During recent years we have seen and assisted at a significantly increased number of twin births. The main reason for this increase in the frequency of twin births is the increasing number of so called “induced pregnancies”, whether through hormonal stimulation or artificial insemination techniques.It is well known1 that twins have high mortality and morbidity rates during the perinatal and the following period. The characteristics of conception and pregnancy can determine the development of several pathologies, including prematurity and intrauterine growth (...) retardation, …. (shrink)

An axiom of medical research ethics is that a protocol is moral only if it has a “favorable risk-benefit ratio”. This axiom is usually interpreted in the following way: a medical research protocol is moral only if it has a positive expected value -- that is, if it is likely to do more good (to both subjects and society) than harm. I argue that, thus interpreted, the axiom has two problems. First, it is unusable, because it requires (...) us to know more about the potential outcomes of research than we ever could. Second, it is false, because it conflicts with the so-called “soft paternalist” principles of liberal democracy. In place of this flawed rule I propose a new way of making risk-benefit assessments, one that does comport with the principles of liberalism. I argue that a protocol is moral only if it would be entered into by competent subjects who are informed about the protocol. The new rule this eschews all pseudo-utilitarian calculation about the protocol’s likely harms and benefits. (shrink)

Research ethics committees (RECs) evaluate whether the risk-benefit ratio of a study is acceptable. Decentralized clinical trials (DCTs) are a novel approach for conducting clinical trials that potentially bring important benefits for research, including several collateral benefits. The position of collateral benefits in risk-benefit assessments is currently unclear. DCTs raise therefore questions about how these benefits should be assessed. This paper aims to reconsider the different types of research benefits, and their position in risk- (...) class='Hi'>benefit assessments. We first propose a categorization of research benefits, based on the types of benefits that can be distinguished from the literature and ethical guidelines. Secondly, we will reconsider the position of collateral benefits. We argue that these benefits are not fundamentally different from other benefits of research and can therefore be included in risk-benefit assessments of DCTs. (shrink)

Though antiretroviral therapy is the standard of care for people living with HIV, its treatment limitations, burdens, stigma and costs lead to continued interest in HIV cure research. Early-phase cure trials, particularly those that include analytic treatment interruption, involve uncertain and potentially high risk, with minimal chance of clinical benefit. Some question whether such trials should be offered, given the risk/benefit imbalance, and whether those who choose to participate are acting rationally. We address these questions through (...) a longitudinal decision-making study nested in a Thai acute HIV research cohort. In-depth interviews revealed central themes about decisions to join. Participants felt they possessed an important identity as members of the acute cohort, viewing their bodies as uniquely suited to both testing and potentially benefiting from HIV cure approaches. While acknowledging risks of ATI, most perceived they were given an opportunity to interrupt treatment, to test their own bodies and increase normalcy in a safe, highly monitored circumstance. They were motivated by potential benefits to themselves, the investigators and larger acute cohort, and others with HIV. They believed their own trial experiences and being able to give back to the community were sufficient to offset participation risks. These decisions were driven by the specific circumstances experienced by our participants. Judging risk/benefit ratios without appreciating these lived experiences can lead to false determinations of irrational decision- making. While this does not minimise vital oversight considerations about risk reduction and protection from harm, it argues for inclusion of a more participant-centered approach. (shrink)

Interventions to decrease acquisition and transmission of sexually transmitted diseases among African American women using text messages versus small-group delivery modalities pose distinct research risks and benefits. Determining the relative risk–benefit ratio of studies using these different modalities has relied on the expertise of investigators and their institutional review boards. In this study, African American women participated in focus groups and surveys to elicit and compare risks and benefits inherent in these two intervention delivery modalities, focusing on (...) issues such as convenience, privacy, and stigma of participation. Some risk/benefit variables were implicated in willingness to participate the two intervention modalities. (shrink)

Research protocols must have a reasonable balance of risks and anticipated benefits to be ethically and legally acceptable. This article explores three characteristics of research on reproductive genetic technologies that complicate the assessment of the risk-benefit ratio for such research. First, a number of different people may be affected by a research protocol, raising the question of who should be considered to be the subject of reproductive genetic research. Second, such research could involve a wide range of (...) possible harms and benefits, making the evaluation and comparison of those harms and benefits a challenging task. Finally, the risk-benefit ratio for this type of research is difficult to estimate because such research can have unpredictable, long-term implications. The article aims to facilitate the assessment of risk-benefit ratios in research on reproductive genetic technologies by proposing and defending some guidelines for dealing with each of these complicating factors. (shrink)

David KC Cooper,1 David Ayares21Thomas E Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh, PA, USA; 2Revivicor, Blacksburg, VA, USA: The transplantation of organs and cells from pigs into humans could overcome the critical and continuing problem of the lack of availability of deceased human organs and cells for clinical transplantation. Developments in the genetic engineering of pigs have enabled considerable progress to be made in the experimental laboratory in overcoming the immune barriers to successful xenotransplantation. With regard to (...) pig organ xenotransplantation, antibody- and cell-mediated rejection have largely been overcome, and the current major barrier is the development of coagulation dysregulation. This is believed to be due to a combination of immune activation of the vascular endothelial cells of the graft and molecular incompatibilities between the pig and primate coagulation–anticoagulation systems. Pigs with new genetic modifications specifically directed to this problem are now becoming available. With regard to less complex tissues, such as islets, neuronal cells, and corneas, the remaining barriers are less problematic, and graft survival in nonhuman primate models extends for >1 year in all three cases. In planning the initial clinical trials, consideration will be concentrated on the risk–benefit ratio, based to a large extent on the results of preclinical studies in nonhuman primates. If the benefit to the patient is anticipated to be high, eg, insulin-independent control of glycemia, and the potential risks low, eg, minimal risk of transfer of a porcine infectious agent, then a clinical trial would be justified.Keywords: infection, pigs, genetically-engineered, xenotransplantation, islets, xenotransplantation, organs. (shrink)

Stem cells are likely to be used as an alternate source of biological material for neural transplantation to treat Parkinson’s disease in the not too distant future. Among the several ethical criteria that must be fulfilled before proceeding with clinical research, a favourable benefit to risk ratio must be obtained. The potential benefits to the participant and to society are evaluated relative to the risks in an attempt to offer the participants a reasonable choice. Through examination of (...) preclinical studies transplanting stem cells in animals and the transplantation of fetal tissue in patients with Parkinson’s disease, a current set of potential benefits and risks for neural transplantation of stem cells in clinical research of Parkinson’s disease are derived. The potential benefits to research participants undergoing stem cell transplantation are relief of parkinsonian symptoms and decreasing doses of parkinsonian drugs. Transplantation of stem cells as a treatment for Parkinson’s disease may benefit society by providing knowledge that can be used to help determine better treatments in the future. The risks to research participants undergoing stem cell transplantation include tumour formation, inappropriate stem cell migration, immune rejection of transplanted stem cells, haemorrhage during neurosurgery and postoperative infection. Although some of these risks are general to neurosurgical transplantation and may not be reduced for participants, the potential risk of tumour formation and inappropriate stem cell migration must be minimised before obtaining a favourable potential benefit to risk calculus and to provide participants with a reasonable choice before they enrol in clinical studies. (shrink)

Newborn screening has evolved to include an increasingly complex spectrum of diseases, raising concerns that screening should be optional and require parental consent. Early detection of disorders like PKU and MCAD is essential to prevent serious disability and death in affected children. These are examples of high benefit-risk ratio disorders because of the irrefutable health benefits of early detection, coupled with the low risks of treatment. The dire consequences of not diagnosing an infant with a treatable disorder (...) because of parental refusal to screen are wholly unacceptable. Thus, we believe that newborn screening for disorders with high benefit-risk ratios should continue to be mandatory. (shrink)

Objectives: There are indications that institutional review board members do not find it easy to assess the risks and benefits in medical experiments, although this is their principal duty. This study examined how IRB members assessed the risk/benefit ratio of a specific phase II breast cancer clinical trial.Participants and methods: The trial was evaluated by means of a questionnaire administered to 43 members of IRBs at six academic hospitals and specialised cancer centres in the Netherlands. The questionnaire (...) addressed: identification and estimation of inconvenience, toxicity, psychosocial distress, and benefits of trial participation to patients; identification and estimation of benefits to future patients and medical science; assessment of the trial’s RBR; and assessment of its ethical acceptability.Results: Most IRB members expected trial participation to involve fairly or very serious inconvenience, fairly severe to sometimes life-threatening toxicity, and serious psychological and social consequences. Conversely, the perceived likelihood of benefits to patients was modest. Most regarded the study as important, and the balance between risks and benefits to be favourable, and believed that the protocol should be approved. The IRB members’ final judgement on the trial’s ethical acceptability was significantly correlated with their RBR assessment of the protocol.Conclusions: Because most patients who participate in clinical trials hope this will prolong their lives, it is suggested that patient information should better describe the anticipated benefits—for example, the likelihood of prolonging life. This would allow patients to make decisions regarding participation based on realistic expectations. (shrink)

Over-enthusiastic newborn screening has often caused substantial harm and has been imposed on the public without adequate information on benefits and risks and without parental consent. This problem will become worse when genomic screening is implemented. For the past 40 years, there has been broad agreement about the criteria for ethically responsible screening, but the criteria have been systematically ignored by policy makers and practitioners. Claims of high benefit and low risk are common, but they require precise definition (...) and documentation, which has often not occurred, undermining claims that involuntary testing is justified. Even when the benefits and risks are well established, it does not automatically follow that involuntary testing is justified, a position supported by the widespread tolerance for parental refusal of immunizations and newborn screening. (shrink)

Research to improve the health of pregnant and fetal patients presents ethical challenges to clinical investigators, institutional review boards, funding agencies, and data safety and monitoring boards. The Common Rule sets out requirements that such research must satisfy but no ethical framework to guide their application. We provide such an ethical framework, based on the ethical concept of the fetus as a patient. We offer criteria for innovation and for Phase I and II and then for Phase III clinical trials (...) to improve the health of pregnant patients and of fetal patients and also criteria to responsibly manage the transition from investigation to clinical practice. Basing ethical criteria for research involving pregnant women on the ethical concept of the fetus as a patient insulates the proposed ethical framework and therefore research on pregnant women from the divisive and politicized concepts and discourses of personhood, fetal rights, and unborn child. (shrink)

Some early phase clinical studies of candidate HIV cure and remission interventions appear to have adverse medical risk–benefit ratios for participants. Why, then, do people participate? And is it ethically permissible to allow them to participate? Recent work in decision theory sheds light on both of these questions, by casting doubt on the idea that rational individuals prefer choices that maximise expected utility, and therefore by casting doubt on the idea that researchers have an ethical obligation not to (...) enrol participants in studies with high risk–benefit ratios. This work supports the view that researchers should instead defer to the considered preferences of the participants themselves. This essay briefly explains this recent work, and then explores its application to these two questions in more detail. (shrink)

Many instances of scientific research impose risks, not just on participants and scientists but also on third parties. This class of social risks unifies a range of problems previously treated as distinct phenomena, including so-called bystander risks, biosafety concerns arising from gain-of-function research, the misuse of the results of dual-use research, and the harm caused by inductive risks. The standard approach to these problems has been to extend two familiar principles from human subjects research regulations—a favorable risk-benefit (...) class='Hi'>ratio and informed consent. We argue, however, that these moral principles will be difficult to satisfy in the context of widely distributed social risks about which affected parties may reasonably disagree. We propose that framing these risks as political rather than moral problems may offer another way. By borrowing lessons from political philosophy, we propose a framework that unifies our discussion of social risks and the possible solutions to them. (shrink)

The COVID-19 pandemic during 2020–2022 raised ethical questions concerning the balance between individual autonomy and the protection of the population, vulnerable individuals and the healthcare system. Pediatric COVID-19 vaccination differs from, for example, measles vaccination in that children were not as severely affected. The main question concerning pediatric vaccination has been whether the autonomy of parents outweighs the protection of the population. When children are seen as mature enough to be granted autonomy, questions arise about whether they have the right (...) to decline vaccination and who should make the decision when parents disagree with each other and/or the child. In this paper, I argue that children should be encouraged to not only take responsibility for themselves, but for others. The discussion of pediatric vaccination in cases where this kind of risk–benefit ratio exists extends beyond the 2020–2022 pandemic. The pandemic entailed a question that is crucial for the future of public health as a global problem, that is, to what extent children should be seen as responsible decision-makers who are capable of contributing to its management and potential solution. I conclude that society should encourage children to cultivate such responsibility, conceived as a virtue, in the context of public health. (shrink)

Research to improve the health of pregnant and fetal patients presents ethical challenges to clinical investigators, institutional review boards, funding agencies, and data safety and monitoring boards. The Common Rule sets out requirements that such research must satisfy but no ethical framework to guide their application. We provide such an ethical framework, based on the ethical concept of the fetus as a patient. We offer criteria for innovation and for Phase I and II and then for Phase III clinical trials (...) to improve the health of pregnant patients and of fetal patients and also criteria to responsibly manage the transition from investigation to clinical practice. Basing ethical criteria for research involving pregnant women on the ethical concept of the fetus as a patient insulates the proposed ethical framework and therefore research on pregnant women from the divisive and politicized concepts and discourses of personhood, fetal rights, and unborn child. (shrink)

In recent decades, researchers have attempted to prospectively identify individuals at high risk of developing psychosis in the hope of delaying or preventing psychosis onset. These psychosis risk individuals are identified as being in an ‘At-Risk Mental State’ (ARMS) through a standardised psychometric interview. However, disclosure of ARMS status has attracted criticism due to concerns about the risk–benefit ratio of disclosure to patients. Only approximately one quarter of ARMS patients develop psychosis after three years, (...) raising concerns about the unnecessary harm associated with such ‘false-positive’ results. These harms are especially pertinent when identifying psychosis risk individuals due to potential stigma and discrimination in a young clinical population. A dearth of high-quality evidence supporting interventions for ARMS patients raises further doubts about the benefit accompanying an ARMS disclosure. Despite ongoing discussion in the bioethical literature, these concerns over the ethical justification of disclosure to ARMS patients are not directly addressed in clinical guidelines. In this paper, we aim to provide a unified disclosure strategy grounded in principle-based analysis for ARMS clinicians. After considering the ethical values at stake in ARMS disclosure, and their normative significance, we argue that full disclosure of the ARMS label is favoured in the vast majority of clinical situations due to the strong normative significance of enhancing patients' understanding. We then compare our framework with other approaches to ARMS disclosure and outline its limitations. (shrink)

Systemic risks are risks produced through interconnected non-wrongful actions of individuals, in the sense that an individual's action is a negligible cause of the risk. Due to scale effects of interaction, their consequences can be serious but they are also difficult to predict and assess via a risk assessment. Since we can have good reason to engage in the interconnected activities giving rise to systemic risk, we incur a concurrent collective responsibility to ensure that the risks are (...) fairly distributed and well regulated. James argues that fairness in this context requires taking reasonably available precautions ensuring for each risk-bearer a favourable ratio of expected benefits over expected losses. In sections 2 and 3 we argue that such a conception of fairness applies but only on the condition that the systemic risks created are irreversible risks and that the general background conditions of justice are imperfectly fair. When risks are reversible, compensatory justice can correct for unfairness in risk imposition. Where risks are irreversible, compensatory justice necessarily fails, giving rise to a collective responsibility to regulate fairly ex ante. Additionally, where background conditions of justice are fully fair and the systemic risk is well understood, risk bearers can be said to have consented to the systemic risk. If they are not fair, we argue that the primary political obligation should lie in fixing the fairness of the backgrounds of justice. A related reason for addressing the general background conditions of fairness is that James’ account of fairness in systemic risk imposition encounters a baseline problem. If expected risks and benefits are calculated again an unfair historic background condition, systemic risk imposition would not be fully fair. Section 4 shows why differences in evidentiary uncertainty as to probability and levels of harm and effective responses require a normatively appropriate response in the form of additional precautions. We show that the evidentiary standards set for risk-based cost-benefit analysis have a connection with deontology because they express a postulate of equal treatment in formal terms. Systemic risks can have different possible degrees of epistemological certainty due to factors of social and natural origin, such as more available research funding or higher degrees of complexity for some systemic risks but not others. These differences have to be mitigated by taking even greater precautions in difficult-to-research systemic risks. (shrink)

There has been long-standing, albeit largely implicit, debate over whether investigator intentions are relevant to the ethical appropriateness of clinical research. Some commentators argue that whether investigators intend to collect generalizable knowledge or to benefit subjects is central to the ethics of clinical research. Others do not even mention investigator intentions when evaluating what makes clinical research ethical. To shed light on this debate, the present paper considers the reasons why investigator intentions might be ethically relevant. This analysis reveals (...) that investigator intentions are related to, but distinct from three ethical requirements: whether subjects understand that they are contributing to a project to help others, whether the included interventions have an appropriate risk/benefit ratio, and whether subjects’ interests are adequately protected. Provided these three requirements are satisfied, the ethical appropriateness of clinical research does not depend on what intentions investigators have in conducting it. (shrink)

Smartphones with Global Positioning System (GPS) apps offer simple and accurate tools to collect data on human mobility. However, their associated ethical challenges remain to be assessed. We used the Emanuel framework to assess the ethical concerns of using smartphone GPS to record mobility patterns of young adults in rural South Africa for a larger study on mobility and HIV risk (Sesikhona). We conducted four focus groups (FGDs) with individuals eligible for the Sesikhona study. FGD data were coded using (...) the Emanuel framework. Participants perceived use of smartphone GPS to study human mobility and HIV risk as valuable. They raised concerns about invasion of privacy and confidentiality. Also mentioned were risk/benefit ratio, informed consent and ongoing respect. Concerns expressed provided a useful evidence-base for the development of a guide to inform future participants about ethical issues arising in the use of GPS technology to track mobility and health-related issues. (shrink)

Clinical trials aim to minimise participant risk and generate new clinical knowledge for the wider population. Many military agencies are now investing efforts in pushing towards developing new treatments involving Brain-Computer Interfaces, Gene Therapy and Stem Cells interventions. These trials are targeting smaller disease groups, as such they give rise to novel participant risks of harms that are largely not accommodated by existing practice. This is of most concern with irreversible harms at early trial stages, where participants may forfeit (...) any future therapy, and in personalised medicine, where the individual participant assumes all of the trial risk. Given these new experimental interventions involve high risk of irreversible harms, how much risk should patients be exposed to when participating in experimental testing of innovative technologies? Designing clinical trials which better balance risk/benefit ratios for participants is crucial. The aim of this book chapter is to suggest a new stratified risk framework aimed at minimising the risk-benefit ratio to participants in clinical trials associated with high risk of irrevocable harms. We will argue it demands a higher-level of clinical data capture at earlier trial stages than predicated by current trial doctrine; it also requires publication of all trial data to minimise risk to participants of any future trial. (shrink)

Many opinions and ideas about aging exist. Biological theories have taken hold of the popular and scientific imagination as potential answers to a “cure” for aging. However, it is not clear what exactly is being cured or whether aging could be classified as a disease. Some scientists are convinced that aging will be biologically alterable and that the human lifespan will be vastly extendable. Other investigators believe that aging is an elusive target that may only be “statistically” manipulatable through a (...) better understanding of the operational principles of systems situated within complex environments. Not only is there confusion over definitions but also as to the safety of any potential intervention. Curing cell death, for example, may lead to cell cancer. The search for a cure for aging is not a clearly beneficial endeavour. This paper will first, describe contemporary ideas about aging processes and second, describe several current life extension technologies. Third, it analyses these theories and technologies, focusing on two representative and differing scientific points of view. The paper also considers the public health dilemma that arises from life extension research and examines two issues, risk/benefit ratio and informed consent, that are key to developing ethical guidelines for life extension technologies. (shrink)

The sex ratio at birth in China exhibits a major occurrence of “missing women” due to the high son preference in Chinese culture. Clearly, the large gender discrepancy in China can be explained not only by ethical, moral, or social fairness theories but also by the economic benefits of women's particular abilities, experiences, and talents. This article examines the influence of female chief financial officers on information disclosure violations in order to highlight women's positive contributions. Our data imply that (...) having a female CFO can dramatically lower the number of companies that fail to disclose information. The results are strong after controlling endogeneity with propensity score matching, Heckman's two-stage self-selection model, and CFO change, as well as controlling the gender of the chairman and chief executive officer, utilizing different study periods, and using exogenous shock. We further examined the moderate effects of CFO power and external monitoring, and we found that CFO power magnifies the negative effect of female CFO on violations; the more the power, the more the negative effect of female CFO on violations. We also found that when the firm has effective external monitoring, there are fewer future infractions of information disclosure. (shrink)

This paper argues against considering incidental fndings as potential benefts of research when assessing the social value of proposed research, determining the appropriateness of a study's risk/beneft ratio, and identifying and disclosing the risks and benefts of participation during informed consent. The possibility of generating IFs should be disclosed during informed consent as neither a risk nor beneft, but as a possible outcome collateral to participation. Whether specifc IFs will be disclosed when identifed is a separate question (...) whose answer is material to determining whether IFs constitute a risk or a potential indirect beneft of participation. Finally, three types of IF should be distinguished and treated diferently during informed consent: those that will be routinely generated , those that can reasonably be characterized in terms of their nature and frequency of generation , and those of unpredictable nature and frequency that can be characterized only in general terms. Research protocols should provide a rationale for sharing or not sharing IFs of these three types with participants. Regulatory review of such plans should not, however, be confused with regarding IFs as potential benefts when assessing the study's risk/beneft ratio or merit. (shrink)

Theoretical arguments regarding the effect of corporate social responsibility (CSR) on firm liability risk are abundant; however, empirical evidence about this relationship is scarce. We investigate the relationship between CSR and the personal liability risk of a firm’s directors and officers. We argue that companies with better CSR performance represent a better underwriting risk for directors’ and officers’ (D&O) insurance providers and, therefore, have a lower cost of insurance. Our results show that firms with better CSR performance (...) are more likely to purchase D&O insurance and have a lower premium-to-coverage ratio, known as the insurance rate-on-line. We also show that this risk-reduction effect is stronger for firms that operate in a high-risk environment and have higher sales growth. These results provide evidence that CSR can be used as a risk management tool to mitigate liability risk and suggest which firms benefit most from this effect. (shrink)

Trials with highly unfavourable risk–benefit ratios for participants, like HIV cure trials, raise questions about the quality of the consent of research participants. Why, it may be asked, would a person with HIV who is doing well on antiretroviral therapy be willing to jeopardise his health by enrolling in such a trial? We distinguish three concerns: first, how information is communicated to potential participants; second, participants’ motivations for enrolling in potentially high risk research with no prospect of (...) direct benefit; and third, participants’ understanding of the details of the trials in which they enrol. We argue that the communication concern is relevant to the validity of informed consent and the quality of decision making, that the motivation concern does not identify a genuine problem with either the validity of consent or the quality of decision making and that the understanding concern may not be relevant to the validity of consent but is relevant to the quality of decision making. In doing so, we derive guidance points for researchers recruiting and enrolling participants into their HIV cure trials, as well as the research ethics committees reviewing proposed studies. (shrink)

Much of the contemporary debate about the propriety of non-therapeutic circumcision of male infants and boys revolves around the question of risks vs. benefits. With its headline conclusion that the benefits outweigh the risks, the current circumcision policy of the American Academy of Pediatrics [AAP] (released 2012) is a typical instance of this line of thought. Since the AAP states that it cannot assess the true incidence of complications, however, critics have pointed out that this conclusion is unwarranted. In this (...) paper it is argued that the AAP’s conclusion is untenable not only for empirical reasons related to lack of data, but also for logical and conceptual reasons: the concept of risk employed—risk of surgical complications—is too narrow to be useful in the circumcision debate. Complications are not the only harms of circumcision: the AAP and other parties debating the pros and cons of circumcision should conceptualize their analysis more broadly as risk of harm vs. prospect of benefit, thereby factoring in the value of the foreskin to the individual and the physical and ethical harms of removing it from a non-consenting child. (shrink)

Modern antiretroviral therapies are capable of suppressing HIV in the bloodstream to undetectable levels. Nonetheless, people living with HIV must maintain lifelong adherence to ART to avoid the re-emergence of the infection. So despite the existence and efficacy of ART, there is still substantial interest in development of a cure. But HIV cure trials can be risky, their success is as of yet unlikely, and the medical gain of being cured is limited against a baseline of ART access. The medical (...) prospect associated with participation in cure research thus look poor. Are the risks and burdens that HIV cure research places on participants so high that it is unethical, at present, to conduct it? In this paper, I answer ‘no’. I start my argument by describing a foundational way of thinking about the ethical justification for regulatory limits on research risk; I then apply this way of thinking to HIV cure trials. In offering this analysis, I confine my attention to studies enrolling competent adults and I also do not consider risks research may pose to third parties or society. Rather, my concern is to engage with the thought that some trials are so risky that performing them is an ethically unacceptable way to treat the participants themselves. I reject this thought and instead argue that there is no level of risk, no matter how high, that inherently mistreats a participant. (shrink)

Assessing the risk-benefit ratio has always been considered key in designing clinical trials. These benefits can be diverse and may include social value and psychological benefits. When it comes to...

ABSTRACT The 2006 Institute of Medicine (IOM) report, ‘Ethical Considerations for Research Involving Prisoners’, recommended five main changes to current US Common Rule regulations on prisoner research. Their third recommendation was to shift from a category‐based to a risk‐benefit approach to research review, similar to current guidelines on pediatric research. However, prisoners are not children, so risk‐benefit constraints on prisoner research must be justified in a different way from those on pediatric research. In this paper I (...) argue that additional risk‐benefit constraints on prisoner research are unnecessary: the current Common Rule regulations, omitting category‐based restrictions but conjoined with the IOM report's other four main recommendations, ensure that prisoner research is as ethical as non‐prisoner research is. I explain why four problems which which may be more prevalent in prisons and which risk‐benefit constraints may seem to address – coercion, undue inducements, exploitation, and protection from harm – are in fact not solved by adding further risk‐benefit constraints on prisoner research. (shrink)

This paper suggests that “systemic risk” has a distinctive kind of moral significance. Two intuitive data points need to be explained. The first is that the systematic imposition of risk can be wrongful or unjust in and of itself, even if harm never ensues. The second is that, even so, there may be no one in particular to blame. We can explain both ideas in terms of what I call responsibilities of “Collective Due Care.” Collective Due Care arguably (...) precludes purely aggregative cost-benefit decision-making and requires one kind of “precautionary” attitude in public choice. (shrink)

With the rising interest in the field of trauma research, many Institutional Review Boards, policymakers, parents, and others grapple with the impact of trauma-research participation on research participants' well-being. Do individuals who participate in trauma-focused research risk experiencing lasting negative effects from participation? What are the potential benefits that may be gleaned from participation in this work? How can trauma research studies be designed ethically, minimizing the risk to participants? The following review seeks to answer these questions. This (...) review indicates that most studies in this area have found that only a minority of participants experience distress when participating in trauma-focused research. Furthermore, these negative feelings tend to dissipate quickly over time, with the majority of participants self-appraising their participation as positive, rewarding, and beneficial to society. Design characteristics that may serve to minimize participants' risk of experiencing distress are discussed, as well as implications for public policy and future research. (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 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)

BackgroundResearch ethics committees (RECs) are tasked to assess the risks and the benefits of a trial. Currently, two procedure-level approaches are predominant, the Net Risk Test and the Component Analysis.DiscussionBy looking at decision studies, we see that both procedure-level approaches conflate the various risk-benefit tasks, i.e., risk-benefit assessment, risk-benefit evaluation, risk treatment, and decision making. This conflation makes the RECs’ risk-benefit task confusing, if not impossible. We further realize that RECs (...) are not meant to do all the risk-benefit tasks; instead, RECs are meant to evaluate risks and benefits, appraise risk treatment suggestions, and make the final decision.ConclusionAs such, research ethics would benefit from looking beyond the procedure-level approaches and allowing disciplines like decision studies to be involved in the discourse on RECs’ risk-benefit task. (shrink)

A generation ago, we adopted a national system for the protection of human subjects in research. Today, that system is facing new challenges. Many argue that the system has failed to evolve in concert with dramatic changes in the research environment. Accordingly, efforts are underway to reform the existing process to make it both more efficient and more effective. At the same time, many are also reexamining the system in more fundamental ways — going well beyond considerations of policies and (...) compliance and raising questions that go to the very foundations of what constitutes an ethical conduct of human research.Experimentation involving human subjects is a necessary step in the process of translating scientific discovery and technological advancement into procedures and products that offer the prospect of better lives for all of us. It helps us to better understand why we do the things we do and believe what we believe. (shrink)

A generation ago, we adopted a national system for the protection of human subjects in research. Today, that system is facing new challenges. Many argue that the system has failed to evolve in concert with dramatic changes in the research environment. Accordingly, efforts are underway to reform the existing process to make it both more efficient and more effective. At the same time, many are also reexamining the system in more fundamental ways — going well beyond considerations of policies and (...) compliance and raising questions that go to the very foundations of what constitutes an ethical conduct of human research.Experimentation involving human subjects is a necessary step in the process of translating scientific discovery and technological advancement into procedures and products that offer the prospect of better lives for all of us. It helps us to better understand why we do the things we do and believe what we believe. (shrink)

One of the key ethical requirements for biomedical research is that it have an acceptable risk-benefit profile (Emanuel, Wendler, and Grady 2000). The International Conference of Harmonization guidelines mandate that clinical trials should be initiated and continued only if “the anticipated benefits justify the risks” (1996). Guidelines from the Council for International Organizations of Medical Sciences state that biomedical research is acceptable only if the “potential benefits and risks are reasonably balanced” (2002). U.S. federal regulations require that the (...) “risks to subjects” be “reasonable in relation to anticipated benefits, if any, to subjects and the importance of the knowledge” to be gained from the .. (shrink)

In this paper I am concerned with risk–benefit analysis; that is, the comparison of the risks of a situation to its related benefits. We all face such situations in our daily lives and they are very common in medicine too, where risk–benefit analysis has become an important tool for rational decision-making. This paper explores risk–benefit analysis from a logical point of view. In particular, it seeks a better understanding of the common view that decisions (...) should be made by weighing risks against benefits and that an option should be chosen if its benefits outweigh its risks. I devote a good deal of this paper scrutinizing this popular view. Specifically, I demonstrate that this mode of reasoning is logically faulty if “risk” and “benefit” are taken in their absolute sense. But I also show that arguing in favour of an action because its benefits outweigh its risks can be valid if we refer to incremental risks and benefits. (shrink)

In response to adverse events in retroviral gene therapy clinical trials conducted in France to correct for X-linked severe combined immune deficiency disorder (X-SCID), an advisory committee of the Food and Drug Administration convened in October 2002, February 2003, and March 2005, to deliberate and provide recommendations for similarly sponsored research in the United States. A similar National Institutes of Health committee met in February 2003. In this article, I review the transcripts and/or minutes of these meetings to evaluate the (...) extent to which the ethical dimension of the research was engaged even as the molecular and clinical evidence was reviewed. I then provide representative ethical arguments to demonstrate the sort of ethical reasoning that should be included as part of the agenda of such committee meetings. (shrink)

The purpose of this article is to show that animal rights are not necessarily at odds with the use of animals for research. If animals hold basic moral rights similar to those of humans, then we should consequently extend the ethical requirements guiding research with humans to research with animals. The article spells out how this can be done in practice by applying the seven requirements for ethical research with humans proposed by Ezekiel Emanuel, David Wendler and Christine Grady to (...) animal research. These requirements are i) social value, ii) scientific validity, iii) independent review, iv) fair subject selection, v) favorable risk-benefit ratio, vi) informed consent, and vii) respect for research subjects. In practice, this means that we must reform the practice of animal research to make it more similar to research with humans, rather than completely abolish the former. Indeed, if we banned animal research altogether, then we would also deprive animals of its potential benefits – which would be ethically problematic. (shrink)

Risks and benefit evaluation for controlled human infection studies, where healthy volunteers are deliberately exposed to infectious agents to evaluate vaccine efficacy, should be explicit, systematic, thorough, and non‐arbitrary. Decision analysis promotes these qualities using four steps: (1) determining explicit criteria and measures for evaluation, (2) identifying alternatives to the study, (3) defining the models used to estimate the measures for each alternative, and (4) running the models to produce the estimates and compare the alternatives. In this paper, we (...) describe how decision analysis might be applied by funders and regulators, as well as by others contemplating the use of novel controlled human infection studies for vaccine development and evaluation. (shrink)

New fetal therapies offer important prospects for improving health. However, having to consider both the fetus and the pregnant woman makes the risk–benefit analysis of fetal therapy trials challenging. Regulatory guidance is limited, and proposed ethical frameworks are overly restrictive or permissive. We propose a new ethical framework for fetal therapy research. First, we argue that considering only biomedical benefits fails to capture all relevant interests. Thus, we endorse expanding the considered benefits to include evidence-based psychosocial effects of (...) fetal therapies. Second, we reject the commonly proposed categorical risk and/or benefit thresholds for assessing fetal therapy research. Instead, we propose that the individual risks for the pregnant woman and the fetus should be justified by the benefits for them and the study’s social value. Studies that meet this overall proportionality criterion but have mildly unfavorable risk–benefit ratios for pregnant women and/or fetuses may be acceptable. (shrink)