Table 1.

Sources of low predictive validity in preclinical study and proposed solutions.

Sources of low predictive validity	Solutions
Clinically non-predictive populations	Use multiple background strains
	Use multiple genetic models for the same disease
	Outbreed mouse population
	Develop humanized mouse models
Clinically non-predictive behavior	Use multiple complementary behavioral assays
	Validate assays with both clinically successful and failed compounds
	Develop new assays to model neglected disease symptoms
Low construct validity	Preclinically test pharmacokinetics/pharmacodynamics
	Develop behavioral assays that work similarly for humans and mice
	Discover predictive clinical biomarkers shared by humans and mice
	Identify human biomarkers that better recapitulate drug efficacy
Low preclinical statistical power	Pre-register behavioral assays and metrics
	Increase baseline sample sizes
	Independently replicate all successful tests before clinical trials