Pediatric oncology has a strong research culture. Most pediatric oncologists are investigators, involved in clinical care as well as research. As a result, a remarkable proportion of children with cancer enrolls in a trial during treatment. This paper discusses the ethical consequences of the unprecedented integration of research and care in pediatric oncology from the perspective of parents and physicians. An empirical ethical approach, combining (1) a narrative review of (primarily) qualitative studies on parents' and physicians' experiences of the pediatric (...) oncology research practice, and (2) comparison of these experiences with existing theoretical ethical concepts about (pediatric) research. The use of empirical evidence enriches these concepts by taking into account the peculiarities that ethical challenges pose in practice. Analysis of the 22 studies reviewed revealed that the integration of research and care has consequences for the informed consent process, the promotion of the child's best interests, and the role of the physician (doctor vs. scientist). True consent to research is difficult to achieve due to the complexity of research protocols, emotional stress and parents' dependency on their child's physician. Parents' role is to promote their child's best interests, also when they are asked to consider enrolling their child in a trial. Parents are almost never in equipoise on trial participation, which leaves them with the agonizing situation of wanting to do what is best for their child, while being fearful of making the wrong decision. Furthermore, a therapeutic misconception endangers correct assessment of participation, making parents inaccurately attribute therapeutic intent to research procedures. Physicians prefer the perspective of a therapist over a researcher. Consequently they may truly believe that in the research setting they promote the child's best interests, which maintains the existence of a therapeutic misconception between them and parents. Due to the integration of research and care, their different ethical perspectives become intertwined in the daily practice of pediatric oncology. Increasing awareness of what this means for the communication between parents and physicians is essential. Future research should focus on efforts that overcome the problems that the synchronicity of research and care evokes. (shrink)

This book uses the phenomenological interpretive approach of Paul Ricoeur to shed new light on New Testament eschatological expectation. Peter C. de Vries argues for a metaphorical reading of the apocalyptic discourse of Mark 13, based upon neither the author’s intention nor the reader’s reception but latent meaning present in the text itself.

### ­ In Who shall go first? A multicriteria approach to patient selection for first clinical trials of cardiac xenotransplantation, Kögel et al recommend the inclusion of patients who (1) have a (high) medical need for an allograft, (2) have the capacity to benefit from a xenograft, (3) have a ‘real’ choice between enrolment in a first-in-human clinical trial and an alternative life-sustaining treatment option and (4) have no clear record of previous non-compliance.1 As the authors discuss, patient selection must (...) promote the goal of gaining reliable and valid knowledge about the risks and benefits of cardiac xenotransplantation. While the four criteria outlined above certainly promote this goal, we argue it is crucial to add a fifth criterion emphasising the need to include diverse populations, particularly regarding sex, age, ethnicity and socioeconomic background.i In this commentary, we present two arguments for our claim and discuss the impact of neglecting diversity from the first trials on. ### The scientific rationale for including diverse populations First, including diverse populations in the first clinical trials of cardiac xenotransplantation enhances the scientific value of the data by assessing safety and efficacy among various populations. Treatment response can differ among patient (sub)groups as a result of genetic, physiological and socioeconomic factors.2 By including diverse populations from the first trials on, researchers can identify these …. (shrink)

Pain and posttraumatic stress disorder frequently co-occur but underlying mechanisms are not clear. This study aimed to test the development and maintenance of pain and PTSD symptom clusters, i.e., intrusions, avoidance, and hyperarousal. The longitudinal study included 216 adults with burns. PTSD symptom clusters, indexed by the Impact of Event Scale-Revised, and pain, using a graphic numerical rating scale, were measured during hospitalization, 3 and 6 months post-burn. Cross-lagged panel analysis was used to test the relationships between pain and PTSD (...) symptom clusters. Cross-lagged results showed that in-hospital intrusions predicted pain and avoidance 3 months post-burn. In-hospital pain predicted intrusions and avoidance 3 months post-burn and a trend was found for hyperarousal. In the second wave, intrusions predicted pain and hyperarousal. Pain predicted hyperarousal. This study provides support for an entangled relationship between pain and PTSD symptoms, and particularly subscribes the role of intrusions in this bidirectional relationship. To a lesser extent, hyperarousal was unidirectionally related to pain. These results may subscribe the driving role of PTSD, particularly intrusions, which partly supports the Perpetual Avoidance Model. (shrink)

In their article, Luchtenberg and colleagues give voice to the opinions of young people on participation in clinical trials (Luchtenberg et al. 2015). Over time, it has become indisputable that chi...

BackgroundFor many decades, the debate on children’s competence to give informed consent in medical settings concentrated on ethical and legal aspects, with little empirical underpinnings. Recently, data from empirical research became available to advance the discussion. It was shown that children’s competence to consent to clinical research could be accurately assessed by the modified MacArthur Competence Assessment Tool for Clinical Research. Age limits for children to be deemed competent to decide on research participation have been studied: generally children of 11.2 (...) years and above were decision-making competent, while children of 9.6 years and younger were not. Age was pointed out to be the key determining factor in children’s competence. In this article we reflect on policy implications of these findings, considering legal, ethical, developmental and clinical perspectives.DiscussionAlthough assessment of children’s competence has a normative character, ethics, law and clinical practice can benefit from research data. The findings may help to do justice to the capacities children possess and challenges they may face when deciding about treatment and research options. We discuss advantages and drawbacks of standardized competence assessment in children on a case-by-case basis compared to application of a fixed age limit, and conclude that a selective implementation of case-by-case competence assessment in specific populations is preferable. We recommend the implementation of age limits based on empirical evidence. Furthermore, we elaborate on a suitable model for informed consent involving children and parents that would do justice to developmental aspects of children and the specific characteristics of the parent-child dyad.SummaryPrevious research outcomes showed that children’s medical decision-making capacities could be operationalized into a standardized assessment instrument. Recommendations for policies include a dual consent procedure, including both child as well as parents, for children from the age of 12 until they reach majority. For children between 10 and 12 years of age, and in case of children older than 12 years in special research populations of mentally compromised patients, we suggest a case-by-case assessment of children’s competence to consent. Since such a dual consent procedure is fundamentally different from a procedure of parental permission and child assent, and would imply a considerable shift regarding some current legislations, practical implications are elaborated. (shrink)

It is not unusual for researchers to complain about institutional review board (IRB) oversight, but social scientists have a unique set of objections to the work of ethics committees. In an effort to better understand the problems associated with ethics review of social, behavioral, and economic sciences (SBES) research, this article examines 3 different aspects of research ethics committees: (a) the composition of review boards; (b) the guidelines used by these boards to review SBES - and in particular, behavioral health (...) - research; and (c) the actual deliberations of IRBs. The article concludes with recommendations for changes in the review process and with suggestions for filling the gaps in knowledge about the way IRBs work. (shrink)

Psychiatric disorders present distinct clinical challenges which are partly attributable to their multifactorial aetiology and the absence of laboratory tests that can be used to confirm diagnosis or predict risk. Psychiatric disorders are highly heritable, but also polygenic, with genetic risk conferred by interactions between thousands of variants of small effect that can be summarized in a polygenic risk score. We discuss four areas in which the use of polygenic risk scores in psychiatric research and clinical contexts could have ethical (...) implications. First, there is concern that clinical use of polygenic risk scores may exacerbate existing health inequities. Second, research findings regarding polygenic risk could be misinterpreted in stigmatising or discriminatory ways. Third, there are concerns associated with testing minors as well as eugenics concerns elicited by prenatal polygenic risk testing. Fourth, potential challenges that could arise with the feedback and interpretation of high polygenic risk for a psychiatric disorder would require consideration. While there would be extensive overlap with the challenges of feeding back genetic findings in general, the potential clinical use of polygenic risk scoring warrants discussion in its own right, given the recency of this possibility. To this end, we discuss how lay interpretations of risk and genetic information could intersect. Consideration of these factors would be necessary for ensuring effective and constructive communication and interpretation of polygenic risk information which, in turn, could have implications for the uptake of any therapeutic recommendations. Recent advances in polygenic risk scoring have major implications for its clinical potential, however, care should be taken to ensure that communication of polygenic risk does not feed into problematic assumptions regarding mental disorders or support reductive interpretations. (shrink)

Competition among scientists for funding, positions and prestige, among other things, is often seen as a salutary driving force in U.S. science. Its effects on scientists, their work and their relationships are seldom considered. Focus-group discussions with 51 mid- and early-career scientists, on which this study is based, reveal a dark side of competition in science. According to these scientists, competition contributes to strategic game-playing in science, a decline in free and open sharing of information and methods, sabotage of others’ (...) ability to use one’s work, interference with peer-review processes, deformation of relationships, and careless or questionable research conduct. When competition is pervasive, such effects may jeopardize the progress, efficiency and integrity of science. (shrink)

Learning from a text–picture multimedia document is particularly effective if learners can link information within the text and across the verbal and the pictorial representations. The ability to create a mental model successfully and include those implicit links is related to the ability to generate inferences. Text processing research has found that text cohesion facilitates the generation of inferences, and thus text comprehension for learners with poor prior knowledge or reading abilities, but is detrimental for learners with good prior knowledge (...) or reading abilities. Moreover, multimedia research has found a positive effect from adding visual representations to text information, particularly when implementing signaling, which consists of verbal or visual cues designed to guide attention to the pictorial representation of relevant information. We expected that, as with text-only documents, struggling readers would benefit from high text cohesion and that signaling would foster inference generation as well. Further, we hypothesized that better learning outcomes would be observed when text cohesion was low and signaling was present. Our first experimental study investigated the effect of those two factors on three levels of comprehension. Participants were adolescents in prevocational schools, where some of the students are struggling readers. The results showed a trend in favor of high cohesion, but with no significant effect, a significant positive effect of cross-representational signaling on comprehension from local inferences, and no interaction effect. A second experiment focused on signaling only and attention toward the picture, with collection of eye-tracking data in addition to measures of offline comprehension. As this study was conducted with university students, who are expected to have higher reading abilities and thus are less likely to benefit from high cohesion, the material was presented in its low cohesive version. The results showed no effect of conditions on comprehension performances but confirmed differences in processing behaviors. Participants allocated more attention to the pictorial representation in the CRS condition than in the no signaling condition. (shrink)

This article discusses the relation between empirical and normative approaches in bioethics. The issue of dwarf tossing, while admittedly unusual, is chosen as a point of departure because it challenges the reader to look with fresh eyes upon several central bioethical themes, including human dignity, autonomy, and the protection of vulnerable people. After an overview of current approaches to the integration of empirical and normative ethics, we consider five ways that the empirical and normative can be brought together to speak (...) to the problem of dwarf tossing: prescriptive applied ethics, theoretical ethics, critical applied ethics, particularist ethics and integrated empirical ethics. We defend a position of critical applied ethics that allows for a two-way relation between empirical and normative theories. Against efforts fully to integrate the normative and the empirical into one synthesis, we propose that the two should stand in tension and relation to one another. The approach we endorse acknowledges that a social practice can and should be judged both by the gathering of empirical data and by normative ethics. Critical applied ethics uses a five stage process that includes: (a) determination of the problem, (b) description of the problem, (c) empirical study of effects and alternatives, (d) normative weighing and (e) evaluation of the effects of a decision. In each stage, we explore the perspective from both the empirical (sociological) and the normative ethical point of view. We conclude by applying our five-stage critical applied ethics to the example of dwarf tossing. (shrink)

Background Genuine uncertainty on superiority of one intervention over the other is called equipoise. Physician-investigators in randomized controlled trials need equipoise at least in studies with more than minimal risks. Ideally, this equipoise is also present in patient-participants. In pediatrics, data on equipoise are lacking. We hypothesize that 1) lack of equipoise at enrolment among parents may reduce recruitment; 2) lack of equipoise during participation may reduce retention in patients assigned to a less favoured treatment-strategy. Methods We compared preferences of (...) parents/patients at enrolment, documented by a questionnaire, with preferences developed during follow-up by an interview-study to investigate equipoise of child-participants and parents in the BeSt-for-Kids-study. This trial in new-onset Juvenile Idiopathic Arthritis-patients consists of three strategies. One strategy comprises initial treatment with a biological disease-modifying-antirheumatic-drug, currently not standard-of-care. Semi-structured interviews were conducted with 23 parents and 7 patients, median 11 months after enrolment. Results Initially most parents and children were not in equipoise. Parents/patients who refused participation, regularly declined due to specific preferences. Many participating families preferred the biological-first-strategy. They participated to have a chance for this initial treatment, and would even consider stopping trial-participation when not randomized for it. Their conviction of superiority of the biological-first strategy was based on knowledge from internet and close relations. According to four parents, the physician-investigator preferred the biological-first-strategy, but the majority stated that she had no preferred strategy. In phase 2, preferences tended to change to the treatment actually received. Conclusions Lack of equipoise during enrolment did not reduce study recruitment, mainly due to the fact that preferred treatment was only available within the study. Still, when developing a trial it is important to evaluate whether the physicians’ research question is in line with preferences of the patient-group. By exploring so-called ‘informed patient-group’-equipoise, successful recruitment may be enhanced and bias avoided. In our study, lack of equipoise during trial-participation did not reduce retention in those assigned to a less favoured option. We observed a change for preference towards treatment actually received, possibly explained by comparable outcomes in all three arms. (shrink)

The review by De Bie et al. (2023) provides an overview of the current ethical literature on artificial womb technology (AWT). Two characteristics stand out, and provide the basis for our commentar...

For decades, the discussion on children’s competence to consent to medical issues has concentrated around normative concerns, with little progress in clinical practices. Decision-making competence is an important condition in the informed consent model. In pediatrics, clinicians need to strike a proper balance in order to both protect children’s interests when they are not fully able to do so themselves and to respect their autonomy when they are. Children’s competence to consent, however, is currently not assessed in a standardized way. (...) Moreover, the correlation between competence to give informed consent and age in children has never been systematically investigated, nor do we know which factors exactly contribute to children’s competence. (shrink)

The modern critical approach to things hagiographical still wavers when it comes to taking leave of twelve lines of iambic invective, branded with wonderful delicacy of touch on the saintly foreheads of two Palestinian brothers, Theodore and Theophanes, the so-called “Graptoi”. Barry Baldwin, noting that C.A. Trypanis, unlike the great B. Bury and others, was inclined to disbelieve the story, could not help expressing the hope that it was true (An Anthology of Byzantine Poetry, Amsterdam 1985, pp. 142–3). It is (...) of course only one of the many stories concocted by iconodule propaganda. The central question has to be formulated in more general terms: how is history made? History here primarily in the sense of the construction of the past by the Byzantines themselves, was embodied in historical narratives moving between hagiography and historiography. Trying to lay bare the basis and elements of such constructs will always remain a major task of critical historical scholarship. (shrink)

Background The scrutiny surrounding gender-affirming medical treatment (GAMT) for youth has increased, particularly concerning the limited evidence on long-term treatment outcomes. The Standards of Care 8 by the World Professional Association for Transgender Health addresses this by outlining research evidence suggesting “effective” outcomes of GAMT for adolescents. However, claims concerning what are considered “effective” outcomes of GAMT for adolescents remain implicit, requiring further reflection. Methods Using trans negativity as a theoretical lens, we conducted a theory-informed reflexive thematic analysis of the (...) literature cited in the “Research Evidence” section of the SOC8 Adolescents chapter. We selected 16 articles that used quantitative measures to assess GAMT outcomes for youth, examining how “effective” outcomes were framed and interpreted to uncover implicit and explicit normative assumptions within the evidence base. Results A total of 44 different measures were used to assess GAMT outcomes for youth, covering physical, psychological, and psychosocial constructs. We identified four main themes regarding the normative assumptions of “effective” treatment outcomes: (1) doing bad: experiencing distress before GAMT, (2) moving toward a static gender identity and binary presentation, (3) doing better: overall improvement after GAMT, and (4) the absence of regret. These themes reveal implicit norms about what GAMT for youth should achieve, with improvement being the benchmark for “effectiveness.” Discussion We critically reflect on these themes through the lens of trans negativity to challenge what constitutes “effective” GAMT outcomes for youth. We explore how improvement justifies GAMT for youth and address the limitations of this notion. Conclusions We emphasize the need for an explicit discussion on the objectives of GAMT for adolescents. The linear narrative of improvement in GAMT for adolescents is limited and fails to capture the complexity of GAMT experiences. With currently no consensus on how the “effectiveness” of GAMT for adolescents is assessed, this article calls for participatory action research that centers the voices of young TGD individuals. (shrink)

Over the past three or four decades, the concept of medical ethics has changed from a limited set of standards to a broad field of debate and research. We define medical ethics as an arena of moral issues in medicine, rather than a specific discipline. This paper examines how the disciplines of health care ethics and health care law have developed and operated within this arena. Our framework highlights the aspects of jurisdiction and the assignment of responsibilities . This theoretical (...) framework prompted us to study definitions and changing responsibilities in order to describe the development and interaction of health care ethics and health law. We have opted for the context of the Dutch debate about end-of-life decisions as a relevant case study. We argue that the specific Dutch definition of euthanasia as ‘intentionally taking the life of another person by a physician, upon that person’s request’ can be seen as the result of the complex jurisdictional process. This illustrates the more general conclusion that the Dutch debate on end-of-life decisions and the development of the two disciplines must be understood in terms of mutual interaction. (shrink)

Over the past three or four decades, the concept of medical ethics has changed from a limited set of standards to a broad field of debate and research. We define medical ethics as an arena of moral issues in medicine, rather than a specific discipline. This paper examines how the disciplines of health care ethics and health care law have developed and operated within this arena. Our framework highlights the aspects of jurisdiction and the assignment of responsibilities. This theoretical framework (...) prompted us to study definitions and changing responsibilities in order to describe the development and interaction of health care ethics and health law. We have opted for the context of the Dutch debate about end-of-life decisions as a relevant case study. We argue that the specific Dutch definition of euthanasia as ‘intentionally taking the life of another person by a physician, upon that person’s request’ can be seen as the result of the complex jurisdictional process. This illustrates the more general conclusion that the Dutch debate on end-of-life decisions and the development of the two disciplines must be understood in terms of mutual interaction. (shrink)

De Vries' mutation theory has not stood the test of time. The supposed mutations of Oenothera were in reality complex recombination phenomena, ultimately explicable in Mendelian terms, while instances of large-scale mutations were found wanting in other species. By 1915 the mutation theory had begun to lose its grip on the biological community; by de Vries' death in 1935 it was almost completely abandoned. Yet, as we have seen, during the first decade of the present century it achieved (...) an enormous popularity. As this paper has tried to suggest, one of the principal reasons for this was that de Vries' theory served as a banner around which a whole crowd of disaffected Darwinians or anti-Darwinians could rally. However, not all of those who favored de Vries did so for quite the same reasons. Underlying the multitude of views ran several common threads: a dissatisfaction with current Darwinian theory born out of misunderstanding natural selection, a general misunderstanding of the nature of species, and a prejudice against speculative, nontestable theories in biology.Supporters of de Vries were not the only opponents of Darwinism, nor was the mutation theory the only alternative to natural selection. In the early twentieth century a number of theories had been proposed to explain away the problems which Darwin had left unsolved. There was the idea of orthogenesis, championed by the American paleontologists Cope, Osborn and others; organic selection (or orthoplasy) was championed by M. M. Baldwin and C. Lloyd Morgan; there were the concepts of convergent evolution proposed by Hermann Friedmann, the theory of physiological selection by John George Romanes, and the concepts of reproductive divergence by H. M. Vernon. Virtually none of these men either accepted or were strong supporters of the de Vriesian theory, for each had his own particular ‘ism” to advocate as the major factor in evolution. The existence of a large number of such theories, each purporting to be the explanation, was characteristic of evolutionary theory at the turn of the century. It is to a large extent the emphasis on such fragmentary concepts that retarded development of the comprehensive theory of evolution which emerged in the 1920's and 1930's. For the historian, however, a study of these alternative theories is instructive in trying to understand the inherent difficulties which Dawwinian theory posed to biologists at the time. De Vries' mutation theory serves historically as a mirror to reflect the critical mood of a generation hostile to the theory of natural selection.It has often been claimed that it was impossible to understand the mechanism of natural selection until it could be placed in genetic and mathematical terms. It is certainly true that great strides have been made in population genetics and the treatment of evolutionary concepts with mathematical tools in the last forty years. But the very people who developed the genetical and mathematical approach to evolution were already convinced of the essential correctness of Darwinian theory before they started. Advances in an understanding of Mendelian heredity aided greatly in solving one important issue for evolutionists: the origin of variations. And the rigor with which selection acted could best be studied by observing changes in gene frequencies (calculated mathematically) over a number of generations. But as this paper has shown, two of the basic problems which biologists faced in evaluating Darwinian theory at the turn of the century-the nature of species, and the criteria of what constituted an acceptable explanation in biological science-could not be answered directly by mathematics. What mathematical and genetical theory did do was to help convince the skeptics of the validity of the Darwinian proposition.The change in explanatory criteria which many hailed as de Vries' most important contribution to evolutionary theory seems to have been part of a general emergence of twentieth-century biology from the domination of theorizers in the nineteenth. It also marked the emergence of America from the domination of biological, and particularly evolutionary, influence of Europeans. The change occurred in three areas: in the kinds of questions asked: testable versus non-testable; in the kind of data sought: quantitative versus qualitative; and in the kinds of theories proposed: analytical and reductive—the attempt to see complex processes in terms of simpler components-as opposed to synthetic and speculative. Although ultimately wrong in his idea, de Vries and his theories rode high on the wave of “experimentalism” which was the harbinger of a new era in evolutionary theory. (shrink)