Early Completion of Model-Assisted Designs for Dose-Finding Trials
1Biometrics Department, R&D Division, Kyowa Kirin Co, Ltd, Tokyo, Japan.
JCO Precision Oncology
|January 7, 2022
Summary
A novel early completion method for phase I dose-finding trials allows trials to stop when the maximum tolerated dose (MTD) is accurately estimated, reducing patient numbers and accelerating drug development.
Area of Science:
- Clinical Trials
- Pharmacology
- Biostatistics
Background:
- Phase I trials are crucial for determining safe drug dosages.
- Traditional phase I trials can be lengthy and involve many patients.
- Model-assisted designs offer more efficient dose-finding strategies.
Purpose of the Study:
- To introduce a novel early completion method for phase I dose-finding trials.
- To enable trials to halt upon accurate estimation of the maximum tolerated dose (MTD).
- To reduce the number of patients treated and expedite subsequent trial phases.
Main Methods:
- Developed an early completion strategy based on dose-retainment probability and dose-assignment decisions.
- Evaluated the method in two actual phase I clinical trials.
- Conducted computer simulations to assess MTD selection accuracy, early completion rates, and patient numbers.
Main Results:
- Confirmed early completion in two real-world trials.
- Simulations showed maintained MTD selection accuracy compared to standard model-assisted designs.
- Early completion rates ranged from 50% to 90%, with patient reductions of 20%-60%.
Conclusions:
- The proposed early completion method is practical for model-assisted phase I dose-finding trials.
- This approach efficiently identifies the MTD while minimizing patient exposure.
- Facilitates faster progression to efficacy studies and overall drug development timelines.
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