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FDA allows drugs without proven clinical benefit to languish for years on accelerated pathway

BMJ 2021; 374 doi: (Published 30 July 2021) Cite this as: BMJ 2021;374:n1898
  1. Elisabeth Mahase
  1. The BMJ

Criticisms of the US Food and Drug Administration’s accelerated approval process have resurfaced after the recent approval of aducanumab (Aduhelm) for dementia. Elisabeth Mahase finds that the process is plagued by missing efficacy data and questionable evidence

Since the US Food and Drug Administration established its accelerated approval pathway for drugs in 1992, nearly half (112) of the 253 drugs authorised have not been confirmed as clinically effective, an investigation by The BMJ has found.

Of these 112 drugs approved in the past 28 years, a fifth (24) have been on the market for more than five years and some for more than two decades—often with a hefty price tag, shows an in-depth analysis of FDA data1 to 31 December 2020, conducted by The BMJ.

The accelerated pathway allows drugs onto the market before efficacy has been proved. As part of this approval, however, the manufacturer must conduct post-approval studies—known as phase IV confirmatory trials—to “verify the anticipated clinical benefit.” If these trials show no benefit the drug’s approval can be cancelled.

Further analysis of FDA data shows that only 16 drugs approved through the pathway have ever been withdrawn. Most of these were shown to lack efficacy, but in some cases the confirmatory trials were never done. Celecoxib (Celebrex), which was given accelerated approval in 1999 for the treatment of familial adenomatous polyposis, was on the market for 12 years before the FDA finally asked Pfizer to voluntarily withdraw it for this indication because the efficacy trials were never done.2

The BMJ asked the manufacturers of 24 treatments that have been on the market for more than five years whether they had conducted phase IV trials. Six drugs had been withdrawn, approved, or postponed. Of the remaining 18 drugs, relevant trial information was provided for just …

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