Issues in experimental design and endpoint analysis in the study of experimental cytotoxic agents in vivo in breast cancer and other models.

Considerable effort has been placed into the identification of new antineoplastic agents to treat breast cancer and other malignant diseases. The basic approaches, in terms of model selection, endpoints, and data analysis, have changed in the previous few decades. This article deals with many of the issues associated with designing in vivo studies to investigate the activity of experimental and established compounds and their potential interactions. Endpoints for both in situ and excision assays are described, including approaches for determining cell kill, tumor growth delay, survival, and other estimates of activity. Suggestions for approaches that may limit the number of animals also are included, as are possible alternatives for death as an experimental endpoint. Other concerns, such routes for drug administration, drug dosage, and preliminary assessments of toxicity also are addressed. Statistical considerations are only briefly discussed, since these are addressed in detail in the accompanying article by Hanfelt (Hanfelt JJ, Breast Cancer Res Treat 46:279-302, 1997). The approaches suggested within this article are presented to draw attention to many of the key issues in experimental design and are not intended to exclude other approaches.