嚙齒類動物致癌性試驗(yàn)是新藥研發(fā)中非臨床安全性評價(jià)的重要組成部分。致癌性試驗(yàn)周期較長、數(shù)據(jù)量大,其統(tǒng)計(jì)學(xué)方法選用的合理性、科學(xué)性將可能影響試驗(yàn)結(jié)果的結(jié)論。首先介紹了目前致癌性試驗(yàn)常用的生存分析和腫瘤發(fā)生率統(tǒng)計(jì)方法;其次,匯總了生存分析和腫瘤發(fā)生率統(tǒng)計(jì)方法的選用情況;最后,通過比較申報(bào)方、美國食品藥品監(jiān)督管理局審評方和美國國家毒理學(xué)項(xiàng)目中心在統(tǒng)計(jì)學(xué)方法選用的差異,分析和討論了這些差異的來源和影響,并總結(jié)了致癌性試驗(yàn)統(tǒng)計(jì)分析設(shè)計(jì)思路。希望通過對以上內(nèi)容的匯總和分析,能夠?yàn)樾滤幏桥R床致癌性試驗(yàn)提供參考。

Carcinogenicity studies in rodents are important in nonclinical safety evaluation of new drugs. Carcinogenicity studies have long durations and large amounts of data, the appropriateness and selection scientificity of statistical methods are also likely to affect their study results and conclusions. This review firstly introduces statistical methods of survival analysis and tumor incidence currently used in carcinogenicity studies. Secondly, the selection of statistical methods for survival analysis and tumor incidence is summarized. Finally, by comparing the differences between statistical selecting methods chosen by sponsors, the reviewers of the U.S. Food and Drug Administration(FDA) and the National Toxicology Program(NTP), the sources and implication of these differences are analyzed and discussed. Furthermore, the review summarizes the ideas for designing statistical analysis in carcinogenicity studies. We hope that all the summary and analysis above can provide a reference for designing non-clinical carcinogenicity studies.