Animal models of chemotherapy-induced peripheral neuropathy: A machine-assisted systematic review and meta-analysis
Animal models of chemotherapy-induced peripheral neuropathy: A machine-assisted systematic review and meta-analysis
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DOI：
10.1371/journal.pbio.3000243
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发表时间：
2019-05-01
期刊：
影响因子：
9.8
通讯作者：
Sena, Emily S.
中科院分区：
文献类型：
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作者：
Currie, Gillian L.;Angel-Scott, Helena N.;Sena, Emily S.
我们报告了一个系统的审查和荟萃分析的研究使用动物模型化疗诱导的周围神经病变（CIPN）。我们于2012年9月系统检索了5个在线数据库，并于2015年11月使用机器学习和文本挖掘更新了检索，以减少筛选纳入工作量并提高准确性。对于每次比较，我们计算了标准化平均差异（SMD）效应量，然后在随机效应荟萃分析中合并效应。我们评估了研究设计因素的影响，并报告了降低偏倚风险的措施。我们目前的功率分析最常报告的行为测试，包括337出版物。大多数研究（84%）仅使用雄性动物。最常报告的结局指标是对机械单丝的反应引起的肢体退缩。关于减少偏倚风险的措施的报告不多。获得80%把握度（显著性水平为0.05）所需的动物数量在行为试验中差异很大。在这篇关于CIPN动物模型使用的全面总结中，我们确定了临床前CIPN研究价值可能增加的领域。在CIPN建模中使用两种性别的动物，确保结果测量与临床中最相关的结果测量一致，并且动物的疼痛情境行为学可能会提高外部有效性。应采取减少偏倚风险的措施，以提高研究的内部效度。不同的结果措施有不同的统计能力，这可以完善我们的方法在建模CIPN.Author摘要许多常用的和有效的癌症化疗可能会导致禁用的副作用，功能疼痛，麻木，刺痛，和敏感性冷和热的四肢称为化疗引起的周围神经病变（CIPN）。目前还没有有效的治疗或预防这种疾病的方法，已经开发了动物模型来解决这个问题。重要的是，如果要有效地帮助患者，使用CIPN动物模型的实验是稳健和有效的。我们使用了一种系统的方法来识别所有337项已发表的描述使用CIPN动物模型的研究。我们能够确定许多研究在实验设计上是不完美的，只使用雄性动物，评估结果与人类状况的相关性有限。基于荟萃分析，我们为CIPN动物模型社区提供指导，以指导未来的实验，从而提高其实用性和有效性。
We report a systematic review and meta-analysis of research using animal models of chemotherapy-induced peripheral neuropathy (CIPN). We systematically searched 5 online databases in September 2012 and updated the search in November 2015 using machine learning and text mining to reduce the screening for inclusion workload and improve accuracy. For each comparison, we calculated a standardised mean difference (SMD) effect size, and then combined effects in a random-effects meta-analysis. We assessed the impact of study design factors and reporting of measures to reduce risks of bias. We present power analyses for the most frequently reported behavioural tests; 337 publications were included. Most studies (84%) used male animals only. The most frequently reported outcome measure was evoked limb withdrawal in response to mechanical monofilaments. There was modest reporting of measures to reduce risks of bias. The number of animals required to obtain 80% power with a significance level of 0.05 varied substantially across behavioural tests. In this comprehensive summary of the use of animal models of CIPN, we have identified areas in which the value of preclinical CIPN studies might be increased. Using both sexes of animals in the modelling of CIPN, ensuring that outcome measures align with those most relevant in the clinic, and the animal's pain contextualised ethology will likely improve external validity. Measures to reduce risk of bias should be employed to increase the internal validity of studies. Different outcome measures have different statistical power, and this can refine our approaches in the modelling of CIPN.Author summary Many frequently used and effective cancer chemotherapies can cause a disabling side effect that features pain, numbness, tingling, and sensitivity to cold and heat in the extremities known as chemotherapy-induced peripheral neuropathy (CIPN). There are currently no effective therapies to treat or prevent this condition, and animal models have been developed to address this. It is important that experiments using animal models of CIPN are robust and valid if they are to effectively help patients. We used a systematic approach to identify all 337 studies that have been published describing the use of animal models of CIPN. We were able to identify that many studies are imperfect in their experimental design, use only male animals, and assess outcomes with limited relevance to the human condition. Based on a meta-analysis, we provide guidance to the CIPN animal modelling community to guide future experiments that may improve their utility and validity.