Exposure stratified case-cohort designs (original) (raw)

A variant of the case-cohort design is proposed for the situation in which a correlate of the exposure (or prognostic factor) of interest is available for all cohort members, and exposure information is to be collected for a case-cohort sample. The cohort is stratified according to the correlate, and the subcohort is selected by stratified random sampling. A number of possible methods for the analysis of such exposure stratified case-cohort samples are presented and some of their statistical properties developed. The bias and efficiency of the methods are compared to each other, and to randomly sampled case-cohort studies, in a limited computer simulation study. We found that all of the proposed analysis methods performed reasonably well and were more efficient than a randomly sampled case-cohort sample. We conclude that these methods are well suited for the "clinical trials setting" in which subjects enter the study at time zero (at diagnosis or treatment) and a correlate of an expensive prognostic factor is collected for all study subjects at the time of entry to the study. In such studies, a correlate stratified subcohort can be much more cost-efficient for investigation of the expensive prognostic factor than a randomly sampled subcohort.