Trends in Breakthrough Therapy Designations and Approvals Granted by the US Food and Drug Administration, 2012-2020


Dhiksha Balaji, BA G. Caleb Alexander, MD, MS 2, 3 Thomas J. Moore, AB 2 1 Case Western Reserve University School of Medicine, Cleveland, Ohio 2 Center for Drug Safety and Effectiveness, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland 3 Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland


The US Food and Drug Administration (FDA) administers various programs to expedite the development and review of new drugs that aim to treat serious or life-threatening conditions. In 2012, the Congress established one such program, the “Breakthrough Therapy (BT)” Designation, which requires preliminary clinical evidence that demonstrates substantial improvement in a clinically significant endpoint over available therapy [1]. FDA “Approval” occurs after “Designation,” involving assessment of the safety and efficacy of a new drug and determination that the benefits of the product outweigh known risks. While the goal of the BT Designation is to more promptly bring drugs to market that transform patient care, it also provides for approvals based on more limited clinical trial evidence. We characterized patterns in BT Designations and Approvals by the FDA from 2012 through 2020.


The Center for Drug Evaluation and Research (CDER) publicly available data on BT Designation Requests as well as BT Approvals from 2012- 2020 was used for this analysis. Data were collected and analyzed in Microsoft Excel.


The CDER received 917 BT designation requests from 2012 through 2020. The median of requests received was 106 (interquartile range [IQR], 93-125). Of these requests, 375 (40.9%) were granted, 425 (46.3%) were denied, and 117 (12.8%) were withdrawn. The median of requests granted was 46 (IQR, 31-58), median of requests denied was 51 (IQR, 48-53), and median of requests withdrawn was 14 (IQR, 12-17). Designation in an early stage of development did not guarantee approval. Of drugs granted the BT designation, a median of 21 (IQR, 14-34) and mean of 38 (standard deviation, 13.5) were approved as of December 31st, 2020.


When the BT designation was created, it was expected to only support a few drugs [2]. This analysis shows use of the program has been increasing since 2012. Further analysis should examine the quality of the clinical data required for BT designation and the BT drug performance post-approval to assess the function of the BT designation.


1. Darrow JJ, Avorn J, Kesselheim AS. New FDA breakthrough-drug category---implications for patients. N Engl J Med. 2014;370:1252-8. [PMID: 24670173] doi:10.1056/NEJMhle1311493

2. Kesselheim AS, Wang B, Franklin JM, et al. Trends in utilization of FDA expedited drug development and approval programs, 1987-2014: cohort study. BMJ. 2015;351:h4633. [PMID: 26400751] doi:10.1136/bmj.h4633

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