Evaluating the Effects of Design Parameters on the Performances of Phase I Trial Designs

• Activity Number: 355 - Contributed Poster Presentations: Biopharmaceutical Section
• Type: Contributed
• Date/Time: Tuesday, July 30, 2019 : 10:30 AM to 12:20 PM
• Sponsor: Biopharmaceutical Section
• Author(s): Yaqian Zhu* and Wei-Ting Hwang and Yimei Li
• Companies: University of Pennsylvania and University of Pennsylvania and University of Pennsylvania
• Keywords: Phase I trial design; dose finding; maximum tolerated dose; design parameters

Abstract

Numerous designs have been proposed for phase I clinical trials. Although studies have compared their performances, few have considered the effects of changing design parameters. In this article, we review a few popular designs, including the 3+3, continuous reassessment method (CRM), Bayesian optimal interval (BOIN) design, and Keyboard design, and evaluate how varying the number of dose levels, target toxicity rate, maximum sample size, and cohort size could impact the performances through simulations. Our results suggest that, overall, the 3+3 design performs the worst, and BOIN and Keyboard have comparable performance to CRM. For any design, the performance varies with the choice of parameters. In particular, it improves as sample sizes increase, but the magnitude of benefit varies across scenarios. The impact of cohort size on design performances seems to have no clear direction. Therefore, BOIN and Keyboard designs are generally recommended due to their simplicity and good performance. With regard to choices of sample size and cohort size in designing a trial, it is important to perform simulations for the particular clinical settings to aid decision making.