Pediatric research without the potential for clinical benefit is vital to improving pediatric medical care. This research also raises ethical concern and is regarded by courts and commentators as unethical. While at least 10 justifications have been proposed in response, all have fundamental limitations. This article describes and defends a new justification based on the fact that enrollment in clinical research offers children the opportunity to contribute to a valuable project. Contributing as children to valuable projects can benefit individuals in (...) two ways. First, individuals may come to ?embrace? the contributions they made as children. Second, contributing to valuable projects can lead to a better overall life. Because these potential benefits can outweigh small research risks, they provide a justification for pediatric research without the potential for clinical benefit, when it poses low risks and has the potential to benefit others in important ways. (shrink)

The concept of minimal risk has been used to regulate and limit participation by adolescents in clinical trials. It can be understood as setting an absolute standard of what risks are considered minimal or it can be interpreted as relative to the actual risks faced by members of the host community for the trial. While commentators have almost universally opposed a relative interpretation of the environmental risks faced by potential adolescent trial participants, we argue that the ethical concerns against the (...) relative standard may not be as convincing as these commentators believe. Our aim is to present the case for a relative standard of environmental risk in order to open a debate on this subject. We conclude by discussing how a relative standard of environmental risk could be defended in the specific case of an HIV vaccine trial among adolescents in South Africa. (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)

The precautionary principle is often invoked in relation to pregnant women and may be one of the underlying reasons for their continuous underrepresentation in clinical research. The principle is appealing, because potential fetal harm as a result of research participation is considered to be serious and irreversible. In our paper, we explore through conceptual analysis whether and if so how the precautionary principle should apply to pregnant women. We argue that the principle is a decision-making strategy underlying risk-benefit decisions in (...) clinical research, which can be applied to pregnant women. However, the current application is a strong one, leading to the promotion of absolute exclusion or, less often, absolute inclusion of pregnant women. In order to change this paralyzing situation, a shift toward weak precautionary thinking is necessary. Instead of automatic extreme precaution, a balance will be found between harms and potential benefits of including pregnant women in clinical research. (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)

Im Zuge einer Änderung des Arzneimittelgesetzes im November 2016 hat der Deutsche Bundestag beschlossen, dass gruppennützige Arzneimittelforschung mit nicht-einwilligungsfähigen Erwachsenen unter bestimmten Bedingungen erlaubt sein soll. Das entsprechende Gesetz wird voraussichtlich im Jahr 2020 in Kraft treten. Das ethische Problem dieser Forschung besteht darin, dass Personen, die nicht in der Lage sind, ihre Einwilligung in die Forschung zu erteilen, nicht vom medizinischen Fortschritt ausgeschlossen werden sollen. Der Gesetzgeber hat versucht, diesen Konflikt zu lösen, indem er die Zulässigkeit der gruppennützigen Forschung (...) mit nicht-einwilligungsfähigen Erwachsenen an die Voraussetzung geknüpft hat, dass Studienteilnehmer ihre Einwilligung zuvor in einer Probandenverfügung erteilen. Der Beitrag hat das Ziel, die neue Regelung zur gruppennützigen Forschung mit nicht-einwilligungsfähigen Erwachsenen aus ethischer Sicht zu bewerten. Die Frage, ob die Gesetzesänderung weitere Forschung ermöglichen wird, hängt wesentlich davon ab, ob man mit Blick auf Studien, die sowohl eigennützige als auch gruppennützige Maßnahmen umfassen, eine Gesamtbetrachtung oder eine Einzelbetrachtung dieser Studien vorzieht. In unserem Beitrag argumentieren wir für eine Einzelbetrachtung. Es wird weiterhin die Auffassung vertreten, dass die im Gesetzgebungsverfahren vorgeschlagene Probandenverfügung die Selbstbestimmung der Patienten fördern kann, wenn sie mit Blick auf die mit der Teilnahme verbundenen Eingriffe ein Mindestmaß an Bestimmtheit erreicht.Zusammenfassend wird die Auffassung vertreten, dass gruppennützige Forschung mit nicht-einwilligungsfähigen Erwachsenen trotz der genannten Bedenken unter bestimmten Bedingungen ethisch zulässig sein kann. In der Gesamtabwägung erscheint dabei die eindeutige Definition und strenge Beachtung der Bedingungen der EU-Verordnung 536/2014 mit Blick auf einen ethisch gerechtfertigten Einbezug von nicht-einwilligungsfähigen Erwachsenen in gruppennützige Forschung als besonders bedeutsam. (shrink)

Polskie przepisy prawne formułujące warunki dopuszczalności eksperymentu medycznego, a więc ipso facto wyznaczające jego granice, można różnorako interpretować, zwłaszcza w tym zakresie, w jakim określają wymagany dla przeprowadzenia eksperymentu bilans związanych z nim możliwych korzyści i szkód. W artykułach prawniczych komentujących te przepisy w zasadzie jednak brak prób systematycznego i (na tyle, na ile pozwala na to sam przedmiot analizy) ścisłego wyróżnienia tych interpretacji w języku tzw. teorii racjonalnego wyboru (rational choice theory), teorii szczególnie przydatnej w tym kontekście z uwagi (...) na jej rozbudowany aparat pojęciowy pozwalający badać różnorakie konfiguracje relacji między costs i benefits. Artykuł próbuje wypełnić tę lukę: wyróżnione w nim zostały różne interpretacje przepisów prawnych określających warunki dopuszczalności eksperymentu medycznego; interpretacje te zostały również poddane ocenie. (shrink)

The American Journal of Bioethics, Volume 11, Issue 6, Page 29-31, June 2011.

The American Journal of Bioethics, Volume 11, Issue 6, Page 27-29, June 2011.

The concept of minimal risk plays a key role in federal regulations on the protection of human research subjects. Although there has been considerable discussion of the meaning of minimal risk, the question of how this concept should be interpreted in research involving pregnant women and fetuses has not been addressed. This essay reviews the literature on minimal risk and argues for an interpretation of that concept in the context of research involving pregnant women and fetuses.

How should the definition of “minimal risk” in the federal research regulations be interpreted in regard to pregnant women and fetuses? Surprisingly, there has been little discussion of this question. There is, after all, a substantial amount of published work addressing the question of how “minimal risk” should be interpreted. Similarly, there is a large body of literature on the ethics of research involving pregnant women and fetuses, particularly maternal-fetal surgery. However, in neither of these bodies of work can one (...) find an analysis of minimal risk in regard to fetuses or pregnant women.The concept of minimal risk is defined in the regulations as follows:Minimal risk means that the probability and magnitude of harm or discomfort anticipated in the research are not greater in and of themselves than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests. (shrink)

The American Journal of Bioethics, Volume 11, Issue 6, Page 22-23, June 2011.

Non-beneficial paediatric research is vital to improving paediatric healthcare. Nevertheless, it is also ethically controversial. By definition, subjects of such studies are unable to give consent and they are exposed to risks only for the benefit of others, without obtaining any clinical benefits which could compensate those risks. This raises ethical concern that children participating in non-beneficial research are treated instrumentally; that they are reduced to mere instruments for the benefit of science and society. But this would make the research (...) incompatible with the widely endorsed principle of the primacy of the human subject, which stipulates that the interests of the participating individual should prevail over the interests of science and society. This paper deals with this conflict. It analyses solutions to this problem developed in the literature, and shows that they are unsuccessful. Finally, it offers a new idea of how to reconcile the conduct of non-beneficial paediatric research with the PP. The paper argues for a new formula of the PP, and shows that it implies a specific non-comparative definition of the minimal risk threshold. (shrink)

One of the fundamental ethical concerns about biomedical research is that it frequently exposes participants to risks for the benefit of others. To protect participants’ rights and interests in this context, research regulations and guidelines set out a mix of substantive and procedural requirements for research involving humans. Risk thresholds play an important role in formulating both types of requirements. First, risk thresholds serve to set upper risk limits in certain types of research. Second, risk thresholds serve to demarcate risk (...) categories that streamline risk-adapted systems of ethical oversight. But although risk thresholds play such an important role in research governance, there is a need both to better define the existing risk thresholds and to delineate new thresholds in order to develop more risk-adapted systems of research oversight. The present paper examines the existing minimal risk threshold and the surrounding debates with the goal of deriving a systematic approach to setting thresholds of research risk. (shrink)

The American Journal of Bioethics, Volume 11, Issue 6, Page 17-19, June 2011.

Society and social structures play an important role in the formation and evaluation of concepts and practices in clinical ethics. This is evident in the ways the authors in this issue explore a wide range of arguments and concepts in clinical ethics including moral distress and conscience based practice, phenomenological interview techniques and gender dysphoria, continuous deep sedation (CDS) at the end of life, the notion of patient expertise, ethically permissible medical billing practices, the notion of selfhood and patient centered (...) care in dementia patients, and the definition of minimal risk as used in research regulations. (shrink)

Informed consent to medical procedures tends to be construed in terms of principle-based ethics and one or other form of expected utility theory. These constructions leave problems created by imperfect communication; subjective distress and other emotions; imperfect knowledge and incomplete understanding; complexity, and previous experience or the lack of it. There is evidence that people giving consent to therapy or to research participation act intuitively and assess consequences holistically, being influenced more by the magnitude of outcomes than their probability. People (...) avoid decisions they may regret, but modern regret theory has received little attention in discussions of informed consent. This essay suggests ways in which regret may be acknowledged in the consent process and in the assessment of the information that is an intrinsic part of it. (shrink)

The American Journal of Bioethics, Volume 11, Issue 6, Page 23-25, June 2011.

The American Journal of Bioethics, Volume 12, Issue 1, Page 32-34, January 2012.

Bioethics is best viewed as both a second-order discipline and also part of public discourse. Since their goals differ, some bioethical activities are more usefully viewed as advancing public discourse than academic disciplines. For example, the “Universal Declaration on Bioethics and Human Rights” sponsored by the United Nations Educational, Scientific, and Cultural Organization seeks to promote ethical guidance on bioethical issues. From the vantage of philosophical ethics, it fails to rank or specify its stated principles, justify controversial principles, clarify key (...) terms, or say what is meant by calling potentially conflicting norms “foundational.” From the vantage of improving the public discourse about bioethical problems and seeking ethical solutions in the public arena, however, this document may have an important role. The goals and relations between bioethics as a second-order discipline and public discourse are explored. (shrink)

Introduction The bioethics literature reflects significant interest in and concern with the use of genetic and genomic information in various settings. Because psychiatric treatment and research raises unique ethical, legal, and social issues, we conducted a scoping review of the biomedical, bioethics, and psychology literature regarding the application of genetic and genomic tools to psychiatric disorders (as listed in the DSM-5) and two associated behaviors or symptoms to provide a more detailed overview of the state of the field. Objectives The (...) primary objective was to examine the available bioethics, biomedical, and psychology literature on applying genetic and genomic tools to psychiatric disorders (other than neurodevelopmental disorders) and two behaviors or symptoms sometimes associated with them (aggression or violence and suicidality) to identify the disorders to which these tools have been applied, the contexts in or purposes for which they have been applied, the ethical, legal, or social concerns associated with those uses, and proposed recommendations for mitigating those concerns. Methods We used Arksey and O’Malley’s scoping review framework: (1) identify the research question; (2) identify relevant studies; (3) select studies; (4) chart the data; and (5) collate, summarize, and report results (2005). We relied on Levac et al. to inform our application of the framework (2010). The PRISMA extension for scoping reviews checklist informed our reporting (2018). We searched three electronic databases MEDLINE (PubMed), Embase, and PsycInfo (EbscoHost) for peer-reviewed journal articles in English to identify relevant literature. One author screened the initial results and additional screening was done in consultation with other authors. A data extraction form using DSM-5 diagnostic categories (excluding neurodevelopmental disorders) was developed and two authors independently each reviewed approximately half of the articles. Inter-rater reliability was ensured by double-coding approximately 10% of the papers. An additional author independently coded 10% of the articles to audit the data. Results In 365 coded publications, we identified 15 DSM-5 diagnostic categories in addition to the two pre-selected behaviors or symptoms (aggression or violence and suicidality) to which genetic or genomic tools have been applied. We identified 11 settings in or purposes for which these tools were applied. Twenty-two types of ethical, legal, or social concerns associated with the application of genetic or genomic tools to these disorders or behaviors/symptoms were identified along with 13 practices or policies that could mitigate these concerns. Conclusion Genetic and genomic tools have been applied to a wide range of psychiatric disorders. These raise a range of ethical, legal, and social concerns. Additional research is warranted to better understand the concerns and effective ways to address them. Advancing the literature to identify relevant ethical, legal, or social concerns and solutions to those problems likely requires greater attention to specific applications of genetic or genomic tools to particular psychiatric disorders and associated behaviors/symptoms as well as broad stakeholder engagement. (shrink)

The breadth of themes addressed in this issue of the Journal of Medicine and Philosophy is striking. These articles brim with some of the most foundational questions one can ask in bioethics and the philosophy of medicine: Under what circumstances might we risk some harm in pursuit of a greater good? In the setting of experimental therapies, how should we weigh the potential risk and benefit for an individual patient against the broader potential benefit realized for society as a whole? (...) How might we consistently differentiate health from pathology? Under what circumstances might we say that a human being has died? Does acknowledging particular things as good generate duties? Duties for whom and enforced by whom? These articles share a preoccupation with foundational questions that must be addressed in any sound bioethics curriculum, and they make clear that our answers to these questions are not simply theoretical but manifest in policy and in practice. (shrink)

The papers in this volume are largely about research ethics and cover questions of consent, reproduction, pediatric research, ethical codes, and clinical relationships. Half the papers have this common aspect: they are conservative—in the sense of supporting the standard, prevailing, or popular view—but they shift the focus—supporting the standard views in terms of moral factors generally neglected by the literature. The volume provides a diverse set of papers for the reader: variously addressing abstract and concrete problems from within different philosophical (...) traditions. (shrink)

This article reviews four areas of pediatric research in which we have identified questionable levels of allowable risk, exceeding those foreseen by the Commission. They are the following: the categorization of increasingly risky interventions as minimal risk in a variety of protocols; the increasing number of applications for federal panel review of research not otherwise approvable because of higher projected risk levels; research on asymptomatic at risk children; and the inclusion of children and adolescents in placebo-controlled trials for participants of (...) all ages without performing subgroup analysis. While embracing the imperative to include children in research is an encouraging step towards providing the pediatric population with effective medical care and finally eradicating the therapeutic orphan, we must ensure that this research does not become overly permissive. (shrink)

United States federal regulations for pediatric research with no prospect of direct benefit restrict institutional review board (IRB) approval to procedures presenting: 1) no more than "minimal risk" (§ 45CFR46.404); or 2) no more than a "minor increase over minimal risk" if the research is commensurate with the subjects' previous or expected experiences and intended to gain vitally important information about the child's disorder or condition (§ 45CFR46.406) (DHHS 2001). During the 25 years since their adoption, these regulations have helped (...) IRBs balance subject protections with the pursuit of scientific knowledge to advance children's welfare. At the same time, inconsistency in IRB application of these regulations to pediatric protocols has been widespread, in part because of the ambiguity of the regulatory language. During the past decade, three federally-charged committees have addressed these ambiguities: 1) the National Human Research Protections Advisory Committee (NHRPAC) (Washington, DC), 2) the Institute of Medicine (IOM) Committee on the Ethical Conduct of Clinical Research Involving Children (Washington, DC); and 3) the United States Department of Health and Human Services Secretary's Advisory Committee for Human Research Protections (SACHRP) (Washington, DC). The committees have reached similar conclusions on interpretation of language within regulations § § 45CFR46.404 and 406; these conclusions are remarkably consistent with recent international recommendations and those of the original National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research (1977) report from which current regulations are based. Drawing on the committees' public reports, this article identifies the ethical issues posed by ambiguities in regulatory language, summarizes the committees' deliberations, and calls for a national consensus on recommended criteria. (shrink)

Boston Medical Center/Boston University Medical Campus recently reduced certain requirements for human subjects research where this could be done without adversely affecting the rights and welfare of participants, in anticipation of changes in the Final Common Rule. Modifications affected exempt and expedited categories, approval periods, ceding review, Quality Improvement/Quality Assessment activities, and some requirements for pregnant women, prisoners, and children. This case study may assist other institutions in responding to the Final Common Rule.

This article examines international and European regulations on research involving prisoners for consensus, differences, and their consequences, and offers a critical evaluation of the various approaches. Agreement exists that prisoners are at risk of coercion, which might interfere with their ability to provide voluntary informed consent to research. Controversy exists about the magnitude of this risk and the consequences that should follow from this risk. Two strategies are proposed for a method of protecting prisoners that does not lead to discrimination: (...) first, more caution to assure non-coerced consent and second, restrictions on the type of research. Most regulations stress the importance of the principle of equivalence of healthcare in places of detention as part of an efficient protection against research risks and discrimination. All the presented approaches have shortcomings. While 'over-use' of prisoners for research as compared to the general population is ethically unjustified, not granting prisoners access to studies beneficial to their own health because of over-strict regulations is equally unjustified. A middle solution should be preferred, one that grants a minimum of protection together with the lowest possible barriers. Research that does not entail a direct benefit for the individual detainee should be restricted to types of research that have a benefit for detainees as a group and that are of low risk. What will ultimately protect prisoners best, while producing the greatest benefit for them, is access to the same healthcare available to members of the community including research as a true option. (shrink)

The involvement of children in non-beneficial clinical research is extremely important for improving pediatric care, but its ethical acceptability is still disputed. Therefore, various pro-research justifications have been proposed throughout the years. The present essay aims at contributing to the on-going discussion surrounding children’s participation in non-beneficial clinical research. Building on Wendler’s ‘contribution to a valuable project’ justification, but going beyond a risk/benefit analysis, it articulates a pro-research argument which appeals to a phenomenological view on the body and vulnerability. It (...) is claimed that children’s bodies are not mere physical objects, but body-subjects due to which children, as persons, can contribute to research that may hold no direct clinical benefit to them even before they can give informed consent. (shrink)

There is an international consensus that medical research involving humans should only be undertaken in accordance with ethical principles. Paradoxically though, there is no consensus over the kinds of activities that constitute research and should be subject to review. In the UK and elsewhere, research requiring review is distinguished from clinical audit. Unfortunately the two activities are not always easy to differentiate from one another. Moreover, as the volume of audit increases and becomes more formal in response to the demand (...) for evidence-based practice in medicine, the overlap between research and audit grows more acute. Arguably, similar ethical standards and systems for ensuring that those standards are met should be applied regardless of whether or not a project is classified as research or audit. At a time when the research ethics review system in the UK is undergoing significant reform it is important that the opportunity is not missed to address the longstanding research-audit problem. We discuss suggestions for further reform that addresses this issue. (shrink)

Minimal risk is a central concept in the ethical analysis of research with children. It is defined as the risks “. . . ordinarily encountered in daily life . . . .” But the question arises: who is the referent for minimal risk? Commentators in the research ethics literature often answer this question by endorsing one of two possible interpretations: the uniform interpretation or the relative interpretation of minimal risk. We argue that describing the debate over minimal risk as a (...) disagreement between the uniform and the relative interpretation impedes progress on the identification of a justifiable referent for minimal risk. There are two main problems with this approach: constructing the debate over minimal risk as a disagreement between a uniform and a relative interpretation misconstrues the main difference between competing interpretations and neither the uniform nor the relative interpretation identifies one unique and consistent group of children as the referent for minimal risk. We conclude that progress on the debate over minimal risk requires that we abandon the uniform and relative interpretations and address the main moral problem at stake: whether healthy children or the subjects of the research should be the referent for minimal risk. (shrink)

With the delegation of ethical checking mechanisms to the institutional review boards (IRBs), flexible interpretations of overarching research ethics principles differed across scientific and cultural settings. This article is a comparative case study of ethical frameworks for social research in the Philippines and Taiwan. Justifications in choosing the two cases preponderantly focused on data trends regarding research and development (R&D) policy and practice. This article compared the elements observed in the two frameworks, specifically in terms of: national regulations, curricular requirements, (...) procedures for IRB review application, and other arrangements. Findings revealed that the Philippine academe enjoys relative autonomy or described as more fragmented, unlike Taiwan institutions that strictly follow centralized and country-wide standardization. The intensification of research ethics in Taiwan did not, however, hamper R&D efforts. On the contrary, the Taiwan model may have strengthened the current research ecosystem and bolstered confidence in the different sectors, thus generating multi-sectoral funding and collaborations. (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)