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Growth rate analysis and efficient experimental design for tumor xenograft studies.

Hather G, Liu R, Bandi S, Mettetal J, Manfredi M, Shyu WC, Donelan J, Chakravarty A - Cancer Inform (2014)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Global Statistics, Takeda Pharmaceuticals International Co., Cambridge, MA, USA.

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.

No MeSH data available.


Related in: MedlinePlus

Treatment group (gray lines) and vehicle group (black lines) growth curves for two different studies (panels A and B). The traditional T/C and the rate-based T/C were computed using data up to days 7, 14, or 21.
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f2-cin-suppl.4-2014-065: Treatment group (gray lines) and vehicle group (black lines) growth curves for two different studies (panels A and B). The traditional T/C and the rate-based T/C were computed using data up to days 7, 14, or 21.

Mentions: Figure 2 shows examples of the rate-based and traditional T/C computed for two different studies. The calculations were done using the data up to days 7, 14, or 21. The traditional T/C tends to decrease as the study length increases, since the groups become more separated with time. In contrast, the rate-based T/C is normalized to a fixed day, so it is more stable with respect to study length.


Growth rate analysis and efficient experimental design for tumor xenograft studies.

Hather G, Liu R, Bandi S, Mettetal J, Manfredi M, Shyu WC, Donelan J, Chakravarty A - Cancer Inform (2014)

Treatment group (gray lines) and vehicle group (black lines) growth curves for two different studies (panels A and B). The traditional T/C and the rate-based T/C were computed using data up to days 7, 14, or 21.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4264612&req=5

f2-cin-suppl.4-2014-065: Treatment group (gray lines) and vehicle group (black lines) growth curves for two different studies (panels A and B). The traditional T/C and the rate-based T/C were computed using data up to days 7, 14, or 21.
Mentions: Figure 2 shows examples of the rate-based and traditional T/C computed for two different studies. The calculations were done using the data up to days 7, 14, or 21. The traditional T/C tends to decrease as the study length increases, since the groups become more separated with time. In contrast, the rate-based T/C is normalized to a fixed day, so it is more stable with respect to study length.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Global Statistics, Takeda Pharmaceuticals International Co., Cambridge, MA, USA.

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.

No MeSH data available.


Related in: MedlinePlus