Introduction: Screening programs 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 exams received, occurring before the diagnosis date of the matched case. We know of no methodologic evaluations that demonstrate the validity of such case-control studies.

Objective: To examine the possible existence of bias due to design rules.

Methods: We developed a simple deterministic model to calculate expected screening and disease patterns in a cohort. We select cases and matched controls from the cohort and use screening histories to calculate an odds ratio, as is common in practice.

Results: Systematic inclusion of the exam from which diagnosis is made, which is the approach typically used in practice, leads to a positive bias (OR>1 in the absence of any real effect). Systematic exclusion of this exam appears to lead to a negative bias (OR<1).

Discussion: Although our simple approach had several limitations, the results suggest that a commonly used method of conducting case-control studies may yield biased odds ratios. We speculate about possible ways to reduce the bias, perhaps by defining exposure intervals differently. This paper has implications for case-control methodologies.