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UK funding (504 931 £) : ivSyRMAF - l’outil d’examen systématique et de méta-analyse in vivo CAMARADES-NC3Rs Ukri01/10/2013 UK Research and Innovation, Royaume Uni
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ivSyRMAF - l’outil d’examen systématique et de méta-analyse in vivo CAMARADES-NC3Rs
| Abstract | Animals can be used to improve our understanding of a disease and to test the effectiveness of novel treatments. Translating findings from animal studies to humans in a clinical setting has not always been straightforward. We have pioneered the use of systematic review and meta-analysis - tools initially developed to analyse data from human clinical trials - to investigate such translational failure by analysing data from animal studies. We and others have shown that in published reports of in vivo disease modelling studies there are often flaws in their design and conduct, and there is a low prevalence of reporting of measures to reduce the risk of bias. We have also shown that studies at risk of bias tend to give inflated (higher) estimates of treatment effects. As we have made progress, a central objective of our approach has been to support this developing field by sharing our expertise with others who wish to conduct similar reviews in their own areas of research. This involves offering methodological advice and support, a data repository, and access to our data management platform. However, we are approaching the limits of our capacity to do this, and this infrastructure funding would allow us to develop an improved database, with improved capacity for analysis and a web interface; and to provide more organised support including user manuals, online training materials and telephone and in-person advice to those wishing to conduct systematic reviews and meta-analyses. Systematic review and meta-analysis of in vivo studies can provide evidence to change research practice; our work has identified risk of bias and publication bias in in vivo studies, led to Good Laboratory Practice guidelines for stroke modelling (2009), and helped inform the development of the ARRIVE guidelines. Our work is shared with NINDS grant awarding panels prior to funding decisions, informed the NINDS/NIH Transparency paper in Nature (2012; 16 of 64 references were to our work); and thereby informed the recent change in policy at the Nature Publishing Group, requiring reporting of risk of bias items such as randomisation, blinding, inclusion and exclusion criteria and sample size calculations. These issues are fundamental to the 3Rs, partly because of the critical importance of getting the size of the experiment right, and secondly because an experiment at high risk of bias contributes less useful information than an experiment using the same number of animals at low risk of bias; identifying risk of bias items, and how investigators might reduce the risk of bias, is therefore critical to the 3Rs. It is our view that, while much has been achieved over the last 10 years, the utility of in vivo research could be substantially improved by the use of this technique across a much broader range of in vivo models. The purpose of this application is to allow us to be a catalyst for that much wider adoption (the demand for which is already manifest), and to allow those entering the field now to benefit from the learning and the methodological developments which we assimilated through experience. Briefly, this will involve:(i) highlighting the importance of experimental design to improve the validity and statistical rigour of animal studies; (ii) identifying which outcome measures require fewer animals because of the variance observed, (iii) supporting the reduction of the number of animals sacrificed in studies that are too small to detect reliably the effect being sought or unnecessarily too large, , (iv) determining whether high severity tests or multiple tests are necessary, whether lengthy experiments are of added value or whether those of shorter duration are as useful, and (v) assessing publication bias where we anticipate results will be used to drive a change towards reporting of positive, negative and neutral results. |
| Category | Research Grant |
| Reference | NC/L000970/1 |
| Status | Closed |
| Funded period start | 01/10/2013 |
| Funded period end | 30/09/2018 |
| Funded value | £504 931,00 |
| Source | https://gtr.ukri.org/projects?ref=NC%2FL000970%2F1 |
Participating Organisations
| University of Edinburgh |
Cette annonce se réfère à une date antérieure et ne reflète pas nécessairement l’état actuel. L’état actuel est présenté à la page suivante : University OF Edinburgh CHARITY, Edinburgh, Royaume Uni.
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