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Age‐Adjusted Exact Trend Tests in the Event of Rare Occurrences
Author(s) -
Mancuso Jessica Y.,
Ahn Hongshik,
Chen James J.,
Mancuso James P.
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.2002.00403.x
Subject(s) - randomization , statistics , statistical hypothesis testing , multivariate statistics , exact test , hypergeometric distribution , event (particle physics) , econometrics , statistical significance , mathematics , monte carlo method , test (biology) , type i and type ii errors , medicine , computer science , randomized controlled trial , paleontology , physics , quantum mechanics , biology
Summary. 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.