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

Importance Accelerated approval by the US Food and Drug Administration (FDA) grants market authorization for drugs based on clinical trials using surrogate end points likely to anticipate a clinical benefit. The FDA requires postapproval trials to confirm benefit, after which the accelerated approval is converted to a standard approval or is withdrawn. However, trials frequently fail to assess clinical benefit, and expenditure for these drugs may be substantial. Objective To evaluate spending by the Centers for Medicare & Medicaid Services (CMS) on drugs granted FDA accelerated approval before and after confirmation of benefit. Design and Setting This was a cross-sectional study of CMS spending on drugs granted FDA accelerated approval for original indications from 2012 to 2017, with follow-up through 2020. Using data from the Drugs@FDA database and a validated methodology, the characteristics of new drugs granted FDA accelerated approval were identified and analyzed, including indication area, type of drug, type of confirmatory trial end point, orphan designation, number of supplemental indications, and conversion status. Main Outcomes and Measures Overall and annualized spending by Medicare Parts B and D and Medicaid from 2012 to 2020, before and after conversion to standard approval. Analyses were conducted from June 30, 2021, to March 21, 2022. Results From 2012 to 2017, the FDA granted accelerated approval to 38 drugs for 42 original indications. Through 2020, CMS spending for these drugs was $67.9 billion (median [IQR], $329.3 million [$54.4 million-$1.6 billion]). For 22 drugs (58%) that were converted to standard approval on the basis of clinical trial results, annualized spending increased substantially after conversion ($35.0 million vs $199.0 million), and spending after conversion accounted for $51.0 billion (75%) of overall spending. However, only 6 conversions (27%) of the 22 were supported by confirmatory trials evaluating clinical outcomes as primary end points. Drugs evaluated using surrogate end points accounted for $40.3 billion (59%) of CMS spending. Conclusions and Relevance The findings of this cross-sectional study indicate that most of the drugs granted FDA accelerated approval for original indications from 2012 to 2017 lacked confirmatory trials evaluating clinical outcomes to support conversion to standard approval. Automatic coverage mandates produced substantial CMS spending for drugs with unproven clinical benefits. This cross-sectional study evaluates spending by the Centers for Medicare & Medicaid on drugs granted FDA accelerated approval before and after confirmation of benefit from 2012 to 2017 with follow-up through 2020. Question How much do the Centers for Medicare & Medicaid (CMS) spend on drugs granted accelerated approval by the US Food and Drug Administration (FDA), before and after confirmation of the drug's benefit? Findings This cross-sectional study of 38 drugs granted FDA accelerated approval from 2012 to 2017 found that CMS spent nearly $68 billion through 2020, including $51 billion (75%) after conversion to standard approval following confirmatory trial results. However, 59% of the spending was for drugs with confirmatory trials that evaluated surrogate end points. Meaning The findings of this study indicate that many drugs granted FDA accelerated approval lack evidence of clinical benefit, even after being converted to standard approval, yet they account for substantial CMS spending.