Limitations of Subgroup Safety Analyses for Drug-Drug Interaction Evaluation: Insights from the Talazoparib P-gp Inhibitor Case

Impact of concomitant medications (conmeds) on the safety of the investigational agent is often evaluated using subgroup analyses for safety events in patients who received the conmed versus those who did not. Here, we highlight the potential biases and inconclusive results that can arise from such analyses, using talazoparib and P-glycoprotein(P-gp) inhibitors as a case study. Our findings suggest that drug-drug interactions (DDI) dose adjustments should be based on exposure changes rather than safety subgroup analyses.