Retrospective harm benefit analysis of pre-clinical animal research for six treatment interventions.
Retrospective harm benefit analysis of pre-clinical animal research for six treatment interventions.
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DOI：
10.1371/journal.pone.0193758
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发表时间：
2018
期刊：
影响因子：
3.7
通讯作者：
Nicol CJ
中科院分区：
文献类型：
--
作者：
Pound P;Nicol CJ
危害效益分析（HBA）是动物研究法规的基石，被认为是动物伦理的重要保障。HBA涉及权衡动物研究的预期收益与其对动物的预期危害，但人们对这一过程的客观性和责任心表示怀疑。I.探索临床前动物研究对动物的危害，并根据这些研究对人类的益处进行评估; ii.测试执行此类追溯HBA的可行性。从临床前动物研究的样本中系统地提取了有关伤害的数据，这些研究的临床相关性已经通过比较动物研究的系统性综述与相同干预措施（抗纤维蛋白溶解药物治疗出血、双膦酸盐治疗骨质疏松、皮质类固醇治疗脑损伤、替拉扎德治疗卒中、产前皮质类固醇治疗新生儿呼吸窘迫和溶栓剂治疗卒中）的人体研究的系统性综述进行了研究。还根据当前临床实践探索了临床相关性。使用专家小组对伤害的严重度进行分类。研究的质量及其影响得到了考虑。贝特森立方体被用来进行HBA。专家小组对动物伤害最常见的评估是“严重”。报告使用镇痛剂的情况很少见，一些动物（包括大多数新生动物）在没有麻醉或仅轻度麻醉的情况下经历了重大手术。一些动物遭受医源性伤害。许多人在实验后长时间存活，但只有1%的研究报告了术后护理。三分之一的研究报告说，一些动物在终点前死亡。所有研究的质量都很差。在权衡了对动物的实际伤害与这些研究产生的实际临床益处之后，并考虑到研究的质量及其影响，根据Bateson's Cube，只有不到7%的研究是允许的：只有中度双膦酸盐研究似乎可以最大限度地减少对动物的伤害，同时与人类的益处相关。这是第一次在一系列临床前动物研究中系统地探索HBA的责任。进行这些研究时的监管制度未能保护动物免受严重痛苦，也未能确保只进行有益的、科学严谨的研究。我们的研究结果表明，迫切需要：i。审查法规，特别是那些允许动物遭受严重伤害的法规; ii.改革前瞻性评估临床前动物研究的过程，使其符合目的;以及iii.系统地评估临床前动物研究的益处，以便更现实地评估其未来可能的益处。
The harm benefit analysis (HBA) is the cornerstone of animal research regulation and is considered to be a key ethical safeguard for animals. The HBA involves weighing the anticipated benefits of animal research against its predicted harms to animals but there are doubts about how objective and accountable this process is. i. To explore the harms to animals involved in pre-clinical animal studies and to assess these against the benefits for humans accruing from these studies; ii. To test the feasibility of conducting this type of retrospective HBA. Data on harms were systematically extracted from a sample of pre-clinical animal studies whose clinical relevance had already been investigated by comparing systematic reviews of the animal studies with systematic reviews of human studies for the same interventions (antifibrinolytics for haemorrhage, bisphosphonates for osteoporosis, corticosteroids for brain injury, Tirilazad for stroke, antenatal corticosteroids for neonatal respiratory distress and thrombolytics for stroke). Clinical relevance was also explored in terms of current clinical practice. Harms were categorised for severity using an expert panel. The quality of the research and its impact were considered. Bateson’s Cube was used to conduct the HBA. The most common assessment of animal harms by the expert panel was ‘severe’. Reported use of analgesia was rare and some animals (including most neonates) endured significant procedures with no, or only light, anaesthesia reported. Some animals suffered iatrogenic harms. Many were kept alive for long periods post-experimentally but only 1% of studies reported post-operative care. A third of studies reported that some animals died prior to endpoints. All the studies were of poor quality. Having weighed the actual harms to animals against the actual clinical benefits accruing from these studies, and taking into account the quality of the research and its impact, less than 7% of the studies were permissible according to Bateson’s Cube: only the moderate bisphosphonate studies appeared to minimise harms to animals whilst being associated with benefit for humans. This is the first time the accountability of the HBA has been systematically explored across a range of pre-clinical animal studies. The regulatory systems in place when these studies were conducted failed to safeguard animals from severe suffering or to ensure that only beneficial, scientifically rigorous research was conducted. Our findings indicate a pressing need to: i. review regulations, particularly those that permit animals to suffer severe harms; ii. reform the processes of prospectively assessing pre-clinical animal studies to make them fit for purpose; and iii. systematically evaluate the benefits of pre-clinical animal research to permit a more realistic assessment of its likely future benefits.
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影响因子：
7.4
作者：
Andrews NA;Latrémolière A;Basbaum AI;Mogil JS;Porreca F;Rice ASC;Woolf CJ;Currie GL;Dworkin RH;Eisenach JC;Evans S;Gewandter JS;Gover TD;Handwerker H;Huang W;Iyengar S;Jensen MP;Kennedy JD;Lee N;Levine J;Lidster K;Machin I;McDermott MP;McMahon SB;Price TJ;Ross SE;Scherrer G;Seal RP;Sena ES;Silva E;Stone L;Svensson CI;Turk DC;Whiteside G
通讯作者：
Whiteside G
影响因子：
2.7
作者：
Franco, Nuno H.;Olsson, I. Anna S.
通讯作者：
Olsson, I. Anna S.
影响因子：
3.7
作者：
Carbone L;Austin J
通讯作者：
Austin J
影响因子：
3.7
作者：
Davies GF;Greenhough BJ;Hobson-West P;Kirk RG;Applebee K;Bellingan LC;Berdoy M;Buller H;Cassaday HJ;Davies K;Diefenbacher D;Druglitrø T;Escobar MP;Friese C;Herrmann K;Hinterberger A;Jarrett WJ;Jayne K;Johnson AM;Johnson ER;Konold T;Leach MC;Leonelli S;Lewis DI;Lilley EJ;Longridge ER;McLeod CM;Miele M;Nelson NC;Ormandy EH;Pallett H;Poort L;Pound P;Ramsden E;Roe E;Scalway H;Schrader A;Scotton CJ;Scudamore CL;Smith JA;Whitfield L;Wolfensohn S
通讯作者：
Wolfensohn S
影响因子：
9.8
作者：
Baker D;Lidster K;Sottomayor A;Amor S
通讯作者：
Amor S