Current Status of Cardiac Xenotransplantation: Report of a Workshop of the German Heart Transplant Centers, Martinsried, March 3, 2023.

This report comprises the contents of the presentations and following discussions of a workshop of the German Heart Transplant Centers in Martinsried, Germany on cardiac xenotransplantation. The production and current availability of genetically modified donor pigs, preservation techniques during organ harvesting, and immunosuppressive regimens in the recipient are described. Selection criteria for suitable patients and possible solutions to the problem of overgrowth of the xenotransplant are discussed. Obviously microbiological safety for the recipient and close contacts is essential, and ethical considerations to gain public acceptance for clinical applications are addressed. The first clinical trial will be regulated and supervised by the Paul-Ehrlich-Institute as the National Competent Authority for Germany, and the German Heart Transplant Centers agreed to cooperatively select the first patients for cardiac xenotransplantation.

Transformative medical ethics: A framework for changing practice according to normative-ethical requirements.

We propose a step-by-step methodological framework of translational bioethics that aims at changing medical practice according to normative-ethical requirements, which we will thus call "transformative medical ethics." The framework becomes especially important when there is a gap between widely acknowledged, ethically justified normative claims and their realization in the practice of biomedicine and technology (ought-is gap). Building on prior work on translational bioethics, the framework maps a process with six different phases and 12 distinct translational steps. The steps involve various research activities including conceptual philosophical inquiry and (socio-)empirical research. On the one hand, the framework can be used as a heuristic tool to identify barriers to the transformation process. On the other hand, it can provide guidance for researchers and practitioners to develop appropriate (conceptual action and practice) models, which are then implemented and evaluated in specific practice contexts. We use the example of realizing the norm of respect for autonomy in the practice of medical decision-making to illustrate the framework. Further research is required, for example, to theoretically underpin the framework, to apply it to other ought-is gaps, and to evaluate its feasibility and effectiveness in various practice areas. Overall, the framework of transformative medical ethics suggests a strategic process to investigate and promote practice change that is ethically informed in all phases.

[Testicular Cancer Screening in Men Aged 16 Years and Older: IQWiG ThemenCheck Health Technology Assessment Report on Medical, Economic, Social, Ethical, Legal and Organisational Aspects]. / Hodenkrebsscreening bei Männern ab 16 Jahren: IQWiG ThemenCheck Health Technology Assessment-Bericht zu medizinischen, ökonomischen, sozialen, ethischen, rechtlichen und organisatorischen Aspekten.

BACKGROUND: Testicular cancer occurs mainly in young men between 25 and 45 years and is the most common cancer at this age. Possible testicular cancer early detection measures, clinical palpation and scrotal ultrasound (CUS) or testicular self-examination (TSE) in asymptomatic men aged 16 years and older, could perhaps avoid deaths and aggressive late therapies. Therefore, we investigated whether these measures have an additional benefit compared to the current situation. Ethical, legal, social and organisational aspects were considered as well. METHODS: The methodology of this review follows IQWiG's "Allgemeine[n] Methoden Version 5.0". In addition, to estimate the theoretically possible benefits and potential harms of screening, a supplementary presentation was used for the benefit assessment based on published data from tumour registries and data on predictive values from diagnostic studies. RESULTS: No intervention studies were identified, therefore evidence-based statements on additional benefit or harm of the studied interventions could not be made. The epidemiological data showed that per 100,000 men participating in screening annually, a maximum of 1.2 advanced tumours and 0.4 deaths would have been preventable. Harm calculations suggest that with CUS of 100,000 men, 1 to 22 unnecessary testicular exposures or removals might be expected, with TSE it would be 2 cases. However, these data on the possible harm of screening are subject to great uncertainty. CONCLUSIONS: There are no intervention studies demonstrating that the benefit of testicular cancer screening in men aged 16 years and older outweighs the harm. The maximum possible additional benefit is low and chances of detection and cure are good even without screening. At present, testicular cancer screening cannot be recommended.

"Xenotransplantation challenges us as a society": What well-informed citizens think about xenotransplantation.

A citizen's conference on xenotransplantation delivers a cautious 'Yes, but…' endorsement. It also shows how additional knowledge and debate shifted peoples' opinion on this technology.

[Effectiveness and Ethical Evaluation of Nudging to Promote the Self-Management in Diabetes Mellitus Type 2]. / Wirksamkeit und ethische Bewertung von Nudging-Interventionen zur Förderung des Selbstmanagements bei Diabetes Mellitus Typ 2.

BACKGROUND: Nudges offer a wide range of options for protecting health in everyday life that supplements traditional public health measures. Against this background, we conducted initial investigations on the effectiveness and ethical aspects of different nudges for promoting self-management of patients with diabetes mellitus type 2 in the context of Disease Management Programs (DMPs). METHODS: The ethical assessment of the nudges was done within the systematic framework of Marckmann et al. (2015) for public health ethics. The existing evidence on the effectiveness of nudges was summarised by means of a narrative literature review. RESULTS: Target agreements with implementation plans, reminder, feedback reports, shared appointments of patients with physicians, peer mentoring, and behavior contracts are nudging interventions with moderate interference with personal rights and relatively unproblematic ethical requirements, which have demonstrated effectiveness in different contexts. Default enrollment for patient training courses, involvement of partners, confrontation with social norms, and shocking pictures may be effective as well; however, they interfere more deeply with the freedom and privacy of patients and, therefore, are bound to stronger ethical requirements and restrictions. The evidence base is still insufficient, especially for social support measures by relatives and peers. CONCLUSIONS: Nudging offers a wide range of targeted interventions for supporting self-management of patients with chronic diseases, the potential of which has not yet been fully realized. Particularly promising interventions should be tested in pilot studies for their acceptance, effectiveness and cost-effectiveness in the context of DMPs.

[Quality and ethics in healthcare]. / Qualität und Ethik in der Gesundheitsversorgung.

The term "quality" in healthcare is frequently used but defined in different ways. On the one hand, quality describes the nature or characteristic of things and is descriptive in this respect. In quality management and quality assurance, however, the focus is on the normative dimension of quality, referring to the evaluation of structures, processes, or results of actions in the context of healthcare. There are several links between ethical considerations in healthcare and quality of healthcare. First, the provision and assurance of high quality is an ethical imperative, mandated by the principles of beneficence and nonmaleficence. However, for high ethical quality of care, the ethical principles of respect for patient autonomy and justice must also be considered. Last but not least, the determination and justification of what "good" or "high" quality in healthcare means must be reflected from an ethical perspective. This article analyses these ethical dimensions of quality management and quality assurance. To achieve this goal, it first explains which ethical requirements have to be considered as quality criteria in patient care. Subsequently, ethically relevant challenges in determining quality in healthcare are identified based on criteria of outcome quality, and the teaching of professional competencies in medical education is discussed as a possible contribution to quality and quality assurance in healthcare. The paper concludes with considerations on determining and assuring quality under conditions of limited healthcare resources.

Organ transplants of the future: planning for innovations including xenotransplantation.

The future clinical application of animal-to-human transplantation (xenotransplantation) is of importance to society as a whole. Favourable preclinical data relevant to cell, tissue and solid organ xenotransplants have been obtained from many animal models utilizing genetic engineering and protocols of pathogen-free husbandry. Findings have reached a tipping point, and xenotransplantation of solid organs is approaching clinical evaluation, the process of which now requires close deliberation. Such discussions include considering when there is sufficient evidence from preclinical animal studies to start first-in-human xenotransplantation trials. The present article is based on evidence and opinions formulated by members of the European Society for Organ Transplantation who are involved in the Transplantation Learning Journey project. The article includes a brief overview of preclinical concepts and biology of solid organ xenotransplantation, discusses the selection of candidates for first-in-human studies and considers requirements for study design and conduct. In addition, the paper emphasizes the need for a regulatory framework for xenotransplantation of solid organs and the essential requirement for input from public and patient stakeholders.

What does it take to consent to islet cell xenotransplantation?: Insights from an interview study with type 1 diabetes patients and review of the literature.

BACKGROUND: The transplantation of porcine islet cells provides a new potential therapy to treat patients with type 1 diabetes mellitus (T1DM). Compared to other biomedical technologies, xenotransplantation stands out in terms of its involvement of animals as graft sources, as well as the possible transmission of infectious diseases. As these aspects are especially relevant for potential xenotransplantation recipients, it is important to assess their opinion regarding this technology, in particular in terms of the requirements that should be met in the informed consent process for xenotransplantation. METHODS: We conducted qualitative interviews with seven T1DM patients to assess their information needs prior to xenotransplantation. Before the interview, the participants received a model informed consent form for a clinical trial with porcine islet cells transplantation. The interviews were transcribed and analysed using qualitative content analysis. RESULTS: In the interviews, we identified several requirements that are crucial for patients with T1DM in order to consider xenotransplantation as a potential treatment option: therapy-related requirements, professional care and supervision, successful behaviour and attitude management, improving quality of life, and managing control/self-determination challenges. Regarding the informed consent form, several of the participants' questions remained open and should be addressed in more detail. The interviewees stressed the importance of personal consultations. CONCLUSIONS: To become a sustainable therapeutic option, patients especially expected an improved diabetes control and a reduction of diabetes-related burdens. Health-related aspects prove to be pivotal for diabetic patients when considering porcine islet cell transplantation. The use of pigs as source for organ retrievals was not considered as problematic.

Digital contact tracing and exposure notification: ethical guidance for trustworthy pandemic management.

There is growing interest in contact tracing apps (CT apps) for pandemic management. It is crucial to consider ethical requirements before, while, and after implementing such apps. In this paper, we illustrate the complexity and multiplicity of the ethical considerations by presenting an ethical framework for a responsible design and implementation of CT apps. Using this framework as a starting point, we briefly highlight the interconnection of social and political contexts, available measures of pandemic management, and a multi-layer assessment of CT apps. We will discuss some trade-offs that arise from this perspective. We then suggest that public trust is of major importance for population uptake of contact tracing apps. Hasty, ill-prepared or badly communicated implementations of CT apps will likely undermine public trust, and as such, risk impeding general effectiveness.

[Coincidence of Advance Directive and Organ Donor Consent: What Do The Persons Concerned Want? A Survey of German Elderly Citizens]. / Koinzidenz von Patientenverfügung und Zustimmung zur Organspende: was wünschen die Betroffenen? Eine Befragung deutscher Senioren.

AIMS: In the case of acute brain injury, decision-making uncertainties can arise when both an advance decision to refuse treatment and a prior consent to post-mortem organ donation are present. It is yet unknown how the persons concerned view this potential conflict. The present study aims to investigate how frequent this situation is, whether the persons concerned are aware of the potential conflict and what they would prioritize. METHODS: Semi-quantitative cross-sectional survey of senior citizens of a metropolitan region in Germany using a literature-based questionnaire. RESULTS: A total of 236 senior citizens participated in the survey, amounting to 52% of those invited. While 54% of the participants reported to have written advance directives, 46% had expressed their consent to post-mortem organ donation in written or oral form. Altogether, 29% of all participants had issued both types of written documents. The consent to organ donation correlated significantly with the presence of an advance directive. Only 47% of the advance directives contained, according to their authors, statements about organ donation. Dying outside of intensive care was the priority for 51%, while 17% favored donating their organs. About half of the participants accepted transient intensive care measures in the case of presumed or expected brain death, but only a fourth also accepted cardiopulmonary resuscitation in those situations. Knowledge about brain death was scant and the attitudes towards it were rather critical. CONCLUSION: The coincidence of advance directives and organ donation consent is not uncommon in senior citizens and could contribute to low organ donation rates. The heterogeneous attitudes of the surveyed persons as well as their poor knowledge about brain death and the potential conflict studied here underscore the necessity of a high-quality advance care planning process.

[Development of a decision aid for participative advance planning for people with dementia and their relatives]. / Entwicklung einer Entscheidungshilfe für partizipative Vorausplanungen für Menschen mit Demenz und deren Angehörige.

BACKGROUND: Patients with a diagnosis of dementia face various important social and health-related decisions. Due to the progression of the disease it seems crucial that patients try to deal with these decisions early in the course of the disease to have the opportunity to make decisions autonomously. Professional support can help to plan in advance according to the wishes and possibilities in an effective and individualized manner. MATERIAL AND METHODS: The instrument was developed in a multiphase process based on advance care planning and shared decision-making. The prototype was pretested on 8 patient-relative dyads from a special outpatient department for early recognition and adapted as best as possible to their needs. Subsequently, in a pilot study the applicability of the decision aid was tested as an intervention in a further 19 patient-relative dyads with trained conversion attendants (diagnosis of Alzheimer's dementia or mixed form; mini mental state examination, MMSE (Mini-Mental-State-Test-Summenwert) >20 and <27). RESULTS: The result was a written decision-making aid for people with early stage dementia and their relatives, which supports the decision-making process (health care proxy, advance directive, living and care, driving ability). The first results showed good acceptance and handling. Patients and relatives dealt with the individual topics to a high degree and found them to be highly relevant. CONCLUSION: Despite positive feedback from the participants with respect to acceptance and applicability, there were major difficulties in recruiting. In the future, the systematic use of decision support as part of routine care could help to support the decision-making process in this patient group.

[Ethical implications of digital public health]. / Ethische Fragen von Digital Public Health.

Digital technologies in public health have the potential to improve health promotion and disease prevention by the efficient registration, storage, and processing of large amounts of health data. Digital public health also raises - like other technological developments - several ethical issues, which are discussed in this article.A fundamental question in the ethical evaluation of digital public health interventions concerns the goal of the intervention: An intervention should serve the established goals of public health and not financial interests, to realize potential health benefits for the population. In addition, equity issues are especially relevant, because digital public health may reduce or increase health inequalities in the population. Furthermore, the protection of privacy and potentially sensitive health data are relevant. As digital public health applications vary considerably, each application has to be assessed individually regarding its ethical implications. This article therefore presents a normative framework and a methodological approach for the ethical evaluation of digital public health applications. By developing ethically justified recommendations for the design and use of digital public health applications, the ethical evaluation can contribute to an ethically justified practice of digital public health.

[Critical evaluation of the new legal regulation of pharmaceutical trials with adults who lack decision-making capacity: a survey of human research ethics committees in Germany]. / Arzneimittelprüfung an nicht einwilligungsfähigen Erwachsenen: Kritische Bewertung der neuen gesetzlichen Regelung durch medizinische Ethikkommissionen in Deutschland.

BACKGROUND: In Germany, the drug law was revised in 2016 to include new regulations on clinical drug trials with adults who lack decision-making capacity. For the first time, trials with a merely indirect benefit (benefit for other patients with similar characteristics) will be possible if several safeguards are respected. The ethical justification and practicality of this regulation are controversially discussed. OBJECTIVES: (1) Eliciting the current pertinent practice of research ethics committees in Germany regarding research with indirect benefit on adults without decision-making capacity; (2) exploring the possibilities and difficulties of implementing the new law. METHODS: Semiquantitative, anonymous questionnaire among 249 members of all 53 human research ethics committees in Germany. RESULTS: Eighty-four questionnaires were analyzed (response rate 34%). The participants disagreed on assigning research projects to the categories of research with direct benefit to the subject, with an indirect benefit, and without any benefit. Moreover, the criteria of minimum risk and minimum burden were interpreted heterogeneously. More than half of the participants judged the newly introduced research advance directive to be unnecessary, given the legal safeguards in place. The applicability of these directives was doubted because of the strict requirements for anticipatory informed consent and the restricted predictability of future research. CONCLUSION: In spite of the new legal regulation, significant ethical uncertainties remain concerning research with indirect benefit on adults without decision-making capacity. It remains an open question whether we need a better explanation of the law, additional legal regulation, practice evaluation, or a completely new law.

Health Technology Assessment of Public Health Interventions Published 2012 to 2016: An Analysis of Characteristics and Comparison of Methods.

OBJECTIVES: The aim of this study was to provide an overview of the methodological characteristics and compare the assessment methods applied in health technology assessments (HTAs) of public health interventions (PHIs). METHODS: We defined a PHI as a population-based intervention on health promotion or for primary prevention of chronic or nonchronic diseases. HTAs on PHIs were identified by systematically searching the Web pages of members of international HTA networks. We included only full HTA reports published between 2012 and 2016. Two reviewers extracted data on the methods used to assess effectiveness/safety, as well as on economic, social, cultural, ethical, and legal aspects using a-priori standardized tables. RESULTS: We included ten HTAs provided by four different organizations. Of these, all reports assessed the effectiveness of the interventions and conducted economic evaluations, seven investigated social/cultural aspects, and four each considered legal and ethical aspects, respectively. Some reports addressed applicability, context/setting, and intervention fidelity issues in different ways. We found that most HTAs adapted their methods to some extent, for example, by including nonrandomized studies, expanding the search strategy, involving stakeholders, or applying a framework to guide the HTA process. CONCLUSIONS: Our analysis provides a comprehensive overview of methods applied in HTAs on public health interventions. We found that a heterogeneous set of approaches is used to deal with the challenges of evaluating complex public health interventions.

Mobile health ethics and the expanding role of autonomy.

Mhealth technology is mushrooming world-wide and, in a variety of forms, reaches increasing numbers of users in ever-widening contexts and virtually independent from standard medical evidence assessment. Yet, debate on the broader societal impact including in particular mapping and classification of ethical issues raised has been limited. This article, as part of an ongoing empirically informed ethical research project, provides an overview of ethical issues of mhealth applications with a specific focus on implications on autonomy as a key notion in the debate. A multi-stage model of references to the potential of mhealth use for strengthening some or other form of self-determination will be proposed as a descriptive tool. It illustrates an assumed continuum of enhanced autonomy via mhealth broadly conceived: from patient to user autonomy, to improved health literacy, and finally to the vision of supra-individual empowerment and democratised, participatory health and medicine as a whole. On closer examination, however, these references are frequently ambivalent or vague, perpetuating the at times uncritical use of established autonomy concepts in medical ethics. The article suggests zooming in on the range of autonomy-related aspects against the backdrop of digital innovation and datafied health more generally, and on this basis add to existing frameworks for the ethical evaluation of mhealth more specifically.

[Advance Care Planning and its Relevance for Emergency and Intensive Care Medicine]. / Behandlung im Voraus planen ­ Bedeutung für die Intensiv- und Notfallmedizin.

Like in other countries, advance care planning (ACP) is currently being implemented in Germany as a new concept to realise valid and effective advance directives. This concept comprises processes to explore and document individual preferences for future treatment, and to honour them at a time when the person is incapacitated. ACP aims to ensure that patients will be treated according to their preferences when they are no longer capable due to acute health crises or chronic diseases. This paper gives an overview of the concept of ACP with a focus on relevant issues for emergency and intensive care medicine.

Principle-based structured case discussions: do they foster moral competence in medical students? - A pilot study.

BACKGROUND: Recent findings suggest that medical students' moral competence decreases throughout medical school. This pilot study gives preliminary insights into the effects of two educational interventions in ethics classes on moral competence among medical students in Munich, Germany. METHODS: Between 2012 and 2013, medical students were tested using Lind's Moral Competence Test (MCT) prior to and after completing different ethics classes. The experimental group (EG, N = 76) participated in principle-based structured case discussions (PBSCDs) and was compared with a control group with theory-based case discussions (TBCDs) (CG, N = 55). The pre/post C-scores were compared using a Wilcoxon Test, ANOVA and effect-size calculation. RESULTS: The C-score improved by around 3.2 C-points in the EG, and by 0.2 C-points in the CG. The mean C-score difference was not statistically significant for the EG (P = 0.14) or between the two groups (P = 0.34). There was no statistical significance for the teachers' influence (P = 0.54) on C-score. In both groups, students with below-average (M = 29.1) C-scores improved and students with above-average C-scores regressed. The increase of the C-Index was greater in the EG than in the CG. The absolute effect-size of the EG compared with the CG was 3.0 C-points, indicating a relevant effect. CONCLUSION: Teaching ethics with PBSCDs did not provide a statistically significant influence on students' moral competence, compared with TBCDs. Yet, the effect size suggests that PBSCDs may improve moral competence among medical students more effectively. Further research with larger and completely randomized samples is needed to gain definite explanations for the results.

Does facilitated Advance Care Planning reduce the costs of care near the end of life? Systematic review and ethical considerations.

BACKGROUND: While there is increasing evidence that Advance Care Planning has the potential to strengthen patient autonomy and improve quality of care near the end of life, it remains unclear whether it could also reduce net costs of care. AIM: This study aims to describe the cost implications of Advance Care Planning programmes and discusses ethical conflicts arising in this context. DESIGN: We conducted a systematic review based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. DATA SOURCES: We systematically searched the databases PubMed, NHS EED, EURONHEED, Cochrane Library and EconLit. We included empirical studies (no limitation to study type) that investigated the cost implications of Advance Care Planning programmes involving professionally facilitated end-of-life discussions. RESULTS AND DISCUSSION: Seven studies met our inclusion criteria. Four of them used a randomised controlled design, one used a before-after design and two were observational studies. Six studies found reductions in costs of care ranging from USD1041 to USD64,827 per patient, depending on the study period and the cost measurement. One study detected no differences in costs. Studies varied considerably regarding the Advance Care Planning intervention, patient selection and costs measured which may explain some of the variations in findings. NORMATIVE APPRAISAL: Looking at the impact of Advance Care Planning on costs raises delicate ethical issues. Given the increasing pressure to reduce expenditures, there may be concerns that cost considerations could unduly influence the sensitive communication process, thus jeopardising patient autonomy. Safeguards are proposed to reduce these risks. CONCLUSION: The limited data indicate net cost savings may be realised with Advance Care Planning. Methodologically robust trials with clearly defined Advance Care Planning interventions are needed to make the costs and returns of Advance Care Planning transparent.

Difficulties experienced by migrant physicians working in German hospitals: a qualitative interview study.

BACKGROUND: With Germany facing a shortage of doctors, hospitals have been increasingly recruiting physicians from abroad. Studies in other countries have shown that migrant physicians experience various difficulties in their work, which might impact the quality of patient care, physician job satisfaction, and, accordingly, retention. The experiences of migrant doctors in Germany have not been systematically studied so far and will likely differ from experiences migrant physicians make in other contexts. A thorough understanding of challenges faced by this group, however, is needed to develop adequate support structures-as required by the WHO Global Code of Practice on the International Recruitment of Health Personnel. METHODS: A qualitative study was conducted to give an overview of the multifaceted difficulties migrant physicians might face in German hospitals. Twenty semi-structured interviews with foreign-born and foreign-trained physicians were conducted in German. Participants were recruited via the State Chambers of Physicians and snowballing based on a maximum variation sampling strategy varying purposefully by source country and medical specialty. The interviews were recorded, transcribed verbatim, and analysed using qualitative content analysis. RESULTS: Participants described difficulties relating to healthcare institutions, own competencies, and interpersonal interactions. Participants experienced certain legal norms, the regulation of licensure and application for work, and the organization of the hospital environment as inadequate. Most struggled with their lack of setting-specific (language, cultural, clinical, and system) knowledge. Furthermore, behaviour of patients and co-workers was perceived as discriminating or inadequate for other reasons. CONCLUSIONS: This is the first study to describe the broad range of issues migrant physicians experience in Germany. Based on this information, institutional actors should devise support structures to ensure quality of care, physician wellbeing, and retention. For example, training opportunities should be offered where needed to support acquisition of setting-specific knowledge. Discrimination experienced by participants calls for better diversity management as a leadership task in healthcare institutions. Misinformation practices in recruitment could be managed by a voluntary code of ethical conduct. Further research is necessary to identify strategies that adequately address diverging normative positions between migrant health personnel and their patients and colleagues.