What Is a Screening Test?: Misclassification Bias in Observational Studies of Screening for Cancer

OBJECTIVE: To demonstrate the importance of accurately identifying clinical distinctions of subjects in observational studies of screening. DESIGN: Simulated case-control studies. SETTING: The West Haven Veterans Affairs Medical Center. PATIENTS: Fifty-two men diagnosed with prostate cancer in 1988 or 1989 had 252 digital rectal examinations (DREs) in the preceding 5 years. A classification scheme used patient symptoms and the results of prior DREs to assign the last DRE before the diagnosis of cancer to one of the following categories: definite screening, likely screening, probable screening, not screening, or other and unknown. Sixty-five percent of the DREs were classified as definite or likely screening, and another 15% were classified as probable screening. MAIN RESULTS: Changing the definition of a screening DRE from one including to one excluding probable DREs lowered the frequency of screening in case subjects more than it did in case controls, and thus lowered the odds ratio (OR), making screening appear to be more protective. Even when DRE was not protective, the ORs for the effectiveness of screening with the more restrictive definition ranged from 0.21 to 0.83 in 36 simulated case-control studies that differed according to the frequency of screening, the prevalence of cancer in case controls, and the extent of misclassification error. CONCLUSIONS: If clinical distinctions in the performance of screening tests are not classified appropriately, observational studies will misrepresent the proportion of subjects exposed to screening interventions and produce biased results