Mendelson Asher A, Lansdell Casey, Fox-Robichaud Alison E, Liaw Patricia, Arora Jaskirat, Cailhier Jean-François, Cepinskas Gediminas, Charbonney Emmanuel, Dos Santos Claudia, Dwivedi Dhruva, Ellis Christopher G, Fergusson Dean, Fiest Kirsten, Gill Sean E, Hendrick Kathryn, Hunniford Victoria T, Kowalewska Paulina M, Krewulak Karla, Lehmann Christian, Macala Kimberly, Marshall John C, Mawdsley Laura, McDonald Braedon, McDonald Ellen, Medeiros Sarah K, Muniz Valdirene S, Osuchowski Marcin, Presseau Justin, Sharma Neha, Sohrabipour Sahar, Sunohara-Neilson Janet, Vázquez-Grande Gloria, Veldhuizen Ruud A W, Welsh Donald, Winston Brent W, Zarychanski Ryan, Zhang Haibo, Zhou Juan, Lalu Manoj M
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.
Intensive Care Med Exp. 2021 Mar 19;9(1):14. doi: 10.1186/s40635-020-00366-4.
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.
尽管进行了数十年的临床前研究,但尚无通过实验得出的脓毒症治疗方法成功应用于常规临床实践。导致这种转化危机的因素包括脓毒症这种复杂人类病症的临床前模型代表性不足、临床前研究存在偏差以及单一实验室方法的局限性。为克服其中一些缺点,多中心临床前研究(定义为在两个或更多研究实验室按照共同方案和分析进行的研究实验)有望实现最大程度的透明度、提高可重复性并增强普遍性。最终目标是提高临床前脓毒症研究从实验室到临床转化的效率和效果,并改善危及生命感染患者的治疗结果。为此,我们组织了国家临床前脓毒症平台(NPSP)的首次会议。这个由加拿大脓毒症研究人员和利益相关者组成的多中心临床前研究合作项目旨在研究脓毒症的病理生理学,并加速将有前景的治疗方法推进到早期临床试验阶段。强调了综合知识转化和共同决策,以确保该平台的目标与临床研究人员和患者合作伙伴保持一致。来自10个独立实验室的29名参与者出席并讨论了四个主要主题:(1)平台目标;(2)脓毒症动物模型;(3)多中心方法;(4)评估结果。提出了一种用于实验设计的PIRO模型(易感性、损伤、反应、器官功能障碍),以加强与跨学科研究人员和关键利益相关者的联系。该平台是最大化临床前脓毒症研究转化影响的重要资源。