Better governance starts with better words: why responsible human tissue research demands a change of language.

The rise of precision medicine has led to an unprecedented focus on human biological material in biomedical research. In addition, rapid advances in stem cell technology, regenerative medicine and synthetic biology are leading to more complex human tissue structures and new applications with tremendous potential for medicine. While promising, these developments also raise several ethical and practical challenges which have been the subject of extensive academic debate. These debates have led to increasing calls for longitudinal governance arrangements between tissue providers and biobanks that go beyond the initial moment of obtaining consent, such as closer involvement of tissue providers in what happens to their tissue, and more active participatory approaches to the governance of biobanks. However, in spite of these calls, such measures are being adopted slowly in practice, and there remains a strong tendency to focus on the consent procedure as the tool for addressing the ethical challenges of contemporary biobanking. In this paper, we argue that one of the barriers to this transition is the dominant language pervading the field of human tissue research, in which the provision of tissue is phrased as a 'donation' or 'gift', and tissue providers are referred to as 'donors'. Because of the performative qualities of language, the effect of using 'donation' and 'donor' shapes a professional culture in which biobank participants are perceived as passive providers of tissue free from further considerations or entitlements. This hampers the kind of participatory approaches to governance that are deemed necessary to adequately address the ethical challenges currently faced in human tissue research. Rather than reinforcing this idea through language, we need to pave the way for the kind of participatory approaches to governance that are being extensively argued for by starting with the appropriate terminology.

Clarifying responsibility: professional digital health in the doctor-patient relationship, recommendations for physicians based on a multi-stakeholder dialogue in the Netherlands.

BACKGROUND: Implementation of digital health (eHealth) generally involves adapting pre-established and carefully considered processes or routines, and still raises multiple ethical and legal dilemmas. This study aimed to identify challenges regarding responsibility and liability when prescribing digital health in clinical practice. This was part of an overarching project aiming to explore the most pressing ethical and legal obstacles regarding the implementation and adoption of digital health in the Netherlands, and to propose actionable solutions. METHODS: A series of multidisciplinary focus groups with stakeholders who have relevant digital health expertise were analysed through thematic analysis. RESULTS: The emerging general theme was 'uncertainty regarding responsibilities' when adopting digital health. Key dilemmas take place in clinical settings and within the doctor-patient relationship ('professional digital health'). This context is particularly challenging because different stakeholders interact. In the absence of appropriate legal frameworks and codes of conduct tailored to digital health, physicians' responsibility is to be found in their general duty of care. In other words: to do what is best for patients (not causing harm and doing good). Professional organisations could take a leading role to provide more clarity with respect to physicians' responsibility, by developing guidance describing physicians' duty of care in the context of digital health, and to address the resulting responsibilities. CONCLUSIONS: Although legal frameworks governing medical practice describe core ethical principles, rights and obligations of physicians, they do not suffice to clarify their responsibilities in the setting of professional digital health. Here we present a series of recommendations to provide more clarity in this respect, offering the opportunity to improve quality of care and patients' health. The recommendations can be used as a starting point to develop professional guidance and have the potential to be adapted to other healthcare professionals and systems.

Mini-gut feelings: perspectives of people with cystic fibrosis on the ethics and governance of organoid biobanking.

Aim: Organoid technology has enormous potential for precision medicine, such as has recently been demonstrated in the field of cystic fibrosis. However, storage and use of organoids has been associated with ethical challenges and there is currently a lack of harmony in regulation and guidelines to govern the rapid emergence of 'organoid medicine'. Developing sound governance demands incorporation of the perspectives of patients as key stakeholders. Materials & methods: We conducted 17 semi-structured interviews with people with cystic fibrosis to explore their perspectives on the ethics and governance of organoid biobanking. Results: We identified three themes: prioritization of research and trust, ambivalent views on commercial involvement and transparency and control. Conclusion: Our study offers important insights for ethically robust governance of 'organoid medicine'.

Lay abstract Organoids are living tissues that can be grown in a lab out of stem cells, which can replicate some features of actual organs in the body. They can be used to study diseases or develop drugs, but also to test the effectiveness of therapy for a specific patient (which is called precision medicine). Organoid technology is promising for the treatment of cystic fibrosis. At the same, storing and using organoids raises ethical and practical challenges. In order to ensure that the interests of those who provide the cells are respected, we interviewed people with cystic fibrosis. Their motivation to participate in organoid research was high, but at the same time they wanted to know how their organoids are used. In addition, while they did not feel the need to be directly involved in decisions about how their tissue is used, they valued ongoing communication from biobanks about its activities.

Organoids for personalized treatment of Cystic Fibrosis: Professional perspectives on the ethics and governance of organoid biobanking.

BACKGROUND: Organoid technology is emerging rapidly as a valuable tool for precision medicine, particularly in the field of Cystic Fibrosis (CF). However, biobank storage and use of patient-derived organoids raises specific ethical and practical challenges that demand sound governance. We examined the perspectives of professionals affiliated with CF or organoids on the ethical aspects of organoid biobanking for CF precision medicine. By conducting this study parallel to the process of innovation and development of organoid biobanking, its findings are valuable for the design of responsible governance frameworks. METHODS: To identify relevant themes and attitudes we conducted 21 semi-structured qualitative interviews with professionals in the field of organoid technology, biobanking, or CF research and care. RESULTS: We identified three key challenges, as well as the suggestions of professionals on how to address them: (1) The challenges associated with commercial involvement, trust, and ownership, (2) Navigating the blurring boundary between research and clinical care, (3) Appropriate approaches to the informed consent procedure. CONCLUSION: Sound governance of organoid biobanks aimed at precision medicine requires coming to terms with the fact that its stakeholders no longer belong to separate domains. Responsible governance should be aimed at finding a sound, context-sensitive balance between integration of ongoing co-operation and mutual consideration of interests, and maintaining a feasible and sustainable research climate.

Ethical challenges for pediatric liver organoid transplantation.

Liver organoid transplantation may be a less invasive alternative to liver transplant, but is it ethically acceptable to include children with liver disease in a first-in-human clinical trial of this new intervention?

Responsible use of organoids in precision medicine: the need for active participant involvement.

Organoids are three-dimensional multicellular structures grown in vitro from stem cells and which recapitulate some organ function. They are derivatives of living tissue that can be stored in biobanks for a multitude of research purposes. Biobank research on organoids derived from patients is highly promising for precision medicine, which aims to target treatment to individual patients. The dominant approach for protecting the interests of biobank participants emphasizes broad consent in combination with privacy protection and ex ante (predictive) ethics review. In this paradigm, participants are positioned as passive donors; however, organoid biobanking for precision medicine purposes raises challenges that we believe cannot be adequately addressed without more ongoing involvement of patient-participants. In this Spotlight, we argue why a shift from passive donation towards more active involvement is particularly crucial for biobank research on organoids aimed at precision medicine, and suggest some approaches appropriate to this context.

Breeding brains? Patients' and laymen's perspectives on cerebral organoids.

Aim: To explore the perspectives of patients and laymen with regard to the development, use and storage of cerebral organoids, in order to contribute to the ethical debate about this technology. Materials & methods: In depth semi-structured interviews with 28 patients and laymen were conducted. A qualitative thematic analysis was undertaken using a constant comparative method. Results: Three interrelated themes emerged from the empirical material: moral value; willingness to donate; and elements of good governance. Conclusion: Patients and laymen are most concerned about cerebral organoids potentially developing consciousness and potential misuse. They support the use of cerebral organoids under the conditions that donors are adequately informed and that there will be good governance. Perspectives of patients and laymen are helpful to enable responsible development and use of cerebral organoids in practice.

SERIES: eHealth in primary care. Part 2: Exploring the ethical implications of its application in primary care practice.

Background: eHealth promises to increase self-management and personalised medicine and improve cost-effectiveness in primary care. Paired with these promises are ethical implications, as eHealth will affect patients' and primary care professionals' (PCPs) experiences, values, norms, and relationships.Objectives: We argue what ethical implications related to the impact of eHealth on four vital aspects of primary care could (and should) be anticipated.Discussion: (1) EHealth influences dealing with predictive and diagnostic uncertainty. Machine-learning based clinical decision support systems offer (seemingly) objective, quantified, and personalised outcomes. However, they also introduce new loci of uncertainty and subjectivity. The decision-making process becomes opaque, and algorithms can be invalid, biased, or even discriminatory. This has implications for professional responsibilities and judgments, justice, autonomy, and trust. (2) EHealth affects the roles and responsibilities of patients because it can stimulate self-management and autonomy. However, autonomy can also be compromised, e.g. in cases of persuasive technologies and eHealth can increase existing health disparities. (3) The delegation of tasks to a network of technologies and stakeholders requires attention for responsibility gaps and new responsibilities. (4) The triangulate relationship: patient-eHealth-PCP requires a reconsideration of the role of human interaction and 'humanness' in primary care as well as of shaping Shared Decision Making.Conclusion: Our analysis is an essential first step towards setting up a dedicated ethics research agenda that should be examined in parallel to the development and implementation of eHealth. The ultimate goal is to inspire the development of practice-specific ethical recommendations.

European recommendations integrating genetic testing into multidisciplinary management of sudden cardiac death.

Sudden cardiac death (SCD) accounts for 10-20% of total mortality, i.e., one in five individuals will eventually die suddenly. Given the substantial genetic component of SCD in younger cases, postmortem genetic testing may be particularly useful in elucidating etiological factors in the cause of death in this subset. The identification of genes responsible for inherited cardiac diseases have led to the organization of cardiogenetic consultations in many countries worldwide. Expert recommendations are available, emphasizing the importance of genetic testing and appropriate information provision of affected individuals, as well as their relatives. However, the context of postmortem genetic testing raises some particular ethical, legal, and practical (including economic or financial) challenges. The Public and Professional Policy Committee of the European Society of Human Genetics (ESHG), together with international experts, developed recommendations on management of SCD after a workshop sponsored by the Brocher Foundation and ESHG in November 2016. These recommendations have been endorsed by the ESHG Board, the European Council of Legal Medicine, the European Society of Cardiology working group on myocardial and pericardial diseases, the ERN GUARD-HEART, and the Association for European Cardiovascular Pathology. They emphasize the importance of increasing the proportion of both medical and medicolegal autopsies and educating the professionals. Multidisciplinary collaboration is of utmost importance. Public funding should be allocated to reach these goals and allow public health evaluation.

Organoids as hybrids: ethical implications for the exchange of human tissues.

Recent developments in biotechnology allow for the generation of increasingly complex products out of human tissues, for example, human stem cell lines, synthetic embryo-like structures and organoids. These developments are coupled with growing commercial interests. Although commercialisation can spark the scientific and clinical promises, profit-making out of human tissues is ethically contentious and known to raise public concern. The traditional bioethical frames of gift versus market are inapt to capture the resulting practical and ethical complexities. Therefore, we propose an alternative approach to identify, evaluate and deal with the ethical challenges that are raised by the increasing commercialisation of the exchange of sophisticated human tissue products. We use organoid technology, a cutting-edge stem cell technology that enables the cultivation of 'mini-organs' in a dish, as an example. First, we examine the moral value of organoids and recognise them as hybrids that relate to persons and their bodies as well as to technologies and markets in ambiguous ways. Second, we show that commercialisation of organoids is legitimised by a detachment of the instrumental and commercial value of organoids from their associations with persons and their bodies. This detachment is enacted in steps of disentanglement, among which consent and commodification. Third, we contend that far-reaching disentanglement is ethically challenging: (1) Societal interests could be put under pressure, because the rationale for commercialising organoid technology, that is, to stimulate biomedical innovation for the good of society, may not be fulfilled; (2) The interests of donors are made subordinate to those of third parties and the relational moral value of organoids may be insufficiently recognised. Fourth, we propose a 'consent for governance' model that contributes to responsible innovation and clinical translation in this exciting field.

Mini-guts in a dish: Perspectives of adult Cystic Fibrosis (CF) patients and parents of young CF patients on organoid technology.

BACKGROUND: Organoid technology enables the cultivation of human tissues in a dish. Its precision medicine potential could revolutionize the Cystic Fibrosis (CF) field. We provide a first thematic exploration of the patient perspective on organoid technology to set the further research agenda, which is necessary for responsible development of this ethically challenging technology. METHODS: 23 semi-structured qualitative interviews with 14 Dutch adult CF patients and 12 parents of young CF patients to examine their experiences, opinions, and attitudes regarding organoid technology. RESULTS: Four themes emerged: (1) Respondents express a close as well as a distant relationship to organoids; (2) the open-endedness of organoid technology sparks hopes and concerns, (3) commercial use evokes cautiousness. (4) Respondents mention the importance of sound consent procedures, long-term patient engagement, responsible stewardship, and stringent conditions for commercial use. CONCLUSIONS: The precision medicine potential of organoid technology can only be realized if the patient perspective is taken adequately into account.

Postmortem disclosure of genetic information to family members: active or passive?

Advances in next-generation DNA sequencing (NGS) now make it possible, and affordable, to sequence the entire genome of an individual. Routine clinical application is on the horizon. There is a consensus that some subsets of genetic information should be disclosed to patients, but disclosure to their relatives is less consensual. This issue becomes especially salient after a patient's death, when permission can no longer be sought. There has however been little debate on postmortem disclosure. We identify and explain the arguments in favor of and against disclosure of genetic information to the relatives of a deceased patient. We conclude that there are valid reasons to communicate some subsets of genetic information to family members after death, and we propose a passive postmortem disclosure policy.