Comparison of Duration of Postapproval vs Pivotal Trials for Therapeutic Agents Granted US Food and Drug Administration Accelerated Approval, 2009-2018

Abstract

FDA approved 41 new therapeutic agents for 45 indications via the accelerated approval program. Of these, information on trial duration could be + Related articleAuthor affiliations and article information are listed at the end of this article.

Spending by the Centers for Medicare & Medicaid Services Before and After Confirmation of Benefit for Drugs Granted US Food and Drug Administration Accelerated Approval, 2012 to 2017

“…7 Permitted confirmatory trial durations are frequently longer than those for preapproval trials, despite requiring similar times for completion. 8 For this sample, median time from accelerated approval to conversion was 28 months, just more than one-half of the median time permitted by FDA for confirmatory trial results…”

“…61 Finally, we did not account for variation between drugs in the time required to stage postapproval clinical trials, and it is possible that the FDA will consider additional evidence sources that do evaluate clinical outcomes when determining whether to convert drugs to standard approval. However, postapproval trial durations are typically comparable with pivotal trial durations, 8 and in the absence of consistently available public information on the FDA's rationale for conversion determinations, it is not possible to assess how trial logistics or complementary sources of clinical evidence may influence conversion.…”

“…6 The FDA allows drug sponsors an extensive period of time to complete confirmatory trials after an accelerated approval is granted, often more than twice as long as is required to evaluate primary end points. 7,8 Even so, confirmatory trials are frequently delayed and may have limitations similar to those of preapproval studies, including continued use of surrogate end points to evaluate efficacy. [9][10][11] Consequently, clinical benefit may remain uncertain for years after accelerated approval.…”

Use of US Food and Drug Administration Expedited Drug Development and Review Programs by Orphan and Nonorphan Novel Drugs Approved From 2008 to 2021

“… 16 , 17 Expressions of efficacy and/or safety concerns regarding Accelerated Approval drugs, for which clinical benefit requires confirmation in postapproval studies, have been especially prominent in the literature. 18 , 19 , 20 Stakeholders have recommended enhanced FDA enforcement of postmarket study requirements for drugs approved under the Accelerated Approval pathway. 21 Congress is considering changes to the Accelerated Approval program, 22 , 23 , 24 such as strengthening the requirement to conduct appropriate confirmatory studies and authorizing the FDA to require that postmarket studies be underway before issuing marketing authorization.…”

Timing of Confirmatory Trials for Drugs Granted Accelerated Approval Based on Surrogate Measures From 2012 to 2021

“…As required by law, drug manufacturers agree to evaluate clinical benefits in a follow-up trial. The FDA sets a time frame for completion, but confirmatory trials are sometimes delayed . We sought to systematically characterize the frequency of delayed confirmatory trials relative to deadlines set by the FDA.…”