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Small‐Sample Inference for Incomplete Longitudinal Data with Truncation and Censoring in Tumor Xenograft Models
Author(s) -
Tan Ming,
Fang HongBin,
Tian GuoLiang,
Houghton Peter J.
Publication year - 2002
Publication title -
biometrics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.298
H-Index - 130
eISSN - 1541-0420
pISSN - 0006-341X
DOI - 10.1111/j.0006-341x.2002.00612.x
Subject(s) - censoring (clinical trials) , bayesian probability , inference , temozolomide , medicine , truncation (statistics) , irinotecan , statistics , oncology , mathematics , computer science , cancer , chemotherapy , artificial intelligence , colorectal cancer
Summary. In cancer drug development, demonstrating activity in xenograft models, where mice are grafted with human cancer cells, is an important step in bringing a promising compound to humans. A key outcome variable is the tumor volume measured in a given period of time for groups of mice given different doses of a single or combination anticancer regimen. However, a mouse may die before the end of a study or may be sacrificed when its tumor volume quadruples, and its tumor may be suppressed for some time and then grow back. Thus, incomplete repeated measurements arise. The incompleteness or missingness is also caused by drastic tumor shrinkage (<0.01 cm 3 ) or random truncation. Because of the small sample sizes in these models, asymptotic inferences are usually not appropriate. We propose two parametric test procedures based on the EM algorithm and the Bayesian method to compare treatment effects among different groups while accounting for informative censoring. A real xenograft study on a new antitumor agent, temozolomide, combined with irinotecan is analyzed using the proposed methods.