I. Introduction
Direct oral anticoagulants (DOACs) have been increasingly prescribed to patients with non-valvular atrial fibrillation (NVAF) following regulatory approval and guideline recommendations following successful Phase III trials demonstrating their non-inferiority and superiority to warfarin.1-5 However, the results from pivotal trials should be interpreted with caution because of the strict inclusion and exclusion criteria to ensure participant safety and provide clear results for regulatory approval. The Food and Drug Administration recommends that enrolling participants with a wide range of baseline characteristics may create a trial population that more accurately reflects the patients who are likely to take the drug if it is approved and may allow evaluation of the impact of these characteristics on the trial drug’s safety and efficacy.6 The ICH Steering Committee has also stated that as drug development progresses, the study population should be expanded to reflect the target population.7
These recommendations aim to ensure that the results of Phase III trials can be used for a broader range of patients; however, several studies have attempted to assess the generalizability of the results from Phase III trials of DOACs to the extent to which real-world patients with NVAF can be enrolled in Phase III trials. The proportion of real-world patients eligible for the trials varied widely, ranging from 35% to 72%.8-13 There were trends towards low eligibility for ROCKET-AF and high eligibility for ARISTOTLE and RE-LY, presumably because of the CHADS2 score as an inclusion criterion. However, there have been few comparisons of outcomes between eligible and ineligible patients in Phase III trials. This study aimed to determine the proportion of real-world Japanese patients with NVAF eligible for Phase III trials and compare the characteristics and outcomes of ineligible and eligible patients.