Part I: Minimum Quality Threshold in Preclinical Sepsis Studies (MQTiPSS) for Study Design and Humane Modeling Endpoints.
Part I: Minimum Quality Threshold in Preclinical Sepsis Studies (MQTiPSS) for Study Design and Humane Modeling Endpoints.
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DOI：
10.1097/shk.0000000000001243
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发表时间：
2019-01
期刊：
影响因子：
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通讯作者：
Thiemermann C
中科院分区：
文献类型：
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作者：
Zingarelli B;Coopersmith CM;Drechsler S;Efron P;Marshall JC;Moldawer L;Wiersinga WJ;Xiao X;Osuchowski MF;Thiemermann C
临床前动物研究是强制性的，然后才能在临床试验中测试新的治疗方法。然而，由于模型的局限性和与临床条件的不一致性，它们在开发脓毒症新疗法中的应用一直存在争议。考虑到临床脓毒症和脓毒性休克（脓毒症-3）的修订定义，2017年5月在维也纳举行了Wiggers-Bernard会议，提出了临床前脓毒症建模的标准化指南。参与者对2003年至2012年期间发表的260篇关于脓毒症模型的最高引用科学文章进行了文献综述。例如，审查显示，79%的研究使用了小鼠，9%的研究定义了安乐死标准。本报告的第一部分详细介绍了败血症模型中应解决的研究设计和人道建模终点的建议。第一个建议是生存随访应反映败血症模型中使用的感染因子的临床时间进程。此外，建议在脓毒性损伤复制临床护理后开始治疗干预。为了确定新治疗与结局之间的无偏倚和可重现的相关性，治疗的随机化和设盲以及在科学出版物中纳入所有方法学细节至关重要。在所有临床前脓毒症研究中，必须实施高标准的动物福利。因此，建议制定和验证用于监测疼痛和痛苦的具体标准，并对脓毒症动物实施安乐死，以及使用镇痛剂。还提出了一组四个考虑因素，以提高脓毒症模型的翻译潜力。研究设计中应纳入相关生物学变量和合并症，败血症建模应扩展至啮齿动物以外的哺乳动物种属。此外，应考虑源控制的需要（在确定的感染焦点的情况下）。这些建议和考虑被认为是脓毒症动物模型的“最佳实践”，应予以实施。
Pre-clinical 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 pre-clinical 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. Part I of 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 pre-clinical 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 co-morbidities should be included in the study design and sepsis modeling should be extended to mammalian species other than rodents. Additionally, the need for source control (in case of a defined infection focus) should be considered. These recommendations and considerations are proposed as “best practices” for animal models of sepsis that should be implemented.