SyRF–the CAMARADES–NC3Rs in vivo systematic review and meta-analysis facility

Aims

This infrastructure award will maximise the 3Rs potential of undertaking systematic reviews and meta-analyses of animal research.

Background

Systematic reviews and meta-analyses are common practice in clinical research. They remain relatively under-utilised in animal research although recent reviews have illustrated their potential 3Rs benefits for example, supporting a reduction in animal numbers, determining whether high severity tests or multiple tests are necessary, and avoiding the use of uninformative models.

Research details and methods

The award will support the development of online resources and hands on support facilitating the wider use of systematic reviews and meta-analyses by researchers. 

Systematic review and meta-analysis can provide empirical evidence of the impact of internal and external validity of in vivo studies across research domains. We spend substantial time supporting those who wish to conduct such reviews in their own fields through methodological advice and support, a data repository, and access to our database.

This database can now be used in the analysis of diverse data, from animal models of stroke to receptor binding assays. It includes data from over 3,000 publications involving over 80,000 animals. Currently, we curate data on MS Access, accessed by external users via a secure remote desktop connection; migration to an SQL server based database will improve system performance, scalability and accessibility. Providing web based access backed up by the support of a research will substantially improve our effectiveness in supporting such activity. We will also provide user manuals, online training materials and telephone advice.

Our support will include systematic reviews and meta-analyses of preclinical studies, with calculation of summary effect sizes and determination in that model system of the impact of study design features and risk of bias items. For a given disease model, we will identify the outcome measure with the smallest variance. This will help reduce the number of animals used in future studies. We will provide information for power calculations, so that the number of animals sacrificed in studies are neither too small to detect reliably the effect being sought or unnecessarily large. We will determine whether high severity, multiple and lengthy experiments provide more information than low severity, single, short experiments. This will inform ethical considerations about the choice of measures to be used, supporting a reduction in the suffering of the animals. We will undertake secondary analyses investigating issues such as publication bias, and improvements in the quality of study reports over time. 

van Hout GP, Jansen Of Lorkeers SJ, Wever KE, et al. (2016) Translational failure of anti-inflammatory compounds for myocardial infarction: a meta-analysis of large animal models. Cardiovascular Research 109(2): 240-8. doi: 10.1093/cvr/cvv239 

Zwetsloot PP, Végh AM, Jansen Of Lorkeers SJ, van Hout GP, et al. (2016) Cardiac Stem Cell Treatment in Myocardial Infarction: A Systematic Review and Meta-Analysis of Preclinical Studies. Circulation Research 118(8): 1223-32. doi: 10.1161/CIRCRESAHA.115.307676 

Jansen Of Lorkeers SJ, Eding JE, Vesterinen HM, et al. (2015) Similar effect of autologous and allogeneic cell therapy for ischemic heart disease: systematic review and meta-analysis of large animal studies. Circulation Research 116(1): 80-6. doi: 10.1161/CIRCRESAHA.116.304872 

Milidonis X, Marshall I, Macleod MR, Sena ES (2015) Magnetic resonance imaging in experimental stroke and comparison with histology: systematic review and meta-analysis. Stroke 46(3): 843-51. doi: 10.1161/STROKEAHA.114.007560 

Currie GL, Macleod MR (2015) Increasing value and reducing waste in animal models of rheumatological disease. International Journal of Rheumatic Diseases 18(5): 485-7. doi: 10.1111/1756-185X.12703 

Macleod M (2015) Prof Benchie and Dr Athena-A modern tragedy. Evidence-based Preclinical Medicine 2(1): 16-19. doi: 10.1002/ebm2.8 

Macleod MR, Lawson McLean A, Kyriakopoulou A, et al. (2015) Risk of Bias in Reports of In Vivo Research: A Focus for Improvement. PLOS Biology 13(10): e1002273. doi: 10.1371/journal.pbio.1002273 

Vesterinen HM, Connick P, Irvine CM, et al. (2015) Drug repurposing: a systematic approach to evaluate candidate oral neuroprotective interventions for secondary progressive multiple sclerosis. PLOS ONE 10(4): e0117705. doi: 10.1371/journal.pone.0117705 

Egan KJ, Janssen H, Sena ES, et al. (2014) Exercise reduces infarct volume and facilitates neurobehavioral recovery: results from a systematic review and meta-analysis of exercise in experimental models of focal ischemia. Neurorehabilitation and Neural Repair 28(8): 800-12. doi: 10.1177/1545968314521694 

Sena ES, Currie GL, McCann SK, Macleod MR, Howells DW (2014) Systematic reviews and meta-analysis of preclinical studies: why perform them and how to appraise them critically. Journal of Cerebral Blood Flow and Metabolism 34(5): 737-42. doi: 10.1038/jcbfm.2014.28 

Ioannidis JP, Greenland S, Hlatky MA, et al. (2014) Increasing value and reducing waste in research design, conduct, and analysis. Lancet 383(9912): 166-75. doi: 10.1016/S0140-6736(13)62227-8 

Pedder H, Vesterinen HM, Macleod MR, Wardlaw JM (2014) Systematic review and meta-analysis of interventions tested in animal models of lacunar stroke. Stroke 45(2): 563-70. doi: 10.1161/STROKEAHA.113.003128 

Howells DW, Sena ES, Macleod MR (2014) Bringing rigour to translational medicine. Nature Reviews Neurology 10(1): 37-43. doi: 10.1038/nrneurol.2013.232 

Vesterinen HM, Sena ES, Egan KJ, et al. (2014) Meta-analysis of data from animal studies: a practical guide. Journal of Neuroscience Methods 221: 92-102. doi: 10.1016/j.jneumeth.2013.09.010 

Lalu MM, Moher D, Marshall J, et al. (2014) Efficacy and safety of mesenchymal stromal cells in preclinical models of acute lung injury: a systematic review protocol. Systematic Reviews 3: 48. doi: 10.1186/2046-4053-3-48 

Macleod MR (2014) Preclinical research: Design animal studies better. Nature 510(7503): 35. doi: 10.1038/510035a 

McCann SK, Irvine C, Mead GE, et al. (2014) Efficacy of antidepressants in animal models of ischemic stroke: a systematic review and meta-analysis. Stroke 45(10): 3055-63. doi: 10.1161/STROKEAHA.114.006304 

Hirst TC, Vesterinen HM, Conlin S, et al. (2014) A systematic review and meta-analysis of gene therapy in animal models of cerebral glioma: why did promise not translate to human therapy? Evidence-based Preclinical Medicine 1(1): 21-33. doi: 10.1002/ebm2.6 

Batchelor PE, Wills TE, Skeers P, et al. (2013) Meta-analysis of pre-clinical studies of early decompression in acute spinal cord injury: a battle of time and pressure. PLOS ONE 8(8): e72659. doi: 10.1371/journal.pone.0072659 

Batchelor PE, Skeers P, Antonic A, et al. (2013) Systematic review and meta-analysis of therapeutic hypothermia in animal models of spinal cord injury. PLOS ONE 8(8): e71317. doi: 10.1371/journal.pone.0071317 

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Infrastructure grant

Status:

Active

Principal investigator

Professor Malcolm Macleod

Institution

University of Edinburgh

Co-Investigator

Dr Emily Sena

Grant reference number

NC/L000970/1

Award date:

Oct 2013 - Sep 2018

Grant amount

£504,931