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The Biostatistics Journal Club meets on a monthly basis. Send a message to Prof. Keith Williams if you would like to be on the mailing list.

 

The

Biostatistics Journal Club

will meet on

Tuesday, November 3, 2009

COPH 2280 12:00p.m. – 1:00p.m.

The topic of discussion will be

presented by

 

 

Ralph l. kodelL, PH.D.

Professor, Department of Biostatistics

University of Arkansas for Medical Sciences

 

Should we conduct pre-clinical assessments of tumorigenicity
with the Peto or Poly-k test?
 

A comparison of underlying assumptions,
statistical characteristics, and regulatory perspectives.

 

Abstract 

 

The 1980 IARC guidance document on testing for tumorigenicity in long-term animal experiments recommended a statistical test for dose-related trend that stratifies animals dying with tumors of a specific type into fatal and incidental groupings, depending on whether or not, in the judgment of a pathologist, the tumor was the cause of death. The recommended test has become known as Peto’s cause-of-death (COD) test, or simply, the Peto test, in recognition of Richard Peto’s 1974 paper and his lead authorship of the IARC document. The Peto test has been used extensively in the pharmaceutical industry for the evaluation of occult tumors, especially in the United States and Europe. After being favored unofficially by the US Food and Drug Administration’s Center for Drug Evaluation and Research (FDA/CDER) for many years, the Peto test was officially recommended by FDA/CDER in its 2001 draft guidance for industry. In 1988 John Bailer and Chris Portier developed the Poly-k test for tumorigenicity which does not require a COD determination. Instead it relies on the assumption that the distribution of time to tumor onset can be expressed as a function of the kth power of time. Animals dying without tumors contribute to the test statistic according to weights determined by this kth power. Given that k is almost never known, Bailer and Portier recommended using k=3 based on an empirical study. The Poly-3 test is the version most often used and it has been gaining popularity over the years. The 2001 FDA/CDER draft guidance document recommends the Poly-3 test when COD information is unavailable for implementing the Peto test. The US National Toxicology Program (NTP) has adopted the Poly-3 test as the official method for evaluating its animal bioassays for carcinogenesis. In this presentation, the underlying assumptions and structures of the Peto and Poly-k tests are outlined. A limited comparison of their statistical performance in terms of size and power is presented, along with a view of their regulatory standing. Some modifications and generalizations of both tests are mentioned.
 

 

 


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Last updated: 10/29/2009