Adaptive, platform trials assessing therapies for hospitalized COVID-19 patients: Informed consent forms omitted a few important elements of information.

Background: The information provided to participants of adaptive platform trials assessing therapies for COVID-19 inpatients is unknown. We aim to evaluate it by reviewing participant information sheets/informed consent forms (PIS/ICFs). Methods: We searched the Cochrane COVID-19 Study Register and ClinicalTrials.gov (28 March 2022) to identify non-industry-sponsored adaptive platform phase 2+ trials with publicly available protocols and PIS/ICFs, selecting versions closest to the initial one. We assessed the elements of information included in the Good Clinical Practice guidelines and the Declaration of Helsinki as present, absent, or deficient (incompletely described). Results: We included PIS/ICFs of 11 trials (ACCORD-2, ACTIV-1IM, Bari-SolidAct, CATALYST, Discovery, HEAL-COVID, ITAC, RECOVERY, REMAP-COVID, Solidarity and TACTIC-R), which were 4-32 pages long (median (md) = 11). Between two and 11 (md = 6) of the 25 different elements of information assessed were omitted or deficiently described in the PIS/ICFs of the 11 trials. Information about providing trial results, investigators' conflicts of interest, post-study provisions, payment to and anticipated expenses for participants, number of participants, and on whether participants will receive new information that could impact their decision on staying in the trial, were omitted or deficiently described in at least five PIS/ICFs. Conclusions: Investigators failed to include a few important elements of information in the trial's PIS/ICF deemed relevant by international standards. In protocols of future trials, investigators should explain why elements of information specified in the Good Clinical Practice guidelines and/or by the Declaration of Helsinki were omitted from the PIS/ICFs.

Uncertainty, scarcity and transparency: Public health ethics and risk communication in a pandemic.

Communicating public health guidance is key to mitigating risk during disasters and outbreaks, and ethical guidance on communication emphasizes being fully transparent. Yet, communication during the pandemic has sometimes been fraught, due in part to practical and conceptual challenges around being transparent. A particular challenge has arisen when there was both evolving scientific knowledge on COVID-19 and reticence to acknowledge that resource scarcity concerns were influencing public health recommendations. This essay uses the example of communicating public health guidance on masking in the United States to illustrate ethical challenges of developing and conveying public health guidance under twin conditions of uncertainty and resource scarcity. Such situations require balancing two key principles in public health ethics: the precautionary principle and harm reduction. Transparency remains a bedrock value to guide risk communication, but optimizing transparency requires consideration of additional ethical values in developing and implementing risk communication strategies.

Treating Workers as Essential Too: An Ethical Framework for Public Health Interventions to Prevent and Control COVID-19 Infections among Meat-processing Facility Workers and Their Communities in the United States.

Meat is a multi-billion-dollar industry that relies on people performing risky physical work inside meat-processing facilities over long shifts in close proximity. These workers are socially disempowered, and many are members of groups beset by historic and ongoing structural discrimination. The combination of working conditions and worker characteristics facilitate the spread of SARS-CoV-2, the virus that causes COVID-19. Workers have been expected to put their health and lives at risk during the pandemic because of government and industry pressures to keep this "essential industry" producing. Numerous interventions can significantly reduce the risks to workers and their communities; however, the industry's implementation has been sporadic and inconsistent. With a focus on the U.S. context, this paper offers an ethical framework for infection prevention and control recommendations grounded in public health values of health and safety, interdependence and solidarity, and health equity and justice, with particular attention to considerations of reciprocity, equitable burden sharing, harm reduction, and health promotion. Meat-processing workers are owed an approach that protects their health relative to the risks of harms to them, their families, and their communities. Sacrifices from businesses benefitting financially from essential industry status are ethically warranted and should acknowledge the risks assumed by workers in the context of existing structural inequities.

Public acceptability of COVID-19 control measures in Singapore, Hong Kong, and Malaysia: A cross-sectional survey.

BACKGROUND: Several countries have implemented control measures to limit SARS-CoV-2 spread, including digital contact tracing, digital monitoring of quarantined individuals, and testing of travelers. These raise ethical issues around privacy, personal freedoms, and equity. However, little is known regarding public acceptability of these measures. METHODS: In December 2020, we conducted a survey among 3635 respondents in Singapore, Hong Kong, and Malaysia to understand public perceptions on the acceptability of COVID-19 control measures. FINDINGS: Hong Kong respondents were much less supportive of digital contact tracing and monitoring devices than those in Malaysia and Singapore. Around three-quarters of Hong Kong respondents perceived digital contact tracing as an unreasonable restriction of individual freedom; <20% trusted that there were adequate local provisions preventing these data being used for other purposes. This was the opposite in Singapore, where nearly 3/4 of respondents agreed that there were adequate data protection rules locally. In contrast, only a minority of Hong Kong respondents viewed mandatory testing and vaccination for travelers as unreasonable infringements of privacy or freedom. Less than 2/3 of respondents in all territories were willing to be vaccinated against COVID-19, with a quarter of respondents undecided. However, support for differential travel restrictions for vaccinated and unvaccinated individuals was high in all settings. INTERPRETATION: Our findings highlight the importance of sociopolitical context in public perception of public health measures and emphasize the need to continually monitor public attitudes toward such measures to inform implementation and communication strategies.

Telemedicine and Haemodialysis Care during the COVID-19 Pandemic: An Integrative Review of Patient Safety, Healthcare Quality, Ethics and the Legal Considerations in Singapore Practice.

The COVID-19 pandemic has been an unprecedented health crisis for the general population as well as for patients with chronic illnesses such as those requiring maintenance dialysis. Patients suffering from chronic kidney disease requiring dialysis are considered a high-risk population. Multiple reports have highlighted an increased need for intensive care and higher death rates among this group of patients. Most maintenance dialysis patients are in-centre haemodialysis patients who receive treatment in shared facilities (community dialysis centres). The inability to maintain social distancing in these facilities has led to case clustering among patients and staff. This poses a substantial risk to the patients, their household members, and the wider community. To mitigate the risks of COVID-19 transmission, telemedicine was rapidly adopted in the past year by nephrologists and other allied-health staff to provide care via remote consultations and reviews. Telemedicine poses unique challenges even in an era where so much is performed online with a high degree of success and satisfaction. In applying distant clinical care for maintenance haemodialysis patients via telemedicine, there is a need to ensure adequate protection for the health and safety of patients as well as understand the ethical and legal implications of telemedicine. We discussed, in this article, these three core aspects of patient safety and quality, ethics and legal implications in telemedicine, and how each of these is crucial to the safe and effective delivery of care in general as well as unique aspects of this in Singapore.

Professional Oversight of Emergency-Use Interventions and Monitoring Systems: Ethical Guidance From the Singapore Experience of COVID-19.

High degrees of uncertainty and a lack of effective therapeutic treatments have characterized the COVID-19 pandemic and the provision of drug products outside research settings has been controversial. International guidelines for providing patients with experimental interventions to treat infectious diseases outside of clinical trials exist but it is unclear if or how they should apply in settings where clinical trials and research are strongly regulated. We propose the Professional Oversight of Emergency-Use Interventions and Monitoring System (POEIMS) as an alternative pathway based on guidance developed for the ethical provision of experimental interventions to treat COVID-19 in Singapore. We support our proposal with justifications that establish moral duties for physicians to record outcomes data and for institutions to establish monitoring systems for reporting information on safety and effectiveness to the relevant authorities. Institutions also have a duty to support generation of evidence for what constitutes good clinical practice and so should ensure the unproven intervention is made the subject of research studies that can contribute to generalizable knowledge as soon as practical and that physicians remain committed to supporting learning health systems. We outline key differences between POEIMS and other pathways for the provision of experimental interventions in public health emergencies.

Ongoing and future COVID-19 vaccine clinical trials: challenges and opportunities.

Large-scale deployment of COVID-19 vaccines will seriously affect the ongoing phases 2 and 3 randomised placebo-controlled trials assessing SARS-CoV-2 vaccine candidates. The effect will be particularly acute in high-income countries where the entire adult or older population could be vaccinated by late 2021. Regrettably, only a small proportion of the population in many low-income and middle-income countries will have access to available vaccines. Sponsors of COVID-19 vaccine candidates currently in phase 2 or initiating phase 3 trials in 2021 should consider continuing the research in countries with limited affordability and availability of COVID-19 vaccines. Several ethical principles must be implemented to ensure the equitable, non-exploitative, and respectful conduct of trials in resource-poor settings. Once sufficient knowledge on the immunogenicity response to COVID-19 vaccines is acquired, non-inferiority immunogenicity trials-comparing the immune response of a vaccine candidate to that of an authorised vaccine-would probably be the most common trial design. Until then, placebo-controlled, double-blind, crossover trials will continue to play a role in the development of new vaccine candidates. WHO or the Council for International Organizations of Medical Sciences should define an ethical framework for the requirements and benefits for trial participants and host communities in resource-poor settings that should require commitment from all vaccine candidate sponsors from high-income countries.

Immunity certification for COVID-19: ethical considerations.

Restrictive measures imposed because of the coronavirus disease 2019 (COVID-19) pandemic have resulted in severe social, economic and health effects. Some countries have considered the use of immunity certification as a strategy to relax these measures for people who have recovered from the infection by issuing these individuals a document, commonly called an immunity passport. This document certifies them as having protective immunity against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the virus that causes COVID-19. The World Health Organization has advised against the implementation of immunity certification at present because of uncertainty about whether long-term immunity truly exists for those who have recovered from COVID-19 and concerns over the reliability of the proposed serological test method for determining immunity. Immunity certification can only be considered if scientific thresholds for assuring immunity are met, whether based on antibodies or other criteria. However, even if immunity certification became well supported by science, it has many ethical issues in terms of different restrictions on individual liberties and its implementation process. We examine the main considerations for the ethical acceptability of immunity certification to exempt individuals from restrictive measures during the COVID-19 pandemic. As well as needing to meet robust scientific criteria, the ethical acceptability of immunity certification depends on its uses and policy objectives and the measures in place to reduce potential harms, and prevent disproportionate burdens on non-certified individuals and violation of individual liberties and rights.

Les restrictions imposées dans le cadre de la lutte contre la pandémie de maladie à coronavirus 2019 (COVID-19) ont eu de lourdes conséquences économiques, sociales et sanitaires. Certains pays ont envisagé la mise en place d'une stratégie visant à alléger ces restrictions pour les individus guéris en leur octroyant un document communément appelé «passeport d'immunité¼. Ce document atteste qu'ils ont développé une immunité protectrice contre le coronavirus 2 du syndrome respiratoire aigu sévère (SARS-CoV-2), le virus à l'origine de la COVID-19. L'Organisation mondiale de la Santé a déconseillé l'usage du certificat d'immunité pour l'instant, car l'incertitude demeure quant à l'existence réelle d'une immunité à long terme pour ceux qui se sont remis de la COVID-19. En outre, la fiabilité des tests sérologiques censés déterminer si l'individu est immunisé n'est pas avérée. Un tel certificat ne peut être instauré que si les seuils scientifiques en matière d'immunité sont respectés, qu'ils soient fondés sur les anticorps ou sur d'autres critères. Néanmoins, même si le certificat d'immunité est désormais bien accepté par la science, il s'accompagne de nombreuses questions d'ordre éthique en ce qui concerne la limitation des libertés individuelles et la mise en œuvre. Dans le présent document, nous examinons les principales considérations à prendre en compte pour garantir l'acceptabilité éthique du certificat d'immunité visant à lever les mesures de restriction pour certaines personnes durant la pandémie de COVID-19. Cette acceptabilité éthique dépend non seulement de son degré de conformité à des critères scientifiques stricts, mais aussi de son usage, des objectifs politiques ainsi que des mesures mises en place pour atténuer les préjudices potentiels et éviter d'imposer une charge disproportionnée sur les individus dépourvus de certificat, ou de bafouer les droits et libertés de tout un chacun.

Las medidas restrictivas impuestas a causa de la pandemia de la enfermedad coronavirus de 2019 (COVID-19) han tenido graves efectos sociales, económicos y sanitarios. Algunos países han considerado la posibilidad de utilizar la certificación de inmunidad como estrategia para flexibilizar dichas medidas para las personas que se han recuperado de la infección mediante la expedición a dichas personas de un documento, comúnmente denominado pasaporte de inmunidad. Este documento certifica que han desarrollado inmunidad protectora contra el coronavirus-2 del síndrome respiratorio agudo severo (SARS-CoV-2), el virus que causa la COVID-19. La Organización Mundial de la Salud ha desaconsejado la aplicación de la certificación de la inmunidad en la actualidad debido a la incertidumbre sobre si existe realmente una inmunidad a largo plazo para quienes se han recuperado de la COVID-19 y a las preocupaciones sobre la fiabilidad del método de prueba serológica propuesto para determinar la inmunidad. La certificación de la inmunidad solo puede considerarse si se cumplen los umbrales científicos para asegurar la inmunidad, ya sea que se basen en anticuerpos o en otros criterios. Sin embargo, incluso si la certificación de la inmunidad llegara a estar bien respaldada por la ciencia, tiene muchas cuestiones éticas en cuanto a las diferentes restricciones de las libertades individuales y su proceso de aplicación. Examinamos las principales consideraciones sobre la aceptabilidad ética de la certificación de la inmunidad para eximir a los individuos de las medidas restrictivas durante la pandemia de la COVID-19. Además de necesitar cumplir criterios científicos sólidos, la aceptabilidad ética de la certificación de inmunidad depende de sus usos y objetivos de política y de las medidas que se apliquen para reducir los posibles daños y evitar que se impongan cargas desproporcionadas a las personas que no cuenten con dicha certificación y se violen las libertades y derechos individuales.

Top five ethical lessons of COVID-19 that the world must learn.

As the world reflects upon one year since the first cases of coronavirus disease 2019 (COVID-19) and prepare for and experience surges in cases, it is important to identify the most crucial ethical issues that might lie ahead so that countries are able to plan accordingly. Some ethical issues are rather obvious to predict, such as the ethical issues surrounding the use of immunity certificates, contact tracing, and the fair allocation of vaccines globally. Yet, the most significant ethical challenge that the world must address in the next year and beyond is to ensure that we learn the ethical lessons of the first year of this pandemic. Learning from our collective experiences thus far constitutes our greatest moral obligation. Appreciating that decision-making in the context of a pandemic is constrained by unprecedented complexity and uncertainty, beginning in June 2020, an international group of 17 experts in bioethics spanning 15 countries (including low-, middle-, and high-income countries) met virtually to identify what we considered to be the most significant ethical challenges and accompanying lessons faced thus far in the COVID-19 pandemic. Once collected, the group met over the course of several virtual meetings to identify challenges and lessons that are analytically distinct in order to identify common ethical themes under which different challenges and lessons could be grouped. The result, described in this paper, is what this expert group consider to be the top five ethical lessons from the initial experience with COVID-19 that must be learned.

Family Presence for Patients and Separated Relatives During COVID-19: Physical, Virtual, and Surrogate.

During an outbreak or pandemic involving a novel disease such as COVID-19, infected persons may need to undergo strict medical isolation and be separated from their families for public health reasons. Such a practice raises various ethical questions, the characteristics of which are heightened by uncertainties such as mode of transmission and increasingly scarce healthcare resources. For example, under what circumstances should non-infected parents be allowed to stay with their infected children in an isolation facility? This paper will examine ethical issues with three modes of "family presence" or "being there or with" a separated family member during the current COVID-19 pandemic: physical, virtual, and surrogate. Physical visits, stays, or care by family members in isolation facilities are usually prohibited, discouraged, or limited to exceptional circumstances. Virtual presence for isolated patients is often recommended and used to enable communication. When visits are disallowed, frontline workers sometimes act as surrogate family for patients, such as performing bedside vigils for dying patients. Drawing on lessons from past outbreaks such as the 2002-2003 SARS epidemic and the recent Ebola epidemic in West Africa, we consider the ethical management of these modes of family presence and argue for the promotion of physical presence under some conditions.

COVID-19 vaccine development: Time to consider SARS-CoV-2 challenge studies?

While a human challenge study holds the prospect of accelerating the development of a vaccine for the coronavirus SARS-CoV-2, it may be opposed due to risks of harm to participants and researchers. Given the increasing number of human deaths and severe disruption to lives worldwide, we argue that a SARS-CoV-2 challenge study is ethically justifiable as its social value substantially outweighs the risks. Such a study should therefore be seriously considered as part of the global research response towards the COVID-19 pandemic. In this paper, we contribute to the debate by addressing the misperception that a challenge study for the coronavirus would lower scientific and ethical standards for vaccine research and development, and examine how it could be ethically conducted. We also set out information that needs to be disclosed to prospective participants to obtain their consent.

Ethical Implementation of Immunity Passports During the COVID-19 Pandemic.

A number of countries are planning the use of "immunity passports" as a way to ease restrictive measures and allow infected and recovered people to return to work during the COVID-19 pandemic. This paper brings together key scientific uncertainties regarding the use of serological tests to assure immune status and a public health ethics perspective to inform key considerations in the ethical implementation of immunity passport policies. Ill-conceived policies have the potential to cause severe unintended harms that could result in greater inequity, the stigmatization of certain sectors of society, and heightened risks and unequal treatment of individuals due to erroneous test results. Immunity passports could, however, be used to achieve collective benefits and benefits for specific populations besides facilitating economic recovery. We conclude that sector-based policies that prioritize access to testing based on societal need are likely to be fairer and logistically more feasible, while minimizing stigma and reducing incentives for fraud. Clear guidelines need to be set out for which sectors of society should be prioritized for testing, and rigorous mechanisms should be in place to validate test results and identify cases of reinfection.