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With the launch of the Precision Medicine Initiative (PMI) in January 2015, the White House granted a high degree of federal support to an emerging biomedical paradigm. What explains this level of political recognition? Based on literature and policy analysis, we reconstruct the scientific and the legislative paths that led to the political endorsement of precision medicine. First, we describe the proliferation of personalized approaches to therapy ignited by the discovery of hemoprotein cytochrome P450 polymorphism in 1988. Then, we analyze the legislative history of precision medicine, from the unsuccessful introduction of Genomics and Personalized Medicine Acts in the second half of the last decade, to the highly acclaimed PMI. However, scientific progress and political contingency alone do not explain the upheaval of precision medicine as an institutionally supported initiative. On examination, the launch of a Precision Medicine Research Cohort and the incorporation of a participatory ethos into the fabric of the PMI proved to be crucial determinants of the political support for precision medicine. Weaving together the scientific and legislative antecedents of precision medicine, we illuminate how the mutual constitution of science and social order generates political recognition for innovative biomedical paradigms. [ABSTRACT FROM AUTHOR]

What has been called the new mechanistic philosophy conceives of mechanisms as the main providers of biological explanation. We draw on the characterization of the p53 gene in molecular oncology, to show that explaining a biological phenomenon (cancer, in our case) implies instead a dynamic interaction between the mechanistic level—rendered at the appropriate degree of ontological resolution—and far more general explanatory tools that perform a fundamental epistemic role in the provision of biological explanations. We call such tools “explanatory frameworks”. They are called frameworks to stress their higher level of generality with respect to bare mechanisms; on the other hand, they are called explanatory because, as we show in this paper, their importance in explaining biological phenomena is not secondary with respect to mechanisms. We illustrate how explanatory frameworks establish selective and local criteria of causal relevance that drive the search for, characterisation and usage of biological mechanisms. Furthermore, we show that explanatory frameworks allow for changes of scientific perspective on the causal relevance of mechanisms going beyond the account provided by the new mechanistic philosophy. [Copyright &y& Elsevier]

This paper explores the epistemology of extrapolation from model organisms to humans in molecular medicine. We take into account two common views on the issue, the homology view and the disanalogy view. In response to both interpretations, we argue that the foundational basis of extrapolations cannot simply be provided by homology and that relevant disanalogies can, thanks to the techniques of molecular biology, be experimentally controlled and exploited to allow useful and reliable extrapolations. The case of "humanised mice" in the context of cancer stem cell research provides evidence of how animal models can be construed to approximate bona fide causal analogue models of human diseases. To supplement this view we show how the epistemology of model organisms needs to take into account the engineering side of molecular medicine. Model organisms are often manipulated to create analogies or remove disanalogies with the target system. We maintain that highlighting this feature is fundamental to explain what warrants extrapolation in the search for the molecular causes of disease. [ABSTRACT FROM AUTHOR]

In this paper we discuss the conditions for the possession of intentional states (especially beliefs) and for intentional agency. We then explore the implications of an analysis of intentionality in non-human animals for their entitlement to ethical treatment, and review the potential advantages and epistemological difficulties of relying on the scientific study of animal mindedness to draw ethical conclusions. In the end, we argue that ethical debates on the treatment of animals, and in particular considerations about welfare, can benefit considerably from the enterprise of exploring the extent to which non-human animals are minded [ABSTRACT FROM AUTHOR]

Since the first successful application of the gene editing method based on the CRISPR/Cas-system, the technology has demonstrated great potential but also sparked a series of ethical concerns. Some of the issues are already known from earlier gene editing debates. However, the possibility of CRISPR to target genes with high accuracy and the easy application that allows a biohacker to experiment with a simple toolkit ordered online have introduced new ethical challenges. Further, thanks to preprint servers such as bioRxiv, biomedical research results are more and more accessible with little delay after an experiment was conducted. This enables researchers all over the world to participate and conduct their own experiments, making it a global endeavour. Not only does this make it difficult to monitor and regulate the technology but also speeds up the technological development significantly.CRISPR is only one of many examples of recent advancements with potentially high consequences for society at large. We think it is therefore paramount to identify new issues, understand their nature and assess their impact in a timely manner. In this paper, we propose the integration of digital methods into the toolbox of modern empirical bioethics and demonstrate their potential with two examples: We used 1) crawling and network analysis for hypothesis building, and 2) sentiment analysis to assess the public's attitudes towards CRISPR on Twitter over a six and a half years period. [ABSTRACT FROM AUTHOR]

A new active substance called "dersimelagon" (MT-7117) is being tested as an alternative treatment option for Erythropoietic protoporphyria (EPP). At the moment, dersimelagon is being tested both in the US and in Europe in a phase III placebo-controlled RCT. However, given the availability of an already approved treatment option for EPP the use of a placebo arm is questionable from an ethics point of view. We analyze the issue and suggest that a noninferiority active-control trial without placebo is an ethically and scientifically more valid design to test the efficacy of dersimelagon as well as other EPP treatments. [ABSTRACT FROM AUTHOR]

Background: Explainability is one of the most heavily debated topics when it comes to the application of artificial intelligence (AI) in healthcare. Even though AI-driven systems have been shown to outperform humans in certain analytical tasks, the lack of explainability continues to spark criticism. Yet, explainability is not a purely technological issue, instead it invokes a host of medical, legal, ethical, and societal questions that require thorough exploration. This paper provides a comprehensive assessment of the role of explainability in medical AI and makes an ethical evaluation of what explainability means for the adoption of AI-driven tools into clinical practice.Methods: Taking AI-based clinical decision support systems as a case in point, we adopted a multidisciplinary approach to analyze the relevance of explainability for medical AI from the technological, legal, medical, and patient perspectives. Drawing on the findings of this conceptual analysis, we then conducted an ethical assessment using the "Principles of Biomedical Ethics" by Beauchamp and Childress (autonomy, beneficence, nonmaleficence, and justice) as an analytical framework to determine the need for explainability in medical AI.Results: Each of the domains highlights a different set of core considerations and values that are relevant for understanding the role of explainability in clinical practice. From the technological point of view, explainability has to be considered both in terms how it can be achieved and what is beneficial from a development perspective. When looking at the legal perspective we identified informed consent, certification and approval as medical devices, and liability as core touchpoints for explainability. Both the medical and patient perspectives emphasize the importance of considering the interplay between human actors and medical AI. We conclude that omitting explainability in clinical decision support systems poses a threat to core ethical values in medicine and may have detrimental consequences for individual and public health.Conclusions: To ensure that medical AI lives up to its promises, there is a need to sensitize developers, healthcare professionals, and legislators to the challenges and limitations of opaque algorithms in medical AI and to foster multidisciplinary collaboration moving forward. [ABSTRACT FROM AUTHOR]

Effy Vayena and colleagues argue that machine learning in medicine must offer data protection, algorithmic transparency, and accountability to earn the trust of patients and clinicians. [ABSTRACT FROM AUTHOR]

Introduction: Artificial intelligence (AI) has the potential to transform clinical decision-making as we know it. Powered by sophisticated machine learning algorithms, clinical decision support systems (CDSS) can generate unprecedented amounts of predictive information about individuals' health. Yet, despite the potential of these systems to promote proactive decision-making and improve health outcomes, their utility and impact remain poorly understood due to their still rare application in clinical practice. Taking the example of AI-powered CDSS in stroke medicine as a case in point, this paper provides a nuanced account of stroke survivors', family members', and healthcare professionals' expectations and attitudes towards medical AI. Methods: We followed a qualitative research design informed by the sociology of expectations, which recognizes the generative role of individuals' expectations in shaping scientific and technological change. Semi-structured interviews were conducted with stroke survivors, family members, and healthcare professionals specialized in stroke based in Germany and Switzerland. Data was analyzed using a combination of inductive and deductive thematic analysis. Results: Based on the participants' deliberations, we identified four presumed roles that medical AI could play in stroke medicine, including an administrative, assistive, advisory, and autonomous role AI. While most participants held positive attitudes towards medical AI and its potential to increase accuracy, speed, and efficiency in medical decision making, they also cautioned that it is not a stand-alone solution and may even lead to new problems. Participants particularly emphasized the importance of relational aspects and raised questions regarding the impact of AI on roles and responsibilities and patients' rights to information and decision-making. These findings shed light on the potential impact of medical AI on professional identities, role perceptions, and the doctor-patient relationship. Conclusion: Our findings highlight the need for a more differentiated approach to identifying and tackling pertinent ethical and legal issues in the context of medical AI. We advocate for stakeholder and public involvement in the development of AI and AI governance to ensure that medical AI offers solutions to the most pressing challenges patients and clinicians face in clinical care. [ABSTRACT FROM AUTHOR]

Highlights: [•] Familial Alzheimer's disease (FAD) is attracting a growing scientific interest. [•] PSEN2 mutations represent the less common cause of FAD. [•] Mutations of the PSEN2 gene are mostly associated to a “typical” AD phenotype. [•] Improved phenotyping of FAD cases may have a relevant impact. [Copyright &y& Elsevier]

Background: There are intense discussions about the ethical and societal implications of biomedical engineering, but little data to suggest how scientists think about the ethics of their work. The aim of this study is to describe how scientists frame the ethics of their research, with a focus on the field of molecular systems engineering., Methods: Semi-structured qualitative interviews were conducted during 2021-2022, as part of a larger study. This analysis includes a broad question about how participants view ethics as related to their work, with follow up probes about the topics they consider most important. Interviews were transcribed, inductively coded by two researchers to consensus, and analyzed thematically., Results: Twenty-four scientists participated in the study. Interviewees hold positions as professors, principal investigators, and senior staff researchers in universities or research institutes in the United States and Europe. Among those scientists who reported reflecting on ethical considerations in their work, many equated ethics with research ethics topics (e.g., safety, replicability), or with regulation and guidelines. Participants expressed the view that ethical issues are primarily relevant for clinical trials of bioengineered products, or for those working with animal or human subjects. Scientists described their research as "too early" or "not examining anything living" with regard to ethical reflection. Finally, many felt that ethics is seen as territory for experts and therefore beyond scientists' competencies., Conclusions: Molecular systems engineering scientists currently focus on regulatory aspects as the framework for their ethical analyses. They describe using a framework to define when life arises, as a means to determine when further ethical engagement is warranted. Further research is needed to investigate how scientists relate to the ethics of their scientific work, and build consensus around concepts of life, autonomous behavior, and physiological relevance of bioengineered systems.

In the evolving landscape of digital medicine, digital biomarkers have emerged as a transformative source of health data, positioning them as an indispensable element for the future of the discipline. This necessitates a comprehensive exploration of the ethical complexities and challenges intrinsic to this cutting-edge technology. To address this imperative, we conducted a scoping review, seeking to distill the scientific literature exploring the ethical dimensions of the use of digital biomarkers. By closely scrutinizing the literature, this review aims to bring to light the underlying ethical issues associated with the development and integration of digital biomarkers into medical practice., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Andreoletti et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Digital health innovation is expected to transform healthcare, but it also generates ethical and societal concerns, such as privacy risks, and biases that can compound existing health inequalities. While such concerns are widely recognized, existing regulatory principles, oversight methods and ethical frameworks seem out of sync with digital health innovation. New governance and innovation best practices are thus needed to bring such principles to bear with the reality of business, innovation, and regulation.To grant practical insight into best practices for responsible digital health innovation, we conducted a qualitative study based on an interactive engagement methodology. We engaged key stakeholders (n = 46) operating at the translational frontier of digital health. This approach allowed us to identify three clusters of governance and innovation best practices in digital health innovation: i) inclusive co-creation, ii) responsive regulation, and iii) value-driven innovation. Our study shows that realizing responsible digital health requires diverse stakeholders' commitment to adapt innovation and regulation practices, embracing co-creation as the default modus operandi for digital health development. We describe these collaborative practices and show how they can ensure that innovation is neither slowed by overregulation, nor leads to unethical outcomes., (© 2024. The Author(s).)

Recent research has challenged the notion that dementia is an inevitable outcome of age-related cognitive decline, highlighting the possibility of preventing or delaying onset by addressing specific risk factors. This paradigm shift suggests that prevention through lifestyle modifications and early interventions is possible, potentially averting millions of cases worldwide. This study explores the translation of scientific evidence on dementia prevention into public health policy in Switzerland. Combining the analysis of official policy documents and qualitative interviews with stakeholders, the study explores potential barriers and challenges to implementing preventive intervenions or programs, as well as opportunities for improvement. Results indicate a significant gap in incorporating emerging scientific evidence on dementia prevention into health policies and disseminating information to the public in Switzerland. This study underscores the need for a collaborative and coordinated approach to address these barriers and effectively translate scientific findings into preventive policies and campaigns. These insights can inform policy and targeted programs in Switzerland both at the federal and the cantonal level, eventually serving as a model for other countries seeking to translate evidence-based dementia prevention strategies into public health policies. By bridging the gap between research and policy, significant progress can be made in preventing or delaying the onset of dementia, providing significant benefits to individuals, families, and society.

Digital technologies hold promise to modernize healthcare. Such opportunity should be leveraged also to address the needs of rapidly ageing populations. Against this backdrop, this paper examines the use of wearable devices for promoting healthy ageing. Previous work has assessed the prospects of digital technologies for health promotion and disease prevention in older adults. However, to our knowledge, ours is one of the first attempts to specifically address the use of wearables for healthy ageing, and to offer ethical insights for assessing the prospects of leveraging wearable devices in this context. We provide an analysis of the considerable opportunities associated with the use of wearables for healthy ageing, with a focus on the five domains of intrinsic capacity: locomotion, sensory functions, psychological aspects, cognition, and vitality. We then highlight current limitations and ethical challenges of such approach to healthy ageing, including issues related to access, inclusion, privacy, surveillance, autonomy, and regulation. We conclude by discussing the implications of our analysis in light of current debates on the ethics of digital health, and suggest measures to address the identified challenges., Competing Interests: the authors declare no competing interests.

Background: Tissue engineering is a multidisciplinary field that combines principles from cell biology, bioengineering, material sciences, medicine and surgery to create functional and viable bioproducts that can be used to repair or replace damaged or diseased tissues in the human body. The complexity of tissue engineering can affect the prospects of efficiently translating scientific discoveries in the field into scalable clinical approaches that could benefit patients. Organizational challenges may play a key role in the clinical translation of tissue engineering for the benefit of patients., Methods: To gain insight into the organizational aspects of tissue engineering that may create impediments to efficient clinical translation, we conducted a retrospective qualitative case study of one tissue engineering multi-site translational project on knee cartilage engineered tissue grafts. We collected qualitative data using a set of different methods: semi-structured interviews, documentary research and audio-visual content analysis., Results: Our study identified various challenges associated to first-in-human trials in tissue engineering particularly related to: logistics and communication; research participant recruitment; clinician and medical student participation; study management; and regulation., Conclusions: While not directly generalizable to other types of advanced therapies or to regenerative medicine in general, our results offer valuable insights into organizational barriers that may prevent efficient clinical translation in the field of tissue engineering., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s) 2024.)

Data access and data sharing are vital to advance medicine. A growing number of public private partnerships are set up to facilitate data access and sharing, as private and public actors possess highly complementary health data sets and treatment development resources. However, the priorities and incentives of public and private organizations are frequently in conflict. This has complicated partnerships and sparked public concerns around ethical issues such as trust, justice or privacy-in turn raising an important problem in business and data ethics: how can ethical theory inform the practice of public and private partners to mitigate misaligned incentives, and ensure that they can deliver societally beneficial innovation? In this paper, we report on the development of the Swiss Personalized Health Network's ethical guidelines for health data sharing in public private partnerships. We describe the process of identifying ethical issues and engaging core stakeholders to incorporate their practical reality on these issues. Our report highlights core ethical issues in health data public private partnerships and provides strategies for how to overcome these in the Swiss health data context. By agreeing on and formalizing ethical principles and practices at the beginning of a partnership, partners and society can benefit from a relationship built around a mutual commitment to ethical principles. We present this summary in the hope that it will contribute to the global data sharing dialogue., Competing Interests: Competing InterestsEffy Vayena and Alessandro Blasimme received an expert fee from Roche in 2020. Effy Vayena is a member in IQVIA’s ethics advisory panel and in Merck KGaA’s Digital Ethics Advisory Panel. Constantin Landers, Kelly Ormond, and Caroline Brall have no financial interests to declare., (© The Author(s) 2023.)

The online space has become a digital public square, where individuals interact and share ideas on the most trivial to the most serious of matters, including discussions of controversial ethical issues in science, technology and medicine. In the last decade, new disciplines like computational social science and social data science have created methods to collect and analyse such data that have considerably expanded the scope of social science research. Empirical bioethics can benefit from the integration of such digital methods to investigate novel digital phenomena and trace how bioethical issues take shape online.Here, using concrete examples, we demonstrate how novel methods based on digital approaches in the social sciences can be used effectively in the domain of bioethics. We show that a digital turn in bioethics research aligns with the established aims of empirical bioethics, integrating with normative analysis and expanding the scope of the discipline, thus offering ways to reinforce the capacity of bioethics to tackle the increasing complexity of present-day ethical issues in science and technology. We propose to call this domain of research in bioethics digital bioethics ., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Pediatric health care providers caring for patients and families with genetic disease will encounter a range of ethical issues. These include traditional pediatric health care issues, such as surrogate decision making and end-of-life care. Genetic testing raises the importance of informed consent for potential risks that move beyond the oft discussed physical risks and into longer term concepts such as psychological impact, privacy and potential discrimination. Predictive testing in childhood also raises questions of whether the child has an autonomy interest in delaying testing until they have decision making capacity to do so on their own. And finally, treatments including gene therapies and gene editing, may raise issues of identity for families dealing with genetic disease., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Drugs addressing unmet medical needs can change the lives of millions. Developing and validating new drugs can, however, take many years. To streamline the assessment of new drugs, regulatory agencies have long established shortened review pathways. Among these programs, Accelerated Approval (AA) has recently come under scrutiny due to the U.S. Food and Drug Administration's decision to authorize Aducanumab, the first Alzheimer's disease drug. This decision attracted fierce criticism due to the allegedly insufficient evidence about the safety and efficacy of the drug. While considerable scholarly attention has been devoted to this case, the ethical aspects of the AA regulatory pathway have so far remained relatively unexplored. In this paper, we set out to fill this gap. We illustrate six conditions that should be met for AA to be ethically acceptable: moral solicitude, evidence, risk mitigation, impartiality, sustainability, and transparency. We discuss such conditions and suggest practical steps to implement them in regulatory and oversight processes. Taken together, our six conditions represent a benchmark for assessing the ethical validity of AA processes and decisions., (© 2023 The Authors. Bioethics published by John Wiley & Sons Ltd.)

As digital technologies such as smartphones and fitness bands become more ubiquitous, individuals can engage in self-monitoring and self-care, gaining greater control over their health trajectories along the life-course. These technologies appeal particularly to young people, who are more familiar with digital devices. How this digital transformation facilitates health promotion is therefore a topic of animated debate. However, most research to date focuses on the promise and peril of digital health promotion (DHP) in high-income settings, while DHP in low- and middle-income countries (LMICs) remain largely unexplored. This narrative review aims to fill this gap by critically examining key ethical challenges of implementing DHP in LMICs, with a focus on young people. In the existing literature, we identified potential impediments as well as enabling conditions. Aspects to consider in unlocking the potential of DHP include (1) addressing the digital divide and structural injustice in data-related practices; (2) engaging the target population and responding to their specific needs given their economic, cultural, and social contexts; (3) monitoring the quality and impact of DHP over time; and (4) improving responsible technology governance and its implementation. Addressing these concerns could result in meaningful health benefits for populations lacking access to more conventional healthcare resources., Competing Interests: We have read the journal’s policy and the authors of this manuscript declare no competing interests. EV is a member of IQVIA’s ethics advisory panel and a member of Merck KGaA digital ethics advisory panel., (Copyright: © 2023 Ferretti et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Human pluripotent stem cells can be used to derive in vitro models recapitulating post-implantation human embryos. While useful for research purposes, such integrated embryo models raise ethical issues that need to be addressed to facilitate ethically appropriate policies and regulations that permit scientific ingenuity and medical progress., Competing Interests: Declaration of interests J.S. is a member of Merck KGaA’s Ethics Advisory Panel and Stem Cell Research Oversight Committee; a member of IQVIA’s Ethics Advisory Panel; a member of Aspen Neurosciences Clinical Advisory Panel; was a member of a Merck Data Monitoring Committee; and was a consultant to Biogen., (Copyright © 2023 Elsevier Inc. All rights reserved.)