FDA's Project Optimus Aims to Optimize Dose Selection for Better Benefit-Risk Tradeoff

Strategic Insights -

A groundbreaking study published in Biometrics aims to revolutionize the approach to dose selection in clinical trials. The US Food and Drug Administration (FDA) has launched Project Optimus to shift the focus from the maximum tolerated dose to the optimal biological dose (OBD). This new approach seeks to optimize the benefit-risk tradeoff, and researchers at the University of Texas MD Anderson Cancer Center propose a novel design, Randomized Optimal SElection (ROSE), to achieve this goal. According to the study, a sample size of 15-40 patients per dosage arm typically results in a percentage of correct selection of the optimal dose ranging from 60% to 70%.

Key Takeaways:

  • The FDA's Project Optimus aims to optimize dose selection by focusing on the optimal biological dose (OBD) rather than the maximum tolerated dose.
  • The proposed Randomized Optimal SElection (ROSE) design minimizes sample size while ensuring the probability of correct selection of the OBD at pre-specified accuracy levels.
  • The ROSE design is simple to implement and involves a straightforward comparison of the difference in response rates between two dose arms against a predetermined decision boundary.
  • Simulations studies demonstrate that the ROSE design exhibits desirable operating characteristics in correctly identifying the OBD.
  • The study suggests that a sample size of 15-40 patients per dosage arm typically results in a percentage of correct selection of the optimal dose ranging from 60% to 70%.
  • The FDA's guidance recommends conducting randomized trials comparing multiple doses.
  • The National Cancer Institute, National Institute of Diabetes and Digestive and Kidney Diseases, and the U.S. Food and Drug Administration have supported this research.
  • The study has been peer-reviewed and published in Biometrics, 2025;81(4).

Statistics:

  • 15-40 patients per dosage arm are typically required to achieve a percentage of correct selection of the optimal dose ranging from 60% to 70%.
  • 60-70% correct selection of the optimal dose is achievable with a sample size of 15-40 patients per dosage arm.
  • 2025 is the year the research was published.
  • 81(4) is the volume and issue number of the publication in Biometrics.

Sources:

  • Randomized optimal selection design for dose optimization. Biometrics, 2025;81(4)
  • NewsRx. Researchers at University of Texas MD Anderson Cancer Center Report Findings in Science (Randomized optimal selection design for dose optimization). Clinical Trials Week. October 20, 2025; p 2634.