title: Growth rate analysis and efficient experimental design for tumor xenograft studies.
abstract: Human tumor xenograft studies are the primary means to evaluate the biological activity of anticancer agents in late-stage preclinical drug discovery. The variability in the growth rate of human tumors established in mice and the small sample sizes make rigorous statistical analysis critical. The most commonly used summary of antitumor activity for these studies is the T/C ratio. However, alternative methods based on growth rate modeling can be used. Here, we describe a summary metric called the rate-based T/C, derived by fitting each animal's tumor growth to a simple exponential model. The rate-based T/C uses all of the data, in contrast with the traditional T/C, which only uses a single measurement. We compare the rate-based T/C with the traditional T/C and assess their performance through a bootstrap analysis of 219 tumor xenograft studies. We find that the rate-based T/C requires fewer animals to achieve the same power as the traditional T/C. We also compare 14-day studies with 21-day studies and find that 14-day studies are more cost efficient. Finally, we perform a power analysis to determine an appropriate sample size.
authors.affiliation: Department of Global Statistics, Takeda Pharmaceuticals International Co., Cambridge, MA, USA.
authors.forename: Gregory
authors.initials: G
authors.lastname: Hather
authors.affiliation: Department of Global Statistics, Takeda Pharmaceuticals International Co., Cambridge, MA, USA.
authors.forename: Ray
authors.initials: R
authors.lastname: Liu
authors.affiliation: Department of Research and Development Systems, Takeda Pharmaceuticals International Co., Cambridge, MA, USA.
authors.forename: Syamala
authors.initials: S
authors.lastname: Bandi
authors.affiliation: Department of DMPK, Takeda Pharmaceuticals International Co., Cambridge, MA, USA.
authors.forename: Jerome
authors.initials: J
authors.lastname: Mettetal
authors.affiliation: Department of Cancer Pharmacology, Takeda Pharmaceuticals International Co., Cambridge, MA, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Manfredi
authors.affiliation: Department of DMPK, Takeda Pharmaceuticals International Co., Cambridge, MA, USA.
authors.forename: Wen-Chyi
authors.initials: WC
authors.lastname: Shyu
authors.affiliation: Department of Cancer Pharmacology, Takeda Pharmaceuticals International Co., Cambridge, MA, USA.
authors.forename: Jill
authors.initials: J
authors.lastname: Donelan
authors.affiliation: Department of DMPK, Takeda Pharmaceuticals International Co., Cambridge, MA, USA.
authors.forename: Arijit
authors.initials: A
authors.lastname: Chakravarty
keywords: C; T; design; xenograft