Statistical Issues in Review of Carcinogenicity Using Transgenic Mice

• Activity Number: 123
• Type: Luncheons
• Date/Time: Monday, August 9, 2004 : 12:30 PM to 1:50 PM
• Sponsor: Biopharmaceutical Section
• Author(s): Karl K. Lin*+
• Companies: U.S. Food and Drug Administration
• Keywords: ICH Guideline S1B ; group size ; latency and multiplicity effects

Abstract

The high cost and long time needed to conduct a standard long-term in-vivo carcinogenicity study, and the increased insight into the mechanisms of carcinogenicity due to the advances made in molecular biology have led to the use of transgenic mice as alternative in-vivo approach to the assessment of carcinogenicity. People also feel that genetically altered mice can be better animal surrogates for human cancer because they carry some specifically activated oncogenes that are known to function in both human and animal cancers. The ICH Guideline S1B allows sponsors to conduct one long-term rodent carcinogenicity study together with a short-term test using transgenic rodents. More and more drug companies are following the ICH guideline and conducting carcinogenicity studies using transgenic mice to replace the traditional two-year mouse studies. There are statistical issues such as group size, methods of test of carcinogenicity of new drugs, adjustment for multiplicity etc., in this new preclinical field of drug safety assessment. A recent development in this area of statistical review of carcinogenicity studies within CDER/FDA will be discussed.