title: Matching of controls may lead to biased estimates of specificity in the evaluation of cancer screening tests.
abstract: OBJECTIVE
  In the evaluation of cancer screening tests, cancer-free controls are often matched to cancer cases on factors such as sex and age. We assessed the potential merits and pitfalls of such matching using an example from colorectal cancer (CRC) screening.
  
  
  METHODS
  We compared sex and age distribution of CRC cases and cancer-free people undergoing screening colonoscopy in Germany in 2006 and 2007. We assessed specificity by sex and age of two immunochemical fecal occult blood tests (iFOBTs) in a study among screening colonoscopy participants conducted in the same years, and we assessed the expected impact of matching by sex and age on the validity of specificity estimates at various cut points.
  
  
  RESULTS
  In the screening colonoscopy program, the proportion of men and mean age were 59.6% and 68.6 years among 10,324 CRC patients compared with 45.6% and 64.7 years, respectively, among 997,490 cancer-free participants. The specificity of the iFOBTs was higher among women than among men and decreased with age. Matching of cancer-free controls by age and sex would have led to the underestimation of specificity at all cut points assessed.
  
  
  CONCLUSIONS
  In the evaluation of cancer screening tests, matching of controls may lead to biased estimates of specificity.
authors.affiliation: Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, INF 581, D-69120 Heidelberg, Germany. h.brenner@dkfz.de
authors.forename: Hermann
authors.initials: H
authors.lastname: Brenner
authors.forename: Lutz
authors.initials: L
authors.lastname: Altenhofen
authors.forename: Sha
authors.initials: S
authors.lastname: Tao
mesh_terms: D017677:Age Distribution; D000368:Aged; D000369:Aged, 80 and over; D015982:Bias; D016022:Case-Control Studies; D003113:Colonoscopy / Q000379:methods / Q000706:statistics & numerical data*; D015179:Colorectal Neoplasms / Q000453:epidemiology*; D016208:Databases, Factual; D055088:Early Detection of Cancer / Q000379:methods / Q000706:statistics & numerical data*; D005260:Female; D005858:Germany / Q000453:epidemiology; D006801:Humans; D008297:Male; D008403:Mass Screening / Q000379:methods / Q000706:statistics & numerical data; D008875:Middle Aged; D009780:Occult Blood; D011237:Predictive Value of Tests; D012016:Reference Values; D012307:Risk Factors; D012680:Sensitivity and Specificity; D017678:Sex Distribution