脓毒症临床前研究最低质量标准(MQTiPSS):基于研究设计及人道建模终点的质量标准(全译)  

Minimum quality threshold in pre-clinical sepsis studies(MQTiPSS):quality thresholds for study design and humane modeling endpoints

作　　者：任超[1] 姚人骐 王丽雪 肖献忠 姚咏明[1] Ren Chao;Yao Renqi;Wang Lixue;Xiao Xianzhong;Yao Yongming(Trauma Research Center,Fourth Medical Center of the Chinese PLA General Hospital,Beijing 100048,China;Department of Pathophysiology,School of Basic Medicine Science,Central South University,Sepsis Translational Medicine Key Laboratory of Hunan Province,Changsha 410078,Hunan,China)

机构地区：[1]解放军总医院第四医学中心创伤研究中心,北京100048 [2]中南大学基础医学院病理生理学系,脓毒症转化医学湖南省重点实验室,长沙410078

出　　处：《中华危重病急救医学》2019年第9期1061-1071,共11页Chinese Critical Care Medicine

基　　金：国家自然科学基金(81730057,81801935,81842025,81671895)。

摘　　要：新的治疗经临床试验测试之前,临床前动物研究是一个必需的过程。然而,由于模型的局限性及与临床条件的不一致性,导致其在发现脓毒症新疗法的应用中一直饱受争议。基于临床脓毒症及脓毒性休克修订的定义(Sepsis-3),2017年5月在维也纳召开韦格斯-伯纳德会议,提出了脓毒症临床前研究的标准化指南。与会者对发表于2003至2012年间关于脓毒症建模的260篇最高被引频次的科技论文进行了文献综述。例如:综述表明79%的研究使用了小鼠,但是只有9%的研究对安乐死的标准进行了定义。本报告的第一部分对脓毒症建模中需解决的研究设计及人道建模终点问题予以详细而明确的建议,第一条"推荐"就是病原体相关脓毒症模型的生存率随访应反映该病原体的临床时间进程。此外,建议治疗干预应在脓毒症损伤发生后启动以模拟临床监护。为了明确新疗法与预后之间的无偏倚、可重复性的联系,治疗的随机法和盲法以及在科技论文中详细的方法学介绍是必不可少的。在所有脓毒症临床前研究中必须执行高标准的动物福利。因此,建议发展和批准监测脓毒症动物疼痛、痛苦及安乐死以及使用止疼药的具体标准。我们也提出了4项"考虑",以增强脓毒症模型的转化潜力。研究设计应纳入相关的生物学变量和合并症,且脓毒症建模除了啮齿类动物外应推广至哺乳类动物。此外,应考虑感染源控制的必要性(一旦有明确的感染灶)。这些"推荐"和"考虑"的提出应作为脓毒症动物模型的"最佳实践"而被执行。Preclinical animal studies are mandatory before new treatments can be tested in clinical trials.However,their use in developing new therapies for sepsis has been controversial because of limitations of the models and inconsistencies with the clinical conditions.In consideration of the revised definition for clinical sepsis and septic shock(Sepsis-3),a Wiggers-Bernard Conference was held in Vienna in May 2017 to propose standardized guidelines on preclinical sepsis modeling.The participants conducted a literature review of 260 most highly cited scientific articles on sepsis models published between 2003 and 2012.The review showed,for example,that mice were used in 79%and euthanasia criteria were defined in 9%of the studies.PartⅠof this report details the recommendations for study design and humane modeling endpoints that should be addressed in sepsis models.The first recommendation is that survival follow-up should reflect the clinical time course of the infectious agent used in the sepsis model.Furthermore,it is recommended that therapeutic interventions should be initiated after the septic insult replicating clinical care.To define an unbiased and reproducible association between a new treatment and outcome,a randomization and blinding of treatments as well as inclusion of all methodological details in scientific publications is essential.In all preclinical sepsis studies,the high standards of animal welfare must be implemented.Therefore,development and validation of specific criteria for monitoring pain and distress,and euthanasia of septic animals,as well as the use of analgesics are recommended.A set of four considerations is also proposed to enhance translation potential of sepsis models.Relevant biological variables and comorbidities should be included in the study design and sepsis modeling should be extended to mammalian species other than rodents.In addition,the need for source control(in case of a defined infection focus)should be considered.These recommendations and considerations are proposed as"bes

关 键 词：动物福利 最佳实践 临床前模型 脓毒症 研究设计 

分 类 号：D92[政治法律—法学]