subject's safety or the study objectives at risk. Given the rapid increase in Internet use for health care, a broader evaluation of both the benefits and potential risks of social networking among research participants during the course of a clinical trial appears warranted.     

Sharing the benefits of genetic resources: from biodiversity to human genetics

Benefit sharing aims to achieve an equitable exchange between the granting of access to a genetic resource and the provision of compensation. The Convention on Biological Diversity (CBD), adopted at the 1992 Earth Summit in Rio de Janeiro, is the only international legal instrument setting out obligations for sharing the benefits derived from the use of biodiversity. The CBD excludes human genetic resources from its scope, however, this article considers whether it should be expanded to include those resources, so as to enable research subjects to claim a share of the benefits to be negotiated on a case-by-case basis. Our conclusion on this question is: 'No, the CBD should not be expanded to include human genetic resources.' There are essential differences between human and non-human genetic resources, and, in the context of research on humans, an essentially fair exchange model is already available between the health care industry and research subjects. Those who contribute to research should receive benefits in the form of accessible new health care products and services, suitable for local health needs and linked to economic prosperity (e.g. jobs). When this exchange model does not apply, as is often the case in developing countries, individually negotiated benefit sharing agreements between researchers and research subjects should not be used as 'window dressing'. Instead, national governments should focus their finances on the best economic investment they could make; the investment in population health and health research as outlined by the World Health Organization's Commission on Macroeconomics and Health; whilst international barriers to such spending need to be removed.     

Parent-offspring conflict and the cultural ecology of breast-feeding

Lactation constitutes a major focus for research in international health because of its dramatic impact on child survival; evolutionary biology has investigated lactation as an important aspect of parenting strategy, with implications for understanding parent-offspring conflict. These perspectives are brought together in an attempt to develop integrated models for an issue of key international health concern: the duration of exclusive breast-feeding and the timing of weaning. This analysis highlights the relevance of evolutionary theory for practical problems in public health, and it suggests the utility of public health outcomes for addressing evolutionary questions. Thomas McDade received his Ph.D. degree in anthropology from Emory University in 1999 and is currently an assistant professor in the anthropology department at Northwestern University. His research interests include biocultural perspectives on issues related to health and human development, with current attention focused on the cultural and evolutionary ecology of human immune function.     

Attitudes toward Post‐Trial Access to Medical Interventions: A Review of Academic Literature,Legislation, and International Guidelines

There is currently no international consensus around post‐trial obligations toward research participants, community members, and host countries. This literature review investigates arguments and attitudes toward post‐trial access. The literature review found that academic discussions focused on the rights of research participants, but offered few practical recommendations for addressing or improving current practices. Similarly, there are few regulations or legislation pertaining to post‐trial access. If regulatory changes are necessary, we need to understand the current arguments, legislation, and attitudes towards post‐trial access and participants and community members. Given that clinical trials conducted in low‐income countries will likely continue, there is an urgent need for consideration of post‐trial benefits for participants, communities, and citizens of host countries. While this issue may not be as pressing in countries where participants have access to healthcare and medicines through public schemes, it is particularly important in regions where this may not be available.     

NEW DIRECTIONS IN AFRICAN BIOETHICS: WAYS OF INCLUDING PUBLIC HEALTH CONCERNS IN THE BIOETHICS AGENDA

Research ethics is the most developed aspect of bioethics in Africa. Most African countries have set up Institutional Review Boards (IRBs) to provide guidelines for research and to comply with international norms. However, bioethics has not been responsive to local needs and values in the rest of the continent. A new direction is needed in African bioethics. This new direction promotes the development of a locally‐grounded bioethics, shaped by a dynamic understanding of local cultures and informed by structural and institutional problems that impact the public's health, as well as cognisant of the salient contribution of social sciences and social epidemiology which can bring a lasting impact on African local communities. In today's post‐Structural Adjustment Africa, where healthcare has been liberalized and its cost increased, a bioethics agenda that focuses essentially on disease management and clinical work remains blind in the face of a structural marginalization of the masses of poor. Instead, the multidimensional public health crisis, with which most African countries are confronted, calls for a bioethics agenda that focuses primarily, but not exclusively, on health promotion and advocacy. Such an approach to bioethics reckons with the macro‐determinants of health and well‐being and places clinical and research ethics in the broader context of population's health. The same approach underscores the need to become political, not only by addressing health policymaking processes and procedures, but also by becoming an advocacy forum that includes other constituencies equipped with the potentialities to impact the population's health.     

Moral residue and health justice for the global south: Addressing past issues through current interventions and research

This paper introduces the concept of moral residue to global health, and shows how its presence undermines crucial interventions and research, especially in the global south. Lingering feelings of anxiety, anger, blame or frustration often exist among local populations, where previous interventions or research have left traces of harm and/or exploitation. The existence of such feelings reflects the presence of moral residue, recognizing the moral experiences of epistemic injustices, which in turn undermines critical interventions and research through outright rejection or passive non‐compliance among affected populations. While such situations have been variously interpreted and relevant strategies developed to address the issues, little to no consideration is made on the implications of moral residue experiences in global health contexts and how to address them. This paper demonstrates the presence of moral residue in global health and proffers an African ethical approach, a harmony framework, for addressing moral residue issues, as part of a holistic approach towards tackling population health crises without compromising health gains for affected populations in the global south.     

Pathways to Obesity Prevention: Report of a National Institutes of Health Workshop1

There is an extensive research base on obesity treatment and on the health benefits of weight loss, but relatively little research has focused on obesity prevention. This article summarizes results of a workshop conducted by investigators funded under a National Institutes of Health initiative designed to stimulate novel research for obesity prevention. The 20 pilot studies funded under this initiative involved study populations that were diverse with respect to life stage and ethnicity, were conducted in a variety of natural and research settings, and involved a mix of interventions, including face‐to‐face group and individual counseling, as well as mail, telephone, and internet‐based approaches. The workshop, which occurred approximately halfway through the 3‐year funding period, emphasized concepts and experiences related to initiating and conducting obesity prevention studies. Investigators discussed theoretical perspectives as well as various challenges encountered, for example, in study implementation in different clinical and community settings, in working with children and families, and in studying pregnant and postpartum women. Other topics discussed included the difficulty of motivating individuals for prevention of weight gain, relevant cultural and racial/ethnic considerations, and the particular need for valid and practical measures of energy balance, body composition, and physical fitness in obesity prevention research. A key conclusion was that using obesity treatment as the primary paradigm may be a limiting perspective for considering obesity prevention issues. Further insights derived from the workshop deliberations are reflected in a detailed list of recommendations for future obesity prevention research.     

Social value,clinical equipoise,and research in a public health emergency

The 2016 CIOMS International ethical guidelines for health‐related research involving humans states that ‘health‐related research should form an integral part of disaster response’ and that, ‘widespread emergency use [of unproven interventions] with inadequate data collection about patient outcomes must therefore be avoided’ (Guideline 20). This position is defended against two lines of criticism that emerged during the 2014 Ebola outbreak. One holds that desperately ill patients have a moral right to try unvalidated medical interventions (UMIs) and that it is therefore unethical to restrict access to UMIs to the clinical trial context. The second holds that clinical trials in contexts of high‐mortality diseases are morally suspect because equipoise does not exist between a standard of care that offers little prospect of clinical benefit and a UMI that might offer some clinical advantage.     

Realizing the promise of population biobanks: a new model for translation

The promise of science lies in expectations of its benefits to societies and is matched by expectations of the realisation of the significant public investment in that science. In this paper, we undertake a methodological analysis of the science of biobanking and a sociological analysis of translational research in relation to biobanking. Part of global and local endeavours to translate raw biomedical evidence into practice, biobanks aim to provide a platform for generating new scientific knowledge to inform development of new policies, systems and interventions to enhance the public’s health. Effectively translating scientific knowledge into routine practice, however, involves more than good science. Although biobanks undoubtedly provide a fundamental resource for both clinical and public health practice, their potentiating ontology—that their outputs are perpetually a promise of scientific knowledge generation—renders translation rather less straightforward than drug discovery and treatment implementation. Biobanking science, therefore, provides a perfect counterpoint against which to test the bounds of translational research. We argue that translational research is a contextual and cumulative process: one that is necessarily dynamic and interactive and involves multiple actors. We propose a new multidimensional model of translational research which enables us to imagine a new paradigm: one that takes us from bench to bedside to backyard and beyond, that is, attentive to the social and political context of translational science, and is cognisant of all the players in that process be they researchers, health professionals, policy makers, industry representatives, members of the public or research participants, amongst others.     

WHAT IS IT TO BE A DAUGHTER? IDENTITIES UNDER PRESSURE IN DEMENTIA CARE

This article concentrates on the care for people who suffer from progressive dementia. Dementia has a great impact on a person’s well‐being as well as on his or her social environment. Dealing with dementia raises moral issues and challenges for participants, especially for family members. One of the moral issues in the care for people with dementia is centred on responsibilities; how do people conceive and determine their responsibilities towards one another? To investigate this issue we use the theoretical perspective of Margaret Walker. She states that ideas about identity play a crucial role in patterns of normative expectations with regard to the distribution of responsibilities in daily practices of care. The results of this study show how the identity of a family‐member is put under pressure and changes during her loved one’s illness that leads to difficulties and misunderstandings concerning the issue of responsibility. These results offer an insight into the complexities of actual practices of responsibility and highlight the importance for those caring for people with dementia of attending carefully to how they see themselves and how they see other people involved (Who am I? Who do I want to be for the other?). Answers to such questions show what people expect from themselves and from one another, and how they, at any rate, are distributing responsibilities in a given situation. Professional caregivers should take into account that family members might have different ideas about who they are and consequently about what their responsibilities are.