Example of a biomarker that is both prognostic (negatively) and predictive. Assume that patients have been randomized to the experimental and standard therapies. A) For patients receiving the experimental therapy, those who are positive for the biomarker (black curve) have survival similar to those who are negative for the biomarker (gray curve). B) For patients receiving the standard therapy, those who are positive for the biomarker have shorter survival (black dashed curve) compared to those who are negative for the biomarker (gray dashed curve); therefore, the biomarker is negatively prognostic. The biomarker is also predictive for benefit of the experimental therapy (solid curves) relative to the standard therapy (dashed curves) because survival for patients who are positive for the biomarker is substantially longer for those receiving the experimental therapy (black solid curve) compared to standard therapy (black dashed curve); whereas, for patients who are negative for the biomarker (gray curves) the survival distribution is the same regardless of treatment received.