Evaluation of toxicity: statistical considerations

This paper presents some statistical considerations in the evaluation of toxicity in phase III clinical trials in cooperative oncology groups. Analysis is concentrated on the frequency of unacceptable toxicity by treatment period within homogeneous prognostic groups. Relevant toxicity questions are found to be of two types: general and specific. The general questions are common to all trials and either are descriptive or relate to the assessment and etiology of toxicity. The specific questions are built into the design of the study and some are unique to phase III trials. Various aspects of design and analysis are discussed for each type of question, including application of life-table methods for analysis, guidelines for the creation of toxicity indices, and an evaluation of various approaches to answering the fundamental toxicity question in cancer therapy. "Is toxicity really necessary?" The role of toxicity data in final treatment evaluation and the methods for the assessment of late effects of therapy are discussed briefly.