Predictive biomarker graphical approach (PRIME) for Precision medicine

Precision medicine is an evolving area in the medical field and rely on biomarkers to make patient enrichment decisions, thereby providing drug development direction. A traditional statistical approach is to find the cut-off that leads to the minimum p-value of the interaction between the biomarker dichotomized at that cut-off and treatment. Such an approach does not incorporate clinical significance and the biomarker is not evaluated on a continuous scale. We are proposing to evaluate the biomarker in a continuous manner from a predicted risk standpoint, based on the model that includes the interaction between the biomarker and treatment. The predicted risk can be graphically displayed to explain the relationship between the outcome and biomarker, whereby suggesting a cut-off for biomarker positive/negative groups. We adapt the TreatmentSelection approach and extend it to account for covariates via G-computation. Other features include biomarker comparisons using net gain summary measures and calibration to assess the model fit. The PRIME (Predictive biomarker graphical approach) approach is flexible in the type of outcome and covariates considered. A R package is available and examples will be demonstrated.