Age-adjusted exact trend tests in the event of rare occurrences |
| |
Authors: | Mancuso Jessica Y Ahn Hongshik Chen James J Mancuso James P |
| |
Institution: | Pfizer Global Research and Development, Groton, Connecticut 06340, USA. jessica_y_mancuso@groton.pfizer.com |
| |
Abstract: | Preclinical animal carcinogenicity studies are usually concerned with testing the statistical significance of a dose-response relationship. When the response consists of a rare event such as the development of a certain type of tumor, exact statistical methods are often employed. The exact randomization trend test based on the multivariate hypergeometric distribution is less powerful in the presence of treatment-related risks other than the specified response. Particularly, the loss of power becomes more pronounced when competing risks cause progressively higher mortality rates with increasing dose, which is usual in practice. An age-adjusted form of the randomization test is proposed to adjust for this effect. Permutational distribution for Peto's cause-of-death (COD) test is also explored and compared with its asymptotic counterpart by simulation. The use of COD information has been a controversial issue due to the subjectivity in the pathologists' determinations as well as for economic reasons. The proposed age-adjusted exact test does not require COD, and it is shown to compare favorably to the COD tests via an extensive Monte Carlo simulation. Applications of the methods to two real data sets are included. |
| |
Keywords: | Dose–response Exact poly-3 test Exact randomization test Permutation Peto cause-of-death test Survival adjustment |
本文献已被 PubMed 等数据库收录! |
|