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Mendelson AA, Lansdell C, Fox-Robichaud AE, et al. National Preclinical Sepsis Platform: developing a framework for accelerating innovation in Canadian sepsis research. Intensive Care Med Exp. 2021;9(1):14doi: 10.1186/s40635-020-00366-4.
Mendelson, A. A., Lansdell, C., Fox-Robichaud, A. E., Liaw, P., Arora, J., Cailhier, J. F., Cepinskas, G., Charbonney, E., Dos Santos, C., Dwivedi, D., Ellis, C. G., Fergusson, D., Fiest, K., Gill, S. E., Hendrick, K., Hunniford, V. T., Kowalewska, P. M., Krewulak, K., Lehmann, C., Macala, K., Marshall, J. C., Mawdsley, L., McDonald, B., McDonald, E., Medeiros, S. K., Muniz, V. S., Osuchowski, M., Presseau, J., Sharma, N., Sohrabipour, S., Sunohara-Neilson, J., Vázquez-Grande, G., Veldhuizen, R. A. W., Welsh, D., Winston, B. W., Zarychanski, R., Zhang, H., Zhou, J., Lalu, M. M. (2021). National Preclinical Sepsis Platform: developing a framework for accelerating innovation in Canadian sepsis research. Intensive care medicine experimental, 9(1), 14. https://doi.org/10.1186/s40635-020-00366-4
Mendelson, Asher A, et al. "National Preclinical Sepsis Platform: developing a framework for accelerating innovation in Canadian sepsis research." Intensive care medicine experimental vol. 9,1 (2021): 14. doi: https://doi.org/10.1186/s40635-020-00366-4
Mendelson AA, Lansdell C, Fox-Robichaud AE, Liaw P, Arora J, Cailhier JF, Cepinskas G, Charbonney E, Dos Santos C, Dwivedi D, Ellis CG, Fergusson D, Fiest K, Gill SE, Hendrick K, Hunniford VT, Kowalewska PM, Krewulak K, Lehmann C, Macala K, Marshall JC, Mawdsley L, McDonald B, McDonald E, Medeiros SK, Muniz VS, Osuchowski M, Presseau J, Sharma N, Sohrabipour S, Sunohara-Neilson J, Vázquez-Grande G, Veldhuizen RAW, Welsh D, Winston BW, Zarychanski R, Zhang H, Zhou J, Lalu MM. National Preclinical Sepsis Platform: developing a framework for accelerating innovation in Canadian sepsis research. Intensive Care Med Exp. 2021 Mar 19;9(1):14. doi: 10.1186/s40635-020-00366-4. PMID: 33738642; PMCID: PMC7973346.
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Intensive Care Med Exp. 2021 Mar 19;9(1):14. doi: 10.1186/s40635-020-00366-4.

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

Intensive care medicine experimental

Asher A Mendelson, Casey Lansdell, Alison E Fox-Robichaud, Patricia Liaw, Jaskirat Arora, Jean-François Cailhier, Gediminas Cepinskas, Emmanuel Charbonney, Claudia Dos Santos, Dhruva Dwivedi, Christopher G Ellis, Dean Fergusson, Kirsten Fiest, Sean E Gill, Kathryn Hendrick, Victoria T Hunniford, Paulina M Kowalewska, Karla Krewulak, Christian Lehmann, Kimberly Macala, John C Marshall, Laura Mawdsley, Braedon McDonald, Ellen McDonald, Sarah K Medeiros, Valdirene S Muniz, Marcin Osuchowski, Justin Presseau, Neha Sharma, Sahar Sohrabipour, Janet Sunohara-Neilson, Gloria Vázquez-Grande, Ruud A W Veldhuizen, Donald Welsh, Brent W Winston, Ryan Zarychanski, Haibo Zhang, Juan Zhou, Manoj M Lalu,

Affiliations

  1. Department of Medical Biophysics, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, Canada.
  2. Centre for Critical Illness Research, Lawson Health Research Institute, London, ON, Canada.
  3. Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada.
  4. Department of Medicine, McMaster University, Hamilton, ON, Canada.
  5. Thrombosis and Atherosclerosis Research Institute, Hamilton, ON, Canada.
  6. Department of Medical Sciences, McMaster University, Hamilton, ON, Canada.
  7. Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Montreal, QC, Canada.
  8. Département de Médecine, Université de Montréal, Montreal, QC, Canada.
  9. Keenan Research Centre for Biomedical Science, Unity Health Toronto, Toronto, ON, Canada.
  10. Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, ON, Canada.
  11. Department of Medicine, University of Toronto, Toronto, ON, Canada.
  12. Robarts Research Institute, University of Western Ontario, London, ON, Canada.
  13. Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada.
  14. Department of Critical Care Medicine, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
  15. Department of Medicine, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, Canada.
  16. Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, Canada.
  17. Department of Communications, Global Sepsis Alliance, Canada Sector, Toronto, ON, Canada.
  18. Department of Anesthesia, Pain Management and Perioperative Medicine, Dalhousie University, Halifax, NS, Canada.
  19. Department of Critical Care Medicine, Royal Alexandra Hospital, University of Alberta, Edmonton, AB, Canada.
  20. Department of Surgery, University of Toronto, Toronto, ON, Canada.
  21. Department of Critical Care Medicine, University of Toronto, Toronto, ON, Canada.
  22. Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
  23. Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, Vienna, Austria.
  24. School of Epidemiology and Public Health, University of Ottawa, Ottawa, ON, Canada.
  25. Animal Resources Centre, University Health Network, Toronto, ON, Canada.
  26. Department of Internal Medicine, Section of Critical Care, University of Manitoba, Winnipeg, MB, Canada.
  27. Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, MB, Canada.
  28. Department of Medicine, University of Calgary, Calgary, AB, Canada.
  29. Department of Biochemistry and Molecular Biology, University of Calgary, Calgary, AB, Canada.
  30. Department of Internal Medicine, Section of Hematology/Medical Oncology, University of Manitoba, Winnipeg, MB, Canada.
  31. Interdepartmental Division of Critical Care Medicine, Department of Anesthesia, University of Toronto, Toronto, ON, Canada.
  32. Interdepartmental Division of Critical Care Medicine, Department of Physiology, University of Toronto, Toronto, ON, Canada.
  33. Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada. [email protected].
  34. Department of Anesthesiology and Pain Medicine, The Ottawa Hospital, 501 Smyth Road, PO Box 201B, Ottawa, ON, K1H 8L6, Canada. [email protected].

PMID: 33738642 PMCID: PMC7973346 DOI: 10.1186/s40635-020-00366-4

Abstract

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.

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

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