Search

Gene therapy is expected to become a promising treatment, and potentially even a cure, for hemophilia. After several years of research, the first gene therapy product has been granted conditional market authorization by the European Union in August 2022. The recent progress in the field also has implications on the ethical aspects of hemophilia gene therapy. Reviews conducted in the 2000s mainly identified questions on the ethics of conducting early-phase clinical trials. However, since then, the knowledge on safety and efficacy has improved, and the field has moved toward clinical application, a phase that has its own ethical aspects. Therefore, we conducted a narrative review to take stock of the ethical aspects of hemophilia gene therapy. Based on our analysis of the literature, we identified 3 ethical themes. The theme Living up to expectations describes the existing hopes for gene therapy and the unlikelihood of the currently approved product becoming a permanent cure. In the theme Psychosocial impacts, we discuss the fear that gene therapy will impact the identity of people with hemophilia and their need for psychosocial support. The theme Costs and access discusses the expected cost-effectiveness of gene therapy and its implications on accessibility worldwide. We conclude that it may be necessary to change the narratives surrounding gene therapy, from describing it as a cure to describing it as one of the many treatments that temporarily relieve symptoms and that there is a need to reevaluate the desirability of gene therapy for hemophilia, given the availability of other treatments.

Tumour DNA and germline testing, based on DNA-wide sequencing analysis, are becoming more and more routine in clinical-oncology practice. A promising step in medicine, but at the same time leading to challenging ethicolegal questions. An important one is under what conditions individuals (patients and their relatives, research participants) should be recontacted with new information, even if many years have passed since the last contact. Based on legal- and ethical study, we developed a tool to help professionals to decide whether or not to recontact an individual in specific cases. It is based on four assessment criteria: (1) professional relationship (2) clinical impact (3) individual's preferences and (4) feasibility. The tool could also serve as a framework for guidelines on the topic.

Moral sensitivity and moral reasoning are essential competencies biomedical researchers have to develop to make ethical decisions in their daily practices. Previous research has shown that these competencies can be developed through ethics education. However, it is unclear which underlying mechanisms best support the development of these competencies. In this article we argue that the development of moral sensitivity and moral reasoning can be fostered through teaching strategies that tap into students’ moral imagination. We describe how moral imagination can stimulate the development of these competencies through three different merits of moral imagination. Moral imagination can help students to 1) transfer and apply abstract moral concepts to concrete situations and contexts, 2) explore the perspective of others, 3) explore and foresee the moral consequences of different decisions and actions. We explain these three merits of moral imagination in the context of biomedical research and present a theoretical model for how these merits can be used to stimulate the development of moral sensitivity and moral reasoning. Furthermore, we describe multiple teaching strategies for biomedical curricula that tap into the three merits of moral imagination. These teaching strategies can inspire teachers to design ethics education that activates students’ moral imagination for the development of moral sensitivity and moral reasoning.

Despite widespread and worldwide efforts to eradicate vector-borne diseases such as malaria, these diseases continue to have an enormous negative impact on public health. For this reason, scientists are working on novel control strategies, such as gene drive technologies (GDTs). As GDT research advances, researchers are contemplating the potential next step of conducting field trials. An important point of discussion regarding these field trials relates to who should be informed, consulted, and involved in decision-making about their design and launch. It is generally argued that community members have a particularly strong claim to be engaged, and yet, disagreement and lack of clarity exist about how this “community” should be defined and delineated. In this paper, we shed light on this “boundary problem”: the problem of determining how boundaries of inclusion and exclusion in (GDT) community engagement should be drawn. As our analysis demonstrates, the process of defining and delineating a community is itself normative. First, we explicate why it is important to define and delineate the community. Second, we demonstrate that different definitions of community are used and intermingled in the debate on GDTs, and argue in favor of distinguishing geographical, affected, cultural, and political communities. Finally, we propose initial guidance for deciding who should (not) be engaged in decision-making about GDT field trials, by arguing that the definition and delineation of the community should depend on the rationale for engagement and that the characteristics of the community itself can guide the effective design of community engagement strategies.

Gene drive technologies (GDTs) have been proposed as a potential new way to alleviate the burden of malaria, yet have also raised ethical questions. A central ethical question regarding GDTs relates to whether it is morally permissible to intentionally modify or eradicate mosquitoes in this way and how the inherent worth of humans and non-human organisms should be factored into determining this. Existing analyses of this matter have thus far generally relied on anthropocentric and zoocentric perspectives and rejected an individualist biocentric outlook in which all living organisms are taken to matter morally for their own sake. In this paper, we reconsider the implications of taking a biocentric approach and highlight nuances that may not be evident at first glance. First, we shortly discuss biocentric perspectives in general, and then outline Paul Taylor’s biocentric theory of respect for nature. Second, we explore how conflicting claims towards different organisms should be prioritised from this perspective and subsequently apply this to the context of malaria control using GDTs. Our ethical analysis shows that this context invokes the principle of self-defence, which could override the pro tanto concerns that a biocentrist would have against modifying malaria mosquitoes in this way if certain conditions are met. At the same time, the case study of GDTs underlines the relevance of previously posed questions and criticism regarding the internal consistency of Taylor’s egalitarian biocentrism.

In recent years, exposome research has been put forward as the next frontier for the study of human health and disease. Exposome research entails the analysis of the totality of environmental exposures and their corresponding biological responses within the human body. Increasingly, this is operationalized by big-data approaches to map the effects of internal as well as external exposures using smart sensors and multiomics technologies. However, the ethical implications of exposome research are still only rarely discussed in the literature. Therefore, we conducted a systematic review of the academic literature regarding both the exposome and underlying research fields and approaches, to map the ethical aspects that are relevant to exposome research. We identify five ethical themes that are prominent in ethics discussions: the goals of exposome research, its standards, its tools, how it relates to study participants, and the consequences of its products. Furthermore, we provide a number of general principles for how future ethics research can best make use of our comprehensive overview of the ethical aspects of exposome research. Lastly, we highlight three aspects of exposome research that are most in need of ethical reflection: the actionability of its findings, the epidemiological or clinical norms applicable to exposome research, and the meaning and action–implications of bias.

Background The NIA-AA research framework proposes a purely biological definition of Alzheimer’s disease (AD). This implies that AD can be diagnosed based on biomarker abnormalities, irrespective of clinical manifestation. While this brings opportunities, it also raises challenges. We aimed to provide an overview of considerations regarding the disclosure of AD pathology before the onset of dementia. Methods A systematic literature review was conducted and reported according to PRISMA guidelines. We searched PubMed, Embase, APA PsycINFO, and Web of Science Core Collection (on 10 December 2020) for references on conveying AD biomarker results to individuals without dementia. Our query combined variations on the terms Alzheimer’s disease, disclosure, or diagnosis, preclinical or prodromal, and biomarkers. Two reviewers independently screened the resulting 6860 titles and abstracts for eligibility and examined 162 full-text records for relevance. We included theoretical articles in English, on communicating amyloid and/or tau results to individuals with mild cognitive impairment, subjective cognitive decline, or normal cognition. MAXQDA-software was used for inductive data analysis. Results We included 27 publications. From these, we extracted 26 unique considerations, which we grouped according to their primary relevance to a clinical, personal, or societal context. Clinical considerations included (lack of) validity, utility, and disclosure protocols. Personal considerations covered psychological and behavioral implications, as well as the right to (not) know. Finally, societal considerations comprised the risk of misconception, stigmatization, and discrimination. Overall, views were heterogeneous and often contradictory, with emphasis on harmful effects. Conclusions We found 26 diverse and opposing considerations, related to a clinical, personal, or societal context, which are relevant to diagnosing AD before dementia. The theoretical literature tended to focus on adverse impact and rely on common morality, while the motivation for and implications of biomarker testing are deeply personal. Our findings provide a starting point for clinicians to discuss biomarker-based diagnosis with their patients, which will become even more relevant in light of the conditional approval of a first disease-modifying drug for AD.

Over the last decades science communication theory appears to have evolved at a much faster pace than science communication practice. Scientists seem willing to step into the public domain, but a genuine two-way interaction with the public is only rarely observed. We argue that part of this discrepancy between theory and practice may actually be caused by the lacking of a clear description of the modern expert role; the role a scientist should take in contemporary science communication. In this contribution we use an example of good practice—the Dutch dialogue on human germline genetic modification—to inform theory. We analyse guiding principles for the design and execution of this dialogue and observe expert behavior in three separate dialogue sessions. With the combined findings, we present a detailed description of the modern expert role in terms of three responsibilities, with for each responsibility three prompts for behavior. For the responsibility to share these are to select expert knowledge that is relevant to the goal; to present expert knowledge in a meaningful and accessible language; and to be cautious in sharing personal considerations. For the responsibility to listen and learn these are to consider interactions with members of the public as opportunities to learn; to be patient and supportive; and to assist in stimulating in-depth dialogue. For the responsibility to invest in relationships these are to assist in creating an ambiance of safety and relevance; to preserve trust; and to convey respect for every contribution and every point of view. Each behavioral prompt is further concretized with concomitant actions and practice examples as collected from observing experts in action. The implications for scientists engaging in contemporary science communication, as well as for science communication trainers, are discussed.

Background Digital health technologies are believed to change the patient-physician relationship. Such changes are still speculative, as there are no studies in which both patients and health care professionals are asked for their experiences and perspectives on how digital health affects the patient-physician relationship. Methods We performed a qualitative interview study (n = 25) to identify relevant aspects of the patient-physician relationship as perceived by both health care professionals (n = 14) and patients (n = 11) of a digital monitoring platform for hypertensive disorders related to pregnancy. We focus on roles, responsibilities and medical decision-making. Results Digital monitoring helps patients to better understand their own condition and contributes to shared decision-making in terms of information exchange. Yet for clinical decision-making both patients and health care professionals argue that health care professionals should stay in the lead. The collected data is by some health care professionals considered hard data that allows objective and more standardized decision-making, while others believe digital monitoring requires further interpretation in order to personalize the clinical care to the patient. Conclusion Digital technologies have subtle, yet double-edged, effects on the patient-physician relationship in terms of roles and responsibilities and the value addressed to the digital data. These insights let to 6 ethical recommendations for the implementation of digital health technologies to replace and support clinical care.

Background: Treatment choices for individual patients with an inborn bleeding disorder are increasingly challenging due to increasing options and rising costs for society. We have initiated an integrated interdisciplinary national research program. Objectives: The SYMPHONY consortium strives to orchestrate personalized treatment in patients with an inborn bleeding disorder, by unraveling the mechanisms behind interindividual variations of bleeding phenotype. Patients: The SYMPHONY consortium will investigate patients with an inborn bleeding disorder, both diagnosed and not yet diagnosed. Results: Research questions are categorized under the themes: (1) diagnosis, (2) treatment, and (3) fundamental research, and consist of work packages addressing specific domains. Importantly, collaborations between patients and talented researchers from different areas of expertise promise to augment the impact of the SYMPHONY consortium, leading to unique interactions and intellectual property. Conclusions: SYMPHONY will perform research on all aspects of care, treatment individualization in patients with inborn bleeding disorders, as well as diagnostic innovations and results of molecular genetics and cellular model technology with regard to the hemostatic process. We believe that these research investments will lead to health-care innovations with long-term clinical and societal impact. This consortium has been made possible by a governmental, competitive grant from the Netherlands Organization for Scientific Research (NWO) within the framework of the NWA-ORC Call grant agreement NWA.1160.18.038.

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.

Precision medicine research involving human biological material is becoming an increasingly central component of healthcare, and its potential is quickly growing due to rapid technological progress...

Background Gene drive technologies (GDTs) promote the rapid spread of a particular genetic element within a population of non-human organisms. Potential applications of GDTs include the control of insect vectors, invasive species and agricultural pests. Whether, and if so, under what conditions, GDTs should be deployed is hotly debated. Although broad stances in this debate have been described, the convictions that inform the moral views of the experts shaping these technologies and related policies have not been examined in depth in the academic literature. Methods In this qualitative study, we interviewed GDT experts (n = 33) from different disciplines to identify and better understand their moral views regarding these technologies. The pseudonymized transcripts were analyzed thematically. Results The respondents’ moral views were principally influenced by their attitudes towards (1) the uncertainty related to GDTs; (2) the alternatives to which they should be compared; and (3) the role humans should have in nature. Respondents agreed there is epistemic uncertainty related to GDTs, identified similar knowledge gaps, and stressed the importance of realistic expectations in discussions on GDTs. They disagreed about whether uncertainty provides a rationale to refrain from field trials (‘risks of intervention’ stance) or to proceed with phased testing to obtain more knowledge given the harms of the status quo (‘risks of non-intervention’ stance). With regards to alternatives to tackle vector-borne diseases, invasive species and agricultural pests, respondents disagreed about which alternatives should be considered (un)feasible and (in)sufficiently explored: conventional strategies (‘downstream solutions’ stance) or systematic changes to health care, political and agricultural systems (‘upstream solutions’ stance). Finally, respondents held different views on nature and whether the use of GDTs is compatible with humans’ role in nature (‘interference’ stance) or not (‘non-interference stance’). Conclusions This interview study helps to disentangle the debate on GDTs by providing a better understanding of the moral views of GDT experts. The obtained insights provide valuable stepping-stones for a constructive debate about underlying value conflicts and call attention to topics that deserve further (normative) reflection. Further evaluation of these issues can facilitate the debate on and responsible development of GDTs.

STUDY QUESTION To what extent do characteristics of germline genome editing (GGE) determine whether the general public supports permitting the clinical use of GGE? SUMMARY ANSWER The risk that GGE would cause congenital abnormalities had the largest effect on support for allowing GGE, followed by effectiveness of GGE, while costs, the type of application (disease or enhancement) and the effect on child well-being had moderate effects. WHAT IS KNOWN ALREADY Scientific progress on GGE has increased the urgency of resolving whether and when clinical application of GGE may be ethically acceptable. Various expert bodies have suggested that the treatment characteristics will be key in determining whether GGE is acceptable. For example, GGE with substantial risks (e.g. 15% chance of a major congenital abnormality) may be acceptable to prevent a severe disease but not to enhance non-medical characteristics or traits of an otherwise healthy embryo (e.g. eye colour or perhaps in the future more complex traits, such as intelligence). While experts have called for public engagement, it is unclear whether and how much the public acceptability of GGE is affected by the treatment characteristics proposed by experts. STUDY DESIGN, SIZE, DURATION The vignette-based survey was disseminated in 2018 among 1857 members of the Dutch general public. An online research panel was used to recruit a sample representing the adult Dutch general public. PARTICIPANTS/MATERIALS, SETTING, METHODS A literature review identified the key treatment characteristics of GGE: the effect on the well-being of the future child, use for disease or enhancement, risks for the future child, effectiveness (here defined as the chance of a live birth, assuming that if the GGE was not successful, the embryo would not be transferred), cost and availability of alternative treatments/procedures to prevent the genetic disease or provide enhancement (i.e. preimplantation genetic testing (PGT)), respectively. For each treatment characteristic, 2–3 levels were defined to realistically represent GGE and its current alternatives, donor gametes and ICSI with PGT. Twelve vignettes were created by fractional factorial design. A multinominal logit model assessed how much each treatment characteristic affected participants’ choices. MAIN RESULTS AND THE ROLE OF CHANCE The 1136 respondents (response rate 61%) were representative of the Dutch adult population in several demographics. Respondents were between 18 and 89 years of age. When no alternative treatment/procedure is available, the risk that GGE would cause (other) congenital abnormalities had the largest effect on whether the Dutch public supported allowing GGE (coefficient = −3.07), followed by effectiveness (coefficient = 2.03). Costs (covered by national insurance, coefficient = −1.14), the type of application (disease or enhancement; coefficient = −1.07), and the effect on child well-being (coefficient = 0.97) had similar effects on whether GGE should be allowed. If an alternative treatment/procedure (e.g. PGT) was available, participants were not categorically opposed to GGE, however, they were strongly opposed to using GGE for enhancement (coefficient = −3.37). The general acceptability of GGE was higher than participants’ willingness to personally use it (P LIMITATIONS, REASONS FOR CAUTION Some (e.g. ethnic, religious) minorities were not well represented. To limit complexity, not all characteristics of GGE could be included (e.g. out-of-pocket costs), therefore, the views gathered from the vignettes reflect only the choices presented to the respondents. The non-included characteristics could be connected to and alter the importance of the studied characteristics. This would affect how closely the reported coefficients reflect ‘real-life’ importance. WIDER IMPLICATIONS OF THE FINDINGS This study is the first to quantify the substantial impact of GGE’s effectiveness, costs (covered by national insurance), and effect on child well-being on whether the public considered GGE acceptable. In general, the participants were strikingly risk-averse, in that they weighed the risks of GGE more heavily than its benefits. Furthermore, although only a single study in one country, the results suggests that—if sufficiently safe and effective—the public may approve of using GGE (presumably combined with PGT) instead of solely PGT to prevent passing on a disease. The reported public views can serve as input for future consideration of the ethics and governance of GGE. STUDY FUNDING/COMPETING INTEREST(S) Young Academy of the Royal Dutch Academy of Sciences (UPS/RB/745), Alliance Grant of the Amsterdam Reproduction and Development Research Institute (2017–170116) and National Institutes of Health Intramural Research Programme. No competing interests. TRIAL REGISTRATION NUMBER N/A.

The number of publications on the governance of research with human embryo-like structures (hELS), i.e., 3D aggregates of human (induced) pluripotent stem cells made to model early human development, is growing rapidly. Public involvement is called for in many of these publications, but studies on public perspectives towards this emerging field remain lacking due to its novelty. To reduce the gap in the literature and contribute to the ongoing scholarly debate, we conducted interviews with Dutch lay citizens, health law and health care professionals, and interviewees reasoning from prominent worldviews in the Netherlands. This article reports on these participants’ views about the conceptual and moral qualification of hELS. With regard to the conceptual qualification of hELS, participants believed it should provide a shorthand for their (dis)similarity to human embryos, but differences remained with regard to the features upon which this (dis)similarity should be based. With regard to the moral qualification of hELS, participants believed this should depend on whether or not hELS possessed the features they considered morally relevant, among which those associated with sentience and a potential for continuous human development. Taken together, these findings align well with the arguments and positions traditionally found in related ethical debates and the recently proposed recommendations for the governance of research with hELS specifically. As such, they may also help allay concerns about lay publics not being able to meaningfully participate in debates about the ethical ramifications of (novel) scientific developments.

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.Lay abstractIn this study, we asked patients and laymen for their perspectives and opinions on the development, use and storage of so-called 'brain organoids'. Brain organoids are 3D cell structures that resemble parts of the human brain. These can be used as a model to study the development of the human brain and brain diseases. It is a promising technology that also raises ethical questions. For example, what kind of entity is a brain organoid and what should (and should not) be done with it? Our interview-study shows that patients and laymen are concerned that brain organoids might develop consciousness. They are also concerned about potential misuse of brain organoids. Overall, patients and laymen support the development of brain organoids if donors are well-informed and if responsible use is guaranteed by good governance. For them, good governance involves safety measures, well-defined boundaries to research and ethical oversight. The perspectives of these patients and laymen contribute to further development of brain organoids in a morally justifiable and socially acceptable way.

Over the years, the demand for ART with donated embryos has increased. Treatment can be performed using donated ‘surplus embryos’ from IVF treatment or with embryos intentionally created through so-called ‘double gamete donation’. Embryo donation is particularly sensitive because treatment results in the absence of a genetic link between the parent(s) and the child, creating complex family structures, including full genetic siblings living in another family in the case of surplus embryo donation. In this paper, we explore the ethical acceptability of embryo donation in light of the similarities and differences between surplus embryo donation and double gamete donation. We will argue that no overriding objections to either form of embryo donation exist. First of all, ART with donated embryos respects patients’ reproductive autonomy by allowing them to experience gestational parenthood. It also respects IVF patients’ reproductive autonomy by providing an additional option to discarding or donating surplus embryos to research. Second, an extensive body of empirical research has shown that a genetic link between parent and child is not a condition for a loving caring relationship between parent(s) and child. Third, the low moral status of a pre-implantation embryo signifies no moral duty for clinics to first use available surplus embryos or to prevent the development of (more) surplus embryos through double gamete donation. Fourth, there is no reason to assume that knowledge of having (full or half) genetically related persons living elsewhere provides an unacceptable impact on the welfare of donor-conceived offspring, existing children of the donors, and their respective families. Thus, patients and clinicians should discuss which form of ART would be suitable in their specific situation. To guarantee ethically sound ART with donated embryos certain conditions have to be met. Counselling of IVF patients should involve a discussion on the destination of potential surplus embryos. When counselling donors and recipient(s) a discussion of the significance of early disclosure of the child’s mode of conception, the implications of having children raised in families with whom they share no genetic ties, expectations around information-exchange and contact between donor and recipient families or genetically related siblings is warranted. Importantly, conclusions are mainly drawn from results of empirical studies on single gamete donation families. To evaluate the welfare of families created through surplus embryo donation or double gamete donation additional empirical research on these particular families is warranted.

New developments in the field of biomedicine can have extensive implications for society. To steer research efforts in a responsible direction, biomedical scientists should contribute to a forward-looking ethical, and societal evaluation of new developments. However, the question remains how to equip students sufficiently with the skills they need to contribute to this evaluation. In this paper, we examine how the four dimensions of Responsible Research and Innovation (anticipation, reflexivity, inclusivity, and responsiveness) inform the identification of learning goals and teaching approaches that contribute to developing these skills in biomedical scientists. We suggest that these educational approaches focus on the skills to anticipate intended and unintended outcomes, reflect on the epistemological and moral aspects of research practice, and be inclusive of the variety of voices in society. We argue that if these dimensions are properly integrated into biomedical curricula, they will help students develop the attitudinal aspects necessary for becoming responsive, and prepare them for implementing the dimensions of responsible research into their daily practice. This paper focuses specifically on skills biomedical scientists need for the responsible conduct of research. Therefore, our analysis results, at least in part, in domain-specific recommendations. We invite educators from other disciplines to do the same exercise, as we believe this could lead to tailored educational approaches by which students from various disciplinary backgrounds learn how they each have a role in contributing to socially robust and morally responsible research practice.

In a recent paper we note that oncologists are increasingly ordering genomic sequencing tests directly, without the involvement of clinical geneticists, for the purposes of differential diagnosis and personalised medicine. Non-geneticist clinicians are expected to assist their patients with decision-making about genetic testing, but guidance for doing so is lacking. In our paper, we take key tenets of the strong ethical tradition of informed consent as it has evolved within the practice of clinical genetics and extend them to the ‘mainstream’ setting of oncology. As part of the informed consent process, we argue, oncologists should inform patients about the possibility that suspected germline mutations, variants of uncertain significance (VUS), and unsolicited findings pertaining to other conditions may be detected as such information may be harmful. Also, we argued, patients have a right to opt out of receiving information about such additional findings.

Background: Gene drive technologies (GDTs) bias the inheritance of a genetic element within a population of non-human organisms, promoting its progressive spread across this population. If successful, GDTs may be used to counter intractable problems such as vector-borne diseases. A key issue in the debate on GDTs relates to what governance is appropriate for these technologies. While governance mechanisms for GDTs are to a significant extent proposed and shaped by professional experts, the perspectives of these experts have not been explored in depth.Methods: A total of 33 GDT experts from different professional disciplines were interviewed to identify, better understand, and juxtapose their perspectives on GDT governance. The pseudonymized transcripts were analyzed thematically.Results: Three main themes were identified: (1) engagement of communities, stakeholders, and publics; (2) power dynamics, and (3) decision-making. There was broad consensus amongst respondents that it is important to engage communities, stakeholders, and publics. Nonetheless, respondents had diverging views on the reasons for doing so and the timing and design of engagement. Respondents also outlined complexities and challenges related to engagement. Moreover, they brought up the power dynamics that are present in GDT research. Respondents stressed the importance of preventing the recurrence of historical injustices and reflected on dilemmas regarding whether and to what extent (foreign) researchers can legitimately make demands regarding local governance. Finally, respondents had diverging views on whether decisions about GDTs should be made in the same way as decisions about other environmental interventions, and on the decision-making model that should be used to decide about GDT deployment.Conclusions: The insights obtained in this interview study give rise to recommendations for the design and evaluation of GDT governance. Moreover, these insights point to unresolved normative questions that need to be addressed to move from general commitments to concrete obligations.

Study question What are main themes guiding the attitudes of Dutch professionals and lay citizens with regard to the creation and research use of embryo-like structures? Summary answer The attitudes of Dutch citizens indicate feelings of trust and distrust, distinct ‘embryo’ conceptualizations, competing moral values and beliefs, and criteria for adequate regulatory safeguards. What is known already Researchers are hopeful that the creation and research use of so-called embryo-like structures (ELS), i.e., stem cell-based models that can mimic (parts of) early (human) embryogenesis, may provide a morally less controversial way of studying the period during which most human etiologies rise while also reducing and replacing the use of animals and/or human embryos in research. Scholars in the humanities and social sciences underline that public engagement and support will be essential in harvesting this presumed moral advantage. Studies on the public endorsement of and attitudes towards synthetic embryology remain nevertheless significantly scarce. Study design, size, duration For this qualitative study with a cross-sectional design, data were collected through four semi-structured focus group discussions (N = 33) between August and September 2020. Participants/materials, setting, methods The focus group interviews consisted of one pilot interview (n = 5), two interviews with lay citizens (n = 21), and one interview with professionals (n = 7). The pilot participants and lay citizens were invited based on sociodemographic characteristics of the Dutch public. Professionals were selected from the networks of the authors based on their experience and affinity with ethical and legal debates on emerging biotechnologies. The transcriptions were analyzed using inductive thematic analysis. Main results and the role of chance From our analysis emerged four themes: (1) trust, distrust and ambivalence in synthetic embryology, mainly due to concerns about scientific compliance with societal norms, also in view of a projected future ability of using ELS for reproductive ends; (2) diversity of ELS-conceptualizations, also in terms of their (non-)distinction from ‘natural’ human embryos; (3) grounds for moral value and moral standing, in which a possible potential to grow into a human being and perceived tinkering with nature were considered key issues of moral concern; and (4) conditions for responsible embryo-like research, with an emphasis on legally binding the use of ELS to non-reproductive research purposes. Interestingly, whereas questions on the developmental potential of ELS were critical for both the attitudes of professionals and those of lay citizens, lay citizens were much more concerned that synthetic embryology could fundamentally change human existence for the worse. In particular, lay citizens worried that synthetic embryology could lead to dystopian futures, for instance, because it stimulates a ‘makeable human existence’ or because of a presumed inability to monitor and control scientific progress. These findings may imply a correlation between fear of research and degrees of (un)familiarity with the governance systems of science. Limitations, reasons for caution Qualitative research methods provide rich and in-depth data for an ethical analysis of motivations and intuitions, but do not allow generalizations of the findings to broader publics. Wider implications of the findings The results may provide a useful starting point for further discussion and analysis of adequate regulatory parameters for the creation and research use of ELS. The findings also show that societal dialogue and public consultation can play a significant role in addressing concerns about emerging (bio)technologies. Trial registration number not applicable

Contains fulltext : 215431.pdf (Publisher’s version ) (Closed access) BACKGROUND: Regenerative Medicine (RM) techniques aimed at the musculoskeletal system are increasingly translated to clinical trials and patient care. This revolutionary era in science raises novel ethical challenges. One of these challenges concerns the appropriate choice of the comparator in (randomized controlled) trials, including the ethically contentious use of sham procedures. To date, only general guidelines regarding the choice of the comparator exist. OBJECTIVE: To provide specific guidelines for clinical trial comparator choice in musculoskeletal RM. METHODS: In this manuscript, we discuss the ethics of comparator selection in RM trials. First, we make a classification of RM interventions according to different health states from disease prevention, return to normal health, postponing RM treatment, supplementing RM treatment, substituting RM treatment, improving RM outcome, and slowing progression. Subsequently, per objective, the accompanying ethical points to consider are evaluated with support from the available literature. RESULTS: a sham procedure is demonstrated to be an ethically acceptable comparator in RM trials with certain objectives, but less appropriate for musculoskeletal RM interventions that aim at preventing disease or substituting a surgical treatment. The latter may be compared to 'standard of care'. CONCLUSION: From a scientific perspective, choosing the correct comparator based on ethical guidelines is a step forward in the success of musculoskeletal RM.

Learning healthcare systems have recently emerged as a strategy to continuously use experiences and outcomes of clinical care for research purposes in precision medicine. Although it is known that learning healthcare transitions in general raise important ethical challenges, the ethical ramifications of such transitions in the specific context of precision medicine have not extensively been discussed. Here, we describe three levers that institutions can pull to advance learning healthcare systems in precision medicine: (1) changing testing of individual variability (such as genes); (2) changing prescription of treatments on the basis of (genomic) test results; and/or (3) changing the handling of data that link variability and treatment to clinical outcomes. Subsequently, we evaluate how patients can be affected if one of these levers are pulled: (1) patients are tested for different or more factors than before the transformation, (2) patients receive different treatments than before the transformation and/or (3) patients’ data obtained through clinical care are used, or used more extensively, for research purposes. Based on an analysis of the aforementioned mechanisms and how these potentially affect patients, we analyze why learning healthcare systems in precision medicine need a different ethical approach and discuss crucial points to consider regarding this approach.

The wider availability of genomic sequencing, notably gene panels, in cancer care allows for personalised medicine or the tailoring of clinical management to the genetic characteristics of tumours. While the primary aim of mainstream genomic sequencing of cancer patients is therapy-focussed, genomic testing may yield three types of results beyond the answer to the clinical question: suspected germline mutations, variants of uncertain significance (VUS), and unsolicited findings pertaining to other conditions. Ideally, patients should be prepared beforehand for the clinical and psychosocial consequences of such findings, for themselves and for their family members, and be given the opportunity to autonomously decide whether or not to receive such unsolicited genomic information. When genomic tests are mainstreamed into cancer care, so should accompanying informed consent practices. This paper outlines what mainstream oncologists may learn from the ethical tradition of informed consent for genomic sequencing, as developed within clinical genetics. It argues that mainstream informed consent practices should focus on preparing patients for three types of unsolicited outcomes, briefly and effectively. Also, it argues that when the chance of unsolicited findings is very low, opt-out options need not be actively offered. The use of a layered approach-integrated in information systems -should render informed consent feasible for non-geneticist clinicians in mainstream settings. (Inter) national guidelines for mainstream-ing informed consent for genomic sequencing must be developed.(c) 2021 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

It is time to revisit the “14-day limit”

Contains fulltext : 244228.pdf (Publisher’s version ) (Open Access) Using Parkinson's disease as an exemplary chronic condition, this Commentary discusses ethical aspects of using self-tracking for personal science, as compared to using self-tracking in the context of conducting clinical research on groups of study participants. Conventional group-based clinical research aims to find generalisable answers to clinical or public health questions. The aim of personal science is different: to find meaningful answers that matter first and foremost to an individual with a particular health challenge. In the case of personal science, the researcher and the participant are one and the same, which means that specific ethical issues may arise, such as the need to protect the participant against self-harm. To allow patient-led research in the form of personal science in the Parkinson field to evolve further, the development of a specific ethical framework for self-tracking for personal science is needed.

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.

"Induced pluripotent stem cells (iPSCs) have been praised for overcoming some of the ethical challenges of embryonic stem cell research, including oocyte donation for research and the destruction of human embryos. However, iPSC-research and iPSC-based interventions are not morally neutral alternatives and have their own ethical implications that are not fully understood yet. While there is some understanding of ethical issues surrounding the derivation, storage and use of human tissue, there is less understanding of how iPSC-research affects our society and morality. Consequentially, it is difficult to fully anticipate those implications. The notion of hard and soft impacts could benefit the understanding and anticipation of ethical implications of iPSC-research and interventions. Hard impacts are those direct physical and financial effects of iPSCs that are quantifiable and measurable. So-called soft impacts have a different focus. They consider how a technology or intervention affects our psychology, societal structures, morality and our behavior, hereby influencing the uptake, effects and evaluation of technology. So far, academic literature and researchers focus primarily on hard impacts of iPSC-research. Soft impacts are similarly important and therefore require more academic and regulatory attention. This talk focuses upon these understudied aspects of iPSC-research and technology. The goal is to show that for researchers and ethicists it is important to become aware of the soft impacts of iPSC-research and technology. This awareness could contribute to a broader understanding of the social value of stem cell research, anticipating ethical challenges of iPSC-research and in formulating new virtues for stem cell researchers. "

This commentary outlines challenges with identifying and implementing ethical, legal and societal considerations when initiating large-scale scientific programs and suggests best practices to ensure responsible research. ispartof: EMBO JOURNAL vol:39 issue:19 ispartof: location:England status: published

BackgroundOur human societies and certainly also (bio) medicine are more and more permeated with technology. There seems to be an increasing awareness among bioethicists that an effective and comprehensive approach to ethically guide these emerging biomedical innovations into society is needed. Such an approach has not been spelled out yet for bioethics, while there are frequent calls for ethical guidance of biomedical innovation, also by biomedical researchers themselves. New and emerging biotechnologies require anticipation of possible effects and implications, meaning the scope is not evaluative after a technology has been fully developed or about hypothetical technologies, but real-time for a real biotechnology.Main textIn this paper we aim to substantiate and discuss six ingredients that we increasingly see adopted by ethicists and that together constitute “ethics parallel research”. This approach allows to fulfil two aims: guiding the development process of technologies in biomedicine and providing input for the normative evaluation of such technologies. The six ingredients of ethics parallel research are: (1) disentangling wicked problems, (2) upstream or midstream ethical analysis, (3) ethics from within, (4) inclusion of empirical research, (5) public participation and (6) mapping societal impacts, including hard and soft impacts. We will draw on gene editing, organoid technology and artificial intelligence as examples to illustrate these six ingredients.ConclusionEthics parallel research brings together these ingredients to ethically analyse and proactively or parallel guide technological development. It widens the roles and judgements from the ethicist to a more anticipatory and constructively guiding role. Ethics parallel research is characterised by a constructive, rather than a purely critical perspective, it focusses on developing best-practices rather than outlining worst practice, and draws on insights from social sciences and philosophy of technology.

The ‘one‐way’ expert model of science communication is out of date. The new dialogue model requires from scientists more than just providing expert knowledge to the publics.

Background Learning health care systems (LHSs) have the potential to transform health care. However, this transformation process faces significant challenges. Materials and methods Based on proposals and early examples of LHSs in the literature and conceptual analysis of the LHS mission, we provide four models with distinct organizational and ethical implications that may facilitate the transformation. Results An LHS could be developed in the following ways: by taking away practical impediments that prevent patients and professionals from engaging in scientific research (model 1: optimization LHS); by routinely analyzing observational data from electronic health records and other sources (model 2: comprehensive data LHS); by making clinical decisions based on the outcomes of the aforementioned data analyses and directly evaluating the outcomes in order to continuously improve decision‐making (model 3: real‐time LHS); or by embedding clinical trials into routine care delivery (model 4: full LHS). Conclusions Each model has different ethical implications for consent and oversight. Also, the four‐model approach shows that reorganizing a health care center into an LHS is not an all‐or‐nothing decision. Rather, it is a choice from a menu of possibilities. Instead of discussing the advantages and disadvantages of the LHS menu in its entirety, the medical community should focus on the designs and ethical aspects of each of the separate options.

Background In precision medicine, somatic and germline DNA sequencing are essential to make genome-guided treatment decisions in patients with cancer. However, it can also uncover unsolicited findings (UFs) in germline DNA that could have a substantial impact on the lives of patients and their relatives. It is therefore critical to understand the preferences of patients with cancer concerning UFs derived from whole-exome (WES) or whole-genome sequencing (WGS). Methods In a quantitative multicentre study, adult patients with cancer (any stage and origin of disease) were surveyed through a digital questionnaire based on previous semi-structured interviews. Background knowledge was provided by showing two videos, introducing basic concepts of genetics and general information about different categories of UFs (actionable, non-actionable, reproductive significance, unknown significance). Results In total 1072 patients were included of whom 701 participants completed the whole questionnaire. Overall, 686 (85.1%) participants wanted to be informed about UFs in general. After introduction of four UFs categories, 113 participants (14.8%) changed their answer: 718 (94.2%) participants opted for actionable variants, 537 (72.4%) for non-actionable variants, 635 (87.0%) participants for UFs of reproductive significance and 521 (71.8%) for UFs of unknown significance. Men were more interested in receiving certain UFs than women: non-actionable: OR 3.32; 95%CI 2.05 to 5.37, reproductive significance: OR 1.97; 95%CI 1.05 to 3.67 and unknown significance: OR 2.00; 95%CI 1.25 to 3.21. In total, 244 (33%) participants conceded family members to have access to their UFs while still alive. 603 (82%) participants agreed to information being shared with relatives, after they would pass away. Conclusion Our study showed that the vast majority of patients with cancer desires to receive all UFs of genome testing, although a substantial minority does not wish to receive non-actionable findings. Incorporation of categories in informed consent procedures supports patients in making informed decisions on UFs

Rapid developments in genome technology and a growing interest in personalized healthcare have led to a large rise in the range and use of commercial DNA tests, the so-called direct-to-consumer genetic tests (DTC-GT). DTC-GT can be of a non-medical (e.g. for external characteristics) or medical nature; medical tests mostly indicate relative risks of disease e.g. Alzheimer's disease or certain forms of cancer. Low clinical validity and frequently unknown analytical validity of DTC-GT make it difficult to estimate the clinical usefulness of test results. From an ethical perspective, an increase in autonomy and possible health benefits must be weighed against loss of privacy, inadequate provision of information and the risk of misinterpretation of results, over-diagnosis, overtreatment and higher healthcare costs. It is unclear whether providing and implementing DTC-GT require authorisation under Dutch law in the Population Screening Act (Wet op het Bevolkingsonderzoek) or the Special Medical Procedures Act (Wet op BijzondereMedischeVerrichtingen). Clinical utility of DTC-GT can only increase if there is greater clarity on interpretation and scope of the law and regulations, when DTC-GT companies provide better information and guidance for consumers and when there is more focus on DTC-GT in education and training programmes for healthcare professionals.

Biomedical research often raises ethical questions that are usually addressed ad hoc or in retrospective. Real-time ethical engagement as part of research may be better suited to identify ethical issues.

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.

Molecular pathology is becoming an increasingly important discipline in oncology as molecular tumor characteristics will increasingly determine targeted clinical cancer care. In recent years, many technological advances have taken place that contributed to the development of molecular pathology. However, attention to ethical aspects has been lagging behind as illustrated by the lack of publications or professional guidelines. Existing guidelines or publications on ethical aspects of DNA sequencing are mostly aimed at germline or tumor sequencing in clinical genetics or biomedical research settings. As a result, large differences have been demonstrated in the process of tumor sequencing analysis between laboratories. In this perspective we discuss the ethical issues to consider in molecular pathology by following the process of tumor DNA sequencing analysis from the preanalytical to postanalytical phase. For the successful and responsible use of DNA sequencing in clinical cancer care, several moral requirements must be met, for example, those related to the interpretation and returning of genetic results, informed consent, and the retrospective as well as future use of genetic data for biomedical research. Many ethical issues are new to pathology or more stringent than in current practice because DNA sequencing could yield sensitive and potentially relevant data, such as clinically significant unsolicited findings. The context of molecular pathology is unique and complex, but many issues are similar to those applicable to clinical genetics. As such, existing scholarship in this discipline may be translated to molecular pathology with some adaptations and could serve as a basis for guideline development. For responsible use and further development of clinical cancer care, we recommend that pathologists take responsibility for the adequate use of molecular analyses and be fully aware and capable of dealing with the diverse, complex, and challenging aspects of tumor DNA sequencing, including its ethical issues. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Current advances in biotechnology open up unprecedented possibilities to transform human tissues into complex, valuable tissue products, such as organoids. Here, we propose consent for governance as a leading paradigm for the derivation, storage and use of complex human tissue products to ensure adjustment to changing ethical requirements.

Objective: Next-generation sequencing (NGS) is increasingly being employed in the context of personalized cancer treatment. Anticipating unsolicited findings that may arise during a NGS procedure is a key consideration; however, little is known about cancer patients' intentions, needs, and preferences concerning the return of unsolicited findings. Methods: A qualitative design using individual semi-structured interviews with 24 cancer patients was utilized to explore patients' decisions on whether to receive unsolicited findings from NGS. These interviews were subsequently analyzed using the constant comparative method to develop codes and themes. Results: We identified 4 interrelated themes that emerged in the context of the return of unsolicited findings. First, we describe how cancer patients expressed a strong need to control their lives. Second, we show the importance of family dynamics. Third, the NGS procedure regarding unsolicited findings is perceived as cognitively complex, and fourth, the procedure is also considered emotionally complex. Conclusions: The results of our study contribute to a better understanding of what cancer patients consider important and what may motivate and influence them when making decisions on the disclosure of unsolicited findings following NGS. We show how Joel Feinberg's classification of autonomy may help clinicians to better understand cancer patients' desire for autonomous decision making while also acknowledging the emotional and cognitive difficulties regarding the disclosure of unsolicited findings. These insights could be helpful for clinicians to guide patients through this complex process.