A quantitative analysis of statistical power identifies obesity end points for improved in vivo preclinical study design

The design of well-powered in vivo preclinical studies is a key element in building the knowledge of disease physiology for the purpose of identifying and effectively testing potential

antiobesity drug targets. However, as a result of the complexity of the obese phenotype, there is limited understanding of the variability within and between study animals of macroscopic end

points such as food intake and body composition. This, combined with limitations inherent in the measurement of certain end points, presents challenges to study design that can have

significant consequences for an antiobesity program. Here, we analyze a large, longitudinal study of mouse food intake and body composition during diet perturbation to quantify the

variability and interaction of the key metabolic end points. To demonstrate how conclusions can change as a function of study size, we show that a simulated preclinical study properly

powered for one end point may lead to false conclusions based on secondary end points. We then propose the guidelines for end point selection and study size estimation under different

conditions to facilitate proper power calculation for a more successful in vivo study design.

Pfizer Inc. supported the research of JS, WCT and CJM. Data used in this research were from a study sponsored by the Intramural Research Program of the NIH, NIDDK.

JS, WCT and CJM were employees of Pfizer Inc. during this study. The remaining authors declare no conflict of interest.

Supplementary Information accompanies this paper on International Journal of Obesity website

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