Assessing the Impact of US Food and Drug Administration Breakthrough Therapy Designation Timing on Trial Characteristics and Development Speed

Abstract

The US Congress created the Breakthrough Therapy designation in 2012 to expedite drug development and review through efficient clinical trial design and intensive interaction with US Food and Drug Administration (FDA) reviewers. Yet, of the 116 pivotal trials supporting Breakthrough‐designated drugs approved 2013–2018, 96 (83%) were already underway or completed when the designation was granted, limiting the potential of the designation to influence trial design. We found no difference between these trials and the 20 (17%) that had not yet begun when the designation was granted (which had greater potential to be impacted by the designation) with respect to phase, size, intervention model (single‐arm vs. multi‐arm), or use of surrogate end points under the Accelerated Approval (AA) pathway. This finding suggests that, in contrast to previous studies, observed trial characteristics were not likely attributable to the designation, and instead other factors such as disease category (e.g., oncology) may be driving both trial design and Breakthrough designation. The 20 trials in our sample that began after designation was granted were, however, over 8 months shorter than trials of nondesignated drugs. This suggests that designations granted early in clinical development may reduce trial time by influencing aspects of clinical programs other than design characteristics, such as timelines for FDA responses. Alternately, certain drugs may be more likely to both receive an early designation and have a shorter trial duration, for example, because of therapeutic category or large effect size.