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Study Follows Consequences of Early Confirmatory Trials for Accelerated Approval Indications

In a research letter in JAMA, a team from Harvard Medical School and the London School of Economics and Political Science consider the US Food and Drug Administration's accelerated drug approval pathway, particularly around the performance of required confirmatory trials in relation to the traditional approval or withdrawal processes that followed. Using data for 127 accelerated approvals from 2002 to 2018, the investigators note that confirmatory trials were already underway for 89 of the indications prior to accelerated approval. More than 39 percent of the indications with these early confirmatory trials had progressed to traditional approval or withdrawal in the span of three years, stretching to more than 76 percent by the five-year mark — rates of conversion or withdrawal that outpaced those for indications that had not started on confirmatory trials by the accelerated approval point. "Indications with accelerated approval … that had confirmatory trials started before approval had faster conversion to traditional approval or withdrawal than those that did not, thereby reducing the duration of patient exposure to therapies with uncertain efficacy," they report, though they caution that "there was no statistically significant difference in rates of regulatory outcomes within target timelines by preapproval trial initiation status."