Reproducibility of preclinical animal research improves with heterogeneity of study samples

Single-laboratory studies conducted under highly standardized conditions are the gold standard in preclinical animal research. Using simulations based on 440 preclinical studies across 13 different interventions in animal models of stroke, myocardial infarction, and breast cancer, we compared the ac...

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Bibliographic Details
Published in:PLoS biology 2018-02, Vol.16 (2), p.e2003693-e2003693
Main Authors: Voelkl, Bernhard, Vogt, Lucile, Sena, Emily S, Würbel, Hanno
Format: Article
Language:English
Subjects:
Animal Experimentation - standards
Animal models
Animal research
Animal sciences
Animals
Bias
Breast cancer
Cerebral infarction
Computer simulation
Disease Models, Animal
Food
Heart attacks
Heterogeneity
Laboratories - organization & administration
Laboratory animals
Medicine and Health Sciences
Meta
Meta-analysis
Myocardial infarction
Physical Sciences
Probability
Reproducibility
Reproducibility of Results
Research and Analysis Methods
Research Design - standards
Sample Size
Standardization
Stem cells
Studies
Supervision
Systematic review
Validity
Zoology
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Summary:Single-laboratory studies conducted under highly standardized conditions are the gold standard in preclinical animal research. Using simulations based on 440 preclinical studies across 13 different interventions in animal models of stroke, myocardial infarction, and breast cancer, we compared the accuracy of effect size estimates between single-laboratory and multi-laboratory study designs. Single-laboratory studies generally failed to predict effect size accurately, and larger sample sizes rendered effect size estimates even less accurate. By contrast, multi-laboratory designs including as few as 2 to 4 laboratories increased coverage probability by up to 42 percentage points without a need for larger sample sizes. These findings demonstrate that within-study standardization is a major cause of poor reproducibility. More representative study samples are required to improve the external validity and reproducibility of preclinical animal research and to prevent wasting animals and resources for inconclusive research.
ISSN:1545-7885
1544-9173
1545-7885
DOI:10.1371/journal.pbio.2003693