How to derive ethically appropriate recommendations for action? A methodology for applied ethics.

Researchers in applied ethics, and some areas of bioethics particularly, aim to develop concrete and appropriate recommendations for action in morally relevant real-world situations. When proceeding from more abstract levels of ethical reasoning to such concrete recommendations, however, even with regard to the very same normative principle or norm, it seems possible to develop divergent or even contradictory recommendations for action regarding a certain situation. This may give the impression that such recommendations would be arbitrary and, hence, not well justified. Against this background, we, first, aim at showing that ethical recommendations for action, although being contingent in some sense, are not arbitrary if developed appropriately. For this purpose, we examine two types of contingencies arising in applied ethics reasoning based on recent examples of recommendations for action in the context of the COVID-19 pandemic. In doing so, we refer to a three-step model of ethical reasoning towards recommendations for actions. This, however, leaves open the question of how applied ethics may cope with contingent recommendations for action. Therefore, in a second step, we analyze the role of bridge principles for developing ethically appropriate recommendations for action, i.e., principles which connect normative claims with relevant empirical information to justify certain recommendations for action in a given morally relevant situation. Finally, we discuss some implications for reasoning and reporting in empirically informed ethics.

Joint Interaction and Mutual Understanding in Social Robotics.

Social robotics aims at designing robots capable of joint interaction with humans. On a conceptual level, sufficient mutual understanding is usually said to be a necessary condition for joint interaction. Against this background, the following questions remain open: in which sense is it legitimate to speak of human-robot joint interaction? What exactly does it mean to speak of humans and robots sufficiently understanding each other to account for human-robot joint interaction? Is such joint interaction effectively possible by reference, e.g., to the mere ascription or simulation of understanding? To answer these questions, we first discuss technical approaches which aim at the implementation of certain aspects of human-human communication and interaction in social robots in order to make robots accessible and understandable to humans and, hence, human-robot joint interaction possible. Second, we examine the human tendency to anthropomorphize in this context, with a view to human understanding of and joint interaction with social robots. Third, we analyze the most prominent concepts of mutual understanding and their implications for human-robot joint interaction. We conclude that it is-at least for the time being-not legitimate to speak of human-robot joint interaction, which has relevant implications both morally and ethically.

[AI-Based Self-Tracking of the Mind: Philosophical-Ethical Implications]. / KI-gestützte Selbstvermessung der Psyche: Philosophisch-ethische Implikationen.

OBJECTIVE: AI-based applications are increasingly developed to support users to digitally record, manage and change their emotions, beliefs and behavior patterns. Such forms of self-tracking in the mental sphere are accompanied by a variety of medical benefits in diagnostics, prevention, and therapy. This article pursues the question of which philosophical-ethical implications must be taken into account when dealing with these advantages. METHODS: First, some AI-based applications for self-tracking of mental characteristics and processes are outlined. Subsequently, relevant philosophical-ethical implications are presented. RESULTS: The following aspects prove to be normatively relevant: improvement versus reduction of self-determination; improvement of self-knowledge versus alienation; positive versus negative aspects of self-responsible health care; epistemic challenges of AI applications; difficulties of conceptual and normative definitions in the applications.

Human germline editing in the era of CRISPR-Cas: risk and uncertainty, inter-generational responsibility, therapeutic legitimacy.

BACKGROUND: Clustered Regularly Interspaced Short Palindromic Repeats-associated (CRISPR-Cas) technology may allow for efficient and highly targeted gene editing in single-cell embryos. This possibility brings human germline editing into the focus of ethical and legal debates again. MAIN BODY: Against this background, we explore essential ethical and legal questions of interventions into the human germline by means of CRISPR-Cas: How should issues of risk and uncertainty be handled? What responsibilities arise regarding future generations? Under which conditions can germline editing measures be therapeutically legitimized? For this purpose, we refer to a scenario anticipating potential further development in CRISPR-Cas technology implying improved accuracy and exclusion of germline transmission to future generations. We show that, if certain concepts regarding germline editing are clarified, under such conditions a categorical prohibition of one-generation germline editing of single-cell embryos appears not to be ethically or legally justifiable. CONCLUSION: These findings are important prerequisites for the international debate on the ethical and legal justification of germline interventions in the human embryo as well as for the harmonization of international legal standards.

Lethal privacy: Quantifying life years lost if the right to informational self-determination guides genetic screening for Lynch syndrome.

Genetic relatives of hereditary colorectal cancer patients with Lynch syndrome (LS) are at risk of cancer. Testing both colorectal cancer patients and relatives of mutation carriers for LS allows targeted prevention. However, this could mean disclosing sensitive health data to family members. In light of potential trade-offs between cost-effectiveness and patient privacy, this study investigates the implications of increasing test uptake in Germany. Out of 22 screening strategies for LS, the non-dominated and current German strategies were assessed from the perspective of the statutory health insurance. Life years gained by increased prevention were estimated with Markov models. The effects and implications of different test uptake rates in index patients and their relatives were investigated by scenario analysis. Privacy limitations could yield health gains of up to 2500 undiscounted life years for first-degree relatives of index patients and substantially improve cost-effectiveness. However, this approach may contradict the right to informational self-determination. This study demonstrates the effect higher LS test uptakes could have on the lives and rights of colorectal cancer patients and their relatives. It shows potential conflicts between the efficient use of health care resources on the one hand and reasonable consideration of patient autonomy on the other.

Applying systems biology to biomedical research and health care: a précising definition of systems medicine.

BACKGROUND: Systems medicine has become a key word in biomedical research. Although it is often referred to as P4-(predictive, preventive, personalized and participatory)-medicine, it still lacks a clear definition and is open to interpretation. This conceptual lack of clarity complicates the scientific and public discourse on chances, risks and limits of Systems Medicine and may lead to unfounded hopes. Against this background, our goal was to develop a sufficiently precise and widely acceptable definition of Systems Medicine. METHODS: In a first step, PubMed was searched using the keyword "systems medicine". A data extraction tabloid was developed putting forward a means/ends-division. Full-texts of articles containing Systems Medicine in title or abstract were screened for definitions. Definitions were extracted; their semantic elements were assigned as either means or ends. To reduce complexity of the resulting list, summary categories were developed inductively. In a second step, we applied six criteria for adequate definitions (necessity, non-circularity, non-redundancy, consistency, non-vagueness, and coherence) to these categories to derive a so-called précising definition of Systems Medicine. RESULTS: We identified 185 articles containing the term Systems Medicine in title or abstract. 67 contained at least one definition of Systems Medicine. In 98 definitions, we found 114 means and 132 ends. From these we derived the précising definition: Systems Medicine is an approach seeking to improve medical research (i.e. the understanding of complex processes occurring in diseases, pathologies and health states as well as innovative approaches to drug discovery) and health care (i.e. prevention, prediction, diagnosis and treatment) through stratification by means of Systems Biology (i.e. data integration, modeling, experimentation and bioinformatics). Our study also revealed the visionary character of Systems Medicine. CONCLUSIONS: Our insights, on the one hand, allow for a realistic identification of actual ethical as well as legal issues arising in the context of Systems Medicine and, in consequence, for a realistic debate of questions concerning its matter and (future) handling. On the other hand, they help avoiding unfounded hopes and unrealistic expectations. This especially holds for goals like improving patient participation which are intensely debated in the context of Systems Medicine, however not implied in the concept.

How Do Patients Experience Individualized Medicine? A Qualitative Interview-based Study of Gene Expression Analyses in the Treatment of Breast Cancer.

INTRODUCTION: In recent years, the hopes and expectations associated with so-called individualized medicine have been the subject of intense debate as has the medical potential of this approach. Questions about the uses of gene expression analyses for decisions on adjuvant systemic treatment options for patients with breast cancer have played a prominent role in this debate. There are a number of empirical studies on the effect of gene expression tests on the therapy decisions of physicians and the potentially conflicted decisions for patients. Very little attention has been paid to how patients perceive such approaches, the extent to which they feel included in the therapy decision, and the expectations they associate with such an approach. MATERIAL AND METHODS: Using qualitative explorative interviews, the study looked at how well patients with breast cancer understood the individualized treatment approaches and examined patients' experiences and expectations with regard to gene expression analyses. The sample consisted of 8 patients who were diagnosed with primary hormone receptor-positive, HER2-negative breast cancer between 2013 and 2014 and who underwent gene expression analyses as part of their adjuvant therapy planning. RESULTS: Patients were found to have a quite realistic view of the benefits of gene expression analyses, although it also became clear that the treatment could also raise false hopes. The statements by the interviewed women also illustrated the necessity of continuing to explore the possibilities and limits to joint decision-making in such complex medical contexts as individualized molecular genomic medicine. And finally, the interviews reflected the hope for individualized treatment in the broadest sense of the word. CONCLUSION: The results of the study highlight the challenge of taking psychosocial aspects of medical treatment sufficiently into consideration, given the ever increasing options for molecular genomic individualization.

Using needs-based frameworks for evaluating new technologies: an application to genetic tests.

Given the multitude of newly available genetic tests in the face of limited healthcare budgets, the European Society of Human Genetics assessed how genetic services can be prioritized fairly. Using (health) benefit maximizing frameworks for this purpose has been criticized on the grounds that rather than maximization, fairness requires meeting claims (e.g. based on medical need) equitably. This study develops a prioritization score for genetic tests to facilitate equitable allocation based on need-based claims. It includes attributes representing health need associated with hereditary conditions (severity and progression), a genetic service's suitability to alleviate need (evidence of benefit and likelihood of positive result) and costs to meet the needs. A case study for measuring the attributes is provided and a suggestion is made how need-based claims can be quantified in a priority function. Attribute weights can be informed by data from discrete-choice experiments. Further work is needed to measure the attributes across the multitude of genetic tests and to determine appropriate weights. The priority score is most likely to be considered acceptable if developed within a decision process which meets criteria of procedural fairness and if the priority score is interpreted as "strength of recommendation" rather than a fixed cut-off value.

[Criteria for an ethically adequate prioritisation of individualised treatment strategies]. / Kriterien für eine ethisch angemessene Priorisierung individualisierter Therapiemaßnahmen.

OBJECTIVES: In view of the constant increase of biomedical innovations as well as the demographic change an explicit regulation of health services is inevitable in the German health-care system. Particularly, this applies to so-called individualised treatment measures, which so far only rarely show significant advantages over "classical" treatment measures with mostly substantially higher costs. Against this background, appropriate prioritisation criteria are developed and possibilities as well as limits of their application in the context of individualised medicine are shown. METHODS: The prioritisation criteria are derived in an analytically ethical manner. RESULTS: Based on a basic need-oriented approach of an ethically adequate health care, five prioritisation criteria have been developed: badness/gravity, entrenchment, urgency, benefit and cost-benefit ratio. CONCLUSIONS: The relative weight of the criteria in individual cases cannot be derived in a purely analytical manner but needs to be determined through fair political decision-making processes. Furthermore, empirical data are necessary in order to interpret and weigh the criteria in prioritisation decisions. In the context of individualised treatment strategies benefit assessment is of special interest.

What is personalized medicine: sharpening a vague term based on a systematic literature review.

BACKGROUND: Recently, individualized or personalized medicine (PM) has become a buzz word in the academic as well as public debate surrounding health care. However, PM lacks a clear definition and is open to interpretation. This conceptual vagueness complicates public discourse on chances, risks and limits of PM. Furthermore, stakeholders might use it to further their respective interests and preferences. For these reasons it is important to have a shared understanding of PM. In this paper, we present a sufficiently precise as well as adequate definition of PM with the potential of wide acceptance. METHODS: For this purpose, in a first step a systematic literature review was conducted to understand how PM is actually used in scientific practice. PubMed was searched using the keywords "individualized medicine", "individualised medicine", "personalized medicine" and "personalised medicine" connected by the Boolean operator OR. A data extraction tabloid was developed putting forward a means/ends-division. Full-texts of articles containing the search terms in title or abstract were screened for definitions. Definitions were extracted; according to the means/ends distinction their elements were assigned to the corresponding category. To reduce complexity of the resulting list, summary categories were developed inductively from the data using thematic analysis. In a second step, six well-known criteria for adequate definitions were applied to these categories to derive a so-called precising definition. RESULTS: We identified 2457 articles containing the terms PM in title or abstract. Of those 683 contained a definition of PM and were thus included in our review. 1459 ends and 1025 means were found in the definitions. From these we derived the precising definition: PM seeks to improve stratification and timing of health care by utilizing biological information and biomarkers on the level of molecular disease pathways, genetics, proteomics as well as metabolomics. CONCLUSIONS: Our definition includes the aspects that are specific for developments labeled as PM while, on the other hand, recognizing the limits of these developments. Furthermore, it is supported by the quantitative analysis of PM definitions in the literature, which suggests that it it is widely acceptable and thus has the potential to avoid the above mentioned issues.

Re-focusing the ethical discourse on personalized medicine: a qualitative interview study with stakeholders in the German healthcare system.

BACKGROUND: In recent years, personalized medicine (PM) has become a highly regarded line of development in medicine. Yet, it is still a relatively new field. As a consequence, the discussion of its future developments, in particular of its ethical implications, in most cases can only be anticipative. Such anticipative discussions, however, pose several challenges. Nevertheless, they play a crucial role for shaping PM's further developments. Therefore, it is vital to understand how the ethical discourse on PM is conducted, i.e. on what - empirical and normative - assumptions ethical arguments are based regarding PM's current and future developments. METHODS: To gather this information, we conducted a qualitative interview study with stakeholders in the German health care system. Our purposive sample included 17 representatives of basic research, clinical research, health economics, regulatory authorities, reimbursement institutions, pharmaceutical industry, patient organizations, as well as clinicians and legal experts involved in PM developments or policy making. We used an interview guide with open-ended questions and analyzed transcriptions of the interviews by means of qualitative content analysis. RESULTS: The respondents addressed a multitude of concerns in the context of research on as well as application of personalized preventive and therapeutic measures both on the individual and on the societal level. Interestingly, regarding future developments of PM the ethical evaluation seemed to follow the rule: the less likely its application, the more problematic a PM measure is assessed. The more likely its application, on the other hand, the less problematic it is evaluated. CONCLUSIONS: The results of our study suggest re-focusing the ethical discourse on PM in Germany towards a constructive ethical monitoring which ensures to include only, nevertheless all of the actual and/or potential concerns that are ethically relevant in order to allow balancing them against the actual and potential ethically relevant benefits of PM measures. To render this possible, we propose a strategy for evaluating ethical concerns in the context of PM.