National Preclinical Sepsis Platform: developing a framework for accelerating innovation in Canadian sepsis research

Intensive Care Medicine Experimental

Janet Sunohara-Neilson¹  Jean-François Cailhier²  Emmanuel Charbonney²  Sean E. Gill³  Ruud A. W. Veldhuizen³  Victoria T. Hunniford⁴  Dean Fergusson⁴  Manoj M. Lalu⁵  Justin Presseau⁶  Christian Lehmann⁷  Juan Zhou⁷  Kathryn Hendrick⁸  Karla Krewulak⁹  Kirsten Fiest⁹  Braedon McDonald^1,10  Kimberly Macala^1,11  Ryan Zarychanski^1,12  Gloria Vázquez-Grande^1,13  Laura Mawdsley^1,14  Asher A. Mendelson^1,15  Gediminas Cepinskas^1,15  Christopher G. Ellis^1,16  Ellen McDonald^1,17  Valdirene S. Muniz^1,17  Dhruva Dwivedi^1,17  Alison E. Fox-Robichaud^1,17  Patricia Liaw^1,17  Haibo Zhang^1,18  Claudia dos Santos^1,19  John C. Marshall^2,20  Marcin Osuchowski^2,21  Casey Lansdell^2,22  Paulina M. Kowalewska^2,23  Donald Welsh^2,24  Brent W. Winston^2,25  Sarah K. Medeiros^2,26  Jaskirat Arora^2,26  Sahar Sohrabipour^2,26  Neha Sharma^2,26 

[1] Animal Resources Centre, University Health Network, Toronto, ON, Canada;Centre de Recherche du Centre Hospitalier de l’Université de Montréal, Montreal, QC, Canada;Département de Médecine, Université de Montréal, Montreal, QC, Canada;Centre for Critical Illness Research, Lawson Health Research Institute, London, ON, Canada;Department of Medicine, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, Canada;Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, Canada;Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada;Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada;Department of Anesthesiology and Pain Medicine, The Ottawa Hospital, PO Box 201B, 501 Smyth Road, K1H 8L6, Ottawa, ON, Canada;Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada;School of Epidemiology and Public Health, University of Ottawa, Ottawa, ON, Canada;Department of Anesthesia, Pain Management and Perioperative Medicine, Dalhousie University, Halifax, NS, Canada;Department of Communications, Global Sepsis Alliance, Canada Sector, Toronto, ON, Canada;Department of Critical Care Medicine, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada;Department of Critical Care Medicine, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada;Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada;Department of Critical Care Medicine, Royal Alexandra Hospital, University of Alberta, Edmonton, AB, Canada;Department of Internal Medicine, Section of Critical Care, University of Manitoba, Winnipeg, MB, Canada;Department of Internal Medicine, Section of Hematology/Medical Oncology, University of Manitoba, Winnipeg, MB, Canada;Department of Internal Medicine, Section of Critical Care, University of Manitoba, Winnipeg, MB, Canada;Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, MB, Canada;Department of Medical Biophysics, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, Canada;Department of Medical Biophysics, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, Canada;Centre for Critical Illness Research, Lawson Health Research Institute, London, ON, Canada;Department of Medical Biophysics, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, Canada;Robarts Research Institute, University of Western Ontario, London, ON, Canada;Department of Medicine, McMaster University, Hamilton, ON, Canada;Thrombosis and Atherosclerosis Research Institute, Hamilton, ON, Canada;Keenan Research Centre for Biomedical Science, Unity Health Toronto, Toronto, ON, Canada;Interdepartmental Division of Critical Care Medicine, Department of Anesthesia, University of Toronto, Toronto, ON, Canada;Interdepartmental Division of Critical Care Medicine, Department of Physiology, University of Toronto, Toronto, ON, Canada;Keenan Research Centre for Biomedical Science, Unity Health Toronto, Toronto, ON, Canada;Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, ON, Canada;Department of Medicine, University of Toronto, Toronto, ON, Canada;Keenan Research Centre for Biomedical Science, Unity Health Toronto, Toronto, ON, Canada;Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, ON, Canada;Department of Surgery, University of Toronto, Toronto, ON, Canada;Department of Critical Care Medicine, University of Toronto, Toronto, ON, Canada;Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, Vienna, Austria;Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada;Robarts Research Institute, University of Western Ontario, London, ON, Canada;Robarts Research Institute, University of Western Ontario, London, ON, Canada;Department of Medicine, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, Canada;Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, Canada;Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada;Department of Medicine, University of Calgary, Calgary, AB, Canada;Department of Biochemistry and Molecular Biology, University of Calgary, Calgary, AB, Canada;Thrombosis and Atherosclerosis Research Institute, Hamilton, ON, Canada;Department of Medical Sciences, McMaster University, Hamilton, ON, Canada;

关键词: Sepsis;    Experimental models of sepsis;    Multicentre preclinical;    Translation;    Reproducibility;    Multi-stakeholder;    Integrated knowledge translation;    PIRO;   

DOI  :  10.1186/s40635-020-00366-4

来源: Springer

【 摘 要 】

Despite decades of preclinical research, no experimentally derived therapies for sepsis have been successfully adopted into routine clinical practice. Factors that contribute to this crisis of translation include poor representation by preclinical models of the complex human condition of sepsis, bias in preclinical studies, as well as limitations of single-laboratory methodology. To overcome some of these shortcomings, multicentre preclinical studies—defined as a research experiment conducted in two or more research laboratories with a common protocol and analysis—are expected to maximize transparency, improve reproducibility, and enhance generalizability. The ultimate objective is to increase the efficiency and efficacy of bench-to-bedside translation for preclinical sepsis research and improve outcomes for patients with life-threatening infection. To this end, we organized the first meeting of the National Preclinical Sepsis Platform (NPSP). This multicentre preclinical  research collaboration of Canadian sepsis researchers and stakeholders was established to study the pathophysiology of sepsis and accelerate movement of promising therapeutics into early phase clinical trials. Integrated knowledge translation and shared decision-making were emphasized to ensure the goals of the platform align with clinical researchers and patient partners. 29 participants from 10 independent labs attended and discussed four main topics: (1) objectives of the platform; (2) animal models of sepsis; (3) multicentre methodology and (4) outcomes for evaluation. A PIRO model (predisposition, insult, response, organ dysfunction) for experimental design was proposed to strengthen linkages with interdisciplinary researchers and key stakeholders. This platform represents an important resource for maximizing translational impact of preclinical sepsis research.

【 授权许可】

CC BY