Nancy S. Jecker, Zohar Lederman, and Anita Ho reply.

This letter replies to the letter "Colonial and Neocolonial Barriers to Companion Digital Humans in Africa," by Luís Cordeiro-Rodrigues, in the same, May-June 2024, issue of the Hastings Center Report.

Digital Humans to Combat Loneliness and Social Isolation: Ethics Concerns and Policy Recommendations.

Social isolation and loneliness are growing concerns around the globe that put people at increased risk of disease and early death. One much-touted approach to addressing them is deploying artificially intelligent agents to serve as companions for socially isolated and lonely people. Focusing on digital humans, we consider evidence and ethical arguments for and against this approach. We set forth and defend public health policies that respond to concerns about replacing humans, establishing inferior relationships, algorithmic bias, distributive justice, and data privacy.

Ethical dilemmas in prioritizing patients for scarce radiotherapy resources.

BACKGROUND: Radiotherapy is an essential component of cancer treatment, yet many countries do not have adequate capacity to serve all patients who would benefit from it. Allocation systems are needed to guide patient prioritization for radiotherapy in resource-limited contexts. These systems should be informed by allocation principles deemed relevant to stakeholders. This study explores the ethical dilemmas and views of decision-makers engaged in real-world prioritization of scarce radiotherapy resources at a cancer center in Rwanda in order to identify relevant principles. METHODS: Semi-structured interviews were conducted with a purposive sample of 22 oncology clinicians, program leaders, and clinical advisors. Interviews explored the factors considered by decision-makers when prioritizing patients for radiotherapy. The framework method of thematic analysis was used to characterize these factors. Bioethical analysis was then applied to determine their underlying normative principles. RESULTS: Participants considered both clinical and non-clinical factors relevant to patient prioritization for radiotherapy. They widely agreed that disease curability should be the primary overarching driver of prioritization, with the goal of saving the most lives. However, they described tension between curability and competing factors including age, palliative benefit, and waiting time. They were divided about the role that non-clinical factors such as social value should play, and agreed that poverty should not be a barrier. CONCLUSIONS: Multiple competing principles create tension with the agreed upon overarching goal of maximizing lives saved, including another utilitarian approach of maximizing life-years saved as well as non-utilitarian principles, such as egalitarianism, prioritarianism, and deontology. Clinical guidelines for patient prioritization for radiotherapy can combine multiple principles into a single allocation system to a significant extent. However, conflicting views about the role that social factors should play, and the dynamic nature of resource availability, highlight the need for ongoing work to evaluate and refine priority setting systems based on stakeholder views.

Navigating Informed Consent Requirements and Expectations in Cluster Randomized Trials: Research Ethics Board Members' and Researchers' Views.

Informed consent is a cornerstone of ethical human research. However, as cluster randomized trials (CRTs) are increasingly popular to evaluate health service interventions, especially as health systems aspire toward the learning health system, questions abound how research teams and research ethics boards (REBs) should navigate intertwining consent and data-use considerations. Methodological and ethical questions include who constitute the participants, whose and what types of consent are necessary, and how data from people who have not consented to participation should be managed to optimize the balance of trust in the research enterprise, respect for persons, the promotion of data integrity, and the pursuit of the public good in the research arena. In this paper, we report the findings and lessons learned from a qualitative study examining how researchers and REB members consider the ethical dimensions of when data can be collected and used in CRTs in the evolving research landscape.

Multi-Level Ethical Considerations of Artificial Intelligence Health Monitoring for People Living with Parkinson's Disease.

Artificial intelligence (AI) has garnered tremendous attention in health care, and many hope that AI can enhance our health system's ability to care for people with chronic and degenerative conditions, including Parkinson's Disease (PD). This paper reports the themes and lessons derived from a qualitative study with people living with PD, family caregivers, and health care providers regarding the ethical dimensions of using AI to monitor, assess, and predict PD symptoms and progression. Thematic analysis identified ethical concerns at four intersecting levels: personal, interpersonal, professional/institutional, and societal levels. Reflecting on potential benefits of predictive algorithms that can continuously collect and process longitudinal data, participants expressed a desire for more timely, ongoing, and accurate information that could enhance management of day-to-day fluctuations and facilitate clinical and personal care as their disease progresses. Nonetheless, they voiced concerns about intersecting ethical questions around evolving illness identities, familial and professional care relationships, privacy, and data ownership/governance. The multi-layer analysis provides a helpful way to understand the ethics of using AI in monitoring and managing PD and other chronic/degenerative conditions.

Palliative care providers' roles in medical assistance in dying decision-making triads with patients and families: A qualitative analysis.

OBJECTIVES: Research on medical assistance in dying (MAiD) decision-making indicates that family members and close friends are often involved in making decisions with patients and their care providers. This decision-making model comprising patients, family members, and palliative care providers (PCPs) has been described as a triad. The objective of this study is to understand PCPs' experiences engaging in MAiD-related decision-making triads with patients and their families in Canada. METHODS: Semi-structured qualitative interviews were analyzed using interpretive description. RESULTS: We interviewed 48 specialist PCPs in Vancouver (26) and Toronto (22). Interviews were audio-recorded, professionally transcribed, and coded using a coding framework. PCPs take on 5 notable roles in their work with family members around MAiD. They provide emotional support and counseling, balance confidentiality between patients and families, provide education, coordinate support, and mediate family dynamics. SIGNIFICANCE OF RESULTS: PCPs take on multiple roles in working with patients and families to make decisions about MAiD. As patients and families may require different forms of support throughout the MAiD pathway, PCPs can benefit from institutional and interprofessional resources to enhance their ability to support patients and families in decision-making and bereavement.

Moral uncertainty and distress about voluntary assisted dying prior to legalisation and the implications for post-legalisation practice: a qualitative study of palliative and hospice care providers in Queensland, Australia.

OBJECTIVES: There is little research on moral uncertainties and distress of palliative and hospice care providers (PHCPs) working in jurisdictions anticipating legalising voluntary assisted dying (VAD). This study examines the perception and anticipated concerns of PHCPs in providing VAD in the State of Queensland, Australia prior to legalisation of the practice in 2021. The findings help inform strategies to facilitate training and support the health and well-being of healthcare workers involved in VAD. DESIGN: The study used a qualitative approach to examine and analyse the perception and anticipated concerns of PHCPs regarding challenges of providing assisted dying in Queensland. Fourteen PHCPs were recruited using a purposive sampling strategy to obtain a broad representation of perspectives including work roles, geographical locations and workplace characteristics. Data were collected via one in-depth interview per participant. The transcripts were coded for patterns and themes using an inductive analysis approach following the tradition of Grounded Theory. SETTING: The study was conducted in hospital, hospice, community and residential aged care settings in Queensland, Australia. These included public and private facilities, secular and faith-based facilities, and regional/rural and urban facilities. PARTICIPANTS: Interviews were conducted with fourteen PHCPs: 10 nurses and 4 physicians; 11 female and 3 male. The median number of years of palliative care practice was 17, ranging from 2 to 36 years. For inclusion, participants had to be practising palliative and hospice care providers. RESULTS: PHCPs are divided on whether VAD should be considered part of palliative care. Expectations of moral distress and uncertainty about practising VAD were identified in five areas: handling requests, assessing patient capacity, arranging patient transfers and logistical issues, managing unsuccessful attempts, and dealing with team conflicts and stigma. CONCLUSIONS: The possibility of having to practise VAD causes moral distress and uncertainty for some PHCPs. Procedural clarity can address some uncertainties; moral and psychological distress, however, remains a source of tension that needs support to ensure ongoing care of both patients and PHCPs. The introduction of VAD post-legalisation may present an occasion for further moral education and development of PHCPs.

Procedural fairness for radiotherapy priority setting in a low resource context.

Radiotherapy is an essential component of cancer treatment, yet many countries do not have adequate capacity to serve their populations. This mismatch between demand and supply creates the need for priority setting. There is no widely accepted system to guide patient prioritization for radiotherapy in a low resource context. In the absence of consensus on allocation principles, fair procedures for priority setting should be established. Research is needed to understand what elements of procedural fairness are important to decision makers in diverse settings, assess the feasibility of implementing fair procedures for priority setting in low resource contexts, and improve these processes. This study presents the views of decision makers engaged in everyday radiotherapy priority setting at a cancer center in Rwanda. Semi-structured interviews with 22 oncology physicians, nurses, program leaders, and advisors were conducted. Participants evaluated actual radiotherapy priority setting procedures at the program (meso) and patient (micro) levels, reporting facilitators, barriers, and recommendations. We discuss our findings in relation to the leading Accountability for Reasonableness (AFR) framework. Participants emphasized procedural elements that facilitate adherence to normative principles, such as objective criteria that maximize lives saved. They ascribed fairness to AFR's substantive requirement of relevance more than transparency, appeals, and enforcement. They identified several challenges unresolved by AFR, such as conflicting relevant rationales and unintended consequences of publicity and appeals. Implementing fair procedure itself is resource intensive, a paradox that calls for innovative, context-appropriate solutions. Finally, socioeconomic and structural barriers to care that undermine procedural fairness must be addressed.

Medical assistance in dying legislation: Hospice palliative care providers' perspectives.

BACKGROUND: After over 4 years since medical assistance in dying legalization in Canada, there is still much uncertainty about how this ruling has affected Canadian society. OBJECTIVE: To describe the positive aspects of medical assistance in dying legalization from the perspectives of hospice palliative care providers engaging in medical assistance in dying. DESIGN: In this qualitative descriptive study, we conducted an inductive thematic analysis of semi-structured interviews with hospice palliative care providers. PARTICIPANTS AND SETTING: Multi-disciplinary hospice palliative care providers in acute, community, residential, and hospice care in Vancouver and Toronto, Canada, who have engaged in end-of-life care planning with patients who have inquired about and/or requested medical assistance in dying. ETHICAL CONSIDERATIONS: The research proposal was approved by University of British Columbia Research Ethics Board in Vancouver and University Health Network in Toronto. Participants were informed regarding the research goals, signed a written consent, and were assigned pseudonyms. RESULTS: The 48 participants included hospice palliative care physicians (n = 22), nurses (n = 15), social workers (n = 7), and allied health providers (n = 4). The average interview length was 50 min. Positive aspects of medical assistance in dying legalization were identified at (1) the individual level: (a) a new end-of-life option, (b) patients' last chance to express control over their lives, (c) patient and family comfort and relief, and (d) a unique learning experience for hospice palliative care providers; (2) the team level: (a) supportive collegial relationships, (b) broadened discussions about end-of-life and palliative care, and (c) team debriefs provide opportunities for education and support; and (3) the institutional level: (a) improved processes to facilitate the implementation logistics. CONCLUSION: While being involved in the medical assistance in dying process is complex and challenging, this study sheds light on the positive aspects of medical assistance in dying legalization from the hospice palliative care provider's perspectives. Medical Assistance in Dying legalization has resulted in improved end-of-life conversations between hospice palliative care providers, patients, and their families. Improved communication leads to a better understanding of patients' end-of-life care plans and bridges some of the existing gaps between hospice palliative care and medical assistance in dying.

How does Medical Assistance in Dying affect end-of-life care planning discussions? Experiences of Canadian multidisciplinary palliative care providers.

BACKGROUND: More than a dozen countries have now legalized some form of assisted dying, and additional jurisdictions are considering similar legislations or expanding eligibility criteria. Despite the persistent controversies about the relationship between medicine, palliative care, and assisted dying, many people are interested in assisted dying. Understanding how end-of-life care discussions between patients and specialist palliative care providers may be affected by such legislation can inform end-of-life care delivery in the evolving socio-cultural and legal environment. AIM: To explore how the Canadian Medical Assistance in Dying legislation affects end-of-life care discussions between patients and multidisciplinary specialist palliative care providers. DESIGN: Qualitative thematic analysis of semi-structured interviews. PARTICIPANTS: Forty-eight specialist palliative care providers from Vancouver (n = 26) and Toronto (n = 22) were interviewed in person or by phone. Participants included physicians (n = 22), nurses (n = 15), social workers (n = 7), and allied health professionals (n = 4). RESULTS: Qualitative thematic analysis identified five notable considerations associated with Medical Assistance in Dying affecting end-of-life care discussions: (1) concerns over having proactive conversations about the desire to hasten death, (2) uncertainties regarding wish-to-die statements, (3) conversation complexities around procedural matters, (4) shifting discussions about suffering and quality of life, and (5) the need and challenges of promoting open-ended discussions. CONCLUSION: Medical Assistance in Dying challenges end-of-life care discussions and requires education and support for all concerned to enable compassionate health professional communication. It remains essential to address psychosocial and existential suffering in medicine, but also to provide timely palliative care to ensure suffering is addressed before it is deemed irremediable. Hence, clarification is required regarding assisted dying as an intervention of last resort. Furthermore, professional and institutional guidance needs to better support palliative care providers in maintaining their holistic standard of care.

Unmasking the Ethics of Public Health Messaging in a Pandemic.

Uncertainty is inherent in new and unexpected viral outbreaks such as the current COVID-19 pandemic. It imposes challenges for health officials in soliciting cooperative behavioural changes based on incomplete information. In this paper, we use evolving mask recommendations in the United States as an example to analyse the ethical importance and practical demonstration of trustworthiness in pandemic messaging and decision-making. We argue that responsible public health interventions in the time of uncertainties requires explicit intersecting ethical considerations both in action and in communication to promote trustworthiness. First, as public health decisions have to be made in the face of incomplete and evolving data, health officials need to exhibit competence while committing to epistemic humility. They can explain the methods used in making and updating mask recommendations as well as explicitly acknowledge the need to incorporate sociocultural and other contextual considerations in translating scientific data into mask recommendations. Second, officials and agencies must uphold and communicate decisional transparency as part of their effort to demonstrate accountability and promote the public's understanding of the evolving pandemic. Third, especially since both the pandemic and mask recommendations may have disparate impact on different populations, officials should start with the fair implementation of the least restrictive measures that can help reduce harm.

Moral Distress and Resilience Associated with Cancer Care Priority Setting in a Resource-Limited Context.

BACKGROUND: Moral distress and burnout are highly prevalent among oncology clinicians. Research is needed to better understand how resource constraints and systemic inequalities contribute to moral distress in order to develop effective mitigation strategies. Oncology providers in low- and middle-income countries are well positioned to provide insight into the moral experience of cancer care priority setting and expertise to guide solutions. METHODS: Semistructured interviews were conducted with a purposive sample of 22 oncology physicians, nurses, program leaders, and clinical advisors at a cancer center in Rwanda. Interviews were recorded, transcribed verbatim, and analyzed using the framework method. RESULTS: Participants identified sources of moral distress at three levels of engagement with resource prioritization: witnessing program-level resource constraints drive cancer disparities, implementing priority setting decisions into care of individual patients, and communicating with patients directly about resource prioritization implications. They recommended individual and organizational-level interventions to foster resilience, such as communication skills training and mental health support for clinicians, interdisciplinary team building, fair procedures for priority setting, and collective advocacy for resource expansion and equity. CONCLUSION: This study adds to the current literature an in-depth examination of the impact of resource constraints and inequities on clinicians in a low-resource setting. Effective interventions are urgently needed to address moral distress, reduce clinician burnout, and promote well-being among a critical but strained oncology workforce. Collective advocacy is concomitantly needed to address the structural forces that constrain resources unevenly and perpetuate disparities in cancer care and outcomes. IMPLICATIONS FOR PRACTICE: For many oncology clinicians worldwide, resource limitations constrain routine clinical practice and necessitate decisions about prioritizing cancer care. To the authors' knowledge, this study is the first in-depth analysis of how resource constraints and priority setting lead to moral distress among oncology clinicians in a low-resource setting. Effective individual and organizational interventions and collective advocacy for equity in cancer care are urgently needed to address moral distress and reduce clinician burnout among a strained global oncology workforce. Lessons from low-resource settings can be gleaned as high-income countries face growing needs to prioritize oncology resources.

Relational solidarity and COVID-19: an ethical approach to disrupt the global health disparity pathway.

While the effects of COVID-19 are being felt globally, the pandemic disproportionately affects lower- and middle-income countries (LMICs) by exacerbating existing global health disparities. In this article, we illustrate how intersecting upstream social determinants of global health form a disparity pathway that compromises LMICs' ability to respond to the pandemic. We consider pre-existing disease burden and baseline susceptibility, limited disease prevention resources, and unequal access to basic and specialized health care, essential drugs, and clinical trials. Recognizing that ongoing and underlying disparity issues will require long-term correction efforts, this pathway approach is nonetheless helpful to inform ethical responses to this global pandemic. It can facilitate international cooperation during the pandemic to reduce the disparate burdens among different regions without imposing significant burden on any particular contributor. The pathway approach allows international stakeholders in various social positions to respond to different components of the pathway based on their respective strengths and resources to help break the cycle of global health inequity. Guided by the ethical principles of relational and pragmatic solidarity, we argue for a coordinated global division of labor such that different stakeholders can collaborate to foster equitable healthcare access during this pandemic.

The Surprise Question and Serious Illness Conversations: A pilot study.

BACKGROUND: Serious Illness Conversations aim to discuss patient goals. However, on acute medicine units, seriously ill patients may undergo distressing interventions until death. OBJECTIVES: To investigate the feasibility of using the Surprise Question, "Would you be surprised if this patient died within the next year?" to identify patients who would benefit from early Serious Illness Conversations and study any changes in the interdisciplinary team's beliefs, confidence, and engagement as a result of asking the Surprise Question. DESIGN: A prospective cohort pilot study with two Plan-Do-Study-Act cycles. PARTICIPANTS/CONTEXT: Fifty-eight healthcare professionals working on Acute Medicine Units participated in pre- and post-intervention questionnaires. The intervention involved asking participants the Surprise Question for each patient. Patient charts were reviewed for Serious Illness Conversation documentation. ETHICAL CONSIDERATIONS: Ethical approval was granted by the institutions involved. FINDINGS: Equivocal overall changes in the beliefs, confidence, and engagement of healthcare professionals were observed. Six out of 23 patients were indicated as needing a Serious Illness Conversation; chart review provided some evidence that these patients had more Serious Illness Conversation documentation compared with the 17 patients not flagged for a Serious Illness Conversation. Issues were identified in equating the Surprise Question to a Serious Illness Conversation. DISCUSSION: Appropriate support for seriously ill patients is both a nursing professional and ethical duty. Flagging patients for conversations may act as a filtering process, allowing healthcare professionals to focus on conversations with patients who need them most. There are ethical and practical issues as to what constitutes a "serious illness" and if answering "no" to the Surprise Question always equates to a conversation. CONCLUSION: The barriers of time constraints and lack of training call for institutional change in order to prioritise the moral obligation of Serious Illness Conversations.

The Seismic Shift in End-of-Life Care: Palliative Care Challenges in the Era of Medical Assistance in Dying.

Background: Concerns regarding personal, professional, administrative, and institutional implications of medical assistance in dying (MAiD) are of particular interest to palliative and hospice care providers (PHCPs), who may encounter additional moral distress and professional challenges in providing end-of-life (EOL) care in the new legislative and cultural era. Objective: To explore PHCPs' encountered challenges and resource recommendations for caring for patients considering MAiD. Design: Qualitative thematic analysis of audio-recorded semistructured interviews with PHCPs. Setting/Subjects: Multidisciplinary PHCPs in acute, community, residential, and hospice care in Vancouver, Canada, with experience supporting patients who have made MAiD inquiries or requests. Measurements: Interviews were deidentified, transcribed verbatim, and coded by four researchers using a common coding scheme. Key themes were analyzed. Results: Twenty-six PHCP participants included physicians (n = 7), nurses (n = 12), social workers (n = 5), and spiritual health practitioners (n = 2). Average interview length was 52 minutes (range 35-90). Analysis revealed four broad challenges associated with providing EOL care after MAiD legalization: (1) moral ambiguity and provider distress, (2) family distress, (3) interprofessional team conflict, and (4) impact on palliative care. Participants also recommended three types of resources to support clinicians in delivering quality EOL care to patients contemplating MAiD: (1) education and training, (2) pre- and debriefing for team members, and (3) tailored bereavement support. Conclusions: PHCPs encountered multilevel MAiD-related challenges, but noted improvement in organizational policies and coordination. Resources to enhance training, pre- and debriefing, and tailored bereavement may further support PHCPs in providing high-quality EOL care as they navigate the legislative and cultural shifts.

Towards Equitable AI Interventions for People Who Use Drugs: Key Areas That Require Ethical Investment.

There has been growing investment in artificial intelligence (AI) interventions to combat the opioid-driven overdose epidemic plaguing North America. Although the evidence for the use of technology and AI in medicine is mounting, there are a number of ethical, social, and political implications that need to be considered when designing AI interventions. In this commentary, we describe 2 key areas that will require ethical deliberation in order to ensure that AI is being applied ethically with socially vulnerable populations such as people who use drugs: (1) perpetuation of biases in data and (2) consent. We offer ways forward to guide and provide opportunities for interventionists to develop substance use-related AI technologies that account for the inherent biases embedded within conventional data systems. This includes a discussion of how other data generation techniques (eg, qualitative and community-based approaches) can be integrated within AI intervention development efforts to mitigate the limitations of relying on electronic health record data. Finally, we emphasize the need to involve people who use drugs as stakeholders in all phases of AI intervention development.

A dysfunctional endolysosomal pathway common to two sub-types of demyelinating Charcot-Marie-Tooth disease.

Autosomal dominant mutations in LITAF are responsible for the rare demyelinating peripheral neuropathy, Charcot-Marie-Tooth disease type 1C (CMT1C). The LITAF protein is expressed in many human cell types and we have investigated the consequences of two different LITAF mutations in primary fibroblasts from CMT1C patients using confocal and electron microscopy. We observed the appearance of vacuolation/enlargement of late endocytic compartments (late endosomes and lysosomes). This vacuolation was also observed after knocking out LITAF from either control human fibroblasts or from the CMT1C patient-derived cells, consistent with it being the result of loss-of-function mutations in the CMT1C fibroblasts. The vacuolation was similar to that previously observed in fibroblasts from CMT4J patients, which have autosomal recessive mutations in FIG4. The FIG4 protein is a component of a phosphoinositide kinase complex that synthesises phosphatidylinositol 3,5-bisphosphate on the limiting membrane of late endosomes. Phosphatidylinositol 3,5-bisphosphate activates the release of lysosomal Ca2+ through the cation channel TRPML1, which is required to maintain the homeostasis of endosomes and lysosomes in mammalian cells. We observed that a small molecule activator of TRPML1, ML-SA1, was able to rescue the vacuolation phenotype of LITAF knockout, FIG4 knockout and CMT1C patient fibroblasts. Our data describe the first cellular phenotype common to two different subtypes of demyelinating CMT and are consistent with LITAF and FIG4 functioning on a common endolysosomal pathway that is required to maintain the homeostasis of late endosomes and lysosomes. Although our experiments were on human fibroblasts, they have implications for our understanding of the molecular pathogenesis and approaches to therapy in two subtypes of demyelinating Charcot-Marie-Tooth disease.