Suchard MA, Schuemie MJ, Krumholz HM, et al. – Via developing a comprehensive framework for real-world evidence that allows for comparative effectiveness and safety evaluation across many drugs and outcomes from observational data involving millions of patients, while minimizing inherent bias, experts conducted a systematic, large-scale study under a new-user cohort design to predict the relative risks of 3 primary (acute myocardial infarction, hospitalization for heart failure, and stroke) and 6 secondary efficiency and 46 safety outcomes comparing all first-line classes across a global network of 6 administrative claims and 3 electronic health record databases. This comprehensive framework offered a new way of conducting observational healthcare science at scale. The strategy supports equality among drug classes for starting monotherapy for hypertension—in keeping with prevailing guidelines, with the exclusion of thiazide or thiazide-like diuretics preponderance to angiotensin-converting enzyme inhibitors and the inadequacy of non-dihydropyridine calcium channel blockers.