TABLE 2.

Phases of Evaluation of a Novel Risk Marker^a

Phase	Description
1. Proof of concept	Do novel marker levels differ between subjects with and without outcome?
2. Prospective validation	Does the novel marker predict development of future outcomes in a prospective cohort or nested case-cohort/case-cohort study?
3. Incremental value	Does the novel marker add predictive information to established, standard risk markers?
4. Clinical utility	Does the novel risk marker change predicted risk sufficiently to change recommended therapy?
5. Clinical outcomes	Does use of the novel risk marker improve clinical outcomes, especially when tested in a randomized clinical trial?
6. Cost-effectiveness	Does use of the marker improve clinical outcomes sufficiently to justify the additional costs of testing and treatment?

^aFrom Hlatky et al. (91)