Optimizing Clinical Trial Protocols Using EHR-Derived Heterogeneous Treatment Effects

This study uses electronic health records from the Mayo Clinic Cloud to emulate the DAPA-HF trial and estimate heterogeneous treatment effects with a Meta-S learner. A decision-tree thresholding procedure then defines patient subgroups. In the overall emulated cohort, dapagliflozin was not associated with a statistically significant survival benefit: HR 1.681, 95% CI 0.828-3.413, p=0.1507. HTE-guided stratification identified a low-HTE subgroup with lower mortality, HR 0.203, and a high-HTE subgroup with markedly higher mortality, HR 6.680.