The Ethics of Cancer Screening Based on Race and Ethnicity.

Racial and ethnic disparities in incidence and mortality are well documented for many types of cancer. As a result, there is understandable policy and clinical interest in race- and ethnicity-based clinical screening guidelines to address cancer health disparities. Despite the theoretical benefits, such proposals do not typically address associated ethical considerations. Using the examples of gastric cancer and esophageal adenocarcinoma, which have demonstrated disparities according to race and ethnicity, this article examines relevant ethical arguments in considering screening based on race and ethnicity.Race- and ethnicity-based clinical preventive care services have the potential to improve the balance of harms and benefits of screening. As a result, programs focused on high-risk racial or ethnic groups could offer a practical alternative to screening the general population, in which the screening yield may be too low to demonstrate sufficient effectiveness. However, designing screening according to socially based categorizations such as race or ethnicity is controversial and has the potential for intersectional stigma related to social identity or other structurally mediated environmental factors. Other ethical considerations include miscategorization, unintended negative effects on health disparities, disregard for underlying risk factors, and the psychological costs of being assigned higher risk.Given the ethical considerations, the practical application of race and ethnicity in cancer screening is most relevant in multicultural countries if and only if alternative proxies are not available. Even in those instances, policymakers and clinicians should carefully address the ethical considerations within the historical and cultural context of the intended population. Further research on alternative proxies, such as social determinants of health and culturally based characteristics, could provide more adequate factors for risk stratification.

Exploring health and disease concepts in healthcare practice: an empirical philosophy of medicine study.

In line with recent proposals for experimental philosophy and philosophy of science in practice, we propose that the philosophy of medicine could benefit from incorporating empirical research, just as bioethics has. In this paper, we therefore take first steps towards the development of an empirical philosophy of medicine, that includes investigating practical and moral dimensions. This qualitative study gives insight into the views and experiences of a group of various medical professionals and patient representatives regarding the conceptualization of health and disease concepts in practice and the possible problems that surround them. This includes clinical, epistemological, and ethical issues. We have conducted qualitative interviews with a broad range of participants (n = 17), working in various health-related disciplines, fields and organizations. From the interviews, we highlight several different practical functions of definitions of health and disease. Furthermore, we discuss 5 types of problematic situations that emerged from the interviews and analyze the underlying conceptual issues. By providing theoretical frameworks and conceptual tools, and by suggesting conceptual changes or adaptations, philosophers might be able to help solve some of these problems. This empirical-philosophical study contributes to a more pragmatic way of understanding the relevance of conceptualizing health and disease by connecting the participants' views and experiences to the theoretical debate. Going back and forth between theory and practice will likely result in a more complex but hopefully also better and more fruitful understanding of health and disease concepts.

Preclinical Disease or Risk Factor? Alzheimer's Disease as a Case Study of Changing Conceptualizations of Disease.

Alzheimer's Disease (AD) provides an excellent case study to investigate emerging conceptions of health, disease, pre-disease, and risk. Two scientific working groups have recently reconceptualized AD and created a new category of asymptomatic biomarker positive persons, who are either said to have preclinical AD, or to be at risk for AD. This article examines how prominent theories of health and disease would classify this condition: healthy or diseased? Next, the notion of being "at risk"-a state somewhere in-between health and disease-is considered from various angles. It is concluded that medical-scientific developments urge us to let go of dichotomous ways of understanding disease, that the notion of "risk," conceptualized as an increased chance of getting a symptomatic disease, might be a useful addition to our conceptual framework, and that we should pay more attention to the practical usefulness and implications of the ways in which we draw lines and define concepts.

Early-Phase Clinical Trials of Bio-Artificial Organ Technology: A Systematic Review of Ethical Issues.

Regenerative medicine has emerged as a novel alternative solution to organ failure which circumvents the issue of organ shortage. In preclinical research settings bio-artificial organs are being developed. It is anticipated that eventually it will be possible to launch first-in-human transplantation trials to test safety and efficacy in human recipients. In early-phase transplantation trials, however, research participants could be exposed to serious risks, such as toxicity, infections and tumorigenesis. So far, there is no ethical guidance for the safe and responsible design and conduct of early-phase clinical trials of bio-artificial organs. Therefore, research ethics review committees will need to look to related adjacent fields of research, including for example cell-based therapy, for guidance. In this systematic review, we examined the literature on early-phase clinical trials in these adjacent fields and undertook a thematic analysis of relevant ethical points to consider for early-phase clinical trials of transplantable bio-artificial organs. Six themes were identified: cell source, risk-benefit assessment, patient selection, trial design, informed consent, and oversight and accountability. Further empirical research is needed to provide insight in patient perspectives, as this may serve as valuable input in determining the conditions for ethically responsible and acceptable early clinical development of bio-artificial organs.

Preferences of women with a vulnerable health status towards nudging for adequate pregnancy preparation as investment in health of future generations: a qualitative study.

BACKGROUND: Women with a vulnerable health status, as determined by a low socioeconomic status and poor lifestyle behaviours, are at risk for adverse pregnancy outcomes. Offering tailored preconception lifestyle care can significantly help to improve pregnancy outcomes. We hypothesize that so-called 'nudges' can be a successful way of increasing the uptake of preconception lifestyle care. A nudge is a behavioural intervention that supports healthy choices by making them easier to choose. Nudging, however, raises many moral questions. Effectiveness and respect for autonomy are, among other criteria, required for a nudge to be morally permissible. In general, the target group knows best what they find permissible and what would motivate them to change their lifestyle. Therefore, this study - conducted in women with a vulnerable health status - aimed to identify their preferences towards a nudge, provided via a mobile application that aims to help them adopt healthy lifestyle behaviours by offering rewards.  METHODS: We conducted semi-structured interviews with twelve women with a vulnerable health status. A framework approach was used to analyse the data. A thematic content analysis was conducted on five themes: (1) "Usefulness of an app as an integral information source", (2) "Permissibility and effects of offering rewards", (3) "Preferences regarding content", (4) "Preferences regarding type of rewards and system of allocation", and (5) "Barriers". RESULTS: Of the 12 participants, 11 deemed an app as integral information source concerning the preconception period useful. None of the participants objected to being nudged i.e., being rewarded for healthy behaviour. All participants stated that they would like the app to contain information on healthy nutrition and 8 participants wanted to know how to get pregnant quickly. Furthermore, participants stated that the freedom to choose the timing and content of the reward would increase the probability of successful behavioural change, and having to pay or contact a healthcare provider to access the app may prevent women using the app. CONCLUSIONS: These insights into the preferences of women with a vulnerable health status towards nudging will inform the design of an effective app-based nudge. This may help to improve prepregnancy health as investment in health of current and future generations.

Ethical Issues of Digital Twins for Personalized Health Care Service: Preliminary Mapping Study.

BACKGROUND: The concept of digital twins has great potential for transforming the existing health care system by making it more personalized. As a convergence of health care, artificial intelligence, and information and communication technologies, personalized health care services that are developed under the concept of digital twins raise a myriad of ethical issues. Although some of the ethical issues are known to researchers working on digital health and personalized medicine, currently, there is no comprehensive review that maps the major ethical risks of digital twins for personalized health care services. OBJECTIVE: This study aims to fill the research gap by identifying the major ethical risks of digital twins for personalized health care services. We first propose a working definition for digital twins for personalized health care services to facilitate future discussions on the ethical issues related to these emerging digital health services. We then develop a process-oriented ethical map to identify the major ethical risks in each of the different data processing phases. METHODS: We resorted to the literature on eHealth, personalized medicine, precision medicine, and information engineering to identify potential issues and developed a process-oriented ethical map to structure the inquiry in a more systematic way. The ethical map allows us to see how each of the major ethical concerns emerges during the process of transforming raw data into valuable information. Developers of a digital twin for personalized health care service may use this map to identify ethical risks during the development stage in a more systematic way and can proactively address them. RESULTS: This paper provides a working definition of digital twins for personalized health care services by identifying 3 features that distinguish the new application from other eHealth services. On the basis of the working definition, this paper further layouts 10 major operational problems and the corresponding ethical risks. CONCLUSIONS: It is challenging to address all the major ethical risks that a digital twin for a personalized health care service might encounter proactively without a conceptual map at hand. The process-oriented ethical map we propose here can assist the developers of digital twins for personalized health care services in analyzing ethical risks in a more systematic manner.

Health and disease as practical concepts: exploring function in context-specific definitions.

Despite the longstanding debate on definitions of health and disease concepts, and the multitude of accounts that have been developed, no consensus has been reached. This is problematic, as the way we define health and disease has far-reaching practical consequences. In recent contributions it is proposed to view health and disease as practical- and plural concepts. Instead of searching for a general definition, it is proposed to stipulate context-specific definitions. However, it is not clear how this should be realized. In this paper, we review recent contributions to the debate, and examine the importance of context-specific definitions. In particular, we explore the usefulness of analyzing the relation between the practical function of a definition and the context it is deployed in. We demonstrate that the variety of functions that health and disease concepts need to serve makes the formulation of monistic definitions not only problematic but also undesirable. We conclude that the analysis of the practical function in relation to the context is key when formulating context-specific definitions for health and disease. At last, we discuss challenges for the pluralist stance and make recommendations for future research.

On the reconceptualization of Alzheimer's disease.

In the hope of future treatments to prevent or slow down the disease, there is a strong movement towards an ever-earlier detection of Alzheimer's disease (AD). In conjunction with scientific developments, this has prompted a reconceptualization of AD, as a slowly progressive pathological process with a long asymptomatic phase. New concepts such as 'preclinical' and 'prodromal' AD have been introduced, raising a number of conceptual and ethical questions. We evaluate whether these new concepts are theoretically defensible, in light of theories of health and disease, and whether they should be understood as disease or as an at-risk state. We introduce a pragmatic view on disease concepts and argue that an evaluation of the reconceptualization of AD should also take its aims and effects into account, and assess their ethical acceptability. The reconceptualization of AD is useful to coordinate research into preventive strategies, and may potentially benefit future patients. However, in the short term, early detection and labelling of 'preclinical AD' can potentially harm people. Since there is no treatment available and the predictive value is unclear, it may only create a group of 'patients-in-waiting' who may suffer from anxiety, uncertainty and stigmatization, but will never actually develop dementia. We conclude that only if the promise of preventive medication materializes, will the reconceptualization of AD turn out unequivocally to be for the better. Otherwise, the reconceptualization may do more harm than good.

On the personal utility of Alzheimer's disease-related biomarker testing in the research context.

Many healthy volunteers choose to take part in Alzheimer's disease (AD) prevention studies because they want to know whether they will develop dementia-and what they can do to reduce their risk-and are therefore interested in learning the results of AD biomarker tests. Proponents of AD biomarker disclosure often refer to the personal utility of AD biomarkers, claiming that research participants will be able to use AD biomarker information for personal purposes, such as planning ahead or making important life decisions. In this paper, the claim that AD biomarkers have personal utility for asymptomatic individuals is critically assessed. It demonstrates that in the absence of clinical validity, AD biomarkers cannot have personal utility and do not serve research participants' autonomy. Over the next few years, many research groups will be confronted with participants' preferences to learn the results of AD biomarker tests. When researchers choose to make results available upon explicit request, they should ensure adequate information provision and education, notably on the uncertain clinical significance of AD biomarker information. Routine disclosure of AD biomarkers to cognitively unimpaired individuals in research settings cannot be justified with an appeal to the personal utility of AD biomarker information.

Recent insights into decision-making and their implications for informed consent.

Research from behavioural sciences shows that people reach decisions in a much less rational and well-considered way than was often assumed. The doctrine of informed consent, which is an important ethical principle and legal requirement in medical practice, is being challenged by these insights into decision-making and real-world choice behaviour. This article discusses the implications of recent insights of research on decision-making behaviour for the informed consent doctrine. It concludes that there is a significant tension between the often non-rational choice behaviour and the traditional theory of informed consent. Responsible ways of dealing with or solving these problems are considered. To this end, patient decisions aids (PDAs) are discussed as suitable interventions to support autonomous decision-making. However, current PDAs demand certain improvements in order to protect and promote autonomous decision-making. Based on a conception of autonomy, we will argue which type of improvements are needed.

Toward a global geroethics - gerontology and the theory of the good human life.

Gerontologists have proposed different concepts for ageing well such as 'successful ageing', 'active ageing', and 'healthy ageing'. These conceptions are primarily focused on maintaining health and preventing disease. But they also raise the questions: what is a good life in old age and how can it be achieved? While medical in origin, these concepts and strategies for ageing well also contain ethical advice for individuals and societies on how to act regarding ageing and old age. This connection between gerontology and ethics is overlooked by both schools of thought. We thus develop this research programme for a systematic geroethics in four steps. First, we analyze 'successful ageing' as put forward by Rowe and Kahn as a paradigmatic example of a gerontological conception of ageing well. Then, in a second step, we move from criticisms within gerontology to an ethical perspective; in particular, we want to clarify the problem of the claim of universal validity of conceptions of the good life. In a third constructive step, we explain how the 'capabilities approach' could be applied in this context as a normative foundation for the implicit normative assumptions of gerontological conceptions of ageing well, such as a particular choice of functionings, the ethical relevance of human agency, and the resulting claims of individuals towards society. Finally, using a concept developed by the German philosopher Ursula Wolf, we systematically develop the different aspects of the connection between ageing well and the theory of the good life in their full complexity and show their interconnectedness.

Good health checks according to the general public; expectations and criteria: a focus group study.

BACKGROUND: Health checks or health screenings identify (risk factors for) disease in people without a specific medical indication. So far, the perspective of (potential) health check users has remained underexposed in discussions about the ethics and regulation of health checks. METHODS: In 2017, we conducted a qualitative study with lay people from the Netherlands (four focus groups). We asked what participants consider characteristics of good and bad health checks, and whether they saw a role for the Dutch government. RESULTS: Participants consider a good predictive value the most important characteristic of a good health check. Information before, during and after the test, knowledgeable and reliable providers, tests for treatable (risk factors for) disease, respect for privacy, no unnecessary health risks and accessibility are also mentioned as criteria for good health checks. Participants make many assumptions about health check offers. They assume health checks provide certainty about the presence or absence of disease, that health checks offer opportunities for health benefits and that the privacy of health check data is guaranteed. In their choice for provider and test they tend to rely more on heuristics than information. Participants trust physicians to put the interest of potential health check users first and expect the Dutch government to intervene if providers other than physicians failed to do so by offering tests with a low predictive value, or tests that may harm people, or by infringing the privacy of users. CONCLUSIONS: Assumptions of participants are not always justified, but they may influence the choice to participate. This is problematic because choices for checks with a low predictive value that do not provide health benefits may create uncertainty and may cause harm to health; an outcome diametrically opposite to the one intended. Also, this may impair the relationship of trust with physicians and the Dutch government. To further and protect autonomous choice and to maintain trust, we recommend the following measures to timely adjust false expectations: advertisements that give an accurate impression of health check offers, and the installation of a quality mark.

Ethical acceptability of offering financial incentives for taking antipsychotic depot medication: patients' and clinicians' perspectives after a 12-month randomized controlled trial.

BACKGROUND: A randomized controlled trial 'Money for Medication'(M4M) was conducted in which patients were offered financial incentives for taking antipsychotic depot medication. This study assessed the attitudes and ethical considerations of patients and clinicians who participated in this trial. METHODS: Three mental healthcare institutions in secondary psychiatric care in the Netherlands participated in this study. Patients (n = 169), 18-65 years, diagnosed with schizophrenia, schizoaffective disorder or another psychotic disorder who had been prescribed antipsychotic depot medication, were randomly assigned to receive 12 months of either treatment as usual plus a financial reward for each depot of medication received (intervention group) or treatment as usual alone (control group). Structured questionnaires were administered after the 12-month intervention period. Data were available for 133 patients (69 control and 64 intervention) and for 97 clinicians. RESULTS: Patients (88%) and clinicians (81%) indicated that financial incentives were a good approach to improve medication adherence. Ethical concerns were categorized according to the four-principles approach (autonomy, beneficence, non-maleficence, and justice). Patients and clinicians alike mentioned various advantages of M4M in clinical practice, such as increased medication adherence and improved illness insight; but also disadvantages such as reduced intrinsic motivation, loss of autonomy and feelings of dependence. CONCLUSIONS: Overall, patients evaluated financial incentives as an effective method of improving medication adherence and were willing to accept this reward during clinical treatment. Clinicians were also positive about the use of this intervention in daily practice. Ethical concerns are discussed in terms of patient autonomy, beneficence, non-maleficence and justice. We conclude that this intervention is ethically acceptable under certain conditions, and that further research is necessary to clarify issues of benefit, motivation and the preferred size and duration of the incentive. TRIAL REGISTRATION: Nederlands Trial Register, number NTR2350 .

What is a good health check? An interview study of health check providers' views and practices.

BACKGROUND: Health checks identify (risk factors for) disease in people without symptoms. They may be offered by the government through population screenings and by other providers to individual users as 'personal health checks'. Health check providers' perspective of 'good' health checks may further the debate on the ethical evaluation and possible regulation of these personal health checks. METHODS: In 2015, we interviewed twenty Dutch health check providers on criteria for 'good' health checks, and the role these criteria play in their practices. RESULTS: Providers unanimously formulate a number of minimal criteria: Checks must focus on (risk factors for) treatable/preventable disease; Tests must be reliable and clinically valid; Participation must be informed and voluntary; Checks should provide more benefits than harms; Governmental screenings should be cost-effective. Aspirational criteria mentioned were: Follow-up care should be provided; Providers should be skilled and experienced professionals that put the benefit of (potential) users first; Providers should take time and attention. Some criteria were contested: People should be free to test on any (risk factor for) disease; Health checks should only be performed in people at high risk for disease that are likely to implement health advice; Follow up care of privately funded tests should not drain on collective resources. Providers do not always fulfil their own criteria. Their reasons reveal conflicts between criteria, conflicts between criteria and other ethical values, and point to components in the (Dutch) organisation of health care that hinder an ethical provision of health checks. Moreover, providers consider informed consent a criterion that is hard to establish in practice. CONCLUSIONS: According to providers, personal health checks should meet the same criteria as population screenings, with the exception of cost-effectiveness. Providers do not always fulfil their own criteria. Results indicate that in thinking about the ethics of health checks potential conflicts between criteria and underlying values should be explicated, guidance in weighing of criteria should be provided and the larger context should be taken into account: other actors than providers need to take up responsibility, and ideally benefits and harms of health checks should be weighed against other measures targeting (risk factors for) disease.

Imagining Moral Bioenhancement Practices: Drawing Inspiration from Moral Education, Public Health Ethics, and Forensic Psychiatry.

In this article, we consider contexts or domains in which (future) moral bioenhancement interventions possibly or most likely will be implemented. By looking closely at similar or related existing practices and their relevant ethical frameworks, we hope to identify ethical considerations that are relevant for evaluating potential moral bioenhancement interventions. We examine, first, debates on the proper scope of moral education; second, proposals for identifying early risk factors for antisocial behaviour; and third, the difficult balancing of individual freedom and third party concerns in (forensic) psychiatry. In imagining moral bioenhancement in practice, we observe that unlike other forms of enhancement, moral enhancement fundamentally asks how the interests and preferences of the individual and the interests of others should be weighed (in view of public safety and managing public risk). Highly diverse domains such as education, mental health, and the judicial domain might be involved, and moral bioenhancement might challenge existing institutional settings. Given these highly varied contexts and domains, it appears unlikely that there will be a distinct set of practices that will be referred to as "moral bioenhancement."

Personal utility in genomic testing: is there such a thing?

In ethical and regulatory discussions on new applications of genomic testing technologies, the notion of 'personal utility' has been mentioned repeatedly. It has been used to justify direct access to commercially offered genomic testing or feedback of individual research results to research or biobank participants. Sometimes research participants or consumers claim a right to genomic information with an appeal to personal utility. As of yet, no systematic account of the umbrella notion of personal utility has been given. This paper offers a definition of personal utility that places it in the middle of the spectrum between clinical utility and personal perceptions of utility, and that acknowledges its normative charge. The paper discusses two perspectives on personal utility, the healthcare perspective and the consumer perspective, and argues that these are too narrow and too wide, respectively. Instead, it proposes a normative definition of personal utility that postulates information and potential use as necessary conditions of utility. This definition entails that perceived utility does not equal personal utility, and that expert judgment may be necessary to help determine whether a genomic test can have personal utility for someone. Two examples of genomic tests are presented to illustrate the discrepancies between perceived utility and our proposed definition of personal utility. The paper concludes that while there is room for the notion of personal utility in the ethical evaluation and regulation of genomic tests, the justificatory role of personal utility is not unlimited. For in the absence of clinical validity and reasonable potential use of information, there is no personal utility.

Wish-fulfilling medicine in practice: the opinions and arguments of lay people.

BACKGROUND: Wish-fulfilling medicine appears to be on the rise. It can be defined as 'doctors and other health professionals using medical means (medical technology, drugs, and so on) in a medical setting to fulfil the explicitly stated, prima facie non-medical wish of a patient'. Some instances of wish fulfilling medicine can be understood as 'human enhancements'. AIM: The aim of this study is to map the normative opinions and arguments of lay people about wish-fulfilling medicine. METHODS: We conducted a qualitative study with lay people (five focus groups). We asked their opinions about five cases and the arguments for these opinions. Furthermore, we enquired about the role of the medical profession and the treating physician, and whether the participants saw a role for the government. RESULTS: The opinions and arguments used varied according to the example discussed. For instance, increased familiarity with a procedure like breast enhancement seems to garner more acceptance for that procedure, whereas completely new examples were considered less acceptable. Various different arguments were raised in focus groups; these included: people should be allowed to make up their own minds about this (autonomy); payment of the treatment; and concerns about risks. DISCUSSION: An ethical analysis of the emerging practice of wish-fulfilling medicine should take the normative views of all parties involved into account. Thus, it is important to establish what lay people think about wish-fulfilling medicine and in particular their arguments.

Informed consent in direct-to-consumer personal genome testing: the outline of a model between specific and generic consent.

Broad genome-wide testing is increasingly finding its way to the public through the online direct-to-consumer marketing of so-called personal genome tests. Personal genome tests estimate genetic susceptibilities to multiple diseases and other phenotypic traits simultaneously. Providers commonly make use of Terms of Service agreements rather than informed consent procedures. However, to protect consumers from the potential physical, psychological and social harms associated with personal genome testing and to promote autonomous decision-making with regard to the testing offer, we argue that current practices of information provision are insufficient and that there is a place--and a need--for informed consent in personal genome testing, also when it is offered commercially. The increasing quantity, complexity and diversity of most testing offers, however, pose challenges for information provision and informed consent. Both specific and generic models for informed consent fail to meet its moral aims when applied to personal genome testing. Consumers should be enabled to know the limitations, risks and implications of personal genome testing and should be given control over the genetic information they do or do not wish to obtain. We present the outline of a new model for informed consent which can meet both the norm of providing sufficient information and the norm of providing understandable information. The model can be used for personal genome testing, but will also be applicable to other, future forms of broad genetic testing or screening in commercial and clinical settings.

The ethical desirability of moral bioenhancement: a review of reasons.

BACKGROUND: The debate on the ethical aspects of moral bioenhancement focuses on the desirability of using biomedical as opposed to traditional means to achieve moral betterment. The aim of this paper is to systematically review the ethical reasons presented in the literature for and against moral bioenhancement. DISCUSSION: A review was performed and resulted in the inclusion of 85 articles. We classified the arguments used in those articles in the following six clusters: (1) why we (don't) need moral bioenhancement, (2) it will (not) be possible to reach consensus on what moral bioenhancement should involve, (3) the feasibility of moral bioenhancement and the status of current scientific research, (4) means and processes of arriving at moral improvement matter ethically, (5) arguments related to the freedom, identity and autonomy of the individual, and (6) arguments related to social/group effects and dynamics. We discuss each argument separately, and assess the debate as a whole. First, there is little discussion on what distinguishes moral bioenhancement from treatment of pathological deficiencies in morality. Furthermore, remarkably little attention has been paid so far to the safety, risks and side-effects of moral enhancement, including the risk of identity changes. Finally, many authors overestimate the scientific as well as the practical feasibility of the interventions they discuss, rendering the debate too speculative. SUMMARY: Based on our discussion of the arguments used in the debate on moral enhancement, and our assessment of this debate, we advocate a shift in focus. Instead of speculating about non-realistic hypothetical scenarios such as the genetic engineering of morality, or morally enhancing 'the whole of humanity', we call for a more focused debate on realistic options of biomedical treatment of moral pathologies and the concrete moral questions these treatments raise.