The impact of screening and eliminating preexisting cases on sample size requirements for cancer prevention trials

A cancer prevention trial may seek to test the effectiveness of an intervention in disease-free individuals, but the study population may include subjects with preexisting (but undiagnosed) disease. If sample size calculations assume all events are incident cases, the study will have less power than anticipated because preexisting cases cannot be expected to benefit from the intervention. Sample size can be increased appropriately by using revised event rates that include both preexisting and incident cases. These rates incorporate screening parameters and are applicable to the situation where subjects are screened before randomization. A simple cost model is given that permits examination of the tradeoffs involved in prescreening subjects versus increasing total sample size.