Patiromer utility as an adjunct treatment in patients needing urgent hyperkalaemia management (PLATINUM): design of a multicentre, randomised, double-blind, placebo-controlled, parallel-group study.

INTRODUCTION: Hyperkalaemia is common, life-threatening and often requires emergency department (ED) management; however, no standardised ED treatment protocol exists. Common treatments transiently reducing serum potassium (K+) (including albuterol, glucose and insulin) may cause hypoglycaemia. We outline the design and rationale of the Patiromer Utility as an Adjunct Treatment in Patients Needing Urgent Hyperkalaemia Management (PLATINUM) study, which will be the largest ED randomised controlled hyperkalaemia trial ever performed, enabling assessment of a standardised approach to hyperkalaemia management, as well as establishing a new evaluation parameter (net clinical benefit) for acute hyperkalaemia treatment investigations. METHODS AND ANALYSIS: PLATINUM is a Phase 4, multicentre, randomised, double-blind, placebo-controlled study in participants who present to the ED at approximately 30 US sites. Approximately 300 adult participants with hyperkalaemia (K+ ≥5.8 mEq/L) will be enrolled. Participants will be randomised 1:1 to receive glucose (25 g intravenously <15 min before insulin), insulin (5 units intravenous bolus) and aerosolised albuterol (10 mg over 30 min), followed by a single oral dose of either 25.2 g patiromer or placebo, with a second dose of patiromer (8.4 g) or placebo after 24 hours. The primary endpoint is net clinical benefit, defined as the mean change in the number of additional interventions less the mean change in serum K+, at hour 6. Secondary endpoints are net clinical benefit at hour 4, proportion of participants without additional K+-related medical interventions, number of additional K+-related interventions and proportion of participants with sustained K+ reduction (K+ ≤5.5 mEq/L). Safety endpoints are the incidence of adverse events, and severity of changes in serum K+ and magnesium. ETHICS AND DISSEMINATION: A central Institutional Review Board (IRB) and Ethics Committee provided protocol approval (#20201569), with subsequent approval by local IRBs at each site, and participants will provide written consent. Primary results will be published in peer-reviewed manuscripts promptly following study completion. TRIAL REGISTRATION NUMBER: NCT04443608.

[Time of ethics review of research proposals: results of an observational study]. / Tiempos de evaluación ética de protocolos de investigación: resultados de un estudio observacional.

The review of research protocols by Research Ethics Committees (RECs), essential to ensure the protection of participants, has been managed in the City of Buenos Aires through the PRIISA.BA electronic platform since January 2020. The aim of the present study was to describe ethical review times, their temporal evolution, and predictors of their duration. We conducted an observational study that included all the protocols reviewed between January 2020 and September 2021. Times to approval and to first observation were calculated. Temporal trends in times, and the multivariate association between these and protocol and IRB characteristics were evaluated. 2,781 protocols reviewed in 62 RECs were included. The median time to approval was 29.11 (RIQ 11.29 to 63.35) days, and time to first observation was 8.92 (RIQ 2.05 to 18.18) days. The times were significantly reduced throughout the study period. We detected as variables independently associated with shorter time to approval to be a COVID proposal, having funding and the number of centers to perform the study and having been reviewed by an RECs with more than 10 members. Making observations to the protocol was associated with more time. The results of the present work suggest that ethical review times were reduced during study period. In addition, variables associated with time were identified that could be the object of interventions to improve the process.

Trials using deferred consent in the emergency setting: a systematic review and narrative synthesis of stakeholders' attitudes.

BACKGROUND: Patients with acute conditions often lack the capacity to provide informed consent, and narrow therapeutic windows mean there is no time to seek consent from surrogates prior to treatment being commenced. One method to enable the inclusion of this study population in emergency research is through recruitment without prior consent, often known as 'deferred consent'. However, empirical studies have shown a large disparity in stakeholders' opinions regarding this enrolment method. This systematic review aimed to understand different stakeholder groups' attitudes to deferred consent, particularly in relation to the context in which deferred consent might occur. METHODS: Databases including MEDLINE, EMCare, PsychINFO, Scopus, and HMIC were searched from 1996 to January 2021. Eligible studies focussed on deferred consent processes for adults only, in the English language, and reported empirical primary research. Studies of all designs were included. Relevant data were extracted and thematically coded using a narrative approach to 'tell a story' of the findings. RESULTS: Twenty-seven studies were included in the narrative synthesis. The majority examined patient views (n = 19). Data from the members of the public (n = 5) and health care professionals (n =5) were also reported. Four overarching themes were identified: level of acceptability of deferred consent, research-related factors influencing acceptability, personal characteristics influencing views on deferred consent, and data use after refusal of consent or participant death. CONCLUSIONS: This review indicates that the use of deferred consent would be most acceptable to stakeholders during low-risk emergency research with a narrow therapeutic window and where there is potential for patients to benefit from their inclusion. While the use of narrative synthesis allowed assessment of the included studies, heterogeneous outcome measures meant that variations in study results could not be reliably attributed to the different trial characteristics. Future research should aim to develop guidance for research ethics committees when reviewing trials using deferred consent in emergency research and investigate more fully the views of healthcare professionals which to date have been explored less than patients and members of the public. Trial registration PROSPERO CRD42020223623.

Primary health care research in COVID-19: analysis of the protocols reviewed by the ethics committee of IDIAPJGol, Catalonia.

BACKGROUND: Since March of 2020, the scientific community has been engaged a marathon to answer the different questions that COVID-19 pandemic has brought. During this time, Ethics Committees played an important role in reviewing the research protocols, COVID-19 or not, ensuring that the quality of scientific research is not relaxed by the hasty need for answers. METHODS: Descriptive study from January 2019 to December 2021, comparing COVID-19 protocols to those not COVID-19 related protocols and comparing the work overload. Variables related to the characteristics of the research protocols (i.e. study design, funding…), the principal investigators (gender, PhD degree, professional role…) and outcomes of the Ethics Committee process (requirements of modifications and time until approval) were analyze. RESULTS: The number of sessions increased during COVID-19 pandemics (12 in 2019, 25 in 2020 and 18 in 2021). In total 751 protocols were evaluated during the study period; 513 (68.3%) had an observational design and 434 (57.8%) had no funding. The principal investigator was a woman in 491 (65.4%) studies and a General Practitioner in 330 (43.9%). The mean of the days until the protocol approval was 42.09 days (SD 60.2) with a decrease of 20.1 days from 2019 to 2021. A total of 614 (81.7%) protocols were approved, 336 (54.7%) within the first month after their initial evaluation. Less than half of the protocols were COVID-19 related (208, 44.3%). The COVID-19 protocols main topics were impact on the population (71, 34.1%); and COVID-19 pharmacological treatments (including vaccines) showed a higher increase in 2021 (37, 30.3%). CONCLUSIONS: Despite the work overload during the pandemic due to the increase in the number of meetings and protocols, the IDIAPJGol EC reviewed all of them (COVID-19 or not) adapting to the new situation but according to its criteria of good practices to provide a quick response in the EC opinion. In Primary Health Care the most study designs have been observational studies, many of them with no funding and led by GPs. In 2021 there was an increase in the number of protocols focused on drugs, most likely related to COVID-19 vaccines studies.

Key ethical issues encountered during COVID-19 research: a thematic analysis of perspectives from South African research ethics committees.

BACKGROUND: The COVID-19 pandemic presents significant challenges to research ethics committees (RECs) in balancing urgency of review of COVID-19 research with careful consideration of risks and benefits. In the African context, RECs are further challenged by historical mistrust of research and potential impacts on COVID-19 related research participation, as well as the need to facilitate equitable access to effective treatments or vaccines for COVID-19. In South Africa, an absent National Health Research Ethics Council (NHREC) also left RECs without national guidance for a significant duration of the COVID-19 pandemic. We conducted a qualitative descriptive study that explored the perspectives and experiences of RECs regarding the ethical challenges of COVID-19 research in South Africa. METHODS: We conducted in-depth interviews with 21 REC chairpersons or members from seven RECs at large academic health institutions across South Africa that were actively involved in the review of COVID-19 related research from January to April 2021. In-depth interviews were conducted remotely via Zoom. Interviews (60-125 min) were conducted in English using an in-depth interview guide, until data saturation was achieved. Audio-recordings were transcribed verbatim and field notes were converted into data documents. Line-by-line coding of transcripts was performed, and data were organised into themes and sub-themes. An inductive approach to thematic analysis was used to analyse data. RESULTS: Five main themes were identified, namely: rapidly evolving research ethics landscape, extreme vulnerability of research participants, unique challenges to informed consent, challenges to community engagement during COVID-19, and overlapping research ethics and public health equity issues. Sub-themes were identified for each main theme. CONCLUSIONS: Numerous, significant ethical complexities and challenges were identified by South African REC members in the review of COVID-19 related research. While RECs are resilient and adaptable, reviewer and REC member fatigue were major concerns. The numerous ethical issues identified also highlight the need for research ethics teaching and training, especially in informed consent, as well as the urgent requirement for the development of national guidelines for research ethics during public health emergencies. Further, comparative analysis between different countries is needed to develop the discourse around African RECs and COVID-19 research ethics issues.

Research Ethics during Pandemics: How IRBs Can Prepare.

The Covid-19 pandemic has raised a range of complex challenges for the research community in the United States. This essay uses Covid-19 as a model pandemic illness to consider two such issues that have yet to be fully explored in the ethics literature: first, whether the informed consent process should include a discussion of pandemic risks and, if so, how precisely these risks should be conveyed to potential research participants and, second, whether and under what circumstances vaccination status should be taken into consideration when enrolling subjects in non-pandemic-related studies during a pandemic.

Ethics committees in the time of COVID-19.

BACKGROUND: ethics committees (ECs) protect the rights, safety, and well-being of research participants and ensure the scientific correctness of clinical research. COVID-19 pandemic and the lockdown from 9 March to 16 May 2020 have potentially influenced several activities, including ECs. OBJECTIVES: to assess the impact of COVID-19 outbreak on Italian ECs and their performance during the lockdown. DESIGN: cross-sectional survey. SETTING AND PARTICIPANTS: the survey was conducted in mid-June 2020 in Italy contacting all the 90 local ECs. MAIN OUTCOME MEASURES: amount and kind of activities performed during the lockdown, characteristics of submitted studies and adoption of standard protocols of evaluation of research applications during the pandemic. Chi-square test was used to estimate the differences between territories with higher incidence (HI) and lower incidence (LI) of COVID-19. RESULTS: 258 questionnaires were collected from 46 ECs that participated in the study. Ten were excluded due to missing substantial data. Responses were divided into two groups according to location of EC: the HI (125 responses) and the LI (123 responses). Seventy-five percent of the HI describe an increase in the number of studies submitted, while 53% of the LI does not (p=0.001). Due to the pandemic and its effects on research, the 15% of participants belonging to HI territories reported that consideration and respect of research-related and general ethical principles could have decreased, as well the adoption of standard protocols of evaluation of research applications. EC secretariats located in HI Regions moved to smart working more than in LI ones (75% vs 59%; p=0.001). Where the EC workload increased significantly, it was reported that it was impossible to perform an accurate analysis of the submitted documentation, with the effect of providing a favorable opinion to studies of not excellent quality, though always ensuring the respect of ethical principles and patients' safety. CONCLUSIONS: COVID-19 impact on ECs has been heavier in HI territories, but smart working has been effective in ensuring EC activities and the subsequent activation of clinical studies potentially useful to face the pandemic. Clear differences arise between ECs belonging to the Italian Regions that have recorded a HI of COVID-19 cases compared to those located in Regions with a LI of cases. In some EC members' perception, the high number of studies in the most affected Regions together with the emergency experienced during the lockdown may have exposed ECs to the risk of decreasing the adoption of ethical principles and standard protocols of evaluation of research applications.

Developing a Rapid Response Single IRB Model for Conducting Research During a Public Health Emergency.

Research is foundational for evidence-based management of patients. Clinical research, however, takes time to plan, conduct, and disseminate-a luxury that is rarely available during a public health emergency. The University of Nebraska Medical Center (UNMC) developed a single institutional review board (IRB), with a vision to establish a rapid review resource for a network focused on clinical research of emerging pathogens in the United States. A core aspect of successful initiation of research during a pandemic or epidemic is the ability to operationalize an approach for rapid ethical review of human subject research and conduct those reviews at multiple sites-without losing any of the substantive aspects of ethics review. This process must be cultivated in anticipation of a public health emergency. US guidance for operationalizing IRB review for multisite research in a public health emergency is not well studied and processes are not well established. UNMC sought to address operational gaps and identify the unique procedural needs of rapid response single IRB (RR-sIRB) review of multisite research by conducting a series of preparedness exercises to develop and test the RR-sIRB model. For decades, emergency responder, healthcare, and public health organizations have conducted emergency preparedness exercises to test requirements for emergency response. In this article, we describe 2 types of simulation exercises conducted by UNMC: workshops and tabletops. This effort represents a unique use of emergency preparedness exercises to develop, refine, and test rapid review functions for an sIRB and to validate readiness of regulatory research processes. Such processes are crucial for conducting rapid, ethical, and sound clinical research in public health emergencies.

Challenges and Possible Solutions to Adapting to Virtual Recruitment: Lessons Learned from a Survey Study during the Covid-19 Pandemic.

The Covid-19 pandemic required rapid changes to research protocols, including immediate transitions to recruiting research participants and conducting the informed consent process virtually. This case study details the challenges our research team faced adapting an in-person, behavioral-intervention and survey study to virtual recruitment. We reflect on the impact of these rapid changes on recruitment and retention, discuss protocol changes we made to address these challenges and the needs of potential and enrolled participants, and propose recommendations for future work. Using computer technology to display professional return phone numbers, being flexible by contacting potential participants through various means, minimizing email communication due to added regulatory requirements, and partnering with the institutional review board to shorten and improve the consent document and process were critical to study success. This case study can offer insight to other researchers as they navigate similar processes. Virtual recruitment is likely to continue; it is important to ensure that it facilitates, rather than hinders, equitable and just recruitment practices.

A Survey on Methodological Issues of Clinical Research Studies Reviewed by Independent Ethic Committees during the COVID-19 Pandemic in Italy.

The struggle for information and the hasty search for answers caused by the COVID-19 pandemic threatened the possibility of lowering study quality, as well as ethical committees' review standards during the outbreak. Our investigation aimed to assess the impact of COVID-19 on the quality of clinical research studies submitted to Italian Ethics Committees in the period between April and July 2020. All 91 Italian ethics committees were contacted via email in order to collect anonymized information on the type and quality of COVID-19-related studies submitted to each committee during the study period. The present study summarizes the characteristics of the 184 study applications collected, pointing out, especially, how the quality of the study population and statistical analysis are crucial variables in determining the study approval. Nevertheless, despite the need for high-quality and open scientific information, especially exacerbated by this particular historical period, only a minority of the ethics committees (20.9%) agreed to share their data; such scarce participation, beyond biasing the representativeness of the results obtained by the present study, more importantly, hinders the broader goal of creating trust between researchers and the general public.

Acceptability of donor funding for clinical trials in the UK: a qualitative empirical ethics study using focus groups to elicit the views of research patient public involvement group members, research ethics committee chairs and clinical researchers.

OBJECTIVES: The Plutocratic Proposal is a novel method of funding early phase clinical trials where a single donor funds the entire trial and in so doing secures a place on it. The aim of this study was to identify and explore concerns that may be raised by UK research ethics committees (RECs) when reviewing clinical trials funded in this way. DESIGN: Empirical ethics combining ethical analysis and qualitative data from three focus groups held online using Frith's symbiotic approach. Data were analysed using inductive thematic approach informed by the study aims and ethical analysis. PARTICIPANTS: 22 participants were recruited: 8 research patient public involvement group members, 7 REC chairs and 7 clinical researchers. All were based in the UK. RESULTS: With one exception, participants thought the Plutocratic Proposal may be 'all things considered' acceptable, providing their concerns were met, primary of which was upholding scientific integrity. Other concerns discussed related to the acceptability of the donor securing a place on the trial including: whether this was an unfair distribution of benefits, disclosing the identity of the donor as the funder, protecting the donor from exploitation and funding a single study with multiple donors on the same terms. Some misgivings fell outside the usual REC purview: detrimental impact of donors of bad character, establishing the trustworthiness of the matching agency and its processes and optimising research funding and resources. Despite their concerns, participants recognised that because the donor funds the whole trial, others would also potentially benefit from participating. CONCLUSIONS: We identified concerns about the Plutocratic Proposal. UK RECs may be open to approving studies if these can be addressed. Existing governance processes will do some of this work, but additional REC guidance, particularly in relation to donors securing a place on the trial, may be necessary to help RECs navigate ethical concerns consistently.

Eastern Mediterranean Health Journal [2022; Vol.28, Issue 5]

Eastern Mediterranean Health Journal is the official health journal published by the Eastern Mediterranean Regional Office of the World Health Organization. It is a forum for the presentation and promotion of new policies and initiatives in health services; and for the exchange of ideas concepts epidemiological data research findings and other information with special reference to the Eastern Mediterranean Region. It addresses all members of the health profession medical and other health educational institutes interested NGOs WHO Collaborating Centres and individuals within and outside the Region

المجلة الصحية لشرق المتوسط هى المجلة الرسمية التى تصدرعن المكتب الاقليمى لشرق المتوسط بمنظمة الصحة العالمية. وهى منبر لتقديم السياسات والمبادرات الجديدة فى الصحة العامة والخدمات الصحية والترويج لها، و لتبادل الاراء و المفاهيم والمعطيات الوبائية ونتائج الابحاث وغير ذلك من المعلومات، و خاصة ما يتعلق منها باقليم شرق المتوسط. وهى موجهة الى كل اعضاء المهن الصحية، والكليات الطبية وسائر المعاهد التعليمية، و كذا المنظمات غير الحكومية المعنية، والمراكز المتعاونة مع منظمة الصحة العالمية والافراد المهتمين بالصحة فى الاقليم و خارجه

La Revue de Santé de la Méditerranée Orientale est une revue de santé officielle publiée par le Bureau régional de l’Organisation mondiale de la Santé pour la Méditerranée orientale. Elle offre une tribune pour la présentation et la promotion de nouvelles politiques et initiatives dans le domaine de la santé publique et des services de santé ainsi qu’à l’échange d’idées de concepts de données épidémiologiques de résultats de recherches et d’autres informations se rapportant plus particulièrement à la Région de la Méditerranée orientale. Elle s’adresse à tous les professionnels de la santé aux membres des instituts médicaux et autres instituts de formation médico-sanitaire aux ONG Centres collaborateurs de l’OMS et personnes concernés au sein et hors de la Région.

Ethics and administrative jurisprudence of the rights of subjects of research in pandemic (COVID-19): role of the scientific ethics committees: Chile / Ética y jurisprudencia administrativa de los derechos de los sujetos de investigación en pandemia (COVID-19): función de los comités éticos científicos: Chile

RESUMEN: Todo gobierno debe reaccionar rápida y efectivamente ante cualquier pandemia, Chile no es la excepción y apoyado en el estado de Excepción Constitucional, ha tenido que implementar medidas que podrían involucrar poca información sobre las percepciones de las personas y las reacciones durante la implementación de las restricciones. Las instituciones internacionales de salud han determinado que es un deber moral realizar investigaciones que generen evidencia que promuevan y mejoren la atención de la salud y la mitigación de la pandemia, instando a reducir los "obstáculos" prácticos de la revisión ética. Los objetivos de este trabajo fueron analizar desde las perspectivas de las consideraciones éticas y jurídicas, el rol que cumplen los Comités Éticos Científicos en el manejo y la protección de las personas durante la pandemia de la COVID-19. La metodología de trabajo se basó en la recolección de la información de Instituciones nacionales e internacionales de Salud y luego analizarla según la jurisprudencia administrativa del gobierno de Chile. Se concluye que los cambios de criterios que deben observar los CECs en el proceso de revisión de los protocolos de los proyectos de investigación científica, deben velar por proteger los derechos de los pacientes y sujetos de investigación en cuanto puede involucrar información sensible, más aún, si se consideran las graves consecuencias de su transgresión, dar un sentido distinto al que corresponda a las normas sobre derechos de pacientes, puede resultar en "falta de servicio" y eventual vulneración en los derechos del sujeto de investigación. La labor de los CEC, debe realizarse siempre desde una interpretación restrictiva, reconociendo la función pública que cumplen como parte integrante de la labor ética encomendada por el legislador al efecto.

SUMMARY: Every government must react quickly and effectively to any pandemic, Chile is no exception and supported by the state of Constitutional Exception, it has had to implement measures that could involve little information about people's perceptions and reactions during the implementation of the restrictions. International health institutions have determined that it is a moral duty to carry out research that generates evidence that promotes and improves health care and the mitigation of the pandemic, urging to reduce the practical "obstacles" to ethical review. The objective of this study was to analyze from the perspectives of ethical and legal considerations, the role that Scientific Ethics Committees play in the management and protection of people during the COVID-19 pandemic. The methodology used was based on collecting information from national and international Health Institutions and then analyzing it according to the administrative jurisprudence of the Chilean government. It is concluded that the changes in criteria that the CECs must observe in the process of reviewing the protocols of scientific research projects, must ensure the protection of the rights of patients and research subjects insofar as it may involve sensitive information, even more if the serious consequences of its transgression are considered. Giving a different meaning to the one that corresponds may result in "lack of service" and eventual violation of the rights of the research subject. The task of the CEC, must always be carried out from a restrictive interpretation, recognizing the public function that they fulfill as an integral part of the ethical work entrusted by the legislators to that effect.

Revising the legislation of Ethics Committees to ease biomedical research in humans across the world: lessons from the COVID-19 emergency.

As a legislative domain that considerably influences implementation of biomedical research, the need to improve the legal rules surrounding the organization and functioning of Ethics Committees in public health, toxicology, and clinical medicine is widely recognized within and outside the European Union. Given the often-heard complaints by researchers about the complexity and length of both the application and the review process by Ethics Committees in the authorization of new studies, adjustments to their legislation appears to be warranted. Within the European Union this seems also all the timelier, given the upcoming new regulation of clinical trials to become effective in early 2022. For this process, valuable lessons can be gleaned from the COVID-19 pandemic and the changes in the functioning of Ethics Committees that were adopted to cope with the exceptional circumstances imposed by the health emergency. The pandemic experience clearly indicates that a more responsive and practical system of applications' review by the Ethics Committees can be squared with acceptable levels of transparency and reliability in ethical accountability. For this reason, countries like Italy should consider undertaking a significant revision of the public law rules that govern the review processes of Ethics Committees in light of the pandemic experience. (www.actabiomedica.it).

Ethical, regulatory, and practical barriers to COVID-19 research: A stakeholder-informed inventory of concerns.

INTRODUCTION: SARS-CoV-2 (COVID-19) has caused death and economic injury around the globe. The urgent need for COVID-19 research created new ethical, regulatory, and practical challenges. The next public health emergency could be worse than COVID-19. We must learn about these challenges from the experiences of researchers and Research Ethics Committee professionals responsible for these COVID-19 studies to prepare for the next emergency. MATERIALS AND METHODS: We conducted an online survey to identify the ethical, oversight, and regulatory challenges of conducting COVID-19 research during the early pandemic, and proposed solutions for overcoming these barriers. Using criterion-based, convenience sampling, we invited researchers who proposed or conducted COVID-19 research to complete an anonymous, online survey about their experiences. We administered a separate but related survey to Institutional Review Board (IRB) professionals who reviewed COVID-19 research studies. The surveys included open-ended and demographic items. We performed inductive content analysis on responses to open-ended survey questions. RESULTS: IRB professionals (n = 143) and researchers (n = 211) described 19 types of barriers to COVID-19 research, related to 5 overarching categories: policy and regulatory, biases and misperceptions, institutional and inter-institutional conflicts, risks of harm, and pressure of the pandemic. Researchers and IRB professionals described 8 categories of adaptations and solutions to these challenges: enacting technological solutions; developing protocol-based solutions; disposition and team management; establishing and communicating appropriate standards; national guidance and leadership; maintaining high standards; prioritizing studies before IRB review; and identifying and incorporating experts. DISCUSSION AND CONCLUSIONS: This inventory of challenges represents ongoing barriers to studying the current pandemic, and they represent a risk to research during future public health emergencies. Delays in studies of a pandemic during a pandemic threatens the health and safety of the public. We urge the development of a national working group to address these issues before the next public health emergency arises.