Measuring screening intensity in case-control studies of the efficacy of mammography

Of great interest in studies of screening for breast cancer is the relative efficacy of different screening frequencies (intensities). Prior work has suggested that estimates of the association between screening intensity and outcome in case-control studies would not produce valid results and that only binary indicators (no screens vs. one or more) of exposure can be used. Using case-control studies drawn from simulated cohorts of 30,000-40,000 women, the authors found that biases demonstrated in prior studies can be explained by 1) misclassification of true exposure groups by observed screening history, and 2) differential exposure misclassification of cases and controls. Binary as well as ordered categorical and interval measures can be biased unless they account for misclassification. By combining measurements of screening history from multiple periods of observation of varying lengths and using repeated-measures logistic regression models, the effect of screening intensity can be estimated in the presence of misclassification. Assessing the effect of screening intensity in case-control studies of mammography is possible if principles and methods for misclassification and measurement error guide the analysis.