A dose-finding design for phase I clinical trials based on Bayesian stochastic approximation

BACKGROUND: Current dose-finding designs for phase I clinical trials can correctly select the MTD in a range of 30–80% depending on various conditions based on a sample of 30 subjects. However, there is still an unmet need for efficiency and cost saving. METHODS: We propose a novel dose-finding design based on Bayesian stochastic approximation. The design features utilization of dose level information through local adaptive modelling and free assumption of toxicity probabilities and hyper-parameters. It allows a flexible target toxicity rate and varying cohort size. And we extend it to accommodate historical information via prior effective sample size. We compare the proposed design to some commonly used methods in terms of accuracy and safety by simulation. RESULTS: On average, our design can improve the percentage of correct selection to about 60% when the MTD resides at a early or middle position in the search domain and perform comparably to other competitive methods otherwise. A free online software package is provided to facilitate the application, where a simple decision tree for the design can be pre-printed beforehand. CONCLUSION: The paper proposes a novel dose-finding design for phase I clinical trials. Applying the design to future cancer trials can greatly improve the efficiency, consequently save cost and shorten the development period. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12874-022-01741-3.