US FDA breakthrough therapy designation and consumer drug advertising: a recipe for confusion

In 2012, the US Congress gave the Food and Drug Administration authority to grant “breakthrough therapy” designation to expedite development and regulatory review of new drugs. The designation is used for potential treatments for serious conditions when preliminary evidence suggests they may perform substantially better than available alternatives on “clinically significant endpoints.” Preliminary evidence can include surrogate marker endpoints reasonably likely to predict clinical benefit, such as imaging changes and biomarkers. The programme has been successful in at least one way: an analysis of FDA approved drugs from 2015 to 2022 found that breakthrough designation was associated with a two year reduction in clinical development time.1 However, these therapies are approved on the basis of less rigorous evidence, often a single pivotal clinical trial instead of two, and trials that are smaller and weaker in design.2

Manufacturers had requested around 1400 breakthrough designations for candidate drugs as of October 2023, 537 of which were granted (292 drugs later received FDA approval).3 The numbers have far exceeded initial expectations that one to two drugs would qualify annually.4 The breakthrough designation has received criticism for unintended consequences—including that the title “breakthrough” has led to press releases, news articles, and product labels that have led patients and physicians to overestimate the efficacy of designated therapies.2567

Separately, over the past two decades, the rise in direct-to-consumer pharmaceutical advertising in the United States (one of only two higher income countries that allows it, alongside New Zealand), has continued unabated, eclipsing $6bn annually. Such advertising has generated concerns about overstating the efficacy of new drugs.8910 Critics have …