Some statistical considerations for design of cancer prevention trials

Abstract

Carcinogenesis is believed to occur in at least two stages, initiation and promotion, followed by a preneoplastic lesion which develops into cancer. Cancer prevention trials can be classified as primary if the intervention precedes initiation, secondary if it occurs during promotion, and tertiary if it is applied to a preneoplastic lesion. Tertiary prevention trials resemble treatment trials, but primary and secondary prevention trials may be very different in size, duration, and cost. After reviewing some basic questions which must be addressed in designing any cancer prevention trial, some special design considerations appropriate for primary and secondary prevention trials are discussed. These include the use of factorial designs, group or cluster randomization, special sample size calculations needed for large-scale trials of long duration with cancer incidence as the endpoint, and the idea of the case-cohort approach for monitoring and for subsequent exploratory analysis of trial data.