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Appraising the Balance Between Expedited FDA Approvals & Clinical Evidence

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 (Published in JAMA Health Forum, May 2022)

  • The authors estimated Medicare and Medicaid spending on new drugs granted FDA accelerated approval from 2012 to 2017, before and after conversion to standard approval or withdrawal, and assessed whether evaluation of clinical benefit was associated with differences in spending. They found that for 38 drugs granted accelerated approval by the FDA during this time period that:
    • Medicare and Medicaid spent almost $70 billion through 2020, over $50 billion (75%) was spent after the accelerated approval drugs were converted to standard approval, after their required confirmatory trials were completed, but that almost 60%, accounting for $40 billion of spending was for drugs with confirmatory trials evaluating surrogate endpoints instead of true clinical benefit.
  • Accompanying Op-Ed in The Hill (5/27/2022) - Accelerated Approval: unfulfilled promises for FDA’s expedited review program

Comparison of Duration of Postapproval vs Pivotal Trials for Therapeutic Agents Granted US Food and Drug Administration Accelerated Approval, 2009-2018 (Published in JAMA Network Open, Nov 2021) – Joshua D. Wallach, Reshma Ramachandran, Till Bruckner, Joseph S. Ross

  • The authors compared the duration of post approval trials with that of the pivotal trials used as the basis of FDA approval as well as FDA-established postapproval trial results reporting deadlines, for all drugs receiving accelerated approval between January 1, 2009 and 2018. They found that the median postapproval trial durations were not much longer than pivotal trial durations at 17 months. However, the median time from approval to FDA-established postapproval trial results reporting deadlines for sponsors was 50 months, a median of 30 months more than postapproval trial durations.

Feasibility of Using Real-world Data to Emulate Postapproval Confirmatory Clinical Trials of Therapeutic Agents Granted US Food and Drug Administration Accelerated Approval (Published in JAMA Network Open, Nov 2021) - Joshua D. Wallach, Audrey D. Zhang, MD, Joshua J. Skydel, MD, Victoria L. Bartlett, BA, Sanket S. Dhruva, MD, MHS, Nilay D. Shah, PhD, Joseph S. Ross, MD, MHS

  • The authors examined the feasibility of using real-world data (RWD) to emulate FDA-required postapproval confirmatory trials for all new drugs that received accelerated approval between 2009 and 2018. They found that none of the 50 FDA-required postapproval confirmatory trials granted accelerated approval during this time period could have been feasibly emulated during the real-world data sources of claims or structured electronic health record data.