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

BMJ 2024; 384 doi: (Published 21 February 2024) Cite this as: BMJ 2024;384:e076138
  1. Neeraj G Patel, medical student1,
  2. Ayman Mohammad, medical student2,
  3. Joseph S Ross, professor of medicine and public health345,
  4. Reshma Ramachandran, assistant professor in medicine34
  1. 1Yale School of Medicine, New Haven, CT, USA
  2. 2Icahn School of Medicine at Mount Sinai, New York, NY, USA
  3. 3Section of General Internal Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, CT, USA
  4. 4Yale Collaboration for Regulatory Rigor, Integrity, and Transparency, Yale School of Medicine, New Haven, CT, USA
  5. 5Department of Health Policy and Management, Yale School of Public Health, New Haven, CT, USA
  1. Correspondence to: R Ramachandran reshma.ramachandran{at}

Neeraj G Patel and colleagues examine how drugs approved through the FDA breakthrough pathway are advertised to consumers and argue that the name contributes to overestimation of benefits

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 …

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