Assessing Heterogeneous Risk of Type II Diabetes Associated with Statin Usage: Evidence from Electronic Health Record Data

There have been increased concerns that the use of statins, one of the most commonly prescribed drugs for treating coronary artery disease, is potentially associated with the increased risk of new-onset type II diabetes (T2D). However, because existing clinical studies with limited sample sizes often suffer from selection bias issues, there is no robust evidence supporting as to whether and what kind of populations are indeed vulnerable for developing T2D after taking statins. In this case study, building on the biobank and electronic health record data in the Partner Health System, we introduce a new data analysis pipeline from a biological perspective and a novel statistical methodology that address the limitations in existing studies to: (i) systematically examine heterogeneous treatment effects of stain use on T2D risk, (ii) uncover which patient subgroup is most vulnerable to T2D after taking statins, and (iii) assess the replicability and statistical significance of the most vulnerable subgroup via bootstrap calibration. Our proposed bootstrap calibration approach delivers asymptotically sharp confidence intervals and debiased estimates for the treatment effect of the most vulnerable subgroup in the presence of possibly high-dimensional covariates. By implementing our proposed approach, we find that females with high T2D genetic risk at baseline are indeed at high risk of developing T2D due to statin use, which provides evidences to support future clinical decisions with respect to statin use.