Assessing laboratory evidence for neoplastic activity

A variety of statistical issues which arise in the analysis of tumorigenesis assay data are reviewed. Tumor acceleration appeared as a possibility in the Red Dye 40 situation and that phenomenon is discussed. Experimental design considerations covered include sex, cage locations, and whether there is complete randomization, or whether littermates are stratified across doses, or whether, as in multigeneration studies, all littermates are treated alike. Whichever, the statistical analysis should be appropriate. Statistical techniques must take into account the time-to-response aspect in the detection of palpable tumors along with the complication of censored observation due to interim mortality. A logrank technique for accomplishing this must be further adjusted so as to handle tumors detectable only on necropsy. Dosage effects may be sought in a variety of ways, including alternative procedures for identifying progressive dosage effects. Separate analyses may be conducted for separate tumor sites or types, introducing a multiple-testing aspect. Because of the sparseness of data for many individual tumor sites, the usual multiple-testing procedures have to be modified. Statistical analysis, however, is only a guide to the careful interpretation of results, and the need to take action as a result of that interpretation remains.