Evaluating Markers for Guiding Treatment.

Abstract

The subpopulation treatment effect pattern plot (STEPP) is an appealing method for assessing the clinical impact of a predictive marker on patient outcomes and identifying a promising subgroup for further study. However, its original formulation lacked a decision analytic justification and applied only to a single marker. We derive a decision-analytic result that motivates STEPP. We discuss the incorporation of multiple predictive markers into STEPP using risk difference, cadit, and responders-only benefit functions. Applying STEPP to data from a breast cancer treatment trial with multiple markers, we found that none of the three benefit functions identified a promising subgroup for further study. Applying STEPP to hypothetical data from a trial with 100 markers, we found that all three benefit functions identified promising subgroups as evidenced by the large statistically significant treatment effect in these subgroups. Because the method has desirable decision-analytic properties and yields an informative plot, it is worth applying to randomized trials on the chance there is a large treatment effect in a subgroup determined by the predictive markers.