A novel form of ascertainment bias in case-control studies of cancer screening.

In case-control studies of cancer screening, some have generally admonished investigators against case definitions based on diagnosis dates because of lead-time bias. However, perhaps partly due to vagueness, the admonitions have been frequently ignored. A recurrence-time model simulates case ascertainment when diagnosis must occur within a specific calendar period. The model depends on screening test sensitivity and rate, age-specific preclinical incidence rates, and preclinical duration time and survival time distributions. For one study of sigmoidoscopic screening for colorectal cancer, when the true odds ratio is 1, its estimate is 0.50 to 0.75 under plausible assumptions. This bias can affect any observational study wherein case definition depends on diagnosis times (e.g., health-plan enrollment data). To avoid bias in observational investigations of cancer screening wherein the case definition depends on the diagnosis date, one must ensure that both screening and preclinical incidence do not occur before the case definition period.