Large numbers of patients are needed to obtain additional approvals for new cancer drugs: A retrospective cohort study

Sci Rep. 2023 Sep 26;13(1):16138. doi: 10.1038/s41598-023-42213-y.


Patients endure risk and uncertainty when they participate in clinical trials. We previously estimated that 12,217 patient-participants are required to bring a new cancer drug to market. However, many development efforts are aimed at extending the label of already approved drugs. Herein, we estimate the number of patients required to extend the indication of an FDA approved cancer drug. We identified all anti-cancer drugs approved by the FDA 2012 to 2015. We searched to identify all drug development trajectories (i.e., a series of one or more clinical trials testing a unique drug-indication pairing) launched after FDA approval for each drug. We identified which trajectories produced the following milestones: secondary FDA approvals, secondary FDA approvals achieving substantial clinical benefit in ESMO-MCBS, and recommendations in NCCN clinical practice guidelines. Using the total enrollment, we estimated the number of patients needed to reach each milestone. Forty-two drugs were approved by the FDA between 2012 and 2015, leading to 451 post-approval trajectories enrolling 129,548 patients. Fourteen secondary FDA approvals were identified, of which 4 met the ESMO-MCBS definition of substantial clinical benefit. Fourteen NCCN off-label recommendations were obtained. A total of 9253, 32,387 and 4627 patients were needed to attain an FDA approval, an approval with substantial clinical benefit on ESMO-MCBS, and an NCCN guideline recommendation, respectively. The number of patients needed to obtain a first secondary FDA approval was 16,596. Large numbers of patients are needed to extend the label of prior FDA approved drugs. Label extension after approval entails lower marginal costs for developers. However, extra knowledge available to researchers about a drug's safety and pharmacology after FDA approval does not appear to translate into reduced patient numbers required for developing new cancer applications.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Drug Development
  • Humans
  • Knowledge
  • Neoplasms* / drug therapy
  • Patients
  • Retrospective Studies

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