Efficient Design and Analysis for Tumor Xenograft Efficacy Studies

• Activity Number: 343
• Type: Topic Contributed
• Date/Time: Tuesday, August 6, 2013 : 10:30 AM to 12:20 PM
• Sponsor: International Chinese Statistical Association
• Author(s): Gregory Hather*+ and Ray Liu and Syamala Bandi and Wen Chyi Shyu and Mark Manfredi and Arijit Chakravarty and Jill Donelan
• Companies: Millennium: The Takeda Oncology Company and Millennium : The Takeda Oncology Company and Millennium: The Takeda Oncology Company and Millennium: The Takeda Oncology Company and Millennium: The Takeda Oncology Company and Millennium: The Takeda Oncology Company and Millennium: The Takeda Oncology Company
• Keywords: xenograft ; experimental design ; animal studies ; tumor

Abstract

In vivo efficacy studies are a critical step in preclinical development of cancer drugs. Here, we consider efficacy studies where a human cancer cell line has been implanted in mice. By measuring the tumor volumes over time, scientists can detect differences across treatment groups. However, these so called tumor xenograft studies are labor intensive and can require large numbers of mice. Thus, efficient design and analysis of such experiments is important. In this presentation, we examine a large database of past xenograft studies to answer the following questions: How many mice are needed? How many days should the experiments run for? How should the data be analyzed? Our analysis, based on cost modeling and bootstrap estimation, yielded actionable recommendations for future experiments. We found that the traditional measure of efficacy, T/C, was less efficient than a measure derived from an exponential growth model. We also found that reducing the study length to 14 days and increasing the number of mice resulted in increased power with the same cost. Our power calculations also provided guidance for sample size selection.