Principles Guiding Nonpandemic Critical Care Research During a Pandemic

OBJECTIVES: To describe the importance of critical care clinical research that is not pandemic-focused during pandemic times; outline principles to assist in the prioritization of nonpandemic research during pandemic times; and propose a guiding framework for decisions about whether, when and how to continue nonpandemic research while still honoring the moral and scientific imperative to launch research that is pandemic-focused. DESIGN/DATA SOURCES: Using in-person, email, and videoconference exchanges, we convened an interprofessional clinical research group, conducted a literature review of empirical studies, ethics documents and expert commentaries (2010 to present), and viewed traditional and social media posts (March 2020 to May 2020). Stakeholder consultation involved scientific, ethics, clinical, and administrative leaders. SETTING: Clinical research in the ICU. PATIENTS: Patients with and without coronavirus disease 2019. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: While clinical research should be prioritized to advantage patients with coronavirus disease 2019 in order to care for affected patients, it ideally would not unduly disadvantage patients without coronavirus disease 2019. Thus, timely, rigorous, relevant, and ethical clinical research is needed to improve the care and optimize outcomes for both patients with and without coronavirus disease 2019, acknowledging how many studies that are not exclusively focused on coronavirus disease 2019 remain relevant to patients with coronavirus disease 2019. Considerations to continue nonpandemic-focused research include the status of the pandemic, local jurisdictional guidance, capacity and safety of bedside and research personnel, disposition of patients already enrolled in nonpandemic studies, analyzing characteristics of each nonpandemic-focused study, research oversight, and final reporting requirements. CONCLUSIONS: Deliberation about continuing nonpandemic research should use objective, transparent criteria considering several aspects of the research process such as bedside and research staff safety, infection control, the informed consent model, protocol complexity, data collection, and implementation integrity. Decisions to pause or pursue nonpandemic research should be proportionate, transparent, and revisited as the pandemic abates

REVISE: Re-Evaluating the Inhibition of Stress Erosions in the ICU: a randomised trial protocol

Introduction: The Re-Evaluating the Inhibition of Stress Erosions (REVISE) Trial aims to determine the impact of the proton pump inhibitor pantoprazole compared with placebo on clinically important upper gastrointestinal (GI) bleeding in the intensive care unit (ICU), 90-day mortality and other endpoints in critically ill adults. The objective of this report is to describe the rationale, methodology, ethics and management of REVISE. Methods and analysis: REVISE is an international, randomised, concealed, stratified, blinded parallelgroup individual patient trial being conducted in ICUs in Canada, Australia, Saudi Arabia, UK, US, Kuwait, Pakistan and Brazil. Patients≥18 years old expected to remain invasively mechanically ventilated beyond the calendar day after enrolment are being randomised to either 40 mg pantoprazole intravenously or an identical placebo daily while mechanically ventilated in the ICU. The primary efficacy outcome is clinically important upper GI bleeding within 90 days of randomisation. The primary safety outcome is 90-day all-cause mortality. Secondary outcomes include rates of ventilator-associated pneumonia, Clostridioides difficile infection, new renal replacement therapy, ICU and hospital mortality, and patient-important GI bleeding. Tertiary outcomes are total red blood cells transfused, peak serum creatinine level in the ICU, and duration of mechanical ventilation, ICU and hospital stay. The sample size is 4800 patients; one interim analysis was conducted after 2400 patients had complete 90-day follow-up; the Data Monitoring Committee recommended continuing the trial.Adam M Deane ... Marianne J Chapman ... Alexis Poole ... et al

Enrollment of intensive care unit patients into clinical studies: A trinational survey of researchers' experiences, beliefs, and practices

BackgroundAs critical care practice increases in scope, size, and complexity, enrollment of critically ill patients into clinical studies is increasing.ObjectiveTo understand the experiences, beliefs, and practices of the Canadian Critical Care Trials Group and Australian and New Zealand Intensive Care Society Clinical Trials Group regarding enrollment of critically ill children and adults into clinical studies.MethodsSurvey items generated by the research team were formatted in four domains: experiences, beliefs, practices, and demographics. Five research coordinators and five physicians pretested the survey, providing feedback on clarity and completeness. Intrarater reliability (16 participants, 2 wks apart) was very good.ResultsThe response rate was 284 of 322 (88.2%). Respondents worked in intensive care units with a mean of 20.5 (SD 10) beds, caring for adults (72.2%), pediatric (18.8%), and both groups (9%) of critically ill patients. Clinical research was considered key to the future of improved clinical care. To enhance recruitment efficiency, respondents widely endorsed the effectiveness of increasing participating centers, after-hours, and weekend enrollment (all 3 scores 7 [6-7[sqb], reflecting median [interquartile range] on 1-7 scale). Overall, the effectiveness (6 [4-7]), feasibility (5 [4-6]) and ethics (5 [4-7]) of coenrollment into more than one randomized trial was endorsed. Half of respondents have adopted coenrollment with scientific and psychosocial provisos. Alternative designs, such as factorial and cluster randomized trials, were considered when suitable. Modifications to consent approaches (deferred consent (7 [6-7]), waived consent (7 [6-7]), or consent from two physicians in the absence of a substitute decision maker (6 [5-7])) were considered effective, but beliefs about the feasibility and ethics of some of these approaches varied.ConclusionsClinical research is highly valued by these intensive care unit communities. Strategies to increase capacity involve enhancing recruitment efficiencies, considering alternative study designs and expanding consent procedures. Thoughtfully implementing these strategies may advance the care of critically ill adults and children.Deborah J. Cook, David Blythe, Amanda Rischbieth, Paul C. Hebert, Nicole Zytaruk, Kusum Menon, Simon Erikson, Robert Fowler, Diane Heels-Ansdell, Maureen O. Mead