Study Examines FDA Drug, Device Approvals Based on Nonrandomized Clinical Trials

JAMA Network Open


Media advisory: To contact corresponding author Benjamin Djulbegovic, M.D., Ph.D., email Letisia Marquez at The full study is linked to this news release.

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Bottom Line: How often the U.S. Food and Drug Administration (FDA) has approved drugs and devices based on nonrandomized clinical trials (non-RCTs) and whether those approvals are associated with the sizes of treatment effects were the focus of this study. Applications for 606 drugs from 2012 to August 2018 and for 71 medical devices from 1996 to August 2017 were assessed, and approved applications based on non-RCTs were included in this study called a systematic review and meta-analysis. Of the 677 applications, 68 (10%) were approved by the FDA based on non-RCTs. A meta-analysis was conducted to examine differences between applications that required further testing with RCTs and those that didn’t. The authors report estimated treatment effects were higher for treatments or devices approved based on non-RCTs than for treatments or devices for which further testing in RCTs was required. There was no clear threshold of treatment effect above which no RCTs were requested. A limitation of the study was the small sample size.

Authors: Benjamin Djulbegovic, M.D., Ph.D., City of Hope, Duarte, California, and coauthors



Editor’s Note: The article includes conflict of interest and funding/support disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

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