Estimating mean local posterior predictive benefit for biomarker-guided treatment strategies

Precision medicine has emerged from the awareness that many human diseases are intrinsically heterogeneous with respect to their pathogenesis and composition among patients as well as dynamic over the course therapy. Its successful application relies on our understanding of distinct molecular profiles and their biomarkers which can be used as targets to devise treatment strategies that exploit current understanding of the biological mechanisms of the disease. Precision medicine present challenges to traditional paradigms of clinical translational, however, for which estimates of population-averaged effects from large randomized trials are used as the basis for demonstrating improvements comparative effectiveness. A general approach for estimating the relative effectiveness of biomarker-guided therapeutic strategies is presented herein. The statistical procedure attempts to define the local benefit of a given biomarker-guided therapeutic strategy in consideration of the treatment response surfaces, selection rule, and inter-cohort balance of prognostic determinants. Theoretical and simulation results are provided. Additionally, the methodology is demonstrated through a proteomic study of lower grade glioma.