Bias in case-control studies of screening effectiveness

Screening programs, such as annual mammography, are undertaken to reduce mortality and/or morbidity from chronic diseases such as cancer. Matched case-control studies have been used to assess the effectiveness of screening programs because of their relative simplicity and low cost. In such studies, the exposure history for controls consists of the number of screening examinations received prior to the date of diagnosis of the matched case. The authors know of no methodological evaluations that demonstrate the validity of such case-control studies. To examine the possible existence of bias due to design rules, the authors developed a simple deterministic model, which is used to calculate expected screening and disease patterns in a cohort. Cases and matched controls are selected from the cohort, and their screening histories are used to calculate an odds ratio, as is commonly done in practice. Results utilizing this simple model suggest that systematic inclusion of the examination from which diagnosis is made, which is the approach typically used in practice, leads to a positive bias (odds ratio > 1) in the absence of any real effect. Systematic exclusion of this examination appears to lead to a negative bias (odds ratio < 1). Although this simple approach has several limitations, the results suggest that a commonly used method of conducting case-control studies may yield biased odds ratios. Possible methods to reduce this bias may exist, such as defining exposure intervals differently.