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)

This article describes our efforts to screen and enrol clinical trial participants conscientiously in the COVID-19 pandemic setting. We present the standard screening and enrolment process prior to, and our process of adapting to, the pandemic. Our goal was to develop a way to screen and enrol people for clinical trials that was both equitable and effective. In addition, we outline the steps our research department took to ensure that ethical, clinical and logistical factors were considered when matching a patient (...) to a clinical trial. (shrink)

Forschung an und mit Menschen muss sich legitimieren, d. h. sie muss ihre wissenschaftliche Qualität, Rechtmäßigkeit und ethische Vertretbarkeit aufzeigen. Zu den Rechtfertigungsbedingungen zählt ein „günstiges“ Verhältnis von Nutzen- und Schadenpotenzialen des Forschungsvorhabens. Unabhängige Ethikkommissionen sind den Forschenden zur Seite gestellt, um sie bei der Prüfung und Sicherstellung der genannten Erfordernisse zu unterstützen. Eine zum Gebrauch durch Ethikkommissionen und Forschende entwickelte Nutzen- und Schadentaxonomie sowie ein Schema zur Systematisierung von Chancen-Risiken-Bewertungen wurde nachträglich auf alle Ethikanträge des Jahres 2006 an die (...) Ethikkommission der Medizinischen Fakultät der Universität zu Lübeck angewandt. Unter den 206 analysierten Studienvorhaben lassen 46 % die Chance eines direkten Eigennutzens für die Studienteilnehmer erkennen. Als gruppennützig wurden 12 % der Studienprojekte eingestuft. Sie lassen unmittelbar nach Studienabschluss oder nach wenigen weiteren Studien ein Nutzenpotenzial für Personen mit den gleichen demographischen und klinischen Merkmalen wie die Studienteilnehmer erwarten. 42 % der Ethikanträge bezogen sich auf fremdnützige Studienvorhaben mit Nutzenchancen für die Heilkunde und/oder medizinische Wissenschaft. Das Risiko eines mehr als geringfügigen Eigenschadens wurde bei 53 % der Studien identifiziert. Die Analyse der jeweiligen Nutzenchancen und Schadenrisiken führte bei insgesamt 33 der 206 Studien (16 %) zu einem negativen Ergebnis: Im Urteil der nachträglich durchgeführten Bewertung übertreffen die Nutzenchancen nicht die Schadenrisiken. Studien mit einem mehr als geringfügigen Eigenschadenpotenzial sowie nicht-eigennützige Studien weisen besonders häufig eine negative Gesamtbilanz auf. Eine Prozeduralisierung der Analyse von Chancen und Risiken kann die Transparenz vorgenommener Analyse- und Vergleichsprozesse steigern. Die Kommunikation zwischen Forschenden und Ethikkommissionen sowie unter Ethikkommissionsmitgliedern bei strittigen Studienvorhaben wird erleichtert, die Standardisierung und Harmonisierung der Beratungsabläufe der Ethikkommissionen unterstützt. (shrink)

Forschung an und mit Menschen muss sich legitimieren, d. h. sie muss ihre wissenschaftliche Qualität, Rechtmäßigkeit und ethische Vertretbarkeit aufzeigen. Zu den Rechtfertigungsbedingungen zählt ein „günstiges“ Verhältnis von Nutzen- und Schadenpotenzialen des Forschungsvorhabens. Unabhängige Ethikkommissionen sind den Forschenden zur Seite gestellt, um sie bei der Prüfung und Sicherstellung der genannten Erfordernisse zu unterstützen. Eine zum Gebrauch durch Ethikkommissionen und Forschende entwickelte Nutzen- und Schadentaxonomie sowie ein Schema zur Systematisierung von Chancen-Risiken-Bewertungen wurde nachträglich auf alle Ethikanträge des Jahres 2006 an die (...) Ethikkommission der Medizinischen Fakultät der Universität zu Lübeck angewandt. Unter den 206 analysierten Studienvorhaben lassen 46 % die Chance eines direkten Eigennutzens für die Studienteilnehmer erkennen. Als gruppennützig wurden 12 % der Studienprojekte eingestuft. Sie lassen unmittelbar nach Studienabschluss oder nach wenigen weiteren Studien ein Nutzenpotenzial für Personen mit den gleichen demographischen und klinischen Merkmalen wie die Studienteilnehmer erwarten. 42 % der Ethikanträge bezogen sich auf fremdnützige Studienvorhaben mit Nutzenchancen für die Heilkunde und/oder medizinische Wissenschaft. Das Risiko eines mehr als geringfügigen Eigenschadens wurde bei 53 % der Studien identifiziert. Die Analyse der jeweiligen Nutzenchancen und Schadenrisiken führte bei insgesamt 33 der 206 Studien (16 %) zu einem negativen Ergebnis: Im Urteil der nachträglich durchgeführten Bewertung übertreffen die Nutzenchancen nicht die Schadenrisiken. Studien mit einem mehr als geringfügigen Eigenschadenpotenzial sowie nicht-eigennützige Studien weisen besonders häufig eine negative Gesamtbilanz auf. Eine Prozeduralisierung der Analyse von Chancen und Risiken kann die Transparenz vorgenommener Analyse- und Vergleichsprozesse steigern. Die Kommunikation zwischen Forschenden und Ethikkommissionen sowie unter Ethikkommissionsmitgliedern bei strittigen Studienvorhaben wird erleichtert, die Standardisierung und Harmonisierung der Beratungsabläufe der Ethikkommissionen unterstützt. (shrink)

The principle of clinical equipoise has been variously characterized by ethicists and clinicians as fundamentally flawed, a myth, and even a moral balm. Yet, the principle continues to be treated as the de facto gold standard for conducting randomized control trials in an ethical manner. Why do we hold on to clinical equipoise, despite its shortcomings being widely known and well-advertised? This paper reviews the most important arguments criticizing clinical equipoise as well as what the most prominent proposed alternatives are. (...) In the process, it evaluates the justification for continuing to use clinical equipoise as the gold standard for randomized control trials. (shrink)

The foundations of research ethics are riven with fault lines emanating from a fear that if research is too closely connected to weighty social purposes an imperative to advance the common good through research will justify abrogating the rights and welfare of study participants. The result is an impoverished conception of the nature of research, an incomplete focus on actors who bear important moral responsibilities, and a system of ethics and oversight highly attuned to the dangers of research but largely (...) silent about threats of ineffective, inefficient, and inequitable medical practices and health systems. -/- In For the Common Good: Philosophical Foundations of Research Ethics, Alex John London defends a conception of the common good that grounds a moral imperative with two requirements. The first is to promote research that generates the information necessary to enable key social institutions to effectively, efficiently, and equitably safeguard the basic interests of individuals. The second is to ensure that research is organized as a voluntary scheme of social cooperation that respects its various contributors' moral claims to be treated as free and equal. Connecting research to the goals of a just social order grounds a framework for assessing and managing research risk that reconciles these requirements and justifies key oversight practices in non-paternalistic terms. Reconceiving research ethics as resolving coordination problems and providing credible assurance that these requirements are being met expands the issues and actors that fall within the purview of the field and provides the foundation for a more unified and coherent approach to domestic and international research. -/- This is an open access title available under the terms of a CC BY-NC-ND 4.0 license. It is free to read at Oxford Scholarship Online and offered as a free PDF download from OUP and selected open access locations. (shrink)

Research involving children or other incompetent subjects who are deemed unable to provide informed consent is complex, particularly in the case of research that does not directly benefit the research subjects themselves. The Helsinki Declaration, the World Medical Association's landmark document for research ethics, therefore states that incompetent research subjects must not be included in such research unless it entails only minimal risk and minimal burden. In this paper, we argue that now that research in these groups is expected to (...) expand, this undifferentiated minimal risk and burden requirement does not suffice any more. In the upcoming revision of the Declaration, the paragraph at stake should be refined in such a way that it is not unnecessarily restrictive or more permissive than can be ethically justified. Our first recommendation is to stimulate research ethics committees to identify more accurately those risks and burdens that the research subjects must undergo solely for research purposes by distinguishing between two types of study procedures instead of between two types of studies. Our second recommendation is to allow for exceptions to the minimal risk and burden requirement in cases of exceptionally valuable studies that involve subjects who can give their assent to participate in the study and that involve at most a minor increase over minimal risk and/or burden. (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)

Earlier in the pages of this journal (p 481), Wendler and Miller offered the "net risks test" as an alternative approach to the ethical analysis of benefits and harms in research. They have been vocal critics of the dominant view of benefit-harm analysis in research ethics, which encompasses core concepts of duty of care, clinical equipoise and component analysis. They had been challenged to come up with a viable alternative to component analysis which meets five criteria. The alternative must (1) (...) protect research subjects; (2) allow clinical research to proceed; (3) explain how physicians may offer trial enrolment to their patients; (4) address the challenges posed by research containing a mixture of interventions and (5) define ethical standards according to which the risks and potential benefits of research may be consistently evaluated. This response argues that the net risks test meets none of these criteria and concludes that it is not a viable alternative to component analysis. (shrink)

SUPPORT, a study involving approximately 1,300 premature infants who were randomly assigned to treatment protocols that differed in whether they offered higher or lower levels of oxygen saturation, was purportedly an example of comparative effectiveness research performed in the intensive care unit. However, SUPPORT became highly controversial. One source of controversy involved the proper determination of “reasonably foreseeable risks.” Commentators debated whether randomization to contrasting restrictive strategies that are within existing standard‐of‐care treatments imposed additional “reasonably foreseeable risks” greater than what (...) study participants would have received outside of the research. A second controversial issue had to do with disclosures in informed consent documents. This article explores these issues.We argue that randomization to contrasting restrictive interventions lying at the outer ends of “standard‐of‐care” practices differs in important ways from unrestricted “standard‐of‐care” practices available outside of a proposed study; that research involving such randomization might pose additional “reasonably foreseeable risks” from what occurs in “standard‐of‐care” practices; and that for trials whose study designs are similar to the SUPPORT study, respect for persons requires the disclosure of information about the nature of the experimental procedures and their risks. (shrink)

Hastings Center Report, Volume 52, Issue 5, Page 32-42, September–October 2022.

Risks and burdens in the study participation, as well as an adequate risk-benefit balance, are key concepts for the evaluation of clinical studies by research ethics committees. An adequate assessment and continuous monitoring to ensure compliance of risks and burdens in clinical trials have long been described as a central task in research ethics. However, there is currently no uniform and solid theoretical approach to risk assessment by RECs. Regulatory standards of research ethics such as the Declaration of Helsinki provide (...) only minimal guidance on how risk decisions are considered. Due to discrepancies in the existing literature and guidance documents, adequate risk assessment by RECs remains to be elusive. In this article, we address current definitions of risk and present our own concept of aggregate risk definition. Moreover, we highlight the concept of benefit, the standard of reasonableness with respect to ethics literature and different approaches of risk-benefit assessment. In order to present a comprehensive theoretical approach of risk assessment by RECs, further understanding of the definitions of risk may improve adequate decision-making tasks by RECs. To improve the process of risk assessment by RECs, a dynamic framework will be illustrated, showing step-by-step risk assessment functions. This approach may be a promising tool to ensure adequacy in risk assessment by RECs. (shrink)

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

The protection of human subjects in biomedical research relies on two principal mechanisms: assessing and comparing the risks and potential benefits of proposed research, and obtaining potential subjects' informed consent. While these have been discussed extensively in the literature, no attention has been paid to whether the processes should be different when the objective of an experimental biomedical intervention is to improve individual appearance, performance, or capability rather than to prevent, cure, or mitigate disease . This essay examines this question (...) in order to ensure that subjects in biomedical enhancement research receive adequate protection. (shrink)

There are two critical steps in determining whether a medical experiment involving human subjects can be conducted in an ethical manner: assessing risks and potential benefits and obtaining potential subjects’ informed consent. Although an extensive literature on both of these aspects exists, virtually nothing has been written about human experimentation for which the objective is not to prevent, cure, or mitigate a disease or condition, but to enhance human capabilities. One exception is a 2004 article by Rebecca Dresser on preimplantation (...) genetic modification — one of the most controversial enhancement technologies — in which she states, “Under existing research ethics principles, it would be unethical for investigators to perform modifications exposing embryos expected to develop into healthy children to significant risk in exchange for a possible physical or mental enhancement.” But Dresser does not explain why such an experiment would be unethical under existing principles, and her conclusion is not self-evident. (shrink)

Medical ethics assumes a clear boundary between clinical research and clinical medicine: one produces knowledge for the benefit of future patients, while the other provides optimal care to individuals right now. It also assumes that the two cannot be integrated without sacrificing the needs of the current patient to those of future patients. But integration could allow us to provide better care to everyone, now and in the future.

It is widely agreed that medical researchers who conduct studies in low- and middle-income countries (LMICs) are morally required to ensure that their research benefits the broader host community, not only the subjects. The justification for this moral requirement has not been adequately examined. Most attempts to justify this requirement focus on researchers' interaction with the community as a whole, not on their relationship with their subjects. This paper argues that in some cases, research must benefit the broader host community (...) for researchers to treat subjects and prospective subjects ethically. If research presents substantial net risks to subjects, researchers can ethically ask LMIC citizens to participate only if people in LMICs, normally including people in the host community, stand to benefit. (shrink)

If, as is alleged, challenge trials of vaccines against COVID-19 are likely to save thousands of lives and vastly diminish the economic and social harms of the pandemic while subjecting volunteers to risks that are comparable to kidney donation, then it would seem that the only sensible objection to such trials would be to deny that they have low risks or can be expected to have immense benefits. This essay searches for a philosophical rationale for rejecting challenge trials while supposing (...) that they have huge benefits and relatively low risks. Although it finds some force in objections to challenge trials grounded in the obligations of researchers to limit the harms imposed on some individuals for the benefit of others, it argues that there is no compelling objection to challenge trials of vaccines for COVID-19—if they have the benefits and risks that have been claimed. (shrink)

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

Risk and benefit assessment is one of the fundamental requirements in the ethical review of research involving human participants. As a result, researchers should evaluate and seek to minimize all foreseeable risks involved in their proposed research and members of research ethics committees should evaluate and balance the risks and potential benefits involved in each research proposal as a part of their ethical obligations regarding research protocols. However, current literature provides little detailed guidance on the specifics of how this balancing (...) process should occur. Consequently, this article provides some details of the process to balance risks and benefits in biomedical research and reminds members of research ethics committees of their responsibility to protect those who are vulnerable from exploitation in research projects. (shrink)

BackgroundThe Netherlands is one of the few countries where euthanasia is legal under strict conditions. This study investigates whether Dutch newspaper articles use the term ‘euthanasia’ according to the legal definition and determines what arguments for and against euthanasia they contain.MethodsWe did an electronic search of seven Dutch national newspapers between January 2009 and May 2010 and conducted a content analysis.ResultsOf the 284 articles containing the term ‘euthanasia’, 24% referred to practices outside the scope of the law, mostly relating to (...) the forgoing of life-prolonging treatments and assistance in suicide by others than physicians. Of the articles with euthanasia as the main topic, 36% described euthanasia in the context of a terminally ill patient, 24% for older persons, 16% for persons with dementia, and 9% for persons with a psychiatric disorder. The most frequent arguments for euthanasia included the importance of self-determination and the fact that euthanasia contributes to a good death. The most frequent arguments opposing euthanasia were that suffering should instead be alleviated by better care, that providing euthanasia can be disturbing, and that society should protect the vulnerable.ConclusionsOf the newspaper articles, 24% uses the term ‘euthanasia’ for practices that are outside the scope of the euthanasia law. Typically, the more unusual cases are discussed. This might lead to misunderstandings between citizens and physicians. Despite the Dutch legalisation of euthanasia, the debate about its acceptability and boundaries is ongoing and both sides of the debate are clearly represented. (shrink)

This thesis is a contribution to the ethical justification for clinical research with children. A research subject’s participation in a trial is usually justified, in part, by informed consent. Informed consent helps to uphold the moral principle of respect for persons. But children’s limited ability to make informed choices gives rise to a problem. It is unclear what, if anything, justifies their participation in research. Some research ethicists propose to resolve this problem by appealing to social utility, proxy consent, arguments (...) explaining why it is permissible to expose children to some harm, and an argument concerning the appropriate balance between research harms and benefits. I argue that each of these is a necessary part of the justification for research with children, but that the argument concerning harms and benefits is under-developed. It relies on the concept of minimal risk, but minimal risk is inadequately justified. I propose an interpretation of minimal risk. I defend the idea that minimal risk should be interpreted according to the risks of daily life. I reject the most prominent defense of daily life, which claims that daily risks are morally relevant because they replace, rather than add to, the risks a child would ordinarily face. Instead, I propose that these risks are part of a reasonable trade-off between personal safety and our ability to pursue meaningful lives. I then examine whose daily life should be captured in the concept of minimal risk. I reject arguments that minimal risk should refer to healthy children or the subjects of the research and propose instead that the referent should be children who are not unduly burdened by their lives. I argue that children are not unduly burdened when they fare well and defend the idea that children fare well when they possess sufficiently high degrees of the substantive goods of childhood. I conclude by analyzing a controversial case study using my interpretation of minimal risk. I draw on this case to argue that my interpretation offers clear guidance for research ethics review and contributes to a determination that is more plausible than its rivals. (shrink)