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The US Food and Drug Administration (FDA) must balance the need to bring potentially lifesaving drugs to market with the need to ensure the safety and effectiveness of these drugs. To balance these competing goals, the FDA has increasingly used the accelerated pathway, which is meant for drugs that treat serious conditions and fill an unmet medical need. Approval is based on a surrogate or an early clinical endpoint and is conditional on the completion of confirmatory trials, which are planned prior to the approval process.
Once granted, accelerated drug approvals are subject to withdrawal if “a postmarketing clinical study fails to verify clinical benefit.”1 The FDA defines clinical benefit as prolonging life or improving the quality of life (QoL). Withdrawal of approval is rare. The only drug for which the FDA withdrew approval—as a result of failure of confirmatory data—was bevacizumab for metastatic breast cancer in 2011. However, Medicare and other major insurers still cover bevacizumab for this indication, despite the FDA ruling or the drug’s lack of clinical benefit.
In this issue of JAMA Internal Medicine, Rupp and Zuckerman2 examine 18 cancer drugs that received accelerated FDA approval but were found in postmarketing confirmatory trials to have no overall survival (OS) benefit.3 Less than half of these drugs had been studied using QoL outcomes. Although 6 drugs lack OS or QoL benefit, all but 1 (bevacizumab) have retained their approval and are still on the market.
We suggest 3 improvements to the accelerated pathway for cancer drug approvals. First, confirmatory postmarketing studies for accelerated drug approvals should include both OS and QoL outcomes because these are the 2 facets of clinical benefit currently being used by the FDA. Second, preapproved QoL measures should be published for specific drug classes. Third, anticipated or clinically significant changes in OS and in QoL measures should be defined a priori to facilitate the identification of drugs whose “postmarketing clinical study fails to verify clinical benefit.”
In following the principle of “first, do no harm,” the FDA should promptly withdraw approval for cancer drugs that are proven to have no clinical benefit. Removing these drugs, each of which costs between $20 000 and $170 000 per year, from the market will improve the quality and value of cancer care.
Corresponding Author: Scott R. Bauer, MD, ScM, Division of General Internal Medicine, University of California, San Francisco, 1545 Divisadero St, San Francisco, CA 94115 (email@example.com).
Conflict of Interest Disclosures: None reported.
Bauer SR, Redberg RF. Improving the Accelerated Pathway to Cancer Drug Approvals. JAMA Intern Med. 2017;177(2):278. doi:10.1001/jamainternmed.2016.7777