• Ryan McGinn, Dean A Fergusson, Duncan J Stewart, Arnold S Kristof, Carly C Barron, Bernard Thebaud, Lauralyn McIntyre, Dawn Stacey, Mark Liepmann, Aurore Dodelet-Devillers, Haibo Zhang, Richard Renlund, Elliot Lilley, Gregory P Downey, Earl G Brown, Lucie Côté, Claudia C Dos Santos, Alison E Fox-Robichaud, HussainSabah N ASNADepartment of Anesthesiology and Pain Medicine, The Ottawa Hospital, Faculty of Medicine, University of Ottawa, ON, Canada.Clinical Epidemiology Program, Blueprint Translational Research Group, Ottawa Hospital Research Institute, Ottawa, John G Laffey, Mingyao Liu, Jenna MacNeil, Holly Orlando, Salman T Qureshi, Patricia V Turner, Brent W Winston, Manoj M Lalu, and Canadian Critical Care Translational Biology Group.
• Department of Anesthesiology and Pain Medicine, The Ottawa Hospital, Faculty of Medicine, University of Ottawa, ON, Canada.
• Crit. Care Med. 2021 Feb 1; 49 (2): 311323311-323.

ObjectivesIn many jurisdictions, ethical concerns require surrogate humane endpoints to replace death in small animal models of acute lung injury. Heterogenous selection and reporting of surrogate endpoints render interpretation and generalizability of findings between studies difficult. We aimed to establish expert-guided consensus among preclinical scientists and laboratory animal veterinarians on selection and reporting of surrogate endpoints, monitoring of these models, and the use of analgesia.DesignA three-round consensus process, using modified Delphi methodology, with researchers who use small animal models of acute lung injury and laboratory animal veterinarians who provide care for these animals. Statements on the selection and reporting of surrogate endpoints, monitoring, and analgesia were generated through a systematic search of MEDLINE and Embase. Participants were asked to suggest any additional potential statements for evaluation.SettingA web-based survey of participants representing the two stakeholder groups (researchers, laboratory animal veterinarians). Statements were rated on level of evidence and strength of support by participants. A final face-to-face meeting was then held to discuss results.SubjectsNone.InterventionsNone.Measurements And Main ResultsForty-two statements were evaluated, and 29 were rated as important, with varying strength of evidence. The majority of evidence was based on rodent models of acute lung injury. Endpoints with strong support and evidence included temperature changes and body weight loss. Behavioral signs and respiratory distress also received support but were associated with lower levels of evidence. Participants strongly agreed that analgesia affects outcomes in these models and that none may be necessary following nonsurgical induction of acute lung injury. Finally, participants strongly supported transparent reporting of surrogate endpoints. A prototype composite score was also developed based on participant feedback.ConclusionsWe provide a preliminary framework that researchers and animal welfare committees may adapt for their needs. We have identified knowledge gaps that future research should address.Copyright © 2020 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

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