A Dilemma for Respecting Autonomy: Bridge Technologies and the Hazards of Sequential Decision-Making.

Respect for patient autonomy can apply at two levels: ensuring that patient care reflects their considered values and wishes and honoring patient preferences about how to make momentous decisions. Caregivers who seek to respect patient autonomy in the context of some end-of-life decisions face a dilemma. Because these decisions are fraught, patients may prefer to approach them sequentially, only making decisions at the time they arise. However, respecting patients' preferences for a sequential approach can increase the likelihood that surrogates and care teams wind up in situations in which they lack information needed to ensure patients receive care that conforms to their considered values after they are no longer competent to make decisions for themselves. Sequential decision-making can thus conflict with the goal of ensuring care reflects the wishes of patients. After illustrating how this dilemma can arise in the use of life-sustaining "bridge" technologies, we argue that care teams may be warranted in requiring patients to articulate their wishes in an advance care plan before treatment begins. In some cases, care teams may even be permitted to refuse to undertake certain courses of care, unless patients articulate their wishes in an advance care plan.

Ethically designing research to inform multidimensional, rapidly evolving policy decisions: Lessons learned from the PROMISE HIV Perinatal Prevention Trial.

Research in rapidly evolving policy contexts can lead to the following ethical challenges for sponsors and researchers: the study's standard of care can become different than what patients outside the study receive, there may be political or other pressure to move ahead with unproven interventions, and new findings or revised policies may decrease the relevance of ongoing studies. These ethical challenges are considerable, but not unprecedented. In this article, we review the case of a multinational, randomized, controlled perinatal HIV prevention trial, the "PROMISE" (Promoting Maternal Infant Survival Everywhere) study. PROMISE compared the relative efficacy and safety of interventions to prevent mother to child transmission of HIV. The sponsor engaged an independent international ethics panel to address controversy about the study's standard of care and relevance as national and international guidelines changed. This ethics panel concluded that continuing the PROMISE trial as designed was ethically permissible because: (1) participants in all arms received interventions that were effective, and there was insufficient evidence about whether one intervention was more effective or safer than the other, and (2) data from PROMISE could be useful for a diverse range of stakeholders. In general, trials designed to inform rapidly evolving policy issues should develop mechanisms to revisit social value while recognizing that the value of research varies for diverse stakeholders with legitimate reasons to weigh evidence differently. We conclude by providing four reasons that trials may depart from the standard of care after a change in policy, while remaining ethically justifiable, and by suggesting how to improve existing trial oversight mechanisms to address evolving social value.

Self-Defeating Codes of Medical Ethics and How to Fix Them: Failures in COVID-19 Response and Beyond.

Statements of the core ethical and professional responsibilities of medical professionals are incomplete in ways that threaten fundamental goals of medicine. First, in the absence of explicit guidance for responding to cases in which there is significant uncertainty or disagreement about the relative therapeutic, prophylactic or diagnostic merits of available interventions they perpetuate self-defeating practices. Second, without addressing the role of advertising in shaping patient and community preferences they risk creating moral loopholes that bypass and undermine professional duties of fidelity, honesty and transparency. In both cases, these flaws are exacerbated by an individualism that ignores the critical role of health systems in managing and reducing uncertainty and conflict over best practices, and in communicating with and shaping the expectations of the public. These points are illustrated with examples from the response to COVID-19 and suggestions for reform are proposed.

Solitary death and new lifestyles during and after COVID-19: wearable devices and public health ethics.

BACKGROUND: Solitary death (kodokushi) has recently become recognized as a social issue in Japan. The social isolation of older people leads to death without dignity. With the outbreak of COVID-19, efforts to eliminate solitary death need to be adjusted in line with changes in lifestyle and accompanying changes in social structure. Health monitoring services that utilize wearable devices may contribute to this end. Our goals are to outline how wearable devices might be used to (1) detect emergency situations involving solitary older people and swiftly connect them with medical treatment, to (2) reduce the frequency of deaths that remain undiscovered and (3) to reduce social isolation by promoting social interaction. METHODS: Theoretical and philosophical approaches were adopted to examine ethical issues surrounding the application of wearable devices and cloud-based information processing systems to prevent solitary death in the world with/after COVID-19. MAIN BODY: (1) Technology cannot replace social connections; without social support necessary to foster understanding of the benefits of health management through wearable devices among older adults, such devices may remain unused, or not used properly. (2) Maturity of the technology; systems face the difficult task of detecting and responding to a wide range of health conditions and life-threatening events in time to avert avoidable morbidity and mortality. (3) Autonomy and personhood; promoting the voluntary use of wearable devices that are a part of larger efforts to connect isolated individuals to a community or social services might be effective. Legal force should be avoided if possible. There is some concern that landlords may require an older person to sign a contract agreeing to wear a device. The autonomy of solitary older people should be respected. (4) Governance: policies must be developed to limit access to data from wearables and the purposes for which data can be used. CONCLUSION: If thoughtfully deployed under proper policy constraints, wearable devices offer a way to connect solitary older people to health services and could reduce cases of solitary death while respecting the personhood of the user.

Cluster over individual randomization: are study design choices appropriately justified? Review of a random sample of trials.

BACKGROUND: Novel rationales for randomizing clusters rather than individuals appear to be emerging from the push for more pragmatic trials, for example, to facilitate trial recruitment, reduce the costs of research, and improve external validity. Such rationales may be driven by a mistaken perception that choosing cluster randomization lessens the need for informed consent. We reviewed a random sample of published cluster randomized trials involving only individual-level health care interventions to determine (a) the prevalence of reporting a rationale for the choice of cluster randomization; (b) the types of explicit, or if absent, apparent rationales for the use of cluster randomization; (c) the prevalence of reporting patient informed consent for study interventions; and (d) the types of justifications provided for waivers of consent. We considered cluster randomized trials for evaluating exclusively the individual-level health care interventions to focus on clinical trials where individual randomization is only theoretically possible and where there is a general expectation of informed consent. METHODS: A random sample of 40 cluster randomized trials were identified by implementing a validated electronic search filter in two electronic databases (Ovid MEDLINE and Embase), with two reviewers independently extracting information from each trial. Inclusion criteria were the following: primary report of a cluster randomized trial, evaluating exclusively an individual-level health care intervention, published between 2007 and 2016, and conducted in Canada, the United States, European Union, Australia, or low- and middle-income country settings. RESULTS: Twenty-five trials (62.5%, 95% confidence interval = 47.5%-77.5%) reported an explicit rationale for the use of cluster randomization. The most commonly reported rationales were those with logistical or administrative convenience (15 trials, 60%) and those that need to avoid contamination (13 trials, 52%); five trials (20%) were cited rationales related to the push for more pragmatic trials. Twenty-one trials (52.5%, 95% confidence interval = 37%-68%) reported written informed consent for the intervention, two (5%) reported verbal consent, and eight (20%) reported waivers of consent, while in nine trials (22.5%) consent was unclear or not mentioned. Reported justifications for waivers of consent included that study interventions were already used in clinical practice, patients were not randomized individually, and the need to facilitate the pragmatic nature of the trial. Only one trial reported an explicit and appropriate justification for waiver of consent based on minimum criteria in international research ethics guidelines, namely, infeasibility and minimal risk. CONCLUSION: Rationales for adopting cluster over individual randomization and for adopting consent waivers are emerging, related to the need to facilitate pragmatic trials. Greater attention to clear reporting of study design rationales, informed consent procedures, as well as justification for waivers is needed to ensure that such trials meet appropriate ethical standards.

Weight(s) of complicity.

International non-governmental organisations (INGO) face a dilemma when deciding whether to intervene in crisis situations where their efforts can be exploited or co-opted by others: intervene and risk becoming complicit with wrongdoing or sit on the sidelines and consign vulnerable people to the ravages of neglect or oppression. In "'He who helps the guilty, shares the crime'? INGOs, moral narcissism and complicity in wrongdoing," Buth et al argue that concerns about complicity often stifle ethical debate and encourage moral narcissism. We argue that neglecting concerns about complicity can foster a different form of moral narcissism and that where worries of complicity are present, aid efforts face three types of risk: risks to others created by contributing to wrongful acts or bad outcomes; risks to the moral integrity of the INGO and its personnel; and risks to social trust in the INGO. In the end, we challenge the assumption that there is a unique, ethically best way to reconcile these values. We suggest that the causes of justice and humanity might be better served by a diverse community of INGOs who each gives different weight to these concerns, than if each INGO adopts the same framework for reconciling these competing demands.

Social value, clinical equipoise, and research in a public health emergency.

The 2016 CIOMS International ethical guidelines for health-related research involving humans states that 'health-related research should form an integral part of disaster response' and that, 'widespread emergency use [of unproven interventions] with inadequate data collection about patient outcomes must therefore be avoided' (Guideline 20). This position is defended against two lines of criticism that emerged during the 2014 Ebola outbreak. One holds that desperately ill patients have a moral right to try unvalidated medical interventions (UMIs) and that it is therefore unethical to restrict access to UMIs to the clinical trial context. The second holds that clinical trials in contexts of high-mortality diseases are morally suspect because equipoise does not exist between a standard of care that offers little prospect of clinical benefit and a UMI that might offer some clinical advantage.

Learning health systems, clinical equipoise and the ethics of response adaptive randomisation.

To give substance to the rhetoric of 'learning health systems', a variety of novel trial designs are being explored to more seamlessly integrate research with medical practice, reduce study duration and reduce the number of participants allocated to ineffective interventions. Many of these designs rely on response adaptive randomisation (RAR). However, critics charge that RAR is unethical on the grounds that it violates the principle of equipoise. In this paper, I reconstruct critiques of RAR as holding that it is inconsistent with five important ethical principles. I then argue that these criticisms rest on a faulty view of equipoise encouraged by the idea that a RAR study models the beliefs of a single rational agent about the relative merits of the interventions being studied. I outline a view in which RAR models an idealised health system in which diverse communities of fully informed experts shrink or grow as their constituent members update their expert opinions in light of reliable medical evidence. I show how a proper understanding of clinical equipoise can reconcile this conception of RAR with these five ethical principles. This analysis removes an in-principle objection to RAR and sheds important light on the relationship between clinical equipoise and transient diversity in the scientific community.

Addressing ethical challenges in HIV prevention research with people who inject drugs.

Despite recent advances in HIV prevention and treatment, high HIV incidence persists among people who inject drugs (PWID). Difficult legal and political environments and lack of services for PWID likely contribute to high HIV incidence. Some advocates question whether any HIV prevention research is ethically justified in settings where healthcare system fails to provide basic services to PWID and where implementation of research findings is fraught with political barriers. Ethical challenges in research with PWID include concern about whether research evidence will be translated into practice; concerns that research might exacerbate background risks; and ethical challenges regarding the standard of HIV prevention in research. While these questions arise in other research settings, for research with PWID, these questions are especially controversial. This paper analyses four ethical questions in determining whether research could be ethically acceptable: (1) Can researchers ensure that research does not add to the burden of social harms and poor health experienced by PWID? (2) Should research be conducted in settings where it is uncertain whether research findings will be translated into practice? (3) When best practices in prevention and care are not locally available, what standard of care and prevention is ethically appropriate? (4) Does the conduct of research in settings with oppressive policies constitute complicity? We outline specific criteria to address these four ethical challenges. We also urge researchers to join the call to action for policy change to provide proven safe and effective HIV prevention and harm reduction interventions for PWID around the world.

Adversaries at the Bedside: Advance Care Plans and Future Welfare.

Advance care planning refers to the process of determining how one wants to be cared for in the event that one is no longer competent to make one's own medical decisions. Some have argued that advance care plans often fail to be normatively binding on caretakers because those plans do not reflect the interests of patients once they enter an incompetent state. In this article, we argue that when the core medical ethical principles of respect for patient autonomy, honest and adequate disclosure of information, institutional transparency, and concern for patient welfare are upheld, a policy that would allow for the disregard of advance care plans is self-defeating. This is because when the four principles are upheld, a patient's willingness to undergo treatment depends critically on the willingness of her caretakers to honor the wishes she has outlined in her advance care plan. A patient who fears that her caretakers will not honor her wishes may choose to avoid medical care so as to limit the influence of her caretakers in the future, which may lead to worse medical outcomes than if she had undergone care. In order to avoid worse medical outcomes and uphold the four core principles, caregivers who are concerned about the future welfare of their patients should focus on improving advance care planning and commit to honoring their patients' advance care plans.

Reviewing HIV-Related Research in Emerging Economies: The Role of Government Reviewing Agencies.

Little research has explored the possible effects of government institutions in emerging economies on ethical reviews of multinational research. We conducted semi-structured, in-depth telephone interviews with 15 researchers, Research Ethics Committees (RECs) personnel, and a government agency member involved in multinational HIV Prevention Trials Network (HPTN) research in emerging economies. Ministries of Health (MOH) or other government agencies often play pivotal roles as facilitators or barriers in the research ethics approval process. Government agency RECs reviewing protocols may face particular challenges, as they can lack resources, be poorly organized, have inconsistent review processes and limited expertise, and use differing definitions of national interests, including upholding national reputation and avoiding potential exploitation and stigma of the country's population. The MOH/governmental review body may be affected by power dynamics and politics in study reviews; may consider issues both related and unrelated to research ethics as understood elsewhere; and may prioritize particular diseases, treatments, or interventions over other topics/types of research. Poor communication and deeply-rooted tensions may exist between sponsor and host countries, impeding optimal interactions and reviews. Investigators must understand and plan for the potential effects of governmental agencies on multinational collaborative research, including preserving adequate time for agency review, and contacting these agencies beforehand to address issues that may arise. Better understanding of these issues can aid and advance appropriate global scientific collaboration.

Assessing the Moral Coherence and Moral Robustness of Social Systems: Proof of Concept for a Graphical Models Approach.

This paper presents a proof of concept for a graphical models approach to assessing the moral coherence and moral robustness of systems of social interactions. "Moral coherence" refers to the degree to which the rights and duties of agents within a system are effectively respected when agents in the system comply with the rights and duties that are recognized as in force for the relevant context of interaction. "Moral robustness" refers to the degree to which a system of social interaction is configured to ensure that the interests of agents are effectively respected even in the face of noncompliance. Using the case of conscientious objection of pharmacists to filling prescriptions for emergency contraception as an example, we illustrate how a graphical models approach can help stakeholders identify structural weaknesses in systems of social interaction and evaluate the relative merits of alternate organizational structures. By illustrating the merits of a graphical models approach we hope to spur further developments in this area.

The structure of clinical translation: efficiency, information, and ethics.

The so-called drug pipeline is not really about drugs and not much like a pipeline. It is really about the production and dissemination of information, and it is much more like a web. The misunderstanding leads to a poor understanding of what's wrong with clinical translation and how it can be improved.

Position statement on ethics, equipoise and research on charged particle radiation therapy.

The use of charged-particle radiation therapy (CPRT) is an increasingly important development in the treatment of cancer. One of the most pressing controversies about the use of this technology is whether randomised controlled trials are required before this form of treatment can be considered to be the treatment of choice for a wide range of indications. Equipoise is the key ethical concept in determining which research studies are justified. However, there is a good deal of disagreement about how this concept is best understood and applied in the specific case of CPRT. This report is a position statement on these controversies that arises out of a workshop held at Wolfson College, Oxford in August 2011. The workshop brought together international leaders in the relevant fields (radiation oncology, medical physics, radiobiology, research ethics and methodology), including proponents on both sides of the debate, in order to make significant progress on the ethical issues associated with CPRT research. This position statement provides an ethical platform for future research and should enable further work to be done in developing international coordinated programmes of research.

The ethics of advertising for health care services.

Advertising by health care institutions has increased steadily in recent years. While direct-to-consumer prescription drug advertising is subject to unique oversight by the Federal Drug Administration, advertisements for health care services are regulated by the Federal Trade Commission and treated no differently from advertisements for consumer goods. In this article, we argue that decisions about pursuing health care services are distinguished by informational asymmetries, high stakes, and patient vulnerabilities, grounding fiduciary responsibilities on the part of health care providers and health care institutions. Using examples, we illustrate how common advertising techniques may mislead patients and compromise fiduciary relationships, thereby posing ethical risks to patients, providers, health care institutions, and society. We conclude by proposing that these risks justify new standards for advertising when considered as part of the moral obligation of health care institutions and suggest that mechanisms currently in place to regulate advertising for prescription pharmaceuticals should be applied to advertising for health care services more broadly.

Algorithmic identification of persons with dementia for research recruitment: ethical considerations.

Underdiagnosis, misdiagnosis, and patterns of social inequality that translate into unequal access to health systems all pose barriers to identifying and recruiting diverse and representative populations into research on Alzheimer's disease and Alzheimer's disease related dementias. In response, some have turned to algorithms to identify patients living with dementia using information that is associated with this condition but that is not as specific as a diagnosis. This paper explains six ethical issues associated with the use of such algorithms including the generation of new, sensitive, identifiable medical information for research purposes without participant consent, issues of justice and equity, risk, and ethical communication. It concludes with a discussion of strategies for addressing these issues and prompting valuable research.