title: Comparisons of colorectal cancer mortality between screening participants and the general population are strongly biased unless an incidence-based mortality approach is used.
abstract: OBJECTIVE
  A common approach in the evaluation of screening for colorectal cancer (CRC) is comparing observed numbers of CRC deaths in screening participants with expected numbers derived from CRC mortality in the general population. We aimed to illustrate and quantify an often-overlooked bias that may occur in such studies if CRC mortality in the general population is not restricted by the date of diagnosis (whereas screening participants by definition do not have a prior CRC diagnosis).
  
  
  METHODS
  We illustrate and quantify the expected bias using cancer registry data from the United States.
  
  
  RESULTS
  Unless an incidence-based mortality approach is used, expected numbers of CRC deaths in screening cohorts (and hence estimated screening effects) are substantially overestimated. Overestimation of expected CRC deaths is most severe (more than fivefold) during the first year of follow-up and rapidly decreases in the subsequent years. Nevertheless, overestimation of 5- and 10-year cumulative numbers of expected CRC deaths is still as high as 60-70% and 20-30%, respectively. Substantial bias even persists if the initial years of follow-up are excluded from the analyses.
  
  
  CONCLUSIONS
  Careful restriction of expected CRC deaths by an incidence-based mortality approach is indispensable for deriving valid screening effect estimates.
authors.affiliation: Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, 69120 Heidelberg, Germany; German Cancer Consortium (DKTK), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany. Electronic address: h.brenner@dkfz.de.
authors.forename: Hermann
authors.initials: H
authors.lastname: Brenner
authors.affiliation: Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, 69120 Heidelberg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Hoffmeister
authors.affiliation: Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, 69120 Heidelberg, Germany.
authors.forename: Lina
authors.initials: L
authors.lastname: Jansen
mesh_terms: D000368:Aged; D015982:Bias; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000401:mortality* / Q000517:prevention & control; D055088:Early Detection of Cancer / Q000706:statistics & numerical data; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D012042:Registries; D012107:Research Design; D018426:SEER Program; D014481:United States / Q000453:epidemiology
keywords: Bias; Cohort study; Colorectal cancer; Incidence; Mortality; Screening