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.