title: Impact of cause of death adjudication on the results of the European prostate cancer screening trial.
abstract: The European Randomised Study of Prostate Cancer Screening has shown a 21% relative reduction in prostate cancer mortality at 13 years. The causes of death can be misattributed, particularly in elderly men with multiple comorbidities, and therefore accurate assessment of the underlying cause of death is crucial for valid results. To address potential unreliability of end-point assessment, and its possible impact on mortality results, we analysed the study outcome adjudication data in six countries.
  
  
  
  Latent class statistical models were formulated to compare the accuracy of individual adjudicators, and to assess whether accuracy differed between the trial arms. We used the model to assess whether correcting for adjudication inaccuracies might modify the study results.
  
  
  
  There was some heterogeneity in adjudication accuracy of causes of death, but no consistent differential accuracy by trial arm. Correcting the estimated screening effect for misclassification did not alter the estimated mortality effect of screening.
  
  
  
  Our findings were consistent with earlier reports on the European screening trial. Observer variation, while demonstrably present, is unlikely to have materially biased the main study results. A bias in assigning causes of death that might have explained the mortality reduction by screening can be effectively ruled out.
authors.affiliation: Department of Clinical Epidemiology and Biostatistics, Faculty of Health Sciences, McMaster University, CRL 233, 1280 Main Street, Hamilton, Ontario, Canada L8S 4K1.
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Walter
authors.affiliation: Department of Public Health, Erasmus University Medical Center, Postbus 2040, 3000 CA Rotterdam, The Netherlands.
authors.forename: Harry J
authors.initials: HJ
authors.lastname: de Koning
authors.affiliation: Department of Urology, Sahlgrenska universitetssjukhuset, Bruna stråket 11b v 2 su/sahlgrenska, 41345 Göteborg, Sweden.
authors.forename: Jonas
authors.initials: J
authors.lastname: Hugosson
authors.affiliation: Finnish Cancer Registry, Institute for Statistical and Epidemiological Cancer Research, Unioninkatu 22, FI-00130 Helsinki, Finland.
authors.forename: Kirsi
authors.initials: K
authors.lastname: Talala
authors.affiliation: Department of Public Health, Erasmus University Medical Center, Postbus 2040, 3000 CA Rotterdam, The Netherlands.
authors.forename: Monique J
authors.initials: MJ
authors.lastname: Roobol
authors.affiliation: Department of Urology, Sahlgrenska universitetssjukhuset, Bruna stråket 11b v 2 su/sahlgrenska, 41345 Göteborg, Sweden.|Department of Surgery (Urology Service), Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA.
authors.forename: Sigrid
authors.initials: S
authors.lastname: Carlsson
authors.affiliation: ISPO-Cancer Research and Prevention Institute, Clinical and Descriptive Epidemiology Unit, Via delle Oblate 2, 50141 Florence, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Zappa
authors.affiliation: Provinciaal Instituut Voor Hygiëne (Labo's), Kronenburgstraat 45, 2000 Antwerpen, Belgium.
authors.forename: Vera
authors.initials: V
authors.lastname: Nelen
authors.affiliation: Department of Urology, Kantonsspital Aarau, Aarau, Switzerland.|Department of Urology, Academic Hospital Braunschweig, Braunschweig, Germany.
authors.forename: Maciej
authors.initials: M
authors.lastname: Kwiatkowski
authors.affiliation: Department of Urology, Hospital Universitario de Fuenlabrada, Camino del Molino 2, 28942 FUENLABRADA (Madrid), Spain.
authors.forename: Álvaro
authors.initials: Á
authors.lastname: Páez
authors.affiliation: Wolfson Institute, St Mary University, Charterhouse Square, London EC1M 6BQ, UK.
authors.forename: Sue
authors.initials: S
authors.lastname: Moss
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; D001530:Belgium / Q000453:epidemiology; D002423:Cause of Death; D003644:Death Certificates; D055088:Early Detection of Cancer / Q000706:statistics & numerical data*; D005060:Europe / Q000453:epidemiology; D005387:Finland / Q000453:epidemiology; D006801:Humans; D007558:Italy / Q000453:epidemiology; D008297:Male; D008403:Mass Screening / Q000706:statistics & numerical data*; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000401:mortality*; D012042:Registries / Q000592:standards; D012107:Research Design / Q000706:statistics & numerical data; D013223:Statistics as Topic; D013548:Sweden / Q000453:epidemiology; D013557:Switzerland / Q000453:epidemiology