title: Estimating bias in causes of death ascertainment in the Finnish Randomized Study of Screening for Prostate Cancer.
abstract: BACKGROUND
  Precise cause of death (CoD) ascertainment is crucial in any cancer screening trial to avoid bias from misclassification due to excessive recording of diagnosed cancer as a CoD in death certificates instead of non-cancer disease that actually caused death. We estimated whether there was bias in CoD determination between screening (SA) and control arms (CA) in a population-based prostate cancer (PCa) screening trial.
  
  
  METHODS
  Our trial is the largest component of the European Randomized Study of Screening for Prostate Cancer with more than 80,000 men. Randomly selected deaths in men with PCa (N=442/2568 cases, 17.2%) were reviewed by an independent CoD committee. Median follow-up was 16.8 years in both arms.
  
  
  RESULTS
  Overdiagnosis of PCa was present in the SA as the risk ratio for PCa incidence was 1.19 (95% confidence interval (CI) 1.14-1.24). The hazard ratio (HR) for PCa mortality was 0.94 (95%CI 0.82-1.08) in favor of the SA. Agreement with official CoD registry was 94.6% (κ=0.88) in the SA and 95.4% (κ=0.91) in the CA. Altogether 14 PCa deaths were estimated as false-positive in both arms and exclusion of these resulted in HR 0.92 (95% CI 0.80-1.06).
  
  
  CONCLUSIONS
  A small differential misclassification bias in ascertainment of CoD was present, most likely due to attribution bias (overdiagnosis in the SA). Maximum precision in CoD ascertainment can only be achieved with independent review of all deaths in the diseased population. However, this is cumbersome and expensive and may provide little benefit compared to random sampling.
authors.affiliation: Dept. of Urology, University of Helsinki and Helsinki University Hospital, FI-00029 Helsinki, Finland. Electronic address: tuomas.kilpelainen@hus.fi.
authors.forename: Tuomas P
authors.initials: TP
authors.lastname: Kilpeläinen
authors.affiliation: Department of Surgery, Seinäjoki Central Hospital, FI-60220 Seinäjoki, Finland.
authors.forename: Tuukka
authors.initials: T
authors.lastname: Mäkinen
authors.affiliation: Department of Forensic Medicine, School of Medicine, University of Tampere and Fimlab Laboratories, Tampere University Hospital Region, Finland.
authors.forename: Pekka J
authors.initials: PJ
authors.lastname: Karhunen
authors.affiliation: Dept. of Urology, University of Helsinki and Helsinki University Hospital, FI-00029 Helsinki, Finland.
authors.forename: Jussi
authors.initials: J
authors.lastname: Aro
authors.affiliation: Department of Internal Medicine, Tampere University Hospital, FI-33521 Tampere, Finland.
authors.forename: Jorma
authors.initials: J
authors.lastname: Lahtela
authors.affiliation: Dept. of Urology, University of Helsinki and Helsinki University Hospital, FI-00029 Helsinki, Finland.
authors.forename: Kimmo
authors.initials: K
authors.lastname: Taari
authors.affiliation: Finnish Cancer Registry, FI-00130 Helsinki, Finland.
authors.forename: Kirsi
authors.initials: K
authors.lastname: Talala
authors.affiliation: Dept. of Urology, University of Tampere and Tampere University Hospital, FI-33521 Tampere, Finland.
authors.forename: Teuvo L J
authors.initials: TL
authors.lastname: Tammela
authors.affiliation: School of Health Sciences, University of Tampere, FI-33014 Tampere, Finland.
authors.forename: Anssi
authors.initials: A
authors.lastname: Auvinen
mesh_terms: D000368:Aged; D015982:Bias; D002423:Cause of Death; D055088:Early Detection of Cancer; D005387:Finland / Q000453:epidemiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000453:epidemiology* / Q000401:mortality
keywords: Cause of death; Mass screening; Mortality; Prostate-specific antigen; Prostatic neoplasms; Randomized controlled trials