Our primary focus is on analysis of the concept of voluntariness, with a secondary focus on the implications of our analysis for the concept and the requirements of voluntary informed consent. We propose that two necessary and jointly sufficient conditions must be satisfied for an action to be voluntary: intentionality, and substantial freedom from controlling influences. We reject authenticity as a necessary condition of voluntary action, and we note that constraining situations may or may not undermine voluntariness, depending on the (...) circumstances and the psychological capacities of agents. We compare and evaluate several accounts of voluntariness and argue that our view, unlike other treatments in bioethics, is not a value-laden theory. We also discuss the empirical assessment of individuals? perceptions of the degrees of noncontrol and self-control. We propose use of a particular Decision Making Control Instrument. Empirical research using this instrument can provide data that will help establish appropriate policies and procedures for obtaining voluntary consent to research. (shrink)

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)

Many ethicists maintain that medical research on human subjects that presents no prospect of direct medical benefit must have a prospect of social benefit to be ethical. Payment is not the sort of benefit that justifies exposing subjects to risk. Alan Wertheimer has raised a serious challenge to this view, pointing out that in industry, social value is not considered necessary to make dangerous jobs ethical. This article argues that Wertheimer was correct to think that the ethics of hazard pay (...) should be the same in medical research and in business. Nevertheless, a qualified social benefit requirement should apply in both fields. For a study or a job with significant net physical risk to be ethical, it must have social value beyond the satisfaction of ordinary preferences, including the preference for money. The requirement derives from a non-absolutist version of the doctrine of double effect. If a risky study or a dangerous job has no distinctive social value, and hazard pay is subjects' or workers’ only reason to undergo risks, the very fact that they undergo risk is intended as a means to a financial end. Inviting people to enrol in such a study or to take such a job wrongfully treats people as mere means. By contrast, if a study or a job has social value, people can participate with a primary end other than money, even if they accept compensation. Researchers or employers do not intend but merely foresee risks to subjects or workers. (shrink)

Participant safety and data integrity, critical in trials of new investigational drugs, are achieved through honest participant report and precision in the conduct of procedures. HIV prevention post-trial access studies in middle-income countries potentially offer participants many benefits including access to proven efficacious but unlicensed technologies, ancillary care that often exceeds local standards-of-care, financial reimbursement for participation and possibly unintended benefits if participants choose to share or sell investigational drugs. This case study examines the possibility that this combination of benefits (...) may constitute an undue inducement for some participants in middle-income countries, where economic challenges are prevalent. A case study is presented of a single participant in a cohort of 382 participants who used concealment, fabrication and deception to ensure eligibility for a post-trial access study of an unlicensed HIV prevention technology at potential risk to her health and that of her fetus. A root cause analysis revealed her desire to access HIV prevention during an unplanned pregnancy with a partner whose faithfulness was in question. Researchers should consider implementation of systems to efficiently identify similar cases without inconveniencing the majority of participants Trial registration number NCT01691768. (shrink)

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)

Clinical investigators must engage in just subject recruitment and selection and avoid unduly influencing research participation. There may be tension between the practice of keeping payments to participants low to avoid undue influence and the requirements of justice when recruiting normal healthy volunteers for phase 1 drug studies. By intentionally keeping payments low to avoid unduly influenced participation, investigators, on the recommendation or insistence of institutional review boards, may be targeting or systematically recruiting healthy adult members of lower socio-economic groups (...) for participation in phase 1 studies. Investigators are at risk of routinely failing to fulfill the obligation of justice, which prohibits the systematic targeting and recruiting of subjects for reasons unrelated to the nature of the study. Insofar as we take seriously the obligation to engage in just subject recruitment and selection, I argue that we must acknowledge the implications low payments might have for subject recruitment and selection and examine the effect of low payments. If low payments de facto target the less well-off for phase 1 studies, we must defend the priority ranking of the obligation to avoid undue influence over the obligation of justice or adopt an alternative recruitment approach. This paper identifies a number of alternatives to the current system of low-value payments to research participants. (shrink)

In contrast to most publications on the ethics of paying research subjects, which start by identifying and analyzing major ethical concerns raised by the practice (in particular, risks of undue inducement and exploitation) and end with a set of—more or less well-justified—ethical recommendations for using payment schemes immune to these problems, this paper offers a systematic, principle-based ethical analysis of the practice. It argues that researchers have aprima faciemoral obligation to offer payment to research subjects, which stems from the principle (...) of social beneficence. This principle constitutes an ethical “spine” of the practice. Other ethical principles of research ethics (respect for autonomy, individual beneficence, and justice/fairness) make up an ethical “skeleton” of morally sound payment schemes by providing additional moral reasons for offering participants (1) recompense for reasonable expenses; and (2a) remuneration conceptualized as a reward for their valuable contribution, provided (i) it meets standards of equality, adequacy and non-exploitation, and (ii) it is not overly attractive (i.e., it does not constitute undue inducement for participation or retention, and does not encourage deceptive behaviors); or (2b) remuneration conceptualized as a market-driven price, provided (i) it is necessary and designed to help the study achieve its social and scientific goals, (ii) it does not reinforce wider social injustices and inequalities; (iii) it meets the requirement of non-exploitation; and (iv) it is not overly attractive. The principle of justice provides a strong ethical reason for not offering recompenses for lost wages (or loss of other reasonably expected profits). (shrink)

Research involving human subjects is much more stringently regulated than many other nonresearch activities that appear to be at least as risky. A number of prominent figures now argue that research is overregulated. We argue that the reasons typically offered to justify the present system of research regulation fail to show that research should be subject to more stringent regulation than other equally risky activities. However, there are three often overlooked reasons for thinking that research should be treated as a (...) special case. First, research typically involves the imposition of risk on people who do not benefit from this risk imposition. Second, research depends on public trust. Third, the complexity of the moral decision making required favors ethics committees as a regulative solution for research. (shrink)

1. The opinions expressed are the author's own. They do not reflect any position or policy of the National Institutes of Health, Public Health Service, Department of Health and Human Services, or any of the authors affiliated organizations.

Public investments in genomic and precision medicine have begun to yield clinically useful interventions, most recently, for example, two new, FDA-approved gene therapies for sickle cell disease (F...

Background Increase in global health research undertaken in resource poor settings in the last decade though a positive development has raised ethical concerns relating to potential for exploitation. Some of the suggested strategies to address these concerns include calls for providing universal standards of care, reasonable availability of proven interventions and more recently, promoting the overall social value of research especially in clinical research. Promoting the social value of research has been closely associated with providing fair benefits to various stakeholders (...) involved in research. The debate over what constitutes fair benefits; whether those that addresses micro level issues of justice or those focusing on the key determinants of health at the macro level has continued. This debate has however not benefited from empirical work on what stakeholders consider fair benefits. This study explores practical experiences of stakeholders involved in global health research in Kenya, over what benefits are fair within a developing world context. Methods and results We conducted in-depth interviews with key informants drawn from within the broader health research system in Kenya including researchers from the mainstream health research institutions, networks and universities, teaching hospitals, policy makers, institutional review boards, civil society organisations and community representative groups. The range of benefits articulated by stakeholders addresses both micro and macro level concerns for justice by for instance, seeking to engage with interests of those facilitating research, and the broader systemic issues that make resource poor settings vulnerable to exploitation. We interpret these views to suggest a need for global health research to engage with current crises that face people in these settings as well as the broader systemic issues that produce them. Conclusion Global health research should provide benefits that address both the micro and macro level issues of justice in order to forestall exploitation. Embracing the two is however challenging in terms of how the various competing interests/needs should be balanced ethically, especially in the absence of structures to guide the process. This challenge should point to the need for greater dialogue to facilitate value clarification among stakeholders. (shrink)

On November 14, 1996, an in-depth report on the recruiting and testing practices of Lilly Pharmaceuticals appeared in the Wall Street Journal. Laurie Cohen reported that most pharmaceutical companies had difficulty recruiting healthy subjects to participate in testing of “untried and potentially dangerous” drugs. These companies often had to pay subjects up to $250 a day to ensure adequate enrollment, and some even gave referral bonuses to doctors who sent potential subjects their way. Cohen then exposed how Lilly was able (...) to keep costs down: by recruiting homeless alcoholics to serve as research guinea pigs. “In many ways,” Cohen reported, “the practice is mutually beneficial. For Lilly, it is efficient and limits the risk that subjects will sue if harmed by an experiment or divulge particulars of a drug.” And the subjects “get several weeks or months of free room and board, and in interviews they express voluble gratitude for what they often call easy money.”. (shrink)

In clinical mental health research with children, both child and parent are essential members of the research team. The 3 R's of parent/child team membership are respect, rapport, and recognition. Respect and recognition include fair reimbursement for time, expense, and inconvenience, but the most important compensation for many families is the appreciation of the other team members for their sacrifice and cooperation. Reimbursement, although honoring the principles of justice and respect for persons, raises difficult issues about appropriate amount, particularly in (...) research involving children. The 3 R's are supported by the investigator 5 A's: attitude, adaptability, availability, attachment, and appreciation. Although the principles seem clear in the abstract, implementation encounters many practical problems. Perhaps the most difficult of these is determining the appropriate amount of compensation that avoids undue inducement but not at the expense of the 3 R's and 5 A's. (shrink)

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

The present article highlights ethical challenges and practical solutions to the problems that arise when designing and conducting the fieldwork data collection with the members of violent youth gangs, prison inmates, and arrestees held in police cells in Nigeria. Issues related to the process of seeking approval and then implementing the research, gaining access, achieving informed consent, confidentiality, the use of interpreters, and remuneration are presented through case studies. The conclusion stresses the need for researchers to be well prepared and (...) sensitive to the research participants' community and cultural backgrounds while following ethical practices in multicultural contexts, especially in Africa and other developing nations. (shrink)

In clinical research, informed consent is both a legal document and mechanism for respecting the dignity of participating subjects and protecting their rights and wellbeing. It should include information on the purpose of the research, its justification, and the risks and the benefits involved, so as to enable a subject to decide to participate voluntarily. Because it is the researcher’s duty to ensure protection of the life, health, dignity, integrity, right to self-determination, privacy and confidentiality of the subjects who take (...) part in a study, the researcher must establish a permanent dialogue with them to assess the risks and safety inherent in their participation. This condition becomes a dynamic process that neither begins nor ends when informed consent is signed. It goes beyond legality and becomes a question of ethics and legitimacy. (shrink)

Should egg donors be paid? A negative answer might be offered on the ground that payment for egg donation is coercive. But is this viewpoint tenable? Is the offer of payment for egg donation really coercive? Even if not coercive, might payment for egg donation nonetheless be seen as exploitative? And if so why? The central argument of this paper focuses on the question whether the offer of payment for egg donation is an exploitative inducement and therefore an undue inducement. (...) Another question raised in this paper is whether, given that it is commodifying, payment for egg donation constitutes a failure to recognize the giftedness and true value of human life. (shrink)

ABSTRACT This paper reports on a multidisciplinary meeting held to discuss ethical issues in medical research in the developing world. Many studies, including clinical trials, are conducted in developing countries with a high burden of disease. Conditions under which this research is conducted vary because of differences in culture, public health, political, legal and social contexts specific to these countries. Research practices, including standards of care for participants, may vary as a result. It is therefore not surprising that ethical issues (...) emerge. This meeting sought to identify and discuss these issues from the perspectives of the many actors in such research, including community representatives, with a view to finding ethical and pragmatic solutions to these issues. Dialogue between these actors was also promoted, with a view to identifying the need to develop such dialogue in future. Drawing from the experiences of the speakers, the colloquium attempted to outline some answers to several key questions characterising the field today. Experiences related to epidemiologic research, vaccine trials, drug trials, diagnostic tests and to some fundamental ethical issues in health research. Speakers were from different countries, disciplines and professions. The meeting provided a forum for consultation and debate between different ethics actors. Both encouraging findings and challenges emerged. (shrink)

Paying research participants in developing countries like Uganda raises ethical concerns over potential for undue inducement. This article, based on an exploratory study, reviewed 49 research protocols from a national HIV/AIDS research ethics committee database. Payments mainly adhered to the reimbursement and compensation payment models. Offers made were diverse but basic in order to limit undue inducement. Implications in terms of undue inducement and possible impact on participants and research are discussed. We end by recommending standardization across comparable studies in (...) the interests of promoting high-quality research, altruism, voluntariness, and restraining unfair reimbursement practices in research. (shrink)

ABSTRACT There are disagreements among ethicists on what comprises an “appropriate” good to offer research participants. Debates often focus on the type, quantity, timing, and ethical appropriateness of such offers, particularly in settings where participants may be socio-economically vulnerable, such as in parts of Zambia. This was a Cross-sectional online survey of researchers and Research Ethics Committees (RECs) designed to understand practices, attitudes and policies associated with provision of goods to research participants. Of 122 responding researchers, 69 met eligibility criteria. (...) Responses were also received from five of the six Zambian RECs involved in reviewing research proposals. Forty-nine researchers (71.0%) confirmed previous experience offering goods to participants. Of these, 21 (42.9%) offered participants money only, 18 (36.7%) offered non-monetary goods, while the rest offered both monetary and non-monetary goods. Generally, goods were offered and approved by RECs to compensate for time, lost wages and transportation. One REC and 34.8% of researchers reported being subject to an institutional policy on offering goods to participants. While reimbursement is the main reason for offering goods to participants in Zambia, caution is required when deciding on the type and quantity of goods to offer given the potential for community mistrust and manipulation. (shrink)

Lowering compensation to research subjects to protect them from “undue inducement” is a misguided attempt to shoehorn a concern about exploitation into the framework of autonomy. We suggest that oversight bodies should be less concerned about undue influence than about exploitation of subjects. Avoiding exploitation in human subjects research requires not only increasing compensation, but enhancing the dignity of research participation.

Clinical research is thought to be ethically problematic and is subject to extensive regulation and oversight. Despite frequent endorsement of this view, there has been almost no systematic evaluation of why clinical research might be ethically problematic. As a result, it is difficult to determine whether the regulations to which clinical research is subject address the ethical concerns it raises. Commentators who consider this question at all tend to assume that clinical research is ethically problematic because it exposes some individuals (...) to risks for the benefit of others. Yet, many other activities that expose some individuals to risks for the benefit of others are not subject to extensive regulation and oversight. This difference raises the question of whether clinical research is distinct from these activities in normatively relevant ways and, if so, what implications this difference (or differences) has for how clinical research should be regulated and conducted. The present manuscript attempts to answer this question by comparing clinical research to two other activities that expose some individuals to risks for the benefit of others. This comparison highlights an aspect of clinical research which has received relatively little attention, namely, the active role investigators play in exposing subjects to risks. I argue that this aspect explains much of the ethical concern expressed regarding clinical research. I end by considering the normative significance of this feature and the implications it has for how clinical research should be regulated and conducted. (shrink)

The recent TeGenero phase I trial of a novel monoclonal antibody in healthy volunteers produced a drastic inflammatory reaction in participants receiving the experimental agent. Commentators on the ethics of the research have focused considerable attention on the role of financial considerations: the for-profit status of the biotechnology company and Contract Research Organization responsible respectively for sponsoring and conducting the trial and the amount of monetary compensation to participants. We argue that these financial considerations are largely irrelevant and distort ethical (...) appraisal of this tragic research. Except for administering the antibody to all 6 participants nearly simultaneously, the trial appears to fulfill all of the critical ethical requirements for clinical research—social value, scientific validity, fair subject selection, favorable risk-benefit ratio, independent review, informed consent, and respect for enrolled participants. (shrink)

Introduction Scholars have debated how to define coercion and undue influence, but how institutional review boards (IRBs) view and make decisions about these issues in actual cases has not been explored. Methods I contacted the leadership of 60 US IRBs (every fourth one in the list of the top 240 institutions by National Institutes of Health funding), and interviewed 39 IRB leaders or administrators from 34 of these institutions (response rate=55%), and 7 members. Results IRBs wrestled with defining of ‘coercion’ (...) and ‘undue inducement’, most notably in deciding about participant compensation. IRBs often use these terms synonymously and define undue inducement in varying ways, often wrestling with these issues, relying on ‘gut feelings’, and seeking compromises. Ambiguities arose, partly reflecting underlying tensions: whether subjects should ‘get paid’ versus ‘volunteer’ (ie, whether subjects should be motivated by compensation vs altruism), and whether subjects should be paid differently based on income, given possible resultant selection bias. Lack of consistent standards emerged between and even on single IRBs. Questions arose concerning certain aspects and types of studies; for example, how to view and weigh providing free care in research, whether and how recruitment flyers should mention compensation, and how to avoid coercion in paediatric, developing world, or students research. Conclusions These data, the first to probe qualitatively how IRBs view and approach questions about coercion, undue influence and participant compensation, and to examine how IRBs have reviewed actual cases, reveal several critical ambiguities and dilemmas, and have vital implications for future practice, education, policy and research. (shrink)

Each year thousands of individuals enrol in clinical trials as healthy volunteers to earn money. Some of them pursue research participation as a full-time or at least a part-time job. They call themselves professional or semiprofessional guinea pigs. The practice of paying healthy volunteers raises numerous ethical concerns. Different payment models have been discussed in literature. Dickert and Grady argue for a wage-payment model. This model gives research subjects a standardised hourly wage, and it is based on an assumption that (...) research participation is morally indistinguishable from other forms of unskilled labour. In this paper, I will challenge this assumption. I will argue that human guinea pigging has particular characteristics which taken together make it significantly different from other forms of labour. Participation in research is skill-independent. Healthy volunteers are valuable not because they are skilful persons, but because they are human bodies. The role of research volunteers is mainly passive. They are not asked to produce goods or deliver services. They are paid for enduring unpleasant, painful and risky interventions performed by investigators. Research volunteering involves inherent risks and uncertainties, and subjects have little or no control over their minimisation and materialisation. I conclude that participation in clinical research is a specific kind of activity. It is more like renting out one’s body to strangers, than working. Thus, research participation should not be treated on par with other forms of employment. (shrink)

Background Payment of research participants helps to increase recruitment for research studies, but can pose ethical dilemmas. Research ethics committees (RECs) have a centrally important role in guiding this practice, but standardisation of the ethical approval process in Ireland is lacking. Aim Our aim was to examine REC policies, experiences and concerns with respect to the payment of participants in research projects in Ireland. Method Postal survey of all RECs in Ireland. Results Response rate was 62.5% (n=50). 80% of RECs (...) reported not to have any established policy on the payment of research subjects while 20% had refused ethics approval to studies because the investigators proposed to pay research participants. The most commonly cited concerns were the potential for inducement and undermining of voluntary consent. Conclusions There is considerable variability among RECs on the payment of research participants and a lack of clear consensus guidelines on the subject. The development of standardised guidelines on the payment of research subjects may enhance recruitment of research participants. (shrink)