EANM guidance document: dosimetry for first-in-human studies and early phase clinical trials.

The numbers of diagnostic and therapeutic nuclear medicine agents under investigation are rapidly increasing. Both novel emitters and novel carrier molecules require careful selection of measurement procedures. This document provides guidance relevant to dosimetry for first-in human and early phase clinical trials of such novel agents. The guideline includes a short introduction to different emitters and carrier molecules, followed by recommendations on the methods for activity measurement, pharmacokinetic analyses, as well as absorbed dose calculations and uncertainty analyses. The optimal use of preclinical information and studies involving diagnostic analogues is discussed. Good practice reporting is emphasised, and relevant dosimetry parameters and method descriptions to be included are listed. Three examples of first-in-human dosimetry studies, both for diagnostic tracers and radionuclide therapies, are given.

Surgical radioguidance with beta-emitting radionuclides; challenges and possibilities: A position paper by the EANM.

Radioguidance that makes use of ß-emitting radionuclides is gaining in popularity and could have potential to strengthen the range of existing radioguidance techniques. While there is a strong tendency to develop new PET radiotracers, due to favorable imaging characteristics and the success of theranostics research, there are practical challenges that need to be overcome when considering use of ß-emitters for surgical radioguidance. In this position paper, the EANM identifies the possibilities and challenges that relate to the successful implementation of ß-emitters in surgical guidance, covering aspects related to instrumentation, radiation protection, and modes of implementation.

Sport-related concussion research agenda beyond medical science: culture, ethics, science, policy.

The Concussion in Sport Group guidelines have successfully brought the attention of brain injuries to the global medical and sport research communities, and has significantly impacted brain injury-related practices and rules of international sport. Despite being the global repository of state-of-the-art science, diagnostic tools and guides to clinical practice, the ensuing consensus statements remain the object of ethical and sociocultural criticism. The purpose of this paper is to bring to bear a broad range of multidisciplinary challenges to the processes and products of sport-related concussion movement. We identify lacunae in scientific research and clinical guidance in relation to age, disability, gender and race. We also identify, through multidisciplinary and interdisciplinary analysis, a range of ethical problems resulting from conflicts of interest, processes of attributing expertise in sport-related concussion, unjustifiably narrow methodological control and insufficient athlete engagement in research and policy development. We argue that the sport and exercise medicine community need to augment the existing research and practice foci to understand these problems more holistically and, in turn, provide guidance and recommendations that help sport clinicians better care for brain-injured athletes.

Germline genome modification through novel political, ethical, and social lenses.

Much has been written about gene modifying technologies (GMTs), with a particularly strong focus on human germline genome editing (HGGE) sparked by its unprecedented clinical research application in 2018, shocking the scientific community. This paper applies political, ethical, and social lenses to aspects of HGGE to uncover previously underexplored considerations that are important to reflect on in global discussions. By exploring 4 areas-(1) just distribution of HGGE benefits through a realist lens; (2) HGGE through a national interest lens; (3) "broad societal consensus" through a structural injustice lens; and (4) HGGE through a scientific trustworthiness lens-a broader perspective is offered, which ultimately aims to enrich further debates and inform well-considered solutions for developments in this field. The application of these lenses also brings to light the fact that all discussions about scientific developments involve a conscious or unconscious application of a lens that shapes the direction of our thinking.

Building and Sustaining Public Trust in Health Data Sharing for Musculoskeletal Research: Semistructured Interview and Focus Group Study.

BACKGROUND: Although many people are supportive of their deidentified health care data being used for research, concerns about privacy, safety, and security of health care data remain. There is low awareness about how data are used for research and related governance. Transparency about how health data are used for research is crucial for building public trust. One proposed solution is to ensure that affected communities are notified, particularly marginalized communities where there has previously been a lack of engagement and mistrust. OBJECTIVE: This study aims to explore patient and public perspectives on the use of deidentified data from electronic health records for musculoskeletal research and to explore ways to build and sustain public trust in health data sharing for a research program (known as "the Data Jigsaw") piloting new ways of using and analyzing electronic health data. Views and perspectives about how best to engage with local communities informed the development of a public notification campaign about the research. METHODS: Qualitative methods data were generated from 20 semistructured interviews and 8 focus groups, comprising 48 participants in total with musculoskeletal conditions or symptoms, including 3 carers. A presentation about the use of health data for research and examples from the specific research projects within the program were used to trigger discussion. We worked in partnership with a patient and public involvement group throughout the research and cofacilitated wider community engagement. RESULTS: Respondents were supportive of their health care data being shared for research purposes, but there was low awareness about how electronic health records are used for research. Security and governance concerns about data sharing were noted, including collaborations with external companies and accessing social care records. Project examples from the Data Jigsaw program were viewed positively after respondents knew more about how their data were being used to improve patient care. A range of different methods to build and sustain trust were deemed necessary by participants. Information was requested about: data management; individuals with access to the data (including any collaboration with external companies); the National Health Service's national data opt-out; and research outcomes. It was considered important to enable in-person dialogue with affected communities in addition to other forms of information. CONCLUSIONS: The findings have emphasized the need for transparency and awareness about health data sharing for research, and the value of tailoring this to reflect current and local research where residents might feel more invested in the focus of research and the use of local records. Thus, the provision for targeted information within affected communities with accessible messages and community-based dialogue could help to build and sustain public trust. These findings can also be extrapolated to other conditions beyond musculoskeletal conditions, making the findings relevant to a much wider community.

Bioethics Without Theory?

The question that this paper tries to answer is Q: "Can good academic bioethics be done without commitment to moral theory?" It is argued that the answer to Q is an unequivocal "Yes" for most of what we could call "critical bioethics," that is, the kind of bioethics work that primarily criticizes positions or arguments already in the literature or put forward by policymakers. The answer is also "Yes" for much of empirical bioethics. The second part of the paper then provides an analysis of Q in relation to "constructive bioethics," that is, bioethics work aimed at providing an argument for a particular position. In this part, it is argued that a number of the approaches or methods used that initially look like they involve no commitment to moral theory, nevertheless, involve such a commitment. This is shown to be the case for reflective equilibrium, mid-level theory, the use of theory fragments, and argument by analogy.

Public Reason Requirements in Bioethical Discourse.

This paper analyzes the use of public reason requirements in bioethical discourse and discusses when such requirements are warranted. By a "public reason requirement," I mean a requirement that those involved in a particular discourse or debate only use reasons that can properly be described as public reasons. The first part of the paper outlines the concept of public reasons as developed by John Rawls and others and discusses some of the general criticisms of the concept and its importance. The second part then distinguishes between two types of public reason requirements in bioethics. One type is what I will call the orthodox public reason requirement since it hews closely to the original Rawlsian conception. The second is what I will call the expansive public reason requirement, which departs quite radically from the Rawlsian conception and applies the requirement not to policy discourse or policymaking, but to the actions of individuals. Both types of requirements will be analyzed, and some problems in applying public reason requirements in bioethics will be identified. It will be argued that the expansive public reason requirement is misguided. The concluding part argues that requirements of civic civility and what Rawls terms an "inclusive view" of public reason should be important in bioethical discourse.

Organoids in the Clinic: A Systematic Review of Outcomes.

Research on organoids has undergone significant advances during the last decade. However, outcomes from the use of organoids in clinical trials have not yet been documented. Therefore, there is an urgent need to assess the reporting of clinically relevant outcomes from organoid research in the scientific literature. This article presents a systematic review and appraisal of the published literature in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, together with a synopsis of recent relevant reviews. Surprisingly, no randomized controlled trials have reported clinical outcomes with any types of organoids. We found very few ongoing and registered studies that may provide clinically relevant results within this decade. Our screening and interpretation of the literature, including review articles, indicate a focus on technical and preclinical aspects of organoid research. This is the first systematic review of clinical trials involving organoids. Few clinical studies are planned or already underway, and, so far, no high-quality evidence relating to the clinical outcomes of organoid research has been published. The many promises of organoid research still need to be translated from bench to bed.

Equipoise, standard of care and consent: responding to the authorisation of new COVID-19 treatments in randomised controlled trials.

In response to the COVID-19 pandemic, large-scale research and pharmaceutical regulatory processes have proceeded at a dramatically increased pace with new and effective, evidence-based COVID-19 interventions rapidly making their way into the clinic. However, the swift generation of high-quality evidence and the efficient processing of regulatory authorisation have given rise to more specific and complex versions of well-known research ethics issues. In this paper, we identify three such issues by focusing on the authorisation of molnupiravir, a novel antiviral medicine aimed at reducing the ability of SARS-CoV-2 to multiply in the body, for clinical use by the National Health Service in England and the concomitant testing of molnupiravir through the large-scale Platform Adaptive trial of Novel antiviRals for eArly treatMent of COVID-19 In the Community randomised control trial. By analysing the ways in which the authorisation and clinical use of molnupiravir complicate standard approaches to clinical equipoise, standard of care and participant consent in the PANORAMIC randomised control trial, we will explain some of ethical implications for clinical trials that aim to study the efficacy and safety of new COVID-19 and other therapeutics when conditional authorisation has already been granted and when such treatments have already been made available to patients by national health providers.

The right to a second opinion on Artificial Intelligence diagnosis-Remedying the inadequacy of a risk-based regulation.

In this paper, we argue that patients who are subjects of Artificial Intelligence (AI)-supported diagnosis and treatment planning should have a right to a second opinion, but also that this right should not necessarily be construed as a right to a physician opinion. The right to a second opinion could potentially be satisfied by another independent AI system. Our considerations on the right to second opinion are embedded in the wider debate on different approaches to the regulation of AI, and we conclude the article by providing a number of reasons for preferring a rights-based approach over a risk-based approach.

The Stability of Political Compromise-Abortion Legislation in Denmark and Norway.

In the 1970s, both Denmark and Norway passed abortion legislation that is still the basis for the regulation of abortion in these countries. The legislation was fairly liberal with abortion on demand until 12 weeks of gestation and a permission system for later abortions. This article provides a brief history of the developments leading up to these political compromises and an analysis of the reasons why they have proved remarkably stable. It ends by looking at some factors that may now destabilize 50 years of stable compromise about abortion.

Frailty as a Priority-Setting Criterion for Potentially Lifesaving Treatment-Self-Fulfilling Prophecy, Circularity, and Indirect Discrimination?

Frailty is a state of increased vulnerability to poor resolution of homeostasis after a stressor event. Frailty is most frequently assessed in the old using the Clinical Frailty Scale (CSF) which ranks frailty from 1 to 9. This assessment typically takes less than one minute and is not validated in patients with learning difficulties or those under 65 years old. The National Institute for Health and Care Excellence (NICE) developed guidelines that use "frailty" as one of the priority-setting criteria for how scarce, but potentially lifesaving, health care resources should be allocated during the COVID-19 pandemic. Similar guidelines have been developed elsewhere. This paper discusses the ethical implications of such rationing and argues that this is an unproven and ethically problematic form of health care rationing. It specifically discusses: (1) how the frailty ascription becomes a self-fulfilling prophecy, (2) the problematic use of "frailty" in COVID-19 "triage," (3) the circularity of the link between age and frailty, (4) indirect discrimination because of the use of a seemingly neutral criterion in health care rationing, and (5) the difficult link between comorbidities and frailty. It is found that there was no research into the use of global frailty scores as a criterion for access to acute treatment before January 2020 and so it is concerning how readily frailty scoring has been adopted to ration access to potentially lifesaving treatments. Existing gerontological frailty scoring systems have not been developed for this purpose, and repurposing them creates significant ethical issues.

Towards a concept of embodied autonomy: In what ways can a patient's body contribute to the autonomy of medical decisions?

"Bodily autonomy" has received significant attention in bioethics, medical ethics, and medical law in terms of the general inviolability of a patient's bodily sovereignty and the rights of patients to make choices (e.g., reproductive choices) that concern their own body. However, the role of the body in terms of how it can or does contribute to a patient's capacity for, or exercises of their autonomy in clinical decision-making situations has not been explicitly addressed. The approach to autonomy in this paper is aligned with traditional theories that conceive autonomy in terms of an individual's capacities for, and exercises of rational reflection. However, at the same time, this paper extends these accounts by arguing that autonomy is, in part, embodied. Specifically, by drawing on phenomenological conceptions of the experience of autonomy, we argue that, in principle, the body is a necessary component of the capacity for autonomy. Secondly, through the presentation of two different cases, we highlight ways in which a patient's body can contribute to the autonomy of treatment choices. Ultimately, we hope to encourage others to explore additional conditions under which a concept of embodied autonomy should be employed in medical decision making, how its underlying principles might be operationalised in clinical situations, and its consequences for approaches to patient autonomy in healthcare practice, policy, and law.

Organoid biobanking, autonomy and the limits of consent.

In the debates regarding the ethics of human organoid biobanking, the locus of donor autonomy has been identified in processes of consent. The problem is that, by focusing on consent, biobanking processes preclude adequate engagement with donor autonomy because they are unable to adequately recognize or respond to factors that determine authentic choice. This is particularly problematic in biobanking contexts associated with organoid research or the clinical application of organoids because, given the probability of unforeseen and varying purposes for which a donor's organoids could be employed and given the different ways in which a donor can relate to her biospecimens, a donor can value her organoids differently in different contexts, and her reasons for autonomously permitting use of her cells and tissues in one case may not support an autonomous decision in another. In response, this paper has three aims: first, to make the case for why organoid biobanks ought to respect donor autonomy conceived as authentic choice; second, to explore the autonomy-respecting limits of established and widely prevalent models of biobank consent; and third, to propose certain conditions that organoid biobanks ought to support or facilitate in order to respect donor autonomy.

What is the Foundation of Medical Ethics-Common Morality, Professional Norms, or Moral Philosophy?

This paper considers the relation between medical ethics (ME) and common morality (CM), professional norms, and moral philosophy. It proceeds by analyzing two recent book-length critical analyses of this relationship by Bob Baker in "The Structure of Moral Revolutions-Studies of Changes in the Morality of Abortion, Death, and the Bioethics Revolution" and Rosamond Rhodes in "The Trusted Doctor-Medical Ethics and Professionalism." It argues that despite the strengths of these critical arguments, there is nevertheless a relationship between ME, understood as the professional ethics of the healthcare professions, and both CM and moral philosophy. It also argues that ME cannot and should not be understood purely as the internally developed professional norms of the medical or healthcare professions.

Patient autonomy, clinical decision making, and the Phenomenological reduction.

Phenomenology gives rise to certain ontological considerations that have far-reaching implications for standard conceptions of patient autonomy in medical ethics, and, as a result, the obligations of and to patients in clinical decision-making contexts. One such consideration is the phenomenological reduction in classical phenomenology, a core feature of which is the characterisation of our primary experiences as immediately and inherently meaningful. This paper builds on and extends the analyses of the phenomenological reduction in the works of Husserl, Heidegger, and Merleau-Ponty in order to identify and explain its implications for our current understanding of the principle of respect for patient autonomy and the norms of clinical decision making.

EANM position paper on the role of radiobiology in nuclear medicine.

With an increasing variety of radiopharmaceuticals for diagnostic or therapeutic nuclear medicine as valuable diagnostic or treatment option, radiobiology plays an important role in supporting optimizations. This comprises particularly safety and efficacy of radionuclide therapies, specifically tailored to each patient. As absorbed dose rates and absorbed dose distributions in space and time are very different between external irradiation and systemic radionuclide exposure, distinct radiation-induced biological responses are expected in nuclear medicine, which need to be explored. This calls for a dedicated nuclear medicine radiobiology. Radiobiology findings and absorbed dose measurements will enable an improved estimation and prediction of efficacy and adverse effects. Moreover, a better understanding on the fundamental biological mechanisms underlying tumor and normal tissue responses will help to identify predictive and prognostic biomarkers as well as biomarkers for treatment follow-up. In addition, radiobiology can form the basis for the development of radiosensitizing strategies and radioprotectant agents. Thus, EANM believes that, beyond in vitro and preclinical evaluations, radiobiology will bring important added value to clinical studies and to clinical teams. Therefore, EANM strongly supports active collaboration between radiochemists, radiopharmacists, radiobiologists, medical physicists, and physicians to foster research toward precision nuclear medicine.

Ethics in extracorporeal life support: a narrative review.

During 50 years of extracorporeal life support (ECLS), this highly invasive technology has left a considerable imprint on modern medicine, and it still confronts researchers, clinicians and policymakers with multifarious ethical challenges. After half a century of academic discussion about the ethics of ECLS, it seems appropriate to review the state of the argument and the trends in it. Through a comprehensive literature search on PubMed, we identified three ethical discourses: (1) trials and evidence accompanying the use of ECLS, (2) ECLS allocation, decision-making and limiting care, and (3) death on ECLS and ECLS in organ donation. All included articles were carefully reviewed, arguments extracted and grouped into the three discourses. This article provides a narrative synthesis of these arguments, evaluates the opportunities for mediation and substantiates the necessity of a shared decision-making approach at the limits of medical care.

Pre-diabetes in the elderly and the see-saw model of paternalism.

Pre-diabetes is a risk factor for the development of diabetes, not a disease in its own right. The prevalence increases with age and reaches nearly 50% of those aged over 75 years in the USA. While lifestyle modification and treatment are likely to benefit those with many years of life ahead of them, they are unlikely to benefit patients with a limited life expectancy. Despite this, some very elderly patients in the UK and elsewhere are being labelled as pre-diabetic. While ideal practice would be to carefully consider the impact of any potentially abnormal blood test before it is taken, this is not always possible in routine practice. In this paper, we discuss a pragmatic, ethical approach for clinicians managing pre-diabetic blood tests in very elderly patients. We argue that a 'see-saw' model of paternalism should be used in deciding which patients to inform that they can be labelled as pre-diabetic. Those patients that may benefit from the label should be informed, and those that will not, should not. Where the benefits/drawbacks are unclear, the result and its potential significance should be discussed in depth with the individual patient. We do not advocate withholding information from any patient. Instead we suggest clinicians use individual patient circumstances to contextualise the relevance of pre-diabetes to the patient and consider the benefits and drawbacks before informing them. This approach has the potential to be used for other pre-conditions and risk factors in addition to pre-diabetes.

Gender dysphoria in adolescents: can adolescents or parents give valid consent to puberty blockers?

This article considers the claim that gender diverse minors and their families should not be able to consent to hormonal treatment for gender dysphoria. The claim refers particularly to hormonal treatment with so-called 'blockers', analogues that suspend temporarily pubertal development. We discuss particularly four reasons why consent may be deemed invalid in these cases: (1) the decision is too complex; (2) the decision-makers are too emotionally involved; (3) the decision-makers are on a 'conveyor belt'; (4) the possibility of detransitioning. We examine each of these reasons and we show that none of these stand up to scrutiny, and that some are based on a misunderstanding of the nature and purposes of this stage of treatment and of the circumstances in which it is usually prescribed. Moreover, accepting these claims at face value could have serious negative implications, not just for gender diverse youth, but for many other minors and families and in a much broader range of healthcare settings.