Randomized Clinical Trial or Real-World Evidence: How Historical Events, Public Demand, and the Resulting Laws and Regulations Shaped the Body of Medical Evidence

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Journal of orthopaedic trauma


SUMMARY: The signing of the 21st Centuries Cures Act in 2016 was a confirmational step in a long journey toward an understood use and need for real-world evidence (RWE), even though the Food and Drug Administration (FDA) had the legislative authority to accept RWE since 1962 to demonstrate efficacy. The 21st Century Cures Act, as well as the subsequent FDA guidance published in 2017 and other supporting guidance, documents that since are opening the doors for the clinical and research community. They specifically allow for labeling changes and indication expansion based on RWE. The legislative discussion of efficacy requirements started in the late 1950s, when evidence of effectiveness was not required in the United States before the marketing of a drug or medical device, and calls for the real-world comparative effectiveness research were being made by Senator Estes Kefauver. When the thalidomide tragedy stuck, Congress and the Kennedy Administration rushed to pass a new law to require that drugs be "effective in use." The regulations subsequently drafted by the FDA to enforce the law often required placebo-controlled, randomized clinical trials (RCTs). In the 1980s, some started to label the RCT as the gold standard for medical evidence. The use of real-world data for new indication approval was not specifically prohibited by the 1962 law, but the new 2016 law sent a clear mandate to FDA, requiring the agency to review new forms of evidence such as RWE.

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Lippincott, Williams & Wilkins