The Center for Veterinary Medicine requires a margin of safety study in the target animal. Typically, healthy animals are treated with the proposed, 3 times the proposed, and 5 times the proposed dosage (1X, 3X, and 5X doses). Additionally, animals are exposed to the treatment for a prolonged period, e.g., a daily dose for 6 months if the drug is administered daily. The intention is to exacerbate and exaggerate possible toxic effects both among doses and across time. Selected blood chemistry and physical data are collected periodically throughout the study and, at termination, animals are necropsied with organs and tissues examined for abnormalities. Generally, a minimum of 4 animals per dose per sex are used in the study. Even though the study design may be evident, because a large number of variables are measured repeatedly for a few animals there are many analysis questions. If weight blocks are effective for only a small number of variables, should they be used? Should the data be used to determine a transformation strategy? And, even more questions will be posed by Dr. Luempert.