Questions have been raised over the acceptability of conducting human challenge studies in low and middle income countries. Most of these concerns are based on theoretical considerations and there exists little data on the attitudes of stakeholders in these countries. This study examines the view of researchers and REC members in Thailand regarding the design and conduct of challenge studies in the country. A questionnaire was developed based on ethical frameworks for human challenge (...) studies. The target respondents included those who had experience with health-related research at universities, non-university hospitals, and research institutes. A total of 240 respondents completed the on-line survey. In general, the respondents felt that the ethical issues raised by human challenge studies in LMICS do not differ significantly from those in high income countries, including: scientific rationale, safety, appropriate risks, and robust informed consent process. In contrast, issues that have been described as important for human challenge studies in LMICs were rated as having lower importance, including: a publicly available rationale, national priority, and community engagement. Responses did not vary significantly between researchers in different fields, nor between researchers and REC members. These findings provide an important perspective for assessing existing frameworks for human challenges studies in LMICs. (shrink)

The paper by Lynch et al. raises interesting ethical questions regarding whether and how much SARS-CoV-2 Human Challenge Studies participants should be paid. We appreciate the timely e...

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)

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 challenge studies provide illuminating case studies for several ongoing debates in research ethics, including those related to research risks and payment of participants. Grimwade et al 1 add to previous public engagement, qualitative evidence and philosophical literature on these topics.1–8 The authors advocate revision of research payment policy and practice based on their main finding that members of the public endorse ex ante payment of participants proportional to research-related risk exposure, in addition to post (...) hoc compensation for any lasting harms that occur.1 Although ‘payment for risk’ would diverge from most current research ethics guidelines, it is noteworthy that the difference in payment to participants that their framework would allow might only be small, at least in the case of currently accepted studies. The absolute difference would likely be small because the risk of currently accepted HCS participation is usually very low.9 10 On a ‘value of statistical life’ approach, mirroring actuarial accounting for fatal risks, a 1 in 100 000 risk of death might attract an extra payment of only US$96.1 Most HCS do not involve fatality risks this high, although, on pessimistic estimates, the risk of COVID-19 HCS in young healthy adults might involve similar levels of risk.11 Such risks might arguably be justified by large expected public health benefits,12,9 11 13 but it remains controversial whether higher levels of payment could …. (shrink)

Human challenge studies, in which human research subjects are intentionally exposed to pathogens to contribute to scientific knowledge, raise many ethical complexities. One controversial question is whether it is ethically permissible to include children as participants. Commentary of the past decades endorses the exclusion of children, while new guidance suggests that pediatric human challenge studies can be ethically permissible. This paper argues that neither children's exclusion nor their inclusion are well justified. I examine (...) and reject three arguments for exclusion, but suggest that these arguments establish pediatric human challenge studies as a complex ethical category of research that requires caution. I then argue for a strong presumption against children's inclusion, by drawing on an analogy to children's inclusion in phase I trials, emphasizing a requirement of necessity, and suggesting that accommodating children's vulnerability promotes an age de-escalation approach for pediatric human challenge studies research. In the final section, I suggest a procedure for ethics review. (shrink)

AbstractDuring the Covid-19 pandemic, ethicists and researchers proposed human challenge studies as a way to speed development of a vaccine that could prevent disease and end the global public health crisis. The risks to healthy volunteers of being deliberately infected with a deadly and novel pathogen were not low, but the benefits could have been immense. This essay is a history of the three major efforts to set up a challenge model and run challenge (...) class='Hi'>studies in 2020 and 2021. The pharmaceutical company Johnson and Johnson, the National Institutes of Health in the United States, and a private-public partnership of industry, university, and government partners in Britain all undertook preparations. The United Kingdom’s consortium began their Human Challenge Programme in March of 2021.Beyond documenting each effort, the essay puts these scientific and ethical debates in dialogue with the social, epidemiological, and institutional conditions of the pandemic as well as the commercial, intellectual, and political systems in which medical research and Covid-19 challenge studies operated. It shows how different institutions understood risk, benefit, and social value depending on their specific contexts. Ultimately the example of Covid-19 challenge studies highlights the constructedness of such assessments and reveals the utility of deconstructing them retrospectively so as to better understand the interplay of medical research and research ethics with larger social systems and historical contexts. (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)

Controlled human infection challenge studies (CHIs) involve intentionally exposing research participants to, and/or thereby infecting them with, micro‐organisms. There have been increased calls for more CHIs to be conducted in low‐ and middle‐income countries (LMICs) where many relevant diseases are endemic. This article is based on a research project that identified and analyzed ethical and regulatory issues related to endemic LMIC CHIs via (a) a review of relevant literature and (b) qualitative interviews involving 45 scientists and ethicists (...) with relevant expertise. In this article we argue that though there is an especially strong case for conducting CHIs in endemic (LMIC) settings, certain ethical issues related to the design and conduct of such studies (in such settings) nonetheless warrant particularly careful attention. We focus on ethical implications of endemic LMIC CHIs regarding (a) potential direct benefits for participants, (b) risks to participants, (c) third‐party risks, (d) informed consent, (e) payment of participants, and (f) community engagement. We conclude that there is a strong ethical rationale to conduct (well‐designed) CHIs in endemic LMICs, that certain ethical issues warrant particularly careful consideration, and that ethical analyses of endemic LMIC CHIs can inform current debates in research ethics more broadly. (shrink)

Human infection challenge studies have been proposed as a means to accelerate SARS-CoV2 vaccine development and thereby help to mitigate a prolonged global public health crisis. A key criterion for the ethical acceptability of SARS-CoV2 HCS is that potential benefits outweigh risks. Although the assessment of risks and benefits is meant to be a standard part of research ethics review, systematic comparisons are particularly important in the context of SARS-CoV2 HCS in light of the significant potential benefits (...) and harms at stake as well as the need to preserve public trust in research and vaccines. In this paper we explore several considerations that should inform systematic assessment of SARS-CoV-2 HCS. First, we detail key potential benefits of SARS-CoV-2 HCS including, but not limited to, those related to the acceleration of vaccine development. Second, we identify where modelling is needed to inform risk-benefit assessments. Modelling will be particularly useful in comparing potential benefits and risks of HCS with those of vaccine field trials under different epidemiological conditions and estimating marginal risks to HCS participants in light of the background probabilities of infection in their local community. We highlight interactions between public health policy and research priorities, including situations in which research ethics assessments may need to strike a balance between competing considerations. (shrink)

In controlled human infection studies (CHIs), participants are deliberately exposed to infectious agents in order to better understand the mechanism of infection or disease and test therapies or vaccines. While most CHIs have been conducted in high‐income countries, CHIs have recently been expanding into low‐ and middle‐income countries (LMICs). One potential ethical concern about this expansion is the challenge of obtaining the voluntary informed consent of participants, especially those who may not be literate or have limited education. (...) In some CHIs in LMICs, researchers have attempted to address this potential concern by limiting access to literate or educated populations. In this paper, we argue that this practice is unjustified, as it does not increase the chances of obtaining valid informed consent and therefore unfairly excludes illiterate populations and populations with lower education. Instead, we recommend that investigators improve the informed consent process by drawing on existing data on obtaining informed consent in these populations and interventions aimed at improving their understanding. Based on a literature review, we provide concrete suggestions for how to follow this recommendation and ensure that populations with lower literacy or education are given a fair opportunity to protect their rights and interests in the informed consent process. (shrink)

TB human challenge studies could accelerate TB vaccine development by reducing uncertainty in early-stage vaccine testing, selecting promising vaccine candidates for large-scale field trials, and identifying an immune correlate of protection. However, ethical concerns regarding the exposure of trial participants and bystanders to significant risk have been a limiting factor for TB human challenge models. We analyze the expected social value and risks of different types of TB human challenge models, and conclude that (...) given the massive public health burden of TB, challenge models with even scant probabilities of expediting TB vaccine authorization have enormous expected humanitarian value, saving between 33,000 and 1,375,000 lives over the next ten years. We argue that attenuated M.tb challenge trials can be conducted ethically, and discuss the benefits and drawbacks of conducting virulent M.tb challenge trials. (shrink)

The world’s first COVID-19 human challenge trial using the D614G strain of SARS-CoV-2 is underway in the United Kingdom. The Wellcome Trust is funding challenge stock preparation of the Beta variant (B.1.351) for a follow-up human challenge trial, and researchers at Imperial College London are considering conducting that trial. However, little has been written thus far about the ethical justifiability of human challenge trials with SARS-CoV-2 variants of concern. While vaccine resistance as such (...) does not increase risks for volunteers in COVID-19 challenge trials, we explore two specific characteristics of some variants that may initially be thought to make such trials unethical and conclude that SARS-CoV-2 variant challenge trials can remain ethical. (shrink)

To prepare for potential human infection challenge studies involving SARS-CoV-2, we convened a multidisciplinary working group to address ethical questions regarding whether and how much SAR...

This paper describes the UK Research Ethics Committee’s (REC) preparations and review of the global first SARS-CoV-2 human infection challenge studies. To frame our review, we used the WHO guidance and our UK Health Research Authority ethical review framework. The WHO criteria covered most issues we were concerned about, but we would recommend one further criterion directing RECs to consider alternative research designs. Could research questions be equally well answered by less intrusive studies? The committee met (...) virtually, ensuring broad representation across the UK nations and also ensuring applicants could attend easily. We worked in collaboration with the applicants but while we recognise that such proximity might raise the accusation of ‘collusion’, we made every effort to maintain ‘moral distance’ and all decisions were made by the committee alone. Prior existing processes and policy facilitated training and review but even with this preparation, review took time and this could have hindered a rapid response to the emergency. Review for the various follow-on studies will now be speedier and once the pandemic has subsided, our group could be reconvened in future emergencies. In conclusion, we have tried to make decisions in good faith. We know there is controversy and disagreement and reasonable people may feel we have made the wrong decision. A more detailed analysis, built on the WHO guidance, is provided in online supplemental material. (shrink)

The COVID-19 pandemic has necessitated rapid research to aid in the understanding of the disease and the development of novel therapeutics. One option is to conduct controlled human infection trials (CHITs). In this article I examine the history of deliberate human infection and CHITs and their utilization prior to the COVID-19 pandemic, key ethical considerations of CHITs in the COVID-19 setting, an analysis of the World Health Organization’s (WHO) Key criteria for the ethical acceptability of COVID-19 human (...) challenge studies, and a review of the two COVID-19 CHITs that have already commenced, their compliance with the WHO criteria and other ethical considerations. (shrink)

This commentary shall focus on the central claim made in Lynch et al.’s paper “Promoting Ethical Payment in Human Infection Challenge Studies.” According to their paper, there is a threefold...

Controlled Human Infection Model (CHIM) research involves the infection of otherwise healthy participants with disease often for the sake of vaccine development. The COVID-19 pandemic has emphasised the urgency of enhancing CHIM research capability and the importance of having clear ethical guidance for their conduct. The payment of CHIM participants is a controversial issue involving stakeholders across ethics, medicine and policymaking with allegations circulating suggesting exploitation, coercion and other violations of ethical principles. There are multiple approaches to payment: reimbursement, (...) wage payment and unlimited payment. We introduce a new Payment for Risk Model, which involves paying for time, pain and inconvenience and for risk associated with participation. We give philosophical arguments based on utility, fairness and avoidance of exploitation to support this. We also examine a cross-section of the UK public and CHIM experts. We found that CHIM participants are currently paid variable amounts. A representative sample of the UK public believes CHIM participants should be paid approximately triple the UK minimum wage and should be paid for the risk they endure throughout participation. CHIM experts believe CHIM participants should be paid more than double the UK minimum wage but are divided on the payment for risk. The Payment for Risk Model allows risk and pain to be accounted for in payment and could be used to determine ethically justifiable payment for CHIM participants.Although many research guidelines warn against paying large amounts or paying for risk, our empirical findings provide empirical support to the growing number of ethical arguments challenging this status quo. We close by suggesting two ways (value of statistical life or consistency with risk in other employment) by which payment for risk could be calculated. (shrink)

Eyal et al have recently argued that researchers should consider conducting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) human challenge studies to hasten vaccine development. We have conducted (J. L.) and overseen (L. D.) human challenge studies and agree that they can be useful in developing anti-infective agents. We also agree that adults can autonomously choose to undergo risks with no prospect of direct benefit to themselves. However, we disagree that SARS-CoV-2 challenge (...) class='Hi'>studies are ethically appropriate at this time, for 3 reasons: (1) current scientific knowledge of SARS-CoV-2 infection is insufficient to manage risks; (2) autonomous decision making, while necessary, does not override concerns about risk; and (3) undertaking challenge studies now would imperil confidence in the research enterprise, potentially undermining the global response to the coronavirus disease 2019 (COVID-19) pandemic. (shrink)

There is limited guidance on how to assess the ethical acceptability of research risks that extend beyond research participants to third parties (or “research bystanders”). Community or stakeholder engagement has been proposed as one way to address potential harms to community members, including bystanders. Despite widespread agreement on the importance of community engagement in biomedical research, this umbrella term includes many different goals and approaches, agreement on which is ethically required or recommended for a particular context. We analyse the case (...) of a potential Zika virus human challenge trial to assess whether and how community engagement can help promote the ethical acceptability of research posing risks to bystanders. We conclude that, in addition to having intrinsic value, community engagement can improve the identification of bystander risks, effective approaches to minimizing them, and transparency about bystander risks for host communities. (shrink)

Controlled human infection (CHI) studies involve the deliberate exposure of healthy research participants to infectious agents to study early disease processes and evaluate interventions under controlled conditions with high efficiency. Although CHI studies expose participants to the risk of infection, they are designed to offer investigators unique advantages for studying the pathogenesis of infectious diseases and testing potential vaccines or treatments in humans. One of the central challenges facing investigators involves the fair selection of research subjects to (...) participate in CHI studies. While there is widespread agreement that investigators have a duty to select research participants fairly, this principle also yields conflicting ethical imperatives, for example requiring investigators to both exclude potential participants with co‐morbidities since they face increased risks, but also to include them in order to ensure generalizability. In this paper we defend an account of fair subject selection that is tailored to the context of CHI studies. We identify the considerations of fairness that bear directly on selecting participants for CHI studies and provide investigators and members of IRBs and RECs with a principled way to navigate the conflicting imperatives to which these considerations give rise. (shrink)

Antibiotic resistance is one of the most pressing public health problems humanity faces. Research into new classes of antibiotics and new kinds of treatments – including risky experimental treatments such as phage therapy and vaccines – is an important part of improving our ability to treat infectious diseases. In order to aid this research, we will argue that we should permit researchers to pay people any amount of money to compensate for the risks of participating in clinical trials, including ‘ (...) class='Hi'>challenge studies’ that involve deliberately infecting patients. We think that standard worries about paying for participation in risky research are reducible to concerns that can be addressed with the right screening mechanisms. (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)

Grimwade et al highlight the current lack of a universal, standardised approach to the payment of participants taking part in controlled human infection model studies.1 As they discuss, payment for these studies is controversial, with many voicing arguments for and against higher payments, particularly for those studies which involve significant burdens to the participant. The main concerns about overpayment relate to the concepts of undue inducement or coercion, whereas underpayment raises concern about exploitation and unfair treatment. (...) In many healthy volunteer trials compensation for travel, time and inconvenience are generally accepted as fair payment, but payment for risk is less accepted, with a belief that non-therapeutic studies should only incur minimal risks, so payment for risk should not be necessary.2 This paper argues that payment for risk should be included for CHIM studies. Their findings among members of the UK public and CHIM experts from a variety of centres suggest that there is support for greater risks being associated with higher payments for participants. The amount of compensation offered by a trial has to be approved by an ethics committee/institutional review board, and some research suggests that IRB members have concerns about higher payments being offered, with only approximately one-third agreeing that payment should be offered for risk.3 Without agreement and clear guidance for calculating compensation for these types of trial, there is bound to be …. (shrink)

Ongoing and anticipated COVID-19 human challenge studies in the UK may advance our understanding of COVID-19 and facilitate the licensure of safe, effective, and easily deployable next-generation COVID-19 vaccines and boosters. We argue that international volunteer recruitment for COVID-19 human challenge trials can help promote diversity in these trials and ensure a sufficient number of eligible volunteers, both of which will increase the benefits of challenge research. We explore the ethical ramifications of dealing with (...) unfair background conditions of global vaccine injustice to expand medical research, and conclude that international recruitment for COVID-19 human challenge trials can be conducted ethically provided that several robust protections are in place for volunteers. (shrink)

We largely agree with Grimwade et al ’s1 conclusion that challenge trial participants may ethically be paid, including for risk. Here, we add further arguments, clarify some points from the perspective of economics and indicate areas where economists can support the development of a framework for ethically justifiable payment. Our arguments apply to carefully constructed and monitored controlled human infection model trials that have been appropriately reviewed and approved. Participants in medical studies perform a service. Outside the (...) domain of research participation, there is nearly universal agreement that workers providing a service should be compensated fairly, and that work involving more discomfort and risk should be compensated more generously. Accordingly, labour regulations impose floors, not caps on compensation. Caps, even if intended to protect against undue inducement, also raise concerns about illegal price-fixing that disadvantages workers. Such limits on payment for egg donors have successfully been challenged in court.i Moreover, caps on compensation may harm everyone at risk of infection, not just potential participants. Insufficient compensation may impede the recruitment of enough suitable subjects, for example, when representativeness of the subject sample is required. Delays in vaccine development not only prolong disruption of social, educational and economic activity but also lead to excess infections and deaths. Unlike paid CHIM participants, individuals exposed to such infection do not accept it voluntarily, are not compensated for it, and are unlikely to receive the level of medical supervision afforded to closely monitored CHIM participants. Payment caps can lead to attempts to circumvent the regulation. For example, many countries …. (shrink)

In controlled human infection (CHI) studies, investigators deliberately infect healthy individuals with pathogens in order to study mechanisms of disease or obtain preliminary efficacy data on investigational vaccines and medicines. CHI studies offer a fast and cost‐effective way of generating new scientific insights, prioritizing investigational products for clinical testing, and reducing the risk that large numbers of people are exposed to ineffective or harmful substances in research or in practice. Yet depending on the pathogen, CHI studies (...) can involve significant risks or burdens for participants, pose risks to individuals or communities not involved in the research, and lead to public controversy. It is therefore essential to ensure that the risks of CHI studies are justified by their social value—that is, their potential to generate benefits for society—and that public trust can be maintained. In this paper, we aim to clarify how research sponsors, research ethics committees and other reviewers should judge the social value of CHI studies. We develop a list of relevant considerations for making social value judgments based on the standard view of social value. We then use this list to discuss the example of potentially conducting dengue virus CHI studies in endemic settings. We argue that dengue virus CHI studies in endemic settings would fall on the higher end of the spectrum of social value, mostly because of their potential to redirect all fields of future dengue research. Drawing on this discussion, we derive several general recommendations for how reviewers should judge the social value of CHI studies. (shrink)

Controlled human infection studies (CHIs) involve the intentional infection of human subjects for a scientific aim. Though some past challenge trials have involved serious ethical abuses, in the last few decades, CHIs have had a strong track record of safety. Despite increased attention to the ethics of CHIs during the COVID‐19 pandemic, CHIs remain controversial, and there has been no in‐depth treatment of CHIs through the lens of virtue ethics. In this article, we argue that virtue (...) theory can be helpful for addressing CHIs that present a constellation of controversial, unresolved, and/or under‐regulated ethical issues. We begin with some brief background on virtue ethics. We then substantiate our claim that some CHIs raise a constellation of ethical issues that are unresolved in the ethics literature and/or lack adequate regulatory guidance by demonstrating that CHIs can present indeterminate social value, risks to third parties, limitations on the right to withdraw from research, and questions about the upper limit of allowable risk. We argue that the presence of a virtuous investigator, with virtues such as prudence, compassion, and integrity, is especially important when these unresolved research ethics issues arise, which is the case for certain types of controlled human infection studies. We use the historical example of Walter Reed and the Yellow Fever Commission to illustrate this claim, and we also highlight some contemporary examples. We end by sketching some practical implications of our view, such as ensuring that investigators with experience running CHIs are involved in novel CHI models. (shrink)

The right to withdraw from research without penalty is well established around the world. However, it has been challenged in some corners of bioethics based on concerns about various harms—to participants, to scientific integrity, and to research bystanders—that may stem from withdrawal. These concerns have become particularly salient in emerging debates about the ethics of controlled human infection (CHI) studies in which participants are intentionally infected with pathogens, often in inpatient settings with extensive follow‐up. In this article, I (...) provide support for preserving the right to withdraw from research without penalty and demonstrate that it is also typically justified in the specific context of CHI studies. The right is well aligned with individual freedoms outside the research setting, where autonomous individuals are permitted to engage in behaviors that will foreseeably cause them harm; where they cannot be compelled to satisfy contracts for their services, nor penalized for failure to do so; and where their behavior is not constrained by public health authorities except in extreme circumstances. These freedoms are supported by U.S. law, as well as by ethical analysis that is more globally relevant. The problems associated with the right to withdraw, however, remain. The best approach to addressing them is not to restrict the right but rather to avoid initiating research when withdrawal would be especially problematic. If research proceeds, steps can still be taken to minimize participant withdrawal without infringing the right. Investigators can avoid participant surprise through informed consent focused on a study’s most burdensome aspects and promote study completion through financial incentives. Should participants nonetheless seek to withdraw, investigators may attempt to persuade them not to do so by encouraging consideration of the range of potential harms that may result. Researchers conducting CHI studies and other research from which withdrawal might be especially problematic should prepare for the possibility of participant withdrawal, respect participant requests to withdraw without penalty, and incorporate various measures to avoid such requests. (shrink)

We extend recent conversation about the ethics of human challenge trials to tuberculosis (TB). TB challenge studies could accelerate vaccine development, but ethical concerns regarding risks to trial participants and third parties have been a limiting factor. We analyse the expected social value and risks of different challenge models, concluding that if a TB challenge trial has between a 10% and a 50% chance of leading to the authorisation and near-universal delivery of a more (...) effective vaccine 3–5 years earlier, then the trial would save between 26 400 and 1 100 000 lives over the next 10 years. We also identify five important ethical considerations that differentiate TB from recent human challenge trials: an exceptionally high disease burden with no highly effective vaccine; heightened third party risk following the trial, and, partly for that reason, uniquely stringent biosafety requirements for the trial; risks associated with best available TB treatments; and difficulties with TB disease detection. We argue that there is good reason to consider conducting challenge trials with attenuated strains like Bacillus Calmette-Guérin or attenuatedMycobacterium tuberculosis. (shrink)

Crisis, Rupture and Anxiety: An Interdisciplinary Examination of Contemporary and Historical Human Challenges brings together a range of original contributions that seek to critically interrogate the concept of 'crisis', a seemingly omnipresent and defining metonym of our times. Both international and interdisciplinary in perspective, the leading doctoral scholars and early-career researchers represented in this volume unsettle hegemonic notions of crisis (and possible remedies) by exploring both a very wide range of extant crises (in and of politics, economics, communities, technologies, (...) urban policy, literary representation, media studies, language learning, nationalisms and national identity, and the legitimation of the state), as well as the roots of our contemporary understandings of crisis and the politics of 'crisis representation'. The book is broadly divided into two sections, 'Politics and Society' and 'Arts, Media and Humanities'. Originating in the University of Salford Arts, Media and Social Sciences Postgraduate Research Conference of 2010, Crisis, Rupture and Anxiety provides both an accessible and wide-ranging general introduction to various applications of the concept of crisis, as well providing a more specialist resource for students exploring crisis in one of the many disciplinary fields represented in this collection. Crisis, Rupture and Anxiety will be of particular interest to students with interdisciplinary interests that encompass cultural studies, literary theory, media studies, politics, sociology and urban studies. (shrink)

Even though there is a significant amount of scholarly work examining the ethical issues surrounding human genomics research, little is known about its footing in Malaysia. This study aims to explore the experience of local researchers and research ethics committee (REC) members in developing it in Malaysia. In‐depth interviews were conducted from April to May 2021, and the data were thematically analysed. In advancing this technology, both genomics researchers and REC members have concerns over how this research is being (...) developed in the country especially the absence of a clear ethical and regulatory framework at the national level as a guidance. However, this study argues that it is not a salient issue as there are international guidelines in existence and both researchers and RECs will benefit from a training on the guidelines to ensure genomics research can be developed in an ethical manner. (shrink)

BackgroundHuman infection studies (HIS) are valuable in vaccine development. Deliberate infection, however, creates challenging questions, particularly in low and middle-income countries (LMICs) where HIS are new and ethical challenges may be heightened. Consultation with stakeholders is needed to support contextually appropriate and acceptable study design. We examined stakeholder perceptions about the acceptability and ethics of HIS in Malawi, to inform decisions about planned pneumococcal challenge research and wider understanding of HIS ethics in LMICs.MethodsWe conducted 6 deliberative focus groups (...) and 15 follow-up interviews with research staff, medical students, and community representatives from rural and urban Blantyre. We also conducted 5 key informant interviews with clinicians, ethics committee members, and district health government officials.ResultsStakeholders perceived HIS research to have potential population health benefits, but they also had concerns, particularly related to the safety of volunteers and negative community reactions. Acceptability depended on a range of conditions related to procedures for voluntary and informed consent, inclusion criteria, medical care or support, compensation, regulation, and robust community engagement. These conditions largely mirror those in existing guidelines for HIS and biomedical research in LMICs. Stakeholder perceptions pointed to potential tensions, for example, balancing equity, safety, and relevance in inclusion criteria.ConclusionsOur findings suggest HIS research could be acceptable in Malawi, provided certain conditions are in place. Ongoing assessment of participant experiences and stakeholder perceptions will be required to strengthen HIS research during development and roll-out. (shrink)

In many critical investigations of machine vision, the focus lies almost exclusively on dataset bias and on fixing datasets by introducing more and more diverse sets of images. We propose that machine vision systems are inherently biased not only because they rely on biased datasets but also because theirperceptual topology, their specific way of representing the visual world, gives rise to a new class of bias that we callperceptual bias. Concretely, we define perceptual topology as the set of those inductive (...) biases in machine vision systems that determine its capability to represent the visual world. Perceptual bias, then, describes the difference between the assumed “ways of seeing” of a machine vision system, our reasonable expectations regarding its way of representing the visual world, and its actual perceptual topology. We show how perceptual bias affects the interpretability of machine vision systems in particular, by means of a close reading of a visualization technique called “feature visualization”. We conclude that dataset bias and perceptual bias both need to be considered in the critical analysis of machine vision systems and propose to understand critical machine vision as an important transdisciplinary challenge, situated at the interface of computer science and visual studies/Bildwissenschaft. (shrink)

Plants have been—and, for reasons of human sustenance and creative inspiration, will continue to be—centrally important to societies globally. Yet, plants—including herbs, shrubs, and trees—are commonly characterized in Western thought as passive, sessile, and silent automatons lacking a brain, as accessories or backdrops to human affairs. Paradoxically, the qualities considered absent in plants are those employed by biologists to argue for intelligence in animals. Yet an emerging body of research in the sciences and humanities challenges animal-centred biases in (...) determining consciousness, intelligence, volition, and complex communication capacities amongst living beings. In light of recent theoretical developments in our understandings of plants, this article proposes an interdisciplinary framework for researching flora: human-plant studies. Building upon the conceptual formations of the humanities, social sciences, and plant sciences as advanced by Val Plumwood, Deborah Bird Rose, Libby Robin, and most importantly Matthew Hall and Anthony Trewavas, as well as precedents in the emerging areas of human-animal studies, I will sketch the conceptual basis for the further consideration and exploration of this interdisciplinary framework. (shrink)

The purpose of this research was to understand institutional review board (IRB) challenges regarding youth-focused research submissions and to present advice from administrators. Semistructured self-report questionnaires were sent via e-mail to administrators identified using published lists of universities and hospitals and Internet searches. Of 183 eligible institutions, 49 responded. One half indicated they never granted parental waivers. Among those considering waivers, decision factors included research risks, survey content, and feasibility. Smoking and substance abuse research among children was generally considered more (...) than minimal risk. These findings are consistent with those from a study conducted by Mammel and Kaplan (1995), which investigated IRB practices concerning protocols involving adolescent participants. IRBs and investigators need to become aware of regulations' flexibility to ensure adequate participant protection. Investigators need to limit jargon and assumptions about participants' understanding of research objectives. (shrink)

_The Challenge of Human Rights_ traces the history of human rights theory from classical antiquity through the enlightenment to the modern human rights movement, and analyses the significance of human rights in today’s increasingly globalized world. Provides an engaging study of the origin and the philosophical and political development of human rights discourse. Offers an original defence of human rights. Explores the significance of human rights in the context of increasing globalisation. Confronts (...) the major objections to human rights, including the charge of western ethical imperialism and cultural relativism. Argues that human rights logically culminate in an ethical cosmopolitanism to reflect the moral unity of the human race. (shrink)

Background:Clinical investigation is a growing field employing increasing numbers of nurses. This has created a new specialty practice defined by aspects unique to nursing in a clinical research context: the objectives, setting, and nature of the nurse–participant relationship. The clinical research nurse role may give rise to feelings of ethical conflict between aspects of protocol implementation and the duty of patient advocacy, a primary nursing responsibility. Little is known about whether research nurses experience unique ethical challenges distinct from those experienced (...) by nurses in traditional patient-care settings.Research objectives:The purpose of the study was to describe the nature of ethical challenges experienced by clinical research nurses within the context of their practice.Research design:The study utilized a qualitative descriptive design with individual interviews.Participants and research context:Participating nurses self-identified as having experienced ethical challenges during screening. The majority were Caucasian, female, and worked in outpatient settings. Approximately 50% had > 10 years of research experience.Ethical considerations:The human subjects review board approved the study. Written informed consent was obtained.Findings:Predominant themes were revealed: the inability to provide a probable good, or/do no harm, and dual obligations. The following patterns and subthemes emerged: conflicted allegiances between protocol implementation, needs of the participant, desire to advance science, and tension between the nurse–patient therapeutic relationship versus the research relationship.Discussion:Participants described ethical challenges specific to the research role. The issues are central to the nurse–participant relationship, patient advocacy, the nurse’s role in implementing protocols, and/or advancing science.Conclusion:Ethical challenges related to the specialized role of clinical research nurses were identified. More research is warranted to fully understand their nature and frequency and to identify support systems for resolution. (shrink)

_The Challenge of Human Rights_ traces the history of human rights theory from classical antiquity through the enlightenment to the modern human rights movement, and analyses the significance of human rights in today’s increasingly globalized world. Provides an engaging study of the origin and the philosophical and political development of human rights discourse. Offers an original defence of human rights. Explores the significance of human rights in the context of increasing globalisation. Confronts (...) the major objections to human rights, including the charge of western ethical imperialism and cultural relativism. Argues that human rights logically culminate in an ethical cosmopolitanism to reflect the moral unity of the human race. (shrink)

Epithelial hair follicle stem cells (eHFSCs) are required to generate, maintain and renew the continuously cycling hair follicle (HF), supply cells that produce the keratinized hair shaft and aid in the reepithelialization of injured skin. Therefore, their study is biologically and clinically important, from alopecia to carcinogenesis and regenerative medicine. However, human eHFSCs remain ill defined compared to their murine counterparts, and it is unclear which murine eHFSC markers really apply to the human HF. We address this by (...) reviewing current concepts on human eHFSC biology, their immediate progeny and their molecular markers, focusing on Keratin 15 and 19, CD200, CD34, PHLDA1, and EpCAM/Ber‐EP4. After delineating how human eHFSCs may be selectively targeted experimentally, we close by defining as yet unmet key challenges in human eHFSC research. The ultimate goal is to transfer emerging concepts from murine epithelial stem cell biology to human HF physiology and pathology. (shrink)

Organizations are increasingly finding it challenging to balance economic and environmental performance particularly those that face competitive, regulatory and community pressure. With the increasing pressures for environmental sustainability, this calls for the new formulation of strategies by the manufacturers in order to minimize their products and services negative impact on the environment. Hence, Green Human Resource Management (GHRM) continues to be an important research agenda among the researchers. In Palestine, green issues are new and still developing. Constant study is (...) needed to fully understand and update information regarding this area. Objective: The aim of this paper is to explore the views and level of acceptance of GHRM practices among manufacturing firms in Palestine. Results: Through the use of e-mail survey, 121 responses were obtained to generate the results of the study. The result showed GHRM practices have been practiced to somewhat to a greater extent a firms in Palestine. Findings can be extended to study on the issues in further. Academicians and practitioners can apply this result to their research and business strategies on how to improve sustainable performance and to effectively implement GHRM practices. (shrink)

Controlled human infection model (CHIM) studies involve the intentional exposure of healthy research volunteers to infectious agents. These studies contribute to knowledge about the cause or development of disease and to the advancement of vaccine research. But they also raise ethical questions about the kinds of risks that should be permissible and whether limits should be imposed on research risks in CHIM studies. Two possible risk thresholds have been considered for CHIM studies. The first suggests (...) constraining ethically permissible risks according to a minimal risk threshold and the second endorses a higher risk threshold that excludes irreversible or fatal infections. I argue that neither of these thresholds is persuasive and situate questions about risk thresholds in CHIM studies within a broader debate about permissible risks in research. I argue that risks in CHIM studies should be constrained according to limits on research risks that do not offer corresponding benefits in all studies rather than developing a unique risk threshold for CHIM studies. I then propose five recommendations for the ethical assessment of risk in CHIM studies. (shrink)

The Challenge of Human Rights traces the history of human rights theory from classical antiquity through the enlightenment to the modern human rights movement, and analyses the significance of human rights in today’s increasingly globalized world. Provides an engaging study of the origin and the philosophical and political development of human rights discourse. Offers an original defence of human rights. Explores the significance of human rights in the context of increasing globalisation. Confronts (...) the major objections to human rights, including the charge of western ethical imperialism and cultural relativism. Argues that human rights logically culminate in an ethical cosmopolitanism to reflect the moral unity of the human race. (shrink)

After briefly surveying three generations of comparative sociologists, interdisciplinary regional and trans-regional studies are shown to complement the work of the third generation of comparative sociologists on civilizational analysis and multiple modernities. Drawing examples from the interdisciplinary Persianate studies, promoted by the Association for the Study of Persianate Societies in the last two decades, and by other recent interdisciplinary studies of performance and world literature as well as Caribbean regional studies, it is argued that the rise (...) of interdisciplinary studies in social sciences and humanities may in fact redeem the unfulfilled promise that comparative sociology once offered. These recent studies constitute a significant contribution to our theoretical understanding of different patterns of socio-cultural development beyond the West, whose historical experience gave birth to modern social science disciplines, and thereby to register the historical experience of a very sizeable portion of humankind as the basis for the reconstruction of social theory in the global age. (shrink)

Today’s technological-scientific prospect of posthumanity simultaneously evokes and defies historical understanding. On the one hand, it implies a historical claim of an epochal transformation concerning posthumanity as a new era. On the other, by postulating the birth of a novel, better-than-human subject for this new era, it eliminates the human subject of modern Western historical understanding. In this article, I attempt to understand posthumanity as measured against the story of humanity as the story of history itself. I examine (...) the fate of humanity as the central subject of history in three consecutive steps: first, by exploring how classical philosophies of history achieved the integrity of the greatest historical narrative of history itself through the very invention of humanity as its subject; second, by recounting how this central subject came under heavy criticism by postcolonial and gender studies in the last half-century, targeting the universalism of the story of humanity as the greatest historical narrative of history; and third, by conceptualizing the challenge of posthumanity against both the story of humanity and its criticism. Whereas criticism fragmented history but retained the possibility of smaller-scale narratives, posthumanity does not doubt the feasibility of the story of humanity. Instead, it necessarily invokes humanity, if only in order to be able to claim its supersession by a better-than-human subject. In that, it represents a fundamental challenge to the modern Western historical condition and the very possibility of historical narratives – small-scale or large-scale, fragmented or universal. (shrink)

Tarski’s conceptual analysis of the notion of logical consequence is one of the pinnacles of the process of defining the metamathematical foundations of mathematics in the tradition of his predecessors Euclid, Frege, Russell and Hilbert, and his contemporaries Carnap, Gödel, Gentzen and Turing. However, he also notes that in defining the concept of consequence “efforts were made to adhere to the common usage of the language of every day life.” This paper addresses the issue of what relationship Tarski’s analysis, and (...) Béziau’s further generalization of it in universal logic, have to reasoning in the everyday lives of ordinary people from the cognitive processes of children through to those of specialists in the empirical and deductive sciences. It surveys a selection of relevant research in a range of disciplines providing theoretical and empirical studies of human reasoning, discusses the value of adopting a universal logic perspective, answers the questions posed in the call for this special issue, and suggests some specific research challenges. (shrink)

Ethical conduct is a maxim in scholarly research as well as scholarly endeavour generally. In the case of research involving humans, few if any question the necessity for ethics approval of procedures by ethics boards or committees. However, concerns have been raised about the appropriateness of ethics approval processes for social science research arguing that the orientation of ethics boards and committees to biomedical and experimental scientific research, institutional risk aversion, and other factors lead to over-protection of research participants and (...) overly restrictive processes that delay and sometimes prevent important social science research. This is particularly significant when social science research is required to respond to social, environmental, or health emergencies and in contract research projects for the reasons explained. This analysis of an ethics approval case study adds to increasing concerns that ethics approval processes can have perverse effects in the social sciences. While a single case study does not provide generalizable findings, in-depth analysis of a significant case can identify issues that need to be further explored. Recommendations offer pathways for facilitating social science research including in emergency situations in which timeliness is important and in collaborative approaches such as participatory action research, while maintaining high ethical standards. (shrink)

Trees belong to humanity’s heritage, but they are more than that. Their loss, through catastrophic fires or under business-as-usual, is devastating to many forms of life. Moved by this fact, we begin with an assertion that heritage can have an active role in the design of future places. Written from within the field of architecture, this article focuses on structures that house life. Habitat features of trees and artificial replacement habitats for arboreal wildlife serve as concrete examples. Designs of such (...) habitats need to reflect behaviours, traditions and cultures of birds, bats, and other animals. Our narrative highlights the nonhuman aspect of heritage, seeking to understand how nonhuman stakeholders can act as users and consumers of heritage and not only as its constituents. Our working definition states that more-than-human heritage encompasses tangible and intangible outcomes of historical processes that are of value to human as well as nonhuman stakeholders. From this basis, the article asks how the established notions of heritage can extend to include nonhuman concerns, artefacts, behaviours and cultures. As a possible answer to this question, the hypothesis tested here is that digital information can (1) contribute to the preservation of more-than-human heritage; and (2) illuminate its characteristics for future study and use. This article assesses the potential of three imaging technologies and considers the resulting data within the conceptual framework of more-than-human heritage, illuminating some of its concrete aspects and challenges. (shrink)