Table 1.

Evidence-based criteria for a prognostic gene signature in the path from the laboratory to clinical practice

No.	Concept	Elaboration
1	Proof of concept	Do signature levels differ substantially between patients with and without outcome?
2	Analytical validity	Signature's ability to accurately and reliably measure the genotype of interest between and within laboratories
3	Clinical validity	Does the signature predict risk of outcome in multiple external cohorts or nested case–control/case–cohort studies?
4	Incremental value	Does the signature add enough information to established clinico-pathological prognostic markers or provide a more reproducible measurement of one of them?
5	Clinical impact	Does the signature change predicted risk sufficiently to change recommended therapy?
6	Clinical utility	Does use of the signature improve clinical outcome, especially when prospectively used for treatment decisions in a randomized controlled trial?
7	Cost-effectiveness	Does use of the signature improve clinical outcome sufficiently to justify the additional costs of testing and treatment?