Healthy Volunteers (HVs) who participate in clinical trials are a vulnerable group that deserves specific protection. We assessed the number and types of studies that involve HVs around the world and outline the methodological barriers to their analysis. We found that tens of thousands of HVs are involved every year in clinical trials in a large variety of countries and that the overwhelming majority of studies are not “first-in-human” but pharmacokinetic studies. The two cornerstones for both ethical and (...) safe participation of HVs in clinical trials are properly obtained informed consent, and a minimization of exposure to risk, in particular by avoiding concealed participation in multiple trials. To minimize the risk of exploitation of HVs and their exposure to risk, we propose ways to ensure genuine informed consent, and advocate setting up national Healthy Volunteer volunteer registries as established in France and the U.K. (shrink)

Healthy volunteers in biomedical research often face significant risks in studies that offer them no medical benefits. The U.S. federal research regulations and laws adopted by other countries place no limits on the risks that these participants face. In this essay, I argue that there should be some limits on the risks for biomedical research involving healthy volunteers. Limits on risk are necessary to protect human participants, institutions, and the scientific community from harm. With the exception (...) of self-experimentation, limits on research risks faced by healthy volunteers constitute a type of soft, impure paternalism because participants usually do not fully understand the risks they are taking. I consider some approaches to limiting research risks and propose that healthy volunteers in biomedical research should not be exposed to greater than a 1% chance of serious harm, such as death, permanent disability, or severe illness or injury. While this guideline would restrict research risks, the limits would not be so low that they would prevent investigators from conducting valuable research. They would, however, set a clear upper boundary for investigators and signal to the scientific community and the public that there are limits on the risks that healthy participants may face in research. This standard provides guidance for decisions made by oversight bodies, but it is not an absolute rule. Investigators can enroll healthy volunteers in studies involving a greater than 1% chance of serious harm if they show that the research addresses a compelling public health or social problem and that the risk of serious harm is only slightly more than 1%. The committee reviewing the research should use outside experts to assess these risks. (shrink)

Controlled human malaria infection (CHMI) studies involve the deliberate infection of healthy volunteers with malaria parasites under controlled conditions to study immune responses and/or test drug or vaccine efficacy. An empirical ethics study was embedded in a CHMI study at a Kenyan research programme to explore stakeholders’ perceptions and experiences of deliberate infection and moral implications of these. Data for this qualitative study were collected through focus group discussions, in‐depth interviews and non‐participant observation. Sixty‐nine participants were involved, including (...) CHMI study volunteers, community representatives and research staff. Data were managed using QSR Nvivo 10 and analysed using an inductive‐deductive approach, guided by ethics literature. CHMI volunteers had reasonable understanding of the study procedures. Decisions to join were influenced by study incentives, trust in the research institution, their assessment of associated burdens and motivation to support malaria vaccine development. However, deliberate malaria infection was a highly unusual research strategy for volunteers, community representatives and some study staff. Volunteers’ experiences of physical, emotional and social burdens or harms were often greater than anticipated initially, and fluctuated over time, related to specific procedures and events. Although unlikely to deter volunteers' participation in similar studies in furture, we argue that the dissonance between level of understanding of the burdens involved and actual experiences are morally relevant in relation to community engagement, informed consent processes, and ongoing support for volunteers and research staff. We further argue that ethics oversight of CHMI studies should take account of these issues in deciding whether consent, engagement and the balance of benefits and harms are reasonable in a given context. (shrink)

Clinical trials on healthy volunteers generate unique ethical challenges both because participants accept potential physical risks without the possibility of direct medical benefit and because participants’ financial motivations to enroll in trials could lead to their exploitation. Despite the large volume of published empirical studies and ethical analyses of healthy volunteer research, there has been little concerted effort to change how healthy‐volunteer research is overseen or regulated. A new collaborative effort to do so is the VolREthics (...) (Volunteers in Research and Ethics) Initiative. Launched in 2022, this initiative brings together an international community to engage questions about how healthy volunteers could best be protected from the risks of harm and exploitation while the validity of clinical trials is optimized. (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)

Phase 1 healthy volunteer clinical trials—which financially compensate subjects in tests of drug toxicity levels and side effects—appear to place pressure on each joint of the moral framework justifying research. In this article, we review concerns about phase 1 trials as they have been framed in the bioethics literature, including undue inducement and coercion, unjust exploitation, and worries about compromised data validity. We then revisit these concerns in light of the lived experiences of serial participants who are income-dependent on (...) phase 1 trials. We show how participant experiences shift attention from discrete exchanges, behaviors, and events in the research enterprise to the ongoing and dynamic patterns of serial participation in which individual decision-making is embedded in collective social and economic conditions and shaped by institutional policies. We argue in particular for the ethical significance of structurally diminished voluntariness, routine powerlessness in setting the terms of exchange, and incentive structures that may promote pharmaceutical interests but encourage phase 1 healthy volunteers to skirt important rules. (shrink)

Phase I clinical trials are the first stage of testing new pharmaceuticals in humans. The majority of these studies are conducted under controlled, inpatient conditions using healthy volunteers who are paid for their participation. This article draws on an ethnographic study of six phase I clinics in the United States, including 268 semistructured interviews with research staff and healthy volunteers. In it, I argue that an institutional banalization of risk structures the perceptions of research staff and (...) healthy volunteers participating in the studies. For research staff, there are three mechanisms by which risk becomes banal: a perceived homogeneity of studies, Fordist work regimes, and data-centric discourse. For healthy volunteers, repeat study participation contributes to the institutional banalization of risk both through the process of desensitization to risk and the formation of trust in the clinics. I argue that the institutional banalization of risk also renders invisible ethical concerns about exploitation of underprivileged groups in pharmaceutical research. (shrink)

This article empirically examines how healthy volunteers evaluate and make sense of the risks of phase I clinical drug trials. This is an ethically important topic because healthy volunteers are exposed to risk but can gain no medical benefit from their trial participation. Based on in-depth qualitative interviews with 178 healthy volunteers enrolled in various clinical trials, we found that participants focus on myriad characteristics of clinical trials when assessing risk and making enrolment decisions. (...) These factors include the short-term and long-term effects; required medical procedures; the type of trial, including its design, therapeutic area of investigation, and dosage of the drug; the amount of compensation; and trust in the research clinic. In making determinations about the study risks, participants rely on information provided during the consent process, their own and others’ experiences in clinical trials, and comparisons among studies. Our findings indicate that the informed consent process succeeds in communicating well about certain types of risk information while simultaneously creating lacunae that are problematically filled by participants through their collective experiences and assumptions about risk. We discuss the ethical implications of these findings and make recommendations for improving the consent process in healthy volunteer trials. (shrink)

This article empirically examines how healthy volunteers evaluate and make sense of the risks of phase I clinical drug trials. This is an ethically important topic because healthy volunteers are exposed to risk but can gain no medical benefit from their trial participation. Based on in-depth qualitative interviews with 178 healthy volunteers enrolled in various clinical trials, we found that participants focus on myriad characteristics of clinical trials when assessing risk and making enrolment decisions. (...) These factors include the short-term and long-term effects; required medical procedures; the type of trial, including its design, therapeutic area of investigation, and dosage of the drug; the amount of compensation; and trust in the research clinic. In making determinations about the study risks, participants rely on information provided during the consent process, their own and others’ experiences in clinical trials, and comparisons among studies. Our findings indicate that the informed consent process succeeds in communicating well about certain types of risk information while simultaneously creating lacunae that are problematically filled by participants through their collective experiences and assumptions about risk. We discuss the ethical implications of these findings and make recommendations for improving the consent process in healthy volunteer trials. (shrink)

This article empirically examines how healthy volunteers evaluate and make sense of the risks of phase I clinical drug trials. This is an ethically important topic because healthy volunteers are exposed to risk but can gain no medical benefit from their trial participation. Based on in-depth qualitative interviews with 178 healthy volunteers enrolled in various clinical trials, we found that participants focus on myriad characteristics of clinical trials when assessing risk and making enrolment decisions. (...) These factors include the short-term and long-term effects; required medical procedures; the type of trial, including its design, therapeutic area of investigation, and dosage of the drug; the amount of compensation; and trust in the research clinic. In making determinations about the study risks, participants rely on information provided during the consent process, their own and others’ experiences in clinical trials, and comparisons among studies. Our findings indicate that the informed consent process succeeds in communicating well about certain types of risk information while simultaneously creating lacunae that are problematically filled by participants through their collective experiences and assumptions about risk. We discuss the ethical implications of these findings and make recommendations for improving the consent process in healthy volunteer trials. (shrink)

This article empirically examines how healthy volunteers evaluate and make sense of the risks of phase I clinical drug trials. This is an ethically important topic because healthy volunteers are exposed to risk but can gain no medical benefit from their trial participation. Based on in-depth qualitative interviews with 178 healthy volunteers enrolled in various clinical trials, we found that participants focus on myriad characteristics of clinical trials when assessing risk and making enrolment decisions. (...) These factors include the short-term and long-term effects; required medical procedures; the type of trial, including its design, therapeutic area of investigation, and dosage of the drug; the amount of compensation; and trust in the research clinic. In making determinations about the study risks, participants rely on information provided during the consent process, their own and others’ experiences in clinical trials, and comparisons among studies. Our findings indicate that the informed consent process succeeds in communicating well about certain types of risk information while simultaneously creating lacunae that are problematically filled by participants through their collective experiences and assumptions about risk. We discuss the ethical implications of these findings and make recommendations for improving the consent process in healthy volunteer trials. (shrink)

While risk of harm is an important focus for whether clinical research on humans can and should proceed, there is uncertainty about what constitutes harm to a trial participant. In Phase I trials on healthy volunteers, the purpose of the research is to document and measure safety concerns associated with investigational drugs, and participants are financially compensated for their enrollment in these studies. In this article, we investigate how characterizations of harm are narrated by healthy volunteers (...) in the context of the adverse events they experience during clinical trials. Drawing upon qualitative research, we find that participants largely minimize, deny, or re-attribute the cause of these AEs. We illustrate how participants' interpretations of AEs may be shaped both by the clinical trial environment and their economic motivation to participate. While these narratives are emblematic of the larger ambiguity surrounding harm in the context of clinical trial participation, we argue that these interpretations also problematically maintain the narrative of the safety of clinical trials, the ethics of testing investigational drugs on healthy people, and the rigor of data collected in the specter of such ambiguity. (shrink)

In phase I clinical trials, healthy volunteers are dosed with investigational drugs and subjected to blood draws and other bodily monitoring procedures. In exchange, they are paid. Healthy volunteers are, in a very direct sense, selling access to their bodies for pharmaceutical companies and their associates to run drugs through. In his ethnographic study of socalled professional guinea pigs, Roberto Abadie writes, "Paid volunteers are well aware of the demand for an idealized, perfectly healthy (...) volunteer. They also realize that their body is a valued commodity in clinical trials research". It is perhaps surprising, then, that commodification is little discussed in the bioethics literature on phase I... (shrink)

Figurative elements in language have their own particularities, including words that deviate from their generally accepted definition to amplify our language or to paraphrase an issue. It is still...

There is a long history of medical research that involves intentionally infecting healthy people in order to study diseases and their treatments. Such research—what might be called “human challenge studies”—are an important strand of much current research—for example, in the development of vaccinations. The many international and national guidelines about the proper conduct of medical research do not specifically address human challenge studies. In this paper we review the guidelines on the risk of harm that healthy volunteers (...) may be exposed to in the course of medical research. We examine the ethical arguments that are implicit or explicit in these guidelines. We then ask whether there is reason for limiting such studies on grounds independent of risk of harm. We conclude that the major ethical concern with challenge studies is that of risk of harm and that the fact that a study is a challenge study is not a wrong in itself. (shrink)

Human Infection Studies have emerged as an important research approach with the potential to fast track the global development of vaccines and treatments for infectious diseases, including in low resource settings. Given the high level of burdens involved in many HIS, particularly prolonged residency and biological sampling requirements, it can be challenging to identify levels of study payments that provide adequate compensation but avoid ‘undue’ levels of inducement to participate. Through this embedded ethics study, involving 97 healthy volunteers (...) and other research stakeholders in a malaria HIS programme in Kenya, and using in-depth interviews, focus group discussions and observations during and after a malaria HIS, we give a grounded account of ethical issues emerging in relation to study payments in this setting. While careful community, national, international scientific and ethics review processes meant that risks of serious harm were highly unlikely, the levels of motivation to join HIS seen could raise concerns about study payments being too high. Particular value was placed on the reliability, rather than level, of study payment in this setting, where subsistence livelihoods are common. Study volunteers were generally clear about the study aims at the point of recruitment, and this knowledge was retained over a year later, although most reported experiencing more burdens than anticipated at enrolment. Strict study screening procedures, regular clinical and laboratory monitoring of volunteers, with prompt treatment with antimalarial at predetermined endpoints suggested that the risks of serious harm were highly unlikely. Ethical concerns emerged in relation to volunteers’ attempts to conceal symptoms, hoping to prolong residency periods and increase study payments; and volunteers making decisions that compromised important family relationships and personal values. Our findings support an interpretation that, although study volunteers were keen to join the study to access cash payments, they also paid attention to other features of the study and the general clinical research landscape, including levels of risk associated with study participation. Overall, our analysis shows that the ethical concerns emerging from the study payments can be addressed through practical measures, hinged on reducing burdens and strengthening communication, raising important issues for research policy and planning. (shrink)

Recruitment of healthy children for drugresearch has emerged due in part to several newAmerican laws and policies that have led to asurge in pharmaceutical research involvingchildren-subjects. In this paper, I review theethical and scientific issues and the argumentsin favor and against this new practice.

In this article, we present paradoxical findings from a formative evaluation research project that explores how preadolescent girls understand and feel about their bodies after participating in “Girls on the Run of Los Angeles County”, a girl-serving positive youth development program. Findings from pre/post test data show that girls’ body image improved after participation in GOTR LA, yet many girls also reported the dominant thin ideal and the importance of not being fat as key characteristics of strong and healthy (...) bodies. Ethnographic data suggest that institutional, organizational, and interactional factors contribute to these findings. Institutionalized fat-negative discourses translate into subtle messages regarding health and the body through organizational communications and through interactions between volunteer coaches and participants in ways that solidify dominant conceptions of the feminine body despite explicit programmatic intentions to challenge them. Theoretically, we draw from feminist cultural studies’ work on the gendered body to expand the dominant focus on institutionalized obsessions with thinness through the critical analysis of fat and anti-fat bias. On an applied level, our discussion of unintended program outcomes reveals the complexities in organizational interventions designed to influence girls’ body image. (shrink)

Death of a normal volunteer highlights problems with research review and protection of subjectsHealthy volunteer dies in asthma studyOn July 19, after investigating the death of a previously healthy volunteer, the United States Office for Human Research Protections suspended nearly all federally funded medical research involving human subjects at Johns Hopkins University. The death has been described as “particularly disturbing” because 24 year old Ellen Roche was a healthy volunteer who had nothing to gain by taking part in (...) the study.1 Her death has revived debate about the adequacy of oversight of medical research that followed the death of 18 year old Jesse Gelsinger who volunteered for a gene therapy experiment.Ellen Roche was a 24 year old technician from the Johns Hopkins Asthma and Allergy Centre who volunteered to take part in a study designed to provoke a mild asthma attack in order to help doctors discover the reflex that protects the lungs of healthy people against asthma attacks. After inhaling hexamethonium, a medication used for treating high blood pressure in the 1950s and 60s, Ms Roche became ill. She developed a cough and her condition worsened over the next week until she was put on a ventilator. With her lung tissue breaking down, blood pressure falling and her kidneys beginning to fail, nothing could be done to save her.2 She died on June 2, about a month after entering the study.The Office for Human Research Protections investigated the circumstances of Ms Roche's death and accused the Hopkins Institutional Review Board of failing to take proper precautions. It also evaluated the human subject protection system at Hopkins. The OHRP found that prior to approving the study, Hopkins researcher …. (shrink)

Tremendous development in recent medical science and the consequent discoveries resulting in successful prevention and also cure of different diseases are shared by clinical research involving the human volunteers. Preceding the trials in the human subjects, and to ensure safety, the proposed drug and other interventions are either tested in animals (vivo) or in laboratory (vitro) to evaluate initial safe starting dose for the human beings and to key out the benchmarks for the clinical monitoring for the potential unfavorable (...) effects. These pre human trials might not necessarily protect against the untoward effects in the human beings as happened in the case of thalidomide tragedy, which caused disability and killed thousands of babies born to the mothers, those who took this medicine. Use of healthy human volunteers in the preliminary experiments or phase I clinical trials either reduces or excludes risks of subsequent undesirable effects in the future trails (1). Phase-1 trials are conducted in order to test the safety, reactions and immunogenicity of vaccines in volunteers. Novel treatments for the cancer are first tested in phase 1 trials enrolling the patients with advanced disease, who have exhausted the standard treatment options. Phase-1 oncology trials are the pivot point in the translation of new cancer therapies from bench to bedside. Nevertheless, these trials remain ethically controversial. The controversy stems from the fact that, classically, phase-1 oncology clinical trials involve first-in-human testing of experimental treatment candidates in patients with a terminal diagnosis, who typically have exhausted standard treatment options. Commentators on the ethics of phase-1 clinical trials make diametrically opposed claims about the prospect of direct medical benefit from participation in these trials-benefits that can be attributed to receiving the experimental treatment intervention. One camp of benefit skeptics, inhabited mainly by bioethicists, characterizes this form of research as lacking any reasonable prospect of direct medical benefit. They see an ethical cloud hovering over phase-1 trials, because the vast majority of patients volunteer for phase-1 trials out of a motivation to receive medical benefit. In the view of these skeptics, such patients therefore harbor a ‘therapeutic misconception’ about research participation. This misconception calls into question the validity of informed consent and thereby undercuts the ethical basis of these trials (2). In this paper, I will discuss the ethical justification of the participation of human volunteers in phase-1 trials. (shrink)

Dysfunctional attentional control is observed in patients with mental disorders. However, there is no established neurophysiological method to assess attention in such patients. We showed a discrepancy in alpha-band power in the tasks that evoked internal and external attention event-related alpha-band power changes in healthy subjects during self-reflection and working memory tasks in a preliminary study. In this study, we aimed at elucidating event-related alpha-band power changes in healthy subjects during the tasks, addressing the shortcomings of the previous (...) study. Sixteen healthy volunteers were examined for the event-related power change during the tasks. The results demonstrated the discrepancy of alpha-band ERpow at 8, 10, and 12 Hz in the parieto-occipital area between the WM and SR tasks for a period between a target stimulus and a command stimulus, where a participant switched to internal attention from external attention according to the SR task and remained at external attention according to the WM task. The results suggest that alpha-band ERpow in this area is associated with the direction of attention in response to cognitive stimuli, indicating that the findings of ERpow during the two tasks would potentially aid in the clarification of the pathophysiology of the dysfunctional change in attention in patients with psychiatric disorders. (shrink)

This study explored Christians’ view that living a healthy lifestyle by eating right and exercising was essential to what being a Christian meant to them, theoretically representing internalization of these health behaviors into one’s religious values and identity. Using a secondary data analysis of Pew Research Center survey data, we found that a minority of Christians (16%) internalized a healthy lifestyle; who also tended to be more religious, as expressed by believing in God, reading scripture, praying, and volunteering (...) at church. The results provide preliminary support for the theorized disconnect in religious internalization of certain health behaviors, but not others. However, further exploratory analysis suggests that individuals who are a part of denominations that more recognizably express the importance of a healthy lifestyle as a part of their religious beliefs, and internalize this belief, might subsequently participate in and self-report healthier behavior. (shrink)

Purpose: The cognitive effects of total sleep deprivation on the brain remain poorly understood. Electroencephalography is a very useful tool for detecting spontaneous brain activity in the resting state. Quasi-stable electrical distributions, known as microstates, carry useful information about the dynamics of large-scale brain networks. In this study, microstate analysis was used to study changes in brain activity after 24 h of total sleep deprivation.Participants and Methods: Twenty-seven healthy volunteers were recruited and underwent EEG scans before and after (...) 24 h of TSD. Microstate analysis was applied, and six microstate classes were identified. Topographies and temporal parameters of the microstates were compared between the rested wakefulness and TSD conditions.Results: Microstate class A showed lower global explained variance, frequency of occurrence, and time coverage in TSD than RW, whereas microstate class D displayed higher GEV, frequency of occurrence, and time coverage in TSD compared to RW. Moreover, subjective sleepiness was significantly negatively correlated with the microstate parameters of class A and positively correlated with the microstate parameters of class D. Transition analysis revealed that class B exhibited a higher probability of transition than did classes D and F in TSD compared to RW.Conclusion: The observation suggests alterations of the dynamic brain-state properties of TSD in healthy young male subjects, which may serve as system-level neural underpinnings for cognitive declines in sleep-deprived subjects. (shrink)

Here we identify approximately 40,000 healthy human volunteers who were intentionally exposed to infectious pathogens in clinical research studies dating from late World War II to the early 2000s. Microbial challenge experiments continue today under contemporary human subject research requirements. In fact, we estimated 4,000 additional volunteers who were experimentally infected between 2010 and the present day. We examine the risks and benefits of these experiments and present areas for improvement in protections of participants with respect to (...) safety. These are the absence of maximum limits to risk and the potential for institutional review boards to include questionable benefits to subjects and society when weighing the risks and benefits of research protocols. The lack of a duty of medical care by physician–investigators to research subjects is likewise of concern. The transparency of microbial challenge experiments and the safety concerns raised in this work may stimulate further dialogue on the risks to participants of human experimentation. (shrink)

Reigning regulatory frameworks for biomedical research impose on researchers and research ethics committees an obligation to protect research participants from risks that are unnecessary, disproportionate to potential research benefits, and non-minimized. Where the research has no potential to produce results of direct benefit to the subjects and the subjects are unable to give consent, these requirements are strengthened by an additional condition, that risks should not exceed a certain minimal threshold. In this article, I address the question of whether there (...) should be limits of permissible risks in non-therapeutic research involving competent and healthy subjects. Some commentators argue that competent and informed individuals should have a right to participate even in extremely risky research and that research ethics committees should never reject studies because they are too dangerous. To use David Shaw's expression, competent volunteers should have ‘a right to participate in high-risk research’. I argue that this idea is ill-founded, as it does not take into account the social mission and complex collaborative nature of research practice as well as the inequity of power between researchers and subjects. Imposition of limits on permissible risks for healthy volunteers is justified by the need to protect research enterprise and the need to protect the weaker party, namely the subjects. Also, I suggest that the best way to set boundaries on research risks is to leave the judgment of risk acceptability to research ethics committees. (shrink)

LANGUAGE NOTE | Document text in Chinese; abstract also in English. 以新冠疫苗I期試驗的健康受試者為研究對象，基於深度訪談和虛擬民族志研究方法，採用NVivo11軟體進行編碼分析，發現健康受試者的參與動機多為積極動機，在抉擇過程中曾面臨內外矛盾而深陷糾結與掙扎。文章歸 納出新冠疫苗受試者抉擇過程不同階段的動機與行為特點，即：萌生想法——躍躍欲試的受試者；進退狐疑——踽踽獨行的受試者；備受煎熬——忐忑不安的受試者；解惑釋疑——篤定前行的受試者。旨在真實地還原健康受試者 的抉擇過程，消除社會偏見，為健康受試者和I期試驗去除污名，提升公眾的認知，增强健康受試者的認同感和歸屬感。 Taking the Phase I trial of the 2019-nCoV vaccine as a case study, this paper examines the motivational and psychological development and behavioral patterns of healthy volunteers who participate in different phases of clinical trials for vaccines. The findings of a series of in-depth interviews and virtual ethnographical studies show that participation in a clinical trial such as that for the 2019-nCoV vaccine is a difficult choice (...) for volunteers, as it entails exposure not only to medical risks but also to social prejudice. The paper provides a detailed account of how the volunteers for the Phase I 2019-nCoV vaccine trials made their choice to participate and how they overcame various doubts and fears to serve as responsible research partners. (shrink)

In the US, research payments are technically taxable income. This article argues that tax liability is a form of possible economic and legal risk of paid research participation. Findings are presented from empirical research on Phase I healthy volunteer trials. The article concludes by discussing the implications of these findings for the informed consent process, as well as for broader ethical issues in whether and how payments for research participation should be regulated.

AimsAlcohol consumption could lead to a series of health problems and social issues. In the current study, we investigated the resting-state functional brain networks of healthy volunteers before and after drinking through graph-theory analysis, aiming to ascertain the effects of acute alcohol intake on topology and information processing mode of the functional brain networks.Materials and methodsThirty-three healthy volunteers were enrolled in this experiment. Each volunteer accepted alcohol breathalyzer tests followed by resting-state magnetic resonance imaging at three (...) time points: before drinking, 0.5 h after drinking, and 1 h after drinking. The data obtained were grouped based on scanning time into control group, 0.5-h group and 1-h group, and post-drinking data were regrouped according to breath alcohol concentration (BrAC) into relative low BrAC group (A group; 0.5-h data, n = 17; 1-h data, n = 16) and relative high BrAC group (B group; 0.5-h data, n = 16; 1-h data, n = 17). The graph-theory approach was adopted to construct whole-brain functional networks and identify the differences of network topological properties among all the groups.ResultsThe network topology of most groups was altered after drinking, with the B group presenting the most alterations. For global network measures, B group exhibited increased global efficiency, Synchronization, and decreased local efficiency, clustering coefficient, normalized clustering coefficient, characteristic path length, normalized characteristic path length, as compared to control group. Regarding nodal network measures, nodal clustering coefficient and nodal local efficiency of some nodes were lower in B group than control group. These changes suggested that the network integration ability and synchrony improved, while the segregation ability diminished.ConclusionThis study revealed the effects of acute alcohol intake on the topology and information processing mode of resting-state functional brain networks, providing new perceptions and insights into the effects of alcohol on the brain. (shrink)

Many healthy volunteers choose to take part in Alzheimer’s disease prevention studies because they want to know whether they will develop dementia—and what they can do to reduce their risk—and are therefore interested in learning the results of AD biomarker tests. Proponents of AD biomarker disclosure often refer to the personal utility of AD biomarkers, claiming that research participants will be able to use AD biomarker information for personal purposes, such as planning ahead or making important life decisions. (...) In this paper, the claim that AD biomarkers have personal utility for asymptomatic individuals is critically assessed. It demonstrates that in the absence of clinical validity, AD biomarkers cannot have personal utility and do not serve research participants’ autonomy. Over the next few years, many research groups will be confronted with participants’ preferences to learn the results of AD biomarker tests. When researchers choose to make results available upon explicit request, they should ensure adequate information provision and education, notably on the uncertain clinical significance of AD biomarker information. Routine disclosure of AD biomarkers to cognitively unimpaired individuals in research settings cannot be justified with an appeal to the personal utility of AD biomarker information. (shrink)

Purposeful infection of healthy volunteers with a microbial pathogen seems at odds with acceptable ethical standards, but is an important contemporary research avenue used to study infectious diseases and their treatments. Generally termed ‘controlled human infection studies’, this research is particularly useful for fast tracking the development of candidate vaccines and may provide unique insight into disease pathogenesis otherwise unavailable. However, scarce bioethical literature is currently available to assist researchers and research ethics committees in negotiating the distinct issues (...) raised by research involving purposefully infecting healthy volunteers. In this article, we present two separate challenge studies and highlight the ethical issues of human challenge studies as seen through a well-constructed framework. Beyond the same stringent ethical standards seen in other areas of medical research, we conclude that human challenge studies should also include: independent expert reviews, including systematic reviews; a publicly available rationale for the research; implementation of measures to protect the public from spread of infection beyond the research setting; and a new system for compensation for harm. We hope these additions may encourage safer and more ethical research practice and help to safeguard public confidence in this vital research alternative in years to come. (shrink)

Recent clinical trials show that psychedelics such as LSD and psilocybin can be given safely in controlled conditions, and can cause lasting psychological benefits with one or two administrations. Supervised psychedelic sessions can reduce symptoms of anxiety, depression, and addiction, and improve well-being in healthy volunteers, for months or even years. But these benefits seem to be mediated by "mystical" experiences of cosmic consciousness, which prompts a philosophical concern: do psychedelics cause psychological benefits by inducing false or implausible (...) beliefs about the metaphysical nature of reality? This book is the first scholarly monograph in English devoted to the philosophical analysis of psychedelic drugs. Its central focus is the apparent conflict between the growing use of psychedelics in psychiatry and the philosophical worldview of naturalism. Within the book, Letheby integrates empirical evidence and philosophical considerations in the service of a simple conclusion: this "Comforting Delusion Objection" to psychedelic therapy fails. While exotic metaphysical ideas do sometimes come up, they are not, on closer inspection, the central driver of change in psychedelic therapy. Psychedelics lead to lasting benefits by altering the sense of self, and changing how people relate to their own minds and lives-not by changing their beliefs about the ultimate nature of reality. The upshot is that a traditional conception of psychedelics as agents of insight and spirituality can be reconciled with naturalism (the philosophical position that the natural world is all there is). Controlled psychedelic use can lead to genuine forms of knowledge gain and spiritual growth-even if no Cosmic Consciousness or transcendent divine Reality exists. Philosophy of Psychedelics is an indispensable guide to the literature for researchers already engaged in the field of psychedelic psychiatry, and for researchers-especially philosophers-who want to become acquainted with this increasingly topical field. (shrink)

Renewed research with entheogens (psychedelic substances) has been able to facilitate the occurrence of mystical forms of consciousness in healthy volunteers with a high degree of reliability. This article explores the potential significance of this development for religious scholars, especially those interested in the study of mysticism. The definition of “mystical consciousness” employed in this research is presented and differentiated from visionary/archetypal and other types of alternative mental states. The ways in which entheogens may be employed with skill (...) and maximum safety are discussed. Implications for clarifying confusion in the study of mysticism are considered, along with suggestions for future religious research on this frontier of knowledge. (shrink)

Noradrenergic pathways are involved in mediating the central and peripheral effects of physiological arousal. The aim of the present study was to investigate the role of noradrenergic transmission in moral decision-making. We studied the effects in healthy volunteers of propranolol (a noradrenergic beta-adrenoceptor antagonist) on moral judgement in a set of moral dilemmas pitting utilitarian outcomes (e.g., saving five lives) against highly aversive harmful actions (e.g., killing an innocent person) in a double-blind, placebo-controlled, parallel group design. Propranolol (40 (...) mg orally) significantly reduced heart rate, but had no effect on self-reported mood. Importantly, propranolol made participants more likely to judge harmful actions as morally unacceptable, but only in dilemmas where harms were ‘up close and personal’. In addition, longer response times for such personal dilemmas were only found for the placebo group. Finally, judgments in personal dilemmas by the propranolol group were more decisive. These findings indicate that noradrenergic pathways play a role in responses to moral dilemmas, in line with recent work implicating emotion in moral decision-making. However, contrary to current theorising, these findings also suggest that aversion to harming is not driven by emotional arousal. Our findings are also of significant practical interest given that propranolol is a widely used drug in different settings, and is currently being considered as a potential treatment for post-traumatic stress disorder in military and rescue service personnel. (shrink)

To counter the pandemic caused by severe acute respiratory syndrome coronavirus 2, some have proposed accelerating SARS-CoV-2 vaccine development through controlled human infection trials. These trials would involve the deliberate exposure of relatively few young, healthy volunteers to SARS-CoV-2. We defend this proposal against the charge that there is still too much uncertainty surrounding the risks of COVID-19 to responsibly run such a trial.

Institutional review boards and investigators are used to talking about risks of harm. Both low risks of great harm and high risks of small harm must be disclosed to prospective subjects and should be explained and categorized in ways that help potential subjects to understand and weigh them appropriately. Everyone on an IRB has probably spent time at meetings arguing over whether a three-page bulleted list of risk description is helpful or overkill for prospective subjects. Yet only a small fraction (...) of all the time and attention lavished on risk disclosure has been devoted to discussing whether and when potential benefit to subjects can reasonably be claimed and, if so, how it should be described in the consent form and process.Traditionally, IRBs and regulators have worked to ensure that clear lines can be drawn between research that, by definition, carries no potential for direct benefit — because it uses healthy volunteers or because it is not foreseeably focused on the development of treatments — and research that does have the development of effective treatments as its goal. (shrink)

Response to commentary. We are grateful to Crockett and Craigie for their interesting remarks on our paper. We accept Crockett’s claim that there is a need for caution in drawing inferences about patient groups from work on healthy volunteers in the laboratory. However, we believe that the evidence we cited established a strong presumption that many of the patients who are routinely taking a medication, including many people properly prescribed the medication for a medical condition, have morally significant (...) aspects of their cognition and behavior modified in a way that is unintended and may sometimes be unwelcome. Crockett notes that in some cases the effects of long-term drug use may differ, sometimes markedly, from the effects of short-term use. However, if acute use of a drug affects a neural system involved in mediating moral cognition or behavior, this nevertheless provides some evidence that chronic use of the drug may affect that same system and thus have morally significant effects. It is also plausible, in some cases, that an acute moral effect would give rise to a chronic moral effect via cognitive mechanisms. ... (shrink)