First Do No Harm: A Proposal of an Expert-Guided Framework of Surrogate Humane Endpoints in Preclinical Models of Acute Lung Injury.
First Do No Harm: A Proposal of an Expert-Guided Framework of Surrogate Humane Endpoints in Preclinical Models of Acute Lung Injury.
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首先不造成伤害：急性肺损伤临床前模型中替代人道终点专家指导框架的提案。
DOI：
10.1097/ccm.0000000000004758
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发表时间：
2021
影响因子：
8.8
通讯作者：
Zingarelli,Basilia
中科院分区：
文献类型：
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作者：
Zingarelli,Basilia
作者报告说，利益相关者之间有强烈的共识，认为温度的变化和迅速而明显的体重减轻是实验动物死亡状态的客观生命和临床体征(9)。其他临床生理终点达到德尔菲共识，如严重呼吸困难、胸腹呼吸、湿啁啾音的发生，以及器官衰竭的物理生化指标。这两个专家小组还建议关注其他健康标准的评估，如行为变化（驼背的姿势、不适的迹象、对刺激缺乏反应）。动物福利的一个重要原则是，任何已知会引起人类疼痛和痛苦的疾病都被认为可能会引起动物的疼痛和痛苦，应该通过疼痛管理（例如，镇痛）来减轻（11）。然而，作者报告说，系统评价的出版物没有提供任何证据表明ALI/ARDS的小动物模型会引起明显的痛苦，也没有提供支持使用镇痛药的建议的理由。相反，当向德尔菲专家组提出关于镇痛药的声明时，科学家专家组和实验动物兽医都认为使用镇痛药的益处值得怀疑，因为它可能干扰肺损伤的免疫调节反应。然而，德尔菲专家组强烈同意，根据ALI/ARDS模型的严重程度，对替代终点的监测频率应增加到每天数次(9)。研究方法和发现的透明报告是可重复性的重要组成部分，并提供科学严谨性的明确证据。尽管制定了具体的临床前研究报告指南，如动物研究：报告体内实验（ARRIVE）（12），但作者还指出，在他们的系统评价中选择的科学出版物往往缺乏关于人道替代终点的使用和合理性的关键信息，这使得评估这些终点的有效性变得困难。考虑到这一重要问题，德尔菲专家组强烈一致建议在报告选定的替代人道终点时保持透明度(9)。基于delphi的分析的一个关键事件是参与者有机会面对面讨论推荐的人道替代终点的循证有效性，并分享对偏倚风险的担忧。总体而言，体温下降和体重减轻是死亡的早期预测因素(9)。值得注意的是，这两个参数已被广泛用作各种传染病和败血症啮齿动物模型中可靠的人道替代终点，也被该领域的专家小组提出作为安乐死的标准（13-15）。然而，德尔菲小组的参与者谨慎地承认，依赖于单一的人道替代终点可能会对处于次优健康状态的动物的识别产生偏差，并可能导致研究过早终止。相反，专家组更有信心提出一个综合评分，包括客观因素（体温和体重减轻）和主观因素（行为标志和呼吸窘迫）(9)。总之，考虑到与小动物急性呼吸窘迫综合征/急性呼吸窘迫综合征模型实验设计相关的指南和报告标准的缺乏，McGinn等人(9)承担了这项重要的……
The authors report that there was strong consensus among the stakeholders in considering changes in temperature and rapid and pronounced body weight loss as objective vital and clinical signs of moribund state of the experimental animals (9). Other clinical physiologic endpoints reached Delphi consensus, such as the occurrence of severe dyspnea, thoracoabdominal respiration, and wet chirping sounds, as well as physical and biochemical markers of organ failure. The two expert groups also recommended on focusing on assessment of other well-being criteria such as behavioral changes (hunched posture, signs of discomfort, and lack of response to stimulation). An important principle of animal welfare is that any disease known to cause pain and distress in humans is considered likely to cause pain and distress in animals and should be alleviated through pain management (eg, analgesia)(11). However, the authors reported that none of the publications of the systematic review provided any evidence that small animal models of ALI/ARDS would cause significant distress nor provided a rationale to support the recommendation of the use of analgesia. On the contrary, when statements on analgesics were proposed to the Delphi panel, both expert groups of scientists and laboratory animal veterinarians considered the use of analgesia of questionable benefit, since it could interfere with immunomodulatory responses of lung injury. Nevertheless, there was strong agreement from the Delphi panel that frequency of monitoring for surrogate endpoints should be increased to several times a day according to the severity of the ALI/ARDS model (9). Transparent reporting of research methods and findings is an essential component of reproducibility and offers the unequivocal evidence of scientific rigor. Despite the development of specific reporting guidelines for preclinical research, such as Animal Research: Reporting of In Vivo Experiments (ARRIVE)(12), the authors also noted that the scientific publications selected in their systematic review often lacked key information regarding the use and the rational of humane surrogate endpoints, making difficult the assessment of the validity of these endpoints. In consideration of this important issue, there was strong consensus from the Delphi panel to recommend transparency in reporting selected surrogate humane endpoints (9).A key event of the Delphi-based analysis was the opportunity for the participants to discuss face to face the evidence-based validity of the recommended humane surrogate endpoints and share the concerns of risk of bias. Overall, decreases in whole-body temperature and body weight loss were reasonably justified as early predictors of impending death (9). It is noteworthy that these two parameters have been widely used as reliable humane surrogate endpoints in a variety of rodent models of infectious disease and sepsis and have also been proposed as criteria for euthanasia by panels of experts in the field (13–15). Nevertheless, the participants of the Delphi panel carefully acknowledged that relying on a single humane surrogate endpoint may bias the recognition of animals experiencing suboptimal health and may result in premature study termination. The expert groups were instead more confident in proposing a composite score that includes both objective (body temperature and weight loss) and subjective components (behavioral markers and respiratory distress)(9). In conclusion, considering the paucity of guidelines and reporting standards relating to experimental design of small animal ALI/ARDS models, McGinn et al (9) are to be commended for undertaking this important …
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流行病学概念模型和危重老年人的健康正义。
影响因子：
8.8
作者：
Scheunemann,LeslieP;Girard,TimothyD;Leland,NatalieE
通讯作者：
Leland,NatalieE
体重减轻和体温降低决定了眼部疱疹病毒感染小鼠模型的人道终点。
DOI：
--
发表时间：
2013
期刊：
Journal of the American Association for Laboratory Animal Science : JAALAS
影响因子：
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作者：
Hankenson,FClaire;Ruskoski,Nicholas;vanSaun,Marjorie;Ying,Gui-Shuang;Oh,Jaewook;Fraser,NigelW
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Fraser,NigelW
日本科学委员会关于正确进行动物实验的指南
DOI：
--
发表时间：
2008
期刊：
影响因子：
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作者：
H. Karaki
通讯作者：
H. Karaki
传染病动物模型的人道终点。
影响因子：
2.5
作者：
E. Olfert;D. Godson
通讯作者：
D. Godson
DOI：
10.1097/shk.0000000000001243
发表时间：
2019-01
期刊：
Shock (Augusta, Ga.)
影响因子：
--
作者：
Zingarelli B;Coopersmith CM;Drechsler S;Efron P;Marshall JC;Moldawer L;Wiersinga WJ;Xiao X;Osuchowski MF;Thiemermann C
通讯作者：
Thiemermann C