Most of the literature on phase one trials has focused on ethical and safety issues in research on patients with advanced cancer, but this article focuses on healthy, adult subjects. The article makes six specific recommendations for protecting the rights and welfare of healthy subjects in phase one trials: 1) because phase one trials are short in duaration (usually 1 to 3 months), researchers should gather more data on the short-term and long-term risks of participation in phase one studies by (...) healthy subjects; 2) researchers should develop strict inclusion/exclusion criteria that exclude unhealthy or vulnerable subjects, such as decisionally impaired people, in phase one studies; 3) subjects should not participate in more than one phase one study at the same time and should wait at least 30 days between participating in different studies; 4) researchers should develop a database to keep track of phase one participants; 5) subjects should be guaranteed a minimum wage equivalent to the equivalent type of unskilled labor, but there should be no upper limits on wages; and 6) subjects should be allowed to engage in collective bargaining with research sponsors. *Disclaimer: The ideas and opinions expressed in this article are the authors' personal views and do not represent the views of the National Institute of Environmental Health Sciences, the National Institutes of Health, or the United States government. (shrink)

The general aim of this article is to give a critical interpretation of post-trial obligations towards individual research participants in the Declaration of Helsinki 2013. Transitioning research participants to the appropriate health care when a research study ends is a global problem. The publication of a new version of the Declaration of Helsinki is a great opportunity to discuss it. In my view, the Declaration of Helsinki 2013 identifies at least two clearly different types of post-trial obligations, specifically, access to (...) care after research and access to information after research. The agents entitled to receive post-trial access are the individual participants in research studies. The Declaration identifies the sponsors, researchers and host country governments as the main agents responsible for complying with the post-trial obligations mentioned above. To justify this interpretation of post-trial obligations, I first introduce a classification of post-trial obligations and illustrate its application with examples from post-trial ethics literature. I then make a brief reconstruction of the formulations of post-trial obligations of the Declaration of Helsinki from 2000 to 2008 to correlate the changes with some of the most salient ethical arguments. Finally I advance a critical interpretation of the latest formulation of post-trial obligations. I defend the view that paragraph 34 of ‘Post-trial provisions’ is an improved formulation by comparison with earlier versions, especially for identifying responsible agents and abandoning ambiguous ‘fair benefit’ language. However, I criticize the disappearance of ‘access to other appropriate care’ present in the Declaration since 2004 and the narrow scope given to obligations of access to information after research. (shrink)

There is wide agreement that communities in lower-income countries should benefit when they participate in multinational research. Debate now focuses on how and to what extent these communities should benefit. This debate has identified compelling reasons to reject the claim that whatever benefits a community agrees to accept are necessarily fair. Yet, those who conduct clinical research may conclude from this rejection that there is no reason to involve communities in the process of deciding how they benefit. Against this possibility, (...) the present manuscript argues that involving host communities in this process helps to promote four important goals: protecting host communities, respecting host communities, promoting transparency, and enhancing social value. (shrink)

This paper examines the moral force of exploitation in developing world research agreements. Taking for granted that some clinical research which is conducted in the developing world but funded by developed world sponsors is exploitative, it asks whether a third party would be morally justified in enforcing limits on research agreements in order to ensure more fair and less exploitative outcomes. This question is particularly relevant when such exploitative transactions are entered into voluntarily by all relevant parties, and both research (...) sponsors and host communities benefit from the resulting agreements. I show that defenders of the claim that exploitation ought to be permitted rely on a mischaracterization of certain forms of interference as unjustly paternalistic and two dubious empirical assumptions about the results of regulation. The view I put forward is that by evaluating a system of constraints on international research agreements, rather than individual transaction-level interference, we can better assess the alternatives to permitting exploitative research agreements. (shrink)

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. 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. (edited). (shrink)

Following promulgation of the Nuremberg code in 1947, the ethics of research on human subjects has been a challenging and often contentious topic of debate. Escalation in the use of research participants in low-income countries over recent decades , has intensified the debate on the ethics of international research and led to increasing attention both to exploitation of vulnerable subjects and to considerations of how the 10:90 gap in health and medical research could be narrowed. In 2000, prompted by the (...) discussions over several years that led to the US NIH launching a capacity building programme on research ethics for members of research ethics committees in developing countries, we advanced a ‘new look’ for the ethics of international research.1 Since then progress has been made on several fronts.First, our ideas—considered somewhat radical and impractical at the time—have been provocatively addressed by scholars who have either contested them or advanced similar conceptions of what obligations international researchers have to research participants and communities in low income countries before, during and after clinical trials. Second, those researchers who have been sympathetic to our ideas have either endeavoured to put these into practice or have investigated the feasibility of doing so. Third, the intractability of the 10/90 gap and the escalation of interest in global health have sensitised many to the need to amplify the uptake of these ideas in practice.Here, we briefly review the conceptual and practical developments in international research ethics. While much conceptual progress has been made (and the concepts are now appearing …. (shrink)

Benefit sharing in health research has been the focus of international debates for many years, particularly in developing countries. Whilst increasing attention is being given to frameworks that can guide researchers to determine levels of benefits to participants, there is little empirical research from developing countries on the practical application of these frameworks, including in situations of extreme poverty and vulnerability. In addition, the voices of those who often negotiate and face issues related to benefits in practice - frontline researchers (...) and fieldworkers - are rarely included in these debates. Against this background, this paper reports on experiences of negotiating research participation and benefits as described by fieldworkers, research participants and researchers in two community based studies. (shrink)

ABSTRACT International research enrolling human subjects has raised an ethical concern regarding the just distribution of benefits between the countries that design the research and the host communities. Although several universal declarations have expressed this concern, a gap between theory and practice continues to exist, as well as a significant divergence between the design of the research protocol and the social context where it will be implemented. Although institutional review boards have made a valuable effort to evaluate international research, their (...) sensitivity to the just sharing of research benefits as well as their attention to the social context must be evaluated. This article analyzes the distribution of benefits in a review of international research in Mexico and produces an ethical reflection based on the results. (shrink)

International health research in malaria-endemic settings may include screening for sickle cell disease, given the relationship between this important genetic condition and resistance to malaria, generating questions about whether and how findings should be disclosed. The literature on disclosing genetic findings in the context of research highlights the role of community consultation in understanding and balancing ethically important issues from participants’ perspectives, including social forms of benefit and harm, and the influence of access to care. To inform research practice locally, (...) and contribute to policy more widely, this study aimed to explore the views of local residents in Kilifi County in coastal Kenya on how researchers should manage study-generated information on sickle cell disease and carrier status. (shrink)

Human infection challenge studies (HCS) involve intentionally infecting research participants with pathogens (or other micro-organisms). There have been recent calls for more HCS to be conducted in low-income and middle-income countries (LMICs), where many relevant diseases are endemic. HCS in general, and HCS in LMICs in particular, raise numerous ethical issues. This paper summarises the findings of a project that explored ethical and regulatory issues related to LMIC HCS via (i) a review of relevant literature and (ii) 45 qualitative interviews (...) with scientists and ethicists. Among other areas of consensus, we found that there was widespread agreement that LMIC HCS can be ethically acceptable, provided that they have a sound scientific rationale, are accepted by local communities and meet usual research ethics requirements. Unresolved issues include those related to (i) acceptable approaches to trade-offs between the scientific aim to produce generalisable results and the protection of participants, (iii) the sharing of benefits with LMIC populations, (iii) the acceptable limits to risks and burdens for participants, (iv) the potential for third-party risk and whether the degree of acceptable third-party risk is different in endemic settings, (v) the conditions under which (if any) it would be appropriate to recruit children for disease-causing HCS, (v) appropriate levels of payment to participants and (vi) appropriate governance of (LMIC) HCS. This paper provides preliminary analyses of these ethical considerations in order to (i) inform scientists and policymakers involved in the planning, conduct and/or governance of LMIC HCS and (ii) highlight areas warranting future research. Insofar as this article focuses on HCS in (endemic) settings where diseases are present and/or widespread, much of the analysis provided is relevant to HCS (in HICs or LMICs) involving pandemic diseases including COVID19. (shrink)

This paper discusses the need to focus on the dignity of human participants as a legal and ethical basis for providing post-trial access to healthcare. Debate about post-trial benefits has mostly focused on access to products or interventions proven to be effective in clinical trials. However, such access may be modelled on a broad fair benefits framework that emphasises both collateral benefits and interventional products of research, instead of prescribed post-trial access alone. The wording of the current version of the (...) Declaration of Helsinki could in fact be interpreted to broaden the scope to include other collateral benefits by applying such a broad fair benefits framework. We argue that this possibility should be utilised by low and middle income countries’ health research ethics committees in order to ensure that research participants who enrol in clinical trials so as to receive medical care continue to access care after the trial is concluded, as befits their dignity. Although each LMIC has unique concerns, nonetheless there are common challenges based especially on emerging issues, such as post-trial access to healthcare. Accordingly, the South African perspective is used to draw lessons that can benefit other LMICs. (shrink)

International research, sponsored by for-profit companies, is regularly criticised as unethical on the grounds that it exploits research subjects in developing countries. Many commentators agree that exploitation occurs when the benefits of cooperative activity are unfairly distributed between the parties. To determine whether international research is exploitative we therefore need an account of fair distribution. Procedural accounts of fair bargaining have been popular solutions to this problem, but I argue that they are insufficient to protect against exploitation. I argue instead (...) that a maximin principle of fair distribution provides a more compelling normative account of fairness in relationships characterised by extreme vulnerability and inequality of bargaining potential between the parties. A global tax on international research would provide a mechanism for implementing the maximin account of fair benefits. This model has the capacity to ensure fair benefits and thereby prevent exploitation in international research. (shrink)

Volume 19, Issue 9, September 2019, Page 1-4.

Preventing exploitation in human subjects research requires a benchmark of fairness against which to judge the distribution of the benefits and burdens of a trial. This paper proposes the ideal market and its fair market price as a criterion of fairness. The ideal market approach is not new to discussions about exploitation, so this paper reviews Wertheimer's inchoate presentation of the ideal market as a principle of fairness, attempt of Emanuel and colleagues to apply the ideal market to human subjects (...) research, and Ballantyne's criticisms of both the ideal market and the resulting benchmark of fairness. It argues that the criticism of this particular benchmark is on point, but the rejection of the ideal market is mistaken. After presenting a complete account of the ideal market, this paper proposes a new method for applying the ideal market to human subjects research and illustrates the proposal by considering a sample case. (shrink)

Angela Ballantyne (2010) argues that international research is exploitative when the transactions between researchers and participants who lack basic goods do not provide participants with the maxi...

Most of the literature on phase one trials has focused on ethical and safety issues in research on patients with advanced cancer, but this article focuses on healthy, adult subjects. The article makes six specific recommendations for protecting the rights and welfare of healthy subjects in phase one trials: 1) because phase one trials are short in duaration (usually 1 to 3 months), researchers should gather more data on the short-term and long-term risks of participation in phase one studies by (...) healthy subjects; 2) researchers should develop strict inclusion/exclusion criteria that exclude unhealthy or vulnerable subjects, such as decisionally impaired people, in phase one studies; 3) subjects should not participate in more than one phase one study at the same time and should wait at least 30 days between participating in different studies; 4) researchers should develop a database to keep track of phase one participants; 5) subjects should be guaranteed a minimum wage equivalent to the equivalent type of unskilled labor, but there should be no upper limits on wages; and 6) subjects should be allowed to engage in collective bargaining with research sponsors. *Disclaimer: The ideas and opinions expressed in this article are the authors' personal views and do not represent the views of the National Institute of Environmental Health Sciences, the National Institutes of Health, or the United States government. (shrink)

In the field of bioethics, scholars have begun to consider carefully the impact of structural issues on global population health, including socioeconomic and political factors influencing the disproportionate burden of disease throughout the world. Human rights and social justice are key considerations for both population health and biomedical research. In this paper, I will briefly explore approaches to human rights in bioethics and review guidelines for ethical conduct in international health research, focusing specifically on health research conducted in resource-poor settings. (...) I will demonstrate the potential for addressing human rights considerations in international health research with special attention to the importance of collaborative partnerships, capacity building, and respect for cultural traditions. Strengthening professional knowledge about international research ethics increases awareness of ethical concerns associated with study design and informed consent among researchers working in resource-poor settings. But this is not enough. Technological and financial resources are also necessary to build capacity for local communities to ensure that research results are integrated into existing health systems. Problematic issues surrounding the application of ethical guidelines in resource-poor settings are embedded in social history, cultural context, and the global political economy. Resolving the moral complexities requires a commitment to engaged dialogue and action among investigators, funding agencies, policy makers, governmental institutions, and private industry. (shrink)

In 2004 Emanuel et al. published an influential account of exploitation in international research, which has become known as the 'fair benefits account'. In this paper I argue that the thin definition of fairness presented by Emanuel et al, and subsequently endorsed by Gbadegesin and Wendler, does not provide a notion of fairness that is adequately robust to support a fair benefits account of exploitation. The authors present a procedural notion of fairness – the fair distribution of the benefits of (...) research is to be determined on a case-by-case basis by the parties involved in each study. The fairness of the distribution of benefits is not assessed against an independent normative standard. Emanuel et al.'s account of fairness provides a framework for objecting only to transactions that occur without the fully informed consent of the weaker party. As a result, a debate about exploitation collapses into a debate about consent. This is problematic because, as the proponents of the fair benefits framework acknowledge, neither the trial participants' consent nor the host community's consent preclude exploitation. Attempts to stipulate normative standards of fairness to protect research subjects in developing countries have been controversial and divisive, and it is therefore understandable that bioethicists would be tempted to develop accounts of exploitation that are independent of such prescriptive principles. I conclude, however, that the utility of the fair benefits model of exploitation as a policy tool will ultimately depend on whether a substantive principle of fairness can be developed to underpin it. (shrink)

Imagine a study in which HIV-infected pregnant women are given antiretroviral treatment to determine how effectively it will prevent HIV transmission during childbirth. Each mother’s involvement in this study ends with the birth of her child, at which time her access to antiretrovirals provided by the study also ceases. At the outset of the study, the investigator and sponsor agree that after the child’s birth, they will refer mothers who require treatment for their HIV to a national program that provides (...) antiretroviral treatment and care. Assuming the Institutional Review Board raises no objections to this plan, should the research team consider their ethical obligations to participants fulfilled? If the investigator and sponsor were to consult the Common Rule, they would find little to suggest that there are any further ethical issues to address. (shrink)

The concept of vulnerability has long played a central role in discussions of research ethics. In addition to its rhetorical use, vulnerability has become a term of art in U.S. and international research regulations and guidelines, many of which contain specific provisions applicable to research with vulnerable subjects. Yet, despite the frequency with which the term vulnerability is used, little consensus exists on what it actually means in the context of human subject protection or, more importantly, on how a finding (...) of vulnerability should affect the process of research ethics review.The Common Rule, the centerpiece of the U.S. human subject protection regulations, uses the word vulnerable three times. First, it provides that institutional review boards that regularly review research involving a vulnerable category of subjects should consider including one or more individuals who are knowledgeable about and experienced in working with these subjects. (shrink)

ABSTRACTGlobal demand for human ova in in vitro fertilization has led to its expansion in countries with falling average incomes and rising female unemployment. Paid egg donation in the context of national, regional, and global inequalities has the potential to exploit women who are socioeconomically vulnerable, and indeed there is ample evidence that it does. Structural injustices that render women in middle-income countries – and even some high-income countries – economically vulnerable contribute to a context of ‘omissive coercion’ that is (...) morally troubling. When egg brokers or fertility clinics take advantage of these background structural injustices and prospective ova providers’ vulnerability in order to pay them less than they need to meet their livelihood needs, they engage in exploitation. Analyzing paid egg donation as a form of reproductive labor, however, can direct our attention to reforms that would reduce exploitative instances of this practice. In contrast to those who see... (shrink)

Is there no balm in Gilead; is there no physician there? Why then is not the health of the daughter of my people recovered?In July of 2004, Cambodian sex workers staged a protest of an HIV prevention trial set to enroll 900 sex workers in Phnom Penh, charging the study planners with exploitation. The Cambodian study was one of a series of international clinical trials sponsored by the U.S. National Institutes of Health, U.S. Centers for Disease Control and Prevention, and (...) the Bill and Melinda Gates Foundation testing the safety and efficacy of tenofovir, an antiretroviral drug produced by Gilead Sciences, Inc., to prevent HIV transmission. To date, two of these international studies have been closed and one is suspended, prompting calls for re-examination of the ethics of HIV prevention trials. (shrink)

Interest in the ethics of research on human subjects, stimulated by atrocious human experimentation during WWII and the resultant Nuremberg Code, has been sustained by examples of unethical research in many countries and by proliferation of codes and guidelines. Such interest has intensified in recent years in association with expanding international collaborative research endeavors. The ongoing controversy in international research ethics takes place at two levels. At the practical level it is about the competing concerns of those predominantly interested in (...) doing research to advance knowledge and those who, while supporting the need for research, are more acutely aware of the potential to exploit vulnerable participants, especially in developing countries. At the level of theory the controversy pits ethical universalism against moral relativism.In her recent review of agreements and controversies in international research ethics, Ruth Macklin has concluded that, despite seeming agreement on several issues, many different viewpoints persist. In her view it is unlikely that these will be resolved easily. (shrink)

Returning research results to participants is recognised as an obligation that researchers should always try to fulfil. But can we ascribe the same obligation to researchers who conduct genomics research producing only aggregated findings? And what about genomics research conducted in developing countries? This paper considers Beskow's et al. argument that aggregated findings should also be returned to research participants. This recommendation is examined in the context of genomics research conducted in developing countries. The risks and benefits of attempting such (...) an exercise are identified, and suggestions on ways to avoid some of the challenges are proposed. I argue that disseminating the findings of genomic research to participating communities should be seen as sharing knowledge rather than returning results. Calling the dissemination of aggregate, population level information returning results can be confusing and misleading as participants might expect to receive individual level information. Talking about sharing knowledge is a more appropriate way of expressing and communicating the outcome of population genomic research. Considering the knowledge produced by genomics research a worthwhile output that should be shared with the participants and approaching the exercise as a ‘sharing of knowledge’, could help mitigate the risks of unrealistic expectations and misunderstanding of findings, whilst promoting trusting and long lasting relationships with the participating communities. (shrink)

Research ethics committees (RECs) evaluate whether the risk-benefit ratio of a study is acceptable. Decentralized clinical trials (DCTs) are a novel approach for conducting clinical trials that potentially bring important benefits for research, including several collateral benefits. The position of collateral benefits in risk-benefit assessments is currently unclear. DCTs raise therefore questions about how these benefits should be assessed. This paper aims to reconsider the different types of research benefits, and their position in risk-benefit assessments. We first propose a categorization (...) of research benefits, based on the types of benefits that can be distinguished from the literature and ethical guidelines. Secondly, we will reconsider the position of collateral benefits. We argue that these benefits are not fundamentally different from other benefits of research and can therefore be included in risk-benefit assessments of DCTs. (shrink)

Ballantyne correctly notes the need for clarification as to the standard of fairness that should guide nonexploitative international research on human subjects. When accounts of exploitation are applied to pharmaceutical development (as well as other areas), there is too often an uncritical acceptance that exploitation involves a form of unfairness. Moreover, these authors typically fail to produce an account of fairness by which exploitation should be identified. Ballantyne should be applauded for her attempt to inject greater clarity into these debates. (...) Her preferred standard of fairness is problematic, however. Ballantyne fails to distinguish between at least two forms of exploitation, tied to two distinct forms of unfairness, that can take place in international research on human subjects. As I argue here, the first form of exploitation derives from transactional unfairness where researchers take special unfair advantage of research subjects. The second form of exploitation occurs when researchers take advantage of background injustices that disadvantage research subjects. As a result of this failure to differentiate between different forms of exploitation, Ballantyne misidentifies the requirements of fairness for engaging in nonexploitative international human subject research. (shrink)

Finding an effective microbicide that could substantially lower women’s risk of acquiring HIV infection is an ethical imperative. Women and girls continue to be disproportionally affected by HIV in sub-Saharan Africa. Ethics guidelines for conducting preventive HIV microbicide trials call for steps that intertwine biomedical research and public health. Ethical considerations include adequate studies of the safety of microbicides, the use of placebo controls in future trials once a microbicide is shown to be effective, whether leftover microbicide from a trial (...) that demonstrated efficacy should be made available to the public or used in the control group of a future trial, what preventive measures and treatment should be provided for trial participants during and after the research, and what constitute ‘fair benefits’ to the community or country when a trial is completed. The Global Campaign for Microbicides conducted a study of the benefits being provided to participants in microbicide trials and others, and found substantial evidence that researchers and sponsors are meeting the obligations stated in ethical guidelines. A cautionary tale of an HIV prevention trial that was prematurely halted demonstrates the need for engagement with the community where trials are carried out. (shrink)

Offering cash payments to research subjects is a common recruiting method, but this practice continues to be controversial because of its potential to compromise the protection of human subjects. Some critics question whether researchers should be allowed to offer money at all, citing concerns about commodification of the research subject, invalidation of study results, and increased risks to subjects. Other critics are comfortable with the idea of monetary payments but question how much researchers can pay their subjects, citing concerns about (...) undue inducement, crowding out, and monetary exploitation. Focusing only on the amount researchers can pay their subjects, this paper argues that the federal regulations and guidelines should implement a standard payment formula. It argues for a wage payment model, and critically examines three candidates for a base wage: the nonfarm production wage, the FLSA minimum wage, and a living wage. (shrink)

Determining what constitutes an anticipatable incidental finding from clinical research and defining whether, and when, this IF should be returned to the participant have been topics of discussion in the field of human subject protections for the last 10 years. It has been debated that implementing a comprehensive IF-approach that addresses both the responsibility of researchers to return IFs and the expectation of participants to receive them can be logistically challenging. IFs have been debated at different levels, such as the (...) ethical reasoning for considering their disclosure or the need for planning for them during the development of the research study. Some authors have discussed the methods for re-contacting participants for disclosing IFs, as well as the relevance of considering the clinical importance of the IFs. Similarly, other authors have debated about when IFs should be disclosed to participants. However, no author has addressed how the “actionability” of the IFs should be considered, evaluated, or characterized at the participant's research setting level. This paper defines the concept of “Actionability at the Participant's Research Setting Level” for anticipatable IFs from clinical research, discusses some related ethical concepts to justify the APRSL concept, proposes a strategy to incorporate APRSL into the planning and management of IFs, and suggests a strategy for integrating APRSL at each local research setting. (shrink)

There are now at least two different views that fall under the heading of the “fair benefits” approach (FBA) to international research. These views share a number of important commitments, such as...

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. (shrink)

(2010). Response to Open Peer Commentaries on “How to Do Research Fairly in an Unjust World”. The American Journal of Bioethics: Vol. 10, No. 6, pp. W4-W6.