A multi-batch design to deliver robust estimates of efficacy and reduce animal use - a syngeneic tumour case study
Open Access
- 10 April 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Scientific Reports
- Vol. 10 (1), 1-10
- https://doi.org/10.1038/s41598-020-62509-7
Abstract
Phenotypic plasticity, the ability of a living organism to respond to the environment, can lead to conclusions from experiments that are idiosyncratic to a particular environment. The level of environmental responsiveness can result in difficulties in reproducing studies from the same institute with the same standardised environment. Here we present a multi-batch approach to in-vivo studies to improve replicability of the results for a defined environment. These multi-batch experiments consist of small independent mini-experiments where the data are combined in an integrated data analysis to appropriately assess the treatment effect after accounting for the structure in the data. We demonstrate the method on two case studies with syngeneic tumour models which are challenging due to high variability both within and between studies. Through simulations and discussions, we explore several data analysis options and the optimum design that balances practical constraints of working with animals versus sensitivity and replicability. Through the increased confidence from the multi-batch design, we reduce the need to replicate the experiment, which can reduce the total number of animals used.This publication has 26 references indexed in Scilit:
- Olfactory exposure to males, including men, causes stress and related analgesia in rodentsNature Methods, 2014
- Six red flags for suspect workNature, 2013
- Meta-analyses and Forest plots using a microsoft excel spreadsheet: step-by-step guide focusing on descriptive data analysisBMC Research Notes, 2012
- Interpretation of random effects meta-analysesBMJ, 2011
- Systematic variation improves reproducibility of animal experimentsNature Methods, 2010
- Environmental standardization: cure or cause of poor reproducibility in animal experiments?Nature Methods, 2009
- Understanding Mammalian Genetic Systems: The Challenge of Phenotyping in the MousePLoS Genetics, 2006
- Treatment allocation by minimisationBMJ, 2005
- Genotype–environment interactions in mouse behavior: A way out of the problemProceedings of the National Academy of Sciences of the United States of America, 2005
- Genetics of Mouse Behavior: Interactions with Laboratory EnvironmentScience, 1999