This article concerns the validity of six canonical rules that institutional review boards use to constrain the behavior of investigators. These rules require investigators to design their studies in a scientifically valid way, not pay their subjects to take risks, minimize risks to their subjects, secure for their subjects access to effective interventions post-trial, not pay their subjects too much and allow their subjects to withdraw from the study unconditionally. Enforcement of these rules is problematic because there are other relationships (...) that seem to be like the investigator-subject relationship in all ethically relevant respects, such as the employer-employee and volunteer organizer-volunteer relationships, to which we would not dream of applying these same rules. Applying these rules in one context but not the others is a violation of ethical consistency I label “exceptionalism.” We should conclude that it is time to reexamine the validity of the six rules. (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)

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)

For decades, worries about undue inducement have Pervaded clinical research, and are especially common when research is accompanied by payment or conducted in developing countries. Few ethical judgments carry as much moral opprobrium or are thought to undermine the ethical soundness of a clinical trial as thoroughly as undue inducement. Indeed, the admonition to prevent undue inducement is one of the few explicit instructions in the Common Rules requirements for informed consent.Despite their long history and pervasiveness, charges of undue inducement (...) in clinical research are almost always mistaken. Indeed, I will advance an even more radical claim: Aresearch trial that otherwise fulfills the fundamental ethical requirements for human subjects research inherently cannot create the possibility of undue inducement because substantial risk of serious harm isprecluded. Charges of undue inducement tend to express displaced and mislabeled ethical concerns about other aspects of human subjects research. Consequently, claims of undue inducement should rarely be made, and when they are advanced should be treated with skepticism, placing a heavy burden of proofon those advancing such charges. (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)

Proponents of permitting living kidney sales often argue as follows. Many jobs involve significant risks; people are and should be free to take these risks in exchange for money; the risks involved in giving up a kidney are no greater than the risks involved in acceptable hazardous jobs; so people should be free to give up a kidney for money, too. This paper examines this frequently invoked but rarely analysed analogy. Two objections are raised. First, it is far from clear (...) that kidney sales and dangerous jobs involve comparable risks on an appropriately broad comparison. Second, and more importantly, even if they do involve comparable risks it does not follow that kidney sales must be permitted because dangerous jobs are. The analogy assumes that kidney sales are banned for paternalistic reasons. But there may be other, non-paternalistic reasons for the ban. And paternalists, too, can consistently defend the ban even if kidney sales are no riskier than occupations that they find acceptable. Soft paternalists may want to protect would-be vendors from harms that they have not voluntarily chosen. Egalitarian hard paternalists may want to protect already badly off vendors from further worsening their situation. For neither species of paternalist is the size of the risk prevented decisive. I conclude that the analogy with dangerous jobs, while rhetorically powerful, pulls little real argumentative weight. Future debates on living kidney sales should therefore proceed without it. (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)

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)

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)

What relationship between investigators and subjects of clinical research would best meet the needs and wants of both – and of society, which has an interest not only in clinical research being done but also in its being done well? This series of articles argues that investigators and subjects should work together in a partnership based in shared aims. Other relationships are possible, however, and here I examine two.

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)