Clinical trials of cancer prevention agents: True versus observed prevention effect

Important considerations in the design and conduct of cancer and other long‐term prevention trials include intervention compliance and frequency of events during follow‐up. Each of these can produce observed proportions of events for control and test groups that differ less than anticipated. Methods and approximate ‘rules of thumb’ are presented that relate power and sample size to the impact of compliance and latent intervention effect. Results are based upon specific modifications in well‐known formulae that reflect long‐term prevention trials. Data from an ongoing cancer prevention trial illustrate the methods. Compliance was estimated accurately using the low cost capsule count method.