An assessment of the moral value of neuronal cell models and brain organoids

Advances in stem cell technology enable neuroscientists to develop induced pluripotent stem cell (iPSC)-based neuronal models of varying complexity, ranging from single human brain cells to two-dimensional neuronal cell models and three-dimensional brain organoids. While the discussion on the moral status of brain organoids is taking center stage in the bioethical literature and is invariably linked to the presumed capacity of future brain organoids to develop some form of consciousness, analyses of the moral status of other – less complex – iPSC-based neuronal models are lacking. In this paper we aim to clarify the moral value of various types of existing neuronal models, including brain organoids. We show how it is made up of several layers that may encompass various sorts of considerations, including moral values, the results of empirical research, and biological characteristics. We identify four such layers – instrumental, intrinsic, symbolic, and relational – that are relevant for the assessment of the moral value of neuronal models. We demonstrate that it lies not in a capacity to develop some form of consciousness (which is absent in current iPSC-based neuronal models, including brain organoids), but in other considerations, including the genetic links between models and donors, the ability of models to mimic brain (dys)function, and their symbolic value, all of which are often overlooked in the bioethical literature. Also, we demonstrate that the 'thickness' of the layers (i.e., their moral weight) increases when the neuronal model is more complex. Finally, we discuss the practical-ethical implications of our analysis for the use of neuronal models in research settings, for instance in relation to informed consent and biobank governance. Our four-layer framework can be applied also in moral assessments of other iPSC-based models, including emerging and future cell models

Learning accountable governance: Challenges and perspectives for data-intensive health research networks

Current challenges to sustaining public support for health data research have directed attention to the governance of data-intensive health research networks. Accountability is hailed as an important element of trustworthy governance frameworks for data-intensive health research networks. Yet the extent to which adequate accountability regimes in data-intensive health research networks are currently realized is questionable. Current governance of data-intensive health research networks is dominated by the limitations of a drawing board approach. As a way forward, we propose a stronger focus on accountability as learning to achieve accountable governance. As an important step in that direction, we provide two pathways: (1) developing an integrated structure for decision-making and (2) establishing a dialogue in ongoing deliberative processes. Suitable places for learning accountability to thrive are dedicated governing bodies as well as specialized committees, panels or boards which bear and guide the development of governance in data-intensive health research networks. A continuous accountability process which comprises learning and interaction accommodates the diversity of expectations, responsibilities and tasks in data-intensive health research networks to achieve responsible and effective governance

Experiences and perceptions of continuous deep sedation:An interview study among Dutch patients and relatives

Background: The incidence of continuous deep sedation (CDS) has more than doubled over the last decade in The Netherlands, while reasons for this increase are not fully understood. Patients and relatives have an essential role in deciding on CDS. We hypothesize that the increase in CDS practice is related to the changing role of patients and relatives in deciding on CDS. Objective: To describe perceptions and experiences of patients and relatives with regard to CDS. This insight may help professionals and policymakers to better understand and respond to the evolving practice of CDS. Methods: Qualitative interviews were held with patients and relatives who had either personal experience with CDS as a relative or had contemplated CDS for themselves. Results: The vast majority of respondents appreciated CDS as a palliative care option, and none of the respondents reported (moral) objections to CDS. The majority of respondents prioritized avoiding suffering at the end of life. The patients and families generally considered CDS a palliative care option for which they can choose. Likewise, according to our respondents, the decision to start CDS was made by them, instead of the physician. Negative experiences with CDS care were mostly related to loss of sense of agency, due to insufficient communication or information provision by healthcare professionals. Lack of continuity of care was also a source of distress. We observed a variety in the respondents' understanding of the distinction between CDS and other end-of-life care decisions, including euthanasia. Some perceived CDS as hastening death. Conclusion: The traditional view of CDS as a last resort option for a physician to relieve a patient's suffering at the end of life is not explicit among patients and relatives. Instead, our results show that they perceive CDS as a regular palliative care option. Along with this normalization of CDS, patients and relatives claim a substantial say in the decision-making and are mainly motivated by a wish to avoid suffering and exercise control at the end of life. These distinct views on CDS of patients, their relatives and healthcare providers should be reconciled in guidelines and protocols for CDS. Patient or Public Contribution: One of the authors in our team (G. H.) has experience with CDS as a relative and ensured that the patient/relative viewpoint was adequately reflected in the design and conduct of our study. In the preliminary phase of our study, G. H. adjusted the topic list so it was better adapted to the current practice of CDS. During the data analysis, G. H. read several interviews and took part in the open and critical discussion on central themes and core concepts as an important member of the author team, thereby guaranteeing the central position of the patient/relative perspective in our final research outcome.</p

An assessment of the moral value of neuronal cell models and brain organoids

Advances in stem cell technology enable neuroscientists to develop induced pluripotent stem cell (iPSC)-based neuronal models of varying complexity, ranging from single human brain cells to two-dimensional neuronal cell models and three-dimensional brain organoids. While the discussion on the moral status of brain organoids is taking center stage in the bioethical literature and is invariably linked to the presumed capacity of future brain organoids to develop some form of consciousness, analyses of the moral status of other – less complex – iPSC-based neuronal models are lacking. In this paper we aim to clarify the moral value of various types of existing neuronal models, including brain organoids. We show how it is made up of several layers that may encompass various sorts of considerations, including moral values, the results of empirical research, and biological characteristics. We identify four such layers – instrumental, intrinsic, symbolic, and relational – that are relevant for the assessment of the moral value of neuronal models. We demonstrate that it lies not in a capacity to develop some form of consciousness (which is absent in current iPSC-based neuronal models, including brain organoids), but in other considerations, including the genetic links between models and donors, the ability of models to mimic brain (dys)function, and their symbolic value, all of which are often overlooked in the bioethical literature. Also, we demonstrate that the 'thickness' of the layers (i.e., their moral weight) increases when the neuronal model is more complex. Finally, we discuss the practical-ethical implications of our analysis for the use of neuronal models in research settings, for instance in relation to informed consent and biobank governance. Our four-layer framework can be applied also in moral assessments of other iPSC-based models, including emerging and future cell models

Ethics of Informed Consent for Pragmatic Trials with New Interventions

Objectives: Pragmatic trials evaluate the comparative benefits, risks, and burdens of health care interventions in real-world conditions. Such studies are now recognized as valuable to the perimarketing stage of drug development and evaluation, with early pragmatic trials (EPTs) being explored as a means to generate real-world evidence at the time of regulatory market approval. In this article, we present an analysis of the ethical issues involved in informed consent for EPTs, in light of the generally recognized concern that traditional ethical rules governing randomized clinical trials, such as lengthy informed consent procedures, could threaten the “real world” nature of such trials. Specifically, we examine to what extent modifications (waivers or alterations) to regulatory consent for EPTs would be ethical. Methods: We first identify broadly accepted necessary conditions for modifications of informed consent (namely, the research involves no more than minimal risk of harm, the research is impracticable with regulatory consent, and the alternative to regulatory consent does not violate legitimate patient expectations) and then apply those criteria to the premarket and early postmarket contexts. Results and Conclusions: The analysis shows that neither waivers nor alterations of regulatory consent for premarket EPTs will be ethically permissible. For postmarket EPTs with newly approved interventions, waivers of consent will be ethically problematic, but some studies might be conducted in an ethical manner with alterations to regulatory consent

Symptom evolution in the dying

Objective: Provide insight in the prevalence of symptoms in patients who are in the last days of life. Methods: A retrospective descriptive analysis of data on patients who died between 2012 and 2019 at the age of 18 or older in 1 of 20 Dutch healthcare facilities, including hospitals, inpatient hospices and long-term care facilities. We analysed data from 4 hourly registrations in the Care Programme for the Dying Person, to assess for how many patients symptom-related goals of care were not achieved. We looked at the first 4 hours episode after the start of the Care Programme and the last 4 hours episode prior to death. Results: We analysed records of 2786 patients. In the first 4 hours episode, at least one symptom-related care goal was not achieved for 28.5%-42.8% of patients, depending on the care setting. In the last 4 hours episode, these percentages were 17.5%-26.9%. Care goals concerning pain and restlessness were most often not achieved: percentages varied from 7.3% to 20.9% for pain and from 9.3% to 21.9% for restlessness. Conclusions: Symptom control at the end of life is not optimal in a substantial minority of patients. Systematic assessment and attention as well as further research on symptom management are of the essence

Developments in euthanasia practice in the Netherlands : Balancing professional responsibility and the patient’s autonomy

In 2015, euthanasia accounted for 4.5% of deaths in the Netherlands, of which 93% were performed by a GP. Historically, a conflict of physician’s duties—to alleviate unbearable suffering and at the same time preserve the patient’s life—is central to the justification of euthanasia practice in the Netherlands. However, there seems to be a shift towards a greater emphasis on the patient’s autonomous wish as the primary basis for euthanasia. This shift has consequences for the role and interpretation of the physician’s duties in end-of-life care. This paper aims to describe these developments in euthanasia practice and end-of-life decision-making. We describe important relevant developments and look into the role and the meaning of two dimensions of the concept of ‘patient autonomy’ regarding end-of-life decisions, in particular, the euthanasia request. We claim that the concept of autonomy ‘as a right,’ which can be distinguished from autonomy ‘as an ideal,’ narrows the physician’s window of opportunity to offer end-of-life care other than euthanasia

Developments in euthanasia practice in the Netherlands : Balancing professional responsibility and the patient’s autonomy

In 2015, euthanasia accounted for 4.5% of deaths in the Netherlands, of which 93% were performed by a GP. Historically, a conflict of physician’s duties—to alleviate unbearable suffering and at the same time preserve the patient’s life—is central to the justification of euthanasia practice in the Netherlands. However, there seems to be a shift towards a greater emphasis on the patient’s autonomous wish as the primary basis for euthanasia. This shift has consequences for the role and interpretation of the physician’s duties in end-of-life care. This paper aims to describe these developments in euthanasia practice and end-of-life decision-making. We describe important relevant developments and look into the role and the meaning of two dimensions of the concept of ‘patient autonomy’ regarding end-of-life decisions, in particular, the euthanasia request. We claim that the concept of autonomy ‘as a right,’ which can be distinguished from autonomy ‘as an ideal,’ narrows the physician’s window of opportunity to offer end-of-life care other than euthanasia