The authors acknowledge that there are multiple limitations in comparing different trials, despite the common comparator arm—notably the patient population differs. Variations in the baseline risk of patients in 1 study could influence the absolute rates of the endpoints in that study, confounding the drug–drug comparison being studied. For example, the ROCKET trial (Rivaroxaban-once daily, oral, direct factor Xa inhibition compared with vitamin K antagonism for prevention of stroke and Embolism Trial in Atrial Fibrillation) trial enrolled older patients with higher CHADS2 (Congestive heart failure, Hypertension, Age, Diabetes, Prior Stroke) risk scores, and as such, would be expected to have higher rates of bleeding and stroke—which might influence the relative drug effect seen in this trial. Therefore, 2 variables would differ when comparing a similar endpoint between these 2 trials—the drug being tested and the patient population—and it would be unclear whether any apparent difference observed in the relative efficacy could be attributed to the drug alone. Similarly, the optimal use of warfarin (as measured by the “time in therapeutic range”) also differed between these trials, resulting in another possible source of confounding that could influence the relative efficacy of the drugs when comparing the trials.