Biomedical research is increasingly carried out in low- and middle-income countries. International consensus has largely been achieved around the importance of valid consent and protecting research participants from harm. But what are the responsibilities of researchers and funders to share the benefits of their research with research participants and their communities? After setting out the legal, ethical and conceptual frameworks for benefit sharing, this collection analyses seven historical cases to identify the ethical and policy challenges that arise in relation to (...) benefit sharing. A series of recommendations address possible ways forward to achieve justice for research participants in low- and middle-income countries. (shrink)

ABSTRACTThe provision of gifts and payments for healthy volunteer subjects remains an important topic in global health research ethics. This paper provides empirical insights into theoretical debat...

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)

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)

ABSTRACT In this paper, I support the claim that placing certain restrictions on public access to possible new treatments is morally problematic under some exceptional circumstances. Very ill patients may find that all available standard treatments are unacceptable, either because they are ineffective or have serious adverse effects, and these patients may understandably be desperate to try something new even if this means stepping into the unknown. Faced with certain death, it is rational to want to try something new and (...) to chance a dire outcome. Restricting possible new treatments to research trials may put these treatments scientifically, geographically or economically out of reach of these patients. For those who can get access, research restrictions could weaken, though not necessarily eliminate, the value of consent participants of such trials are able to give. Some participants may therefore be exploited for scientific purposes in the name of public interest. There are nonetheless compelling reasons for keeping some restrictive regulation in this area. (shrink)

ABSTRACT BACKGROUND: The objective of this study was to identify factors motivating women to take part in endometriosis research and to determine if these factors differ for women participating in clinical versus basic science studies. METHODS: A consecutive series of 24 women volunteering for participation in endometriosis‐related research were asked to indicate, in their own words, why they chose to volunteer. In addition, the women were asked to rate, on a scale of 0 to 10, sixteen potentially motivating factors. The (...) information was gathered in the form of an anonymous self‐administered questionnaire. RESULTS: Strong motivating factors (mean score >8) included potential benefit to other women's health, improvement to one's own condition, and participation in scientific advancement. Weak motivating factors (mean score <3) included financial compensation, making one's doctor happy, and use of ‘natural’ products. No difference was detected between clinical and basic science study participants. CONCLUSION: This study is the first study to specifically investigate the factors that motivate women to take part in endometriosis research. Understanding why women choose to take part in such research is important to the integrity of the informed consent process. The factors most strongly motivating women to participate in endometriosis research related to improving personal or public health; the weakest, to financial compensation and pleasing the doctor. (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)

Volume 19, Issue 9, September 2019, Page 48-50.

Although the importance of including vulnerable populations in medical research is widely accepted, identifying how to achieve such inclusion remains a challenge. Ensuring that the language of informed consent is comprehensible to this group is no less of a challenge. Although a variety of interventions show promise for increasing the comprehensibility of informed consent and increasing a climate of exchange, consensus is lacking on which interventions should be used in which situations and current regulations provide little guidance. We argue that (...) the notion of individual autonomy — a foundational principle of informed consent — may be too narrow for some vulnerable populations by virtue of its failure to acknowledge their unique histories and current circumstances. It has a different meaning for members of structured groups like American Indians than for unstructured groups, such as African Americans, whose complicated histories foster group identity. Ensuring broad participation in research and selecting appropriate methods for obtaining informed consent — namely, methods aligned with the source of vulnerability and level of risk — require new ways of thinking that might produce guidelines for matching informed consent models and processes with subpopulations. (shrink)

(2001). The Fiction of 'Undue Inducement': Why Researchers Should Be Allowed to Pay Participants Any Amount of Money for Any Reasonable Research Project. The American Journal of Bioethics: Vol. 1, No. 2, pp. 1g-3g.

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)

Contemporary research ethics policies started with reflection on the atrocities perpetrated upoconcentration camp inmates by Nazi doctors. Apparently, as a consequence of that experience, the policies that now guide human subject research focus on the protection of human subjects by making informed consent the centerpiece of regulatory attention. I take the choice of context for policy design, the initial prioritization of informed consent, and several associated conceptual missteps, to have set research ethics off in the wrong direction. The aim of (...) this paper is to sort out these confusions and their implications and to offer instead a straightforward framework for considering the ethical conduct of human subject research. In the course of this discussion I clarify different senses of autonomy that have been confounded and present more intelligible justifications for informed consent. I also take issue with several of the now accepted dogmas that govern research ethics. These include: the primacy of informed consent, the protection of the vulnerable, the substitution of beneficence for research's social purpose, and the introduction of an untenable distinction between innovation and research. (shrink)

(2001). Is Informed Consent Enough? Monetary Incentives for Research Participation and the Integrity of Biomedicine. The American Journal of Bioethics: Vol. 1, No. 2, pp. 49-51.

Individuals can often take steps to preserve or improve their own health. They can eat appropriate quantities of healthy foods, exercise, and refrain from smoking. They can obtain preventive care and adhere to their physicians’ advice about how best to manage their health. But they often fail to take these steps.A widespread failure to adopt healthy behaviors can significantly erode public health while increasing health care costs. Obesity, for example, increases the risk of heart disease, stroke, liver disease, and certain (...) cancers. By one estimate, it is responsible for almost 10 percent of medical spending in the United States, or about $147 billion per year. Smoking increases the risk of heart disease, stroke, lung disease, and cancer; it accounts for nearly 20 percent of deaths each year in the United States and about $96 billion in health care expenditures. (shrink)

Payment to recruit research subjects is a common practice but raises ethical concerns relating to the potential for coercion or undue influence. We conducted the first national study of IRB members and human subjects protection professionals to explore attitudes as to whether and why payment of research participants constitutes coercion or undue influence. Upon critical evaluation of the cogency of ethical concerns regarding payment, as reflected in our survey results, we found expansive or inconsistent views about coercion and undue influence (...) that may interfere with valuable research. In particular, respondents appear to believe that coercion and undue influence lie on a continuum; by contrast, we argue that they are wholly distinct: whereas undue influence is a cognitive distortion relating to assessment of risks and benefits, coercion is a threat of harm. Because payment is an offer, rather than a threat, payment is never coercive. (shrink)

For valid informed consent, it is crucial that patients or research participants fully understand all that their consent entails. Testing and revising informed consent documents with the assistance of their addressees can improve their understandability. In this study we aimed at further developing a method for testing and improving informed consent documents with regard to readability and test-readers’ understanding and reactions. We tested, revised, and retested template informed consent documents for biobank research by means of 11 focus group interviews with (...) members from the documents’ target population. For the analysis of focus group excerpts we used qualitative content analysis. Revisions were made based on focus group feedback in an iterative process. Focus group participants gave substantial feedback on the original and on the revised version of the tested documents. Revisions included adding and clarifying explanations, including an info-box summarizing the main points of the text and an illustrative graphic. Our results indicate positive effects on the tested and revised informed consent documents in regard to general readability and test-readers’ understanding and reactions. Participatory methods for improving informed consent should be more often applied and further evaluated for both, medical interventions and clinical research. Particular conceptual and methodological challenges need to be addressed in the future. (shrink)

Over the past 5 years, a series of articles in leading American newspapers has revealed the extent to which the conduct of clinical trials may be affected by inducements offered by corporate research sponsors and accepted by some unscrupulous physicians. The cases described were disturbing. They involved physicians engaged in excessive “enrollment activities” in exchange for money. Some of these physicians perpetrated fraud, falsifying their recruitment records in order to increase their profits. Others ignored exclusion criteria designed to ensure the (...) safety of subjects and the validity of research results, referring their patients to research investigating treatments for conditions from which they did not suffer. One of the articles reports that physicians focusing exclusively on commercial research regularly divulge annual incomes upwards of $1,000,000 with profits in excess of $300,000. Two physicians accumulated well over $10,000,000 through clinical trials activities in less than a decade. (shrink)

Contemporary research ethics policies started with reflection on the atrocities perpetrated upon concentration camp inmates by Nazi doctors. Apparently, as a consequence of that experience, the policies that now guide human subject research focus on the protection of human subjects by making informed consent the centerpiece of regulatory attention. I take the choice of context for policy design, the initial prioritization of informed consent, and several associated conceptual missteps, to have set research ethics off in the wrong direction. The aim (...) of this paper is to sort out these confusions and their implications and to offer instead a straightforward framework for considering the ethical conduct of human subject research. In the course of this discussion I clarify different senses of autonomy that have been confounded and present more intelligible justifications for informed consent. I also take issue with several of the now accepted dogmas that govern research ethics. These include: the primacy of informed consent, the protection of the vulnerable, the substitution of beneficence for research's social purpose, and the introduction of an untenable distinction between innovation and research. (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)

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)

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)

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)

Volume 19, Issue 9, September 2019, Page 50-52.

In many cases, the “therapeutic misconception” may be an unavoidable part of the imperfect process of recruitment and consent in medical researchPaul Appelbaum, Loren Roth, and Charles Lidz coined the term “therapeutic misconception” in 1982.1 They described it as the misconception that participating in research is the same as receiving individualised treatment from a physician. It referred to the research subject’s failure to appreciate that the aim of research is to obtain scientific knowledge, and that any benefit to the subject (...) is a by-product of that knowledge. More recent studies by Appelbaum and Lidz have shown that this phenomenon is just as pervasive now as it was twenty four years ago.2 The problem pertains not to any duty of care for researchers but to participants’ unfounded belief in the therapeutic potential of research.3 It is especially acute in phase I oncology trials, which aim to test the toxicity and highest tolerable dose of anticancer drugs.To remedy this situation, many have argued that both clinicians and researchers need to do more in explaining to subjects the differences between experimental research and standard care. Clinicians and researchers recruiting potential subjects for research must present information about the expected risks and benefits of participation in research in a more realistic and straightforward way.4 In one recent examination of consent forms for phase I oncology trials, Sam Horng et al found that, in the section on “benefit”, only one of 272 forms stated that the subjects were expected to benefit. They also found that 11 consent forms stated clearly that subjects would not benefit, 25 forms communicated uncertainty about benefit, and 5 forms said nothing about the chance of benefit. Interestingly, 139 forms alluded to the …. (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)

The acceptance of military directives violating medical ethics and international covenants encouraged by the demonisation of the enemy by the US president in 2002 has effectively removed the right of medical personnel to refuse participation in internationally proscribed actionsMedicine and its traditional ethic of care is today a victim of the current conflict in Iraq and Afghanistan, its uniquely humanising mission rejected by US President George W Bush and his advisors. In denying the applicability of international agreements guaranteeing medicine’s ecumenical (...) role in this conflict they have transformed medicine into just another weapon of tactical significance. The result, predictable in retrospect, has been to make military physicians and nurses complicit—actively or passively—in what Litton calls an “atrocity-producing situation”, resulting in detainee or prisoner abuse.1From the first revelations of detainee torture in US detention camps to recent allegations of continued abuse , the focus of international attention has shifted from the US prosecution of low ranking, non-commissioned military personnel to the context in which the atrocities they committed occurred. “No one up the chain of command has ever been held accountable for what is in these horrifying images,” Center for Constitutional Rights Director Bill Goodman said of recently published photographs of 2004 prisoner torture and abuse.2 “The situation in several areas violates international law and conventions on human rights and torture,” said the UN Special Rapporteur on Torture following a 2006 investigation.3The denial of international law and convention involved the overt disavowal of covenants and conventions that for almost 150 years required medical personnel in the US military to act within the guidelines of a Hippocratic vision of medicine. To understand how fundamental this change has been requires a brief review of the history of medicine’s previously protected status and then a description of …. (shrink)

Objectives: To determine the effects of risk and payment on subjects’ willingness to participate, and to examine how payment influences subjects’ potential behaviours and risk evaluations.Methods: A 3 × 3 , between subjects, completely randomised factorial design was used. Students enrolled at one of five US pharmacy schools read a recruitment notice and informed consent form for a hypothetical study, and completed a questionnaire. Risk level was manipulated using recruitment notices and informed consent documents from hypothetical biomedical research projects. Payment (...) levels were determined using the payment models evaluated by Dickert and Grady as a guide. Five dependent variables were assessed in the questionnaire: willingness to participate, willingness to participate with no payment, propensity to neglect to tell about restricted activities, propensity to neglect to tell about negative effects, and risk rating.Results: Monetary payment had positive effects on respondents’ willingness to participate in research, regardless of the level of risk. However, higher monetary payments did not appear to blind respondents to the risks of a study. Payment had some influence on respondents’ potential behaviours regarding concealing information about restricted activities. However, payment did not appear to have a significant effect on respondents’ propensity to neglect to tell researchers about negative effects.Conclusions: Monetary payments appear to do what they are intended to do: make subjects more willing to participate in research. Concerns about payments blinding subjects to risks could not be substantiated in the present study. However, the findings do raise other concerns—notably the potential for payments to diminish the integrity of a study’s findings. Future research is critical to make sound decisions about the payment of research subjects. (shrink)

In this paper the authors argue that research ethics committees should not be paternalistic by rejecting research that poses risk to people competent to decide for themselves. However it is important they help to ensure valid consent is sought from potential recruits and protect vulnerable people who cannot look after their own best interests. The authors first describe the tragic deaths of Jesse Gelsinger and Ellen Roche. They then discuss the following claims to support their case: competent individuals are epistemologically (...) and ethically in the best position to say which risks are reasonable for them, so RECs should be no more restrictive than the “normal” constraints on people taking risks with themselves; RECs do not judge individual competence ; individual liberty is mostly limited by what serves the public interest, and RECs do not determine public interest; RECs may have a paternalistic role in preventing exploitation of competent people vulnerable to the use of incentives, and in protecting the interests of incompetent people; however, the moral and political authority of RECs has not been established in this respect. (shrink)

There is a growing consensus that the offer of a reasonable compensation for oocyte donation for reproductive treatment is acceptable if it does not compromise voluntary and altruistically motivated donation. However, how to translate this ‘reasonable compensation’ in practice remains unclear as compensation rates offered to oocyte donors between different European Union countries vary significantly. Clinics involved in oocyte donation, as well as those in other medical contexts, might be encouraged in calculating a more consistent and transparent compensation for donors (...) if the elements that constitute a reasonable compensation are explicated. In doing so, lessons can be learnt from living organ donation and medical research participation. Practices in which the elements of a reasonable compensation for the individuals involved have already been more defined in the literature. By means of analogical reasoning, we will outline the different components of a reasonable compensation and subsequently apply these to the context of oocyte donation. We will argue that oocyte donors should first of all be reasonably reimbursed direct expenses related to the donation, without standard remuneration of lost wages. Second, donating oocytes requests a serious time investment, therefore donors are entitled to suitable compensation for their time spent and efforts made. Finally, we will explain that a reasonable compensation consisting of these two components allows for altruism to remain the key value of oocyte donation for reproductive treatment. However, if we acknowledge that donors’ motives are more complex and often include reasons from self-interest, the reasonable compensation may be complemented with modest (non)monetary benefits. (shrink)

As the demand for human eggs for stem cell research increases, debate about appropriate standards for recruitment and compensation of women intensifies. In the majority of cases, the source of eggs for research is women undergoing fertility treatment requiring ovarian stimulation and egg retrieval. The principle of "just participant selection" requires that research subjects be selected from the population that stands to benefit from the research. Based on this principle, infertile women should be actively recruited to donate eggs for fertility-related (...) research only. It is unethical to exclusively or predominantly recruit infertile women to donate eggs for stem cell research that concerns general medical conditions. It is preferable to recruit women from the general population to donate eggs for such research, and these women should be viewed as healthy volunteers. To avoid exploitation, these donors should receive compensation for both the direct and indirect costs associated with their donation. (shrink)

This study documents how people who inject drugs in rural Puerto Rico perceive payments for participating in HIV epidemiological studies. In-depth interviews were conducted among a subset of active PWID older than 18 years of age who had been previously enrolled in a much larger study. Findings suggest that financial compensation was the main motivation for initially enrolling in the parent study. Then, as trust in the researchers developed, participants came to perceive compensation as part of a reciprocal exchange in (...) which they assisted researchers by providing a trustful account of their experiences and researchers reciprocated with financial support. (shrink)