the value of potential new drug targets (target qualification) and have led to calls for proof of concept human studies as the ultimate approach in hypothesis testing for target validation.5 However clinical proof-of concept validation studies are expensive and carry risk, and will always be limited in number. Other challenges arise from the lack of informative biomarkers to guide proof of concept clinical studies and clinical development (for example by patient stratification), subjective clinical endpoints, and high placebo response rates (particularly in major depression)6.
