For a study, researchers sought to look at the frequency of extrapolation beyond pivotal trial data into approved indications in connection to disease severity, disease subtype, and concurrent drug use. Patients in pivotal trials of 105 innovative medication approvals from 2015 to 2017 were identified and compared to the US Food and Drug Administration (FDA) approved indications for the treatments in a cross-sectional analysis. FDA reviews, published material documenting pivotal studies, and the original drug labeling were the primary sources examined. The research took place between July 4, 2019, and June 1, 2021. About 23 extrapolations of trial population features to the approved indication were discovered in 21 of the 105 innovative FDA drug approvals investigated (20%): 12 times (29%) in 2015, 3 times (15%) in 2016, and 6 times (14%) in 2017. Extrapolating trial results to individuals with more severe diseases was the most common (n=14 medications), followed by differences in disease subtype (n=6) and concurrent medication use (n=3). According to the study, extrapolation from pivotal trial results to FDA-approved indications was prevalent. Although extrapolations were based on reasonable clinical predictions, they could limit the generalizability of such indications to specific prescribing decisions. These results pointed to a greater need for close postapproval monitoring to see if new safety issues arose or if effectiveness differed from expectations when these medications were used in larger populations.