Sample size determination in phase I oncology trials based on selection probability of the maximum tolerated dose

• Published in: Japanese Journal of Biometrics Vol. 42; no. 1; pp. 55 - 64
• Main Authors: Kawatsu, Yuta, Tsuchida, Jun, Ando, Shuji, Hirakawa, Akihiro, Sozu, Takashi
• Format: Journal Article
• Language: Japanese; English
• Published: The Biometric Society of Japan 2021
• Subjects: Calculation time-saving; Continual reassessment method; Dose-finding; Dose-limiting toxicity
• ISSN: 0918-4430; 2185-6494
• DOI: 10.5691/jjb.42.55

Phase I oncology clinical trials are designed to evaluate the safety of test drug/s and to determine the recommended dose for subsequent trials. However, the method to determine the required number of participants (sample size) has not been sufficiently developed for these dose-finding studies. The usual approach involves time-consuming calculations using numerical experiments to establish the required sample size that will allow the determination of accurate recommended dose of the test drug/s. In this study, we propose a time-saving method to determine the sample size. This method uses an alternative index of the proportion to accurately select the recommended dose. In the numerical experiments, we compared the performances (sample size, proportion of correctly selected recommended dose, and calculation time for the determination of sample size) of the proposed method with those of the conventional method. The sample size and the proportion of correctly selected recommended dose, determined by the proposed method, were slightly different from those calculated using the conventional method. The calculation time of the proposed method was consistently shorter than that of the conventional method. These results suggest that the proposed method can be used to roughly estimate the sample size of phase I oncology studies.