Effect of comparison group on inference about effect modification by demographic factors in cohort risk regression

Cologne JB, Izumi S, Shimizu Y, Preston DL
Jpn J Biomet 23(2):49-66, 2002

Summary

Epidemiologic cohort studies frequently make use of a comparison group to infer what background rate of death or disease might have occurred in the exposed cohort in the absence of exposure. Unlike cohort analyses utilizing the standardized risk ratio, regression analyses of risk can often be performed without the need for a comparison group, avoiding possible bias in the risk estimate. Demographic factors related to the background rate may also modify the risk (effect modification). Including the comparison group can improve the precision of effect-modification parameter estimates, but if there is inadequate adjustment for heterogeneity between exposed and comparison groups in the background effects of these factors, the effect-modification parameter estimates can be biased. We studied this bias and the precision of effect-modification parameter estimates using theory and simulation. The problem is illustrated using data from studies of radiation exposure of atomic-bomb survivors that include a comparison group selected from distal geographic areas having different gender-specific rates of death. We conclude that, for studies of effect modification in cohorts covering a wide range of exposures including doses close to zero, there may be no advantage to including a comparison group, as long as internal standardization is feasible.