The time is now to start evaluating biomarkers in the clinic.

267 methods. Applying a reverse engineering approach, working backwards from treatment outcome heterogeneity to identify treatmentselection biomarkers (which may not have any direct causal role in the pathophysiology of disease), has already proven to be valid and potentially productive . The clinical utility of such biomarkers rests on their potential to allow practitioners to move beyond the current trialanderror standard, thus shortening time to remission and minimizing exposure to potential adverse effects. Application of treatmentselection biomarkers would further transcend the concept of “clinical stages” of treatment resistance, enabling patients to proceed immediately to more intensive treatments that, under current care models, are withheld until the patient demonstrates nonresponse to standard treatments. Researchers should remain mindful of the seductive nature of the classical forward