Bahor Zsanett, Nunes-Fonseca Cristina, Thomson Lindsay D G, Sena Emily S, Macleod Malcolm R
Centre for Clinical Brain Sciences University of Edinburgh Edinburgh UK.
Division of Psychiatry University of Edinburgh, Royal Edinburgh Hospital Edinburgh UK.
Evid Based Preclin Med. 2016 Dec;3(2):e00022. doi: 10.1002/ebm2.22. Epub 2017 Mar 17.
Psychosis represents a set of symptoms against which current available treatments are not universally effective and are often accompanied by adverse side effects. Clinical management could potentially be improved with a greater understanding of the underlying biology and subsequently with the introduction of novel treatments. Since many clinical drug candidates are identified through modelling, a deeper understanding of the pre-clinical field, might help us understand why translation of results from animal models to inform mental health clinical practice has so far been weak. We set out to give a shallow, but broad unbiased overview of experiments looking at the modelling of psychotic disorders using a systematic review and meta-analysis. This protocol describes the exact methodology we propose to follow in order to quantitatively review both studies characterizing a model and those experiments that investigate the effects of novel therapeutic options. We are interested in assessing the prevalence of the reporting of measures to reduce risk of bias, and the internal and external validity of the animal models and outcome measures used to validate these models. This generation of strong empirical evidence has the potential to identify areas for improvement, make suggestions for future research avenues, and ultimately inform what we think we know to improve the current attrition rate between bench and bedside in psychosis research. A review like this will also support the reduction of animal numbers used in research and the refinement of experiments to maximize their value in informing the field.
精神病表现出一系列症状，目前可用的治疗方法对其并非普遍有效，且常常伴有不良副作用。若能更深入地了解潜在生物学机制，并随后引入新的治疗方法，临床管理可能会得到改善。由于许多临床候选药物是通过建模确定的，因此更深入地了解临床前领域，可能有助于我们理解为何迄今为止，将动物模型的结果转化为心理健康临床实践的情况一直很薄弱。我们着手通过系统综述和荟萃分析，对研究精神障碍建模的实验进行一个浅显但全面且无偏倚的概述。本方案描述了我们提议遵循的具体方法，以便对描述模型的研究以及那些研究新型治疗选择效果的实验进行定量综述。我们感兴趣的是评估减少偏倚风险措施报告的普遍性，以及用于验证这些模型的动物模型和结果测量的内部和外部有效性。这一强有力的实证证据的产生，有可能确定改进领域，为未来的研究途径提出建议，并最终告知我们如何改进精神病研究中从实验室到临床的当前损耗率。这样的综述也将支持减少研究中使用的动物数量，并优化实验以最大限度地提高其在为该领域提供信息方面的价值。
