title: Efficacy versus effectiveness study design within the European screening trial for prostate cancer: consequences for cancer incidence, overall mortality and cancer-specific mortality.
abstract: OBJECTIVE
  To assess the impact of different study designs on outcome data within the European Randomized Study of Screening for Prostate Cancer (ERSPC).
  
  
  METHODS
  Observed data from the Gothenburg centre (effectiveness trial with upfront randomization before informed consent) and the Rotterdam centre (efficacy trial with randomization after informed consent) were compared with expected data, which were retrieved from national cancer registries and life tables. Endpoints were 11-year cumulative prostate cancer (PC) incidence, overall mortality and PC-specific mortality.
  
  
  RESULTS
  In Gothenburg, the 11-year PC incidence was higher than predicted (5.8%) in both the intervention (12.4%) and control arms (7.3%). The observed overall mortality was higher than predicted (15.9%) in both the intervention (17.8%) and control arms (18.5%). The observed PC-specific mortality in the intervention arm was 0.56% versus 0.83% in the control arm, while the expected mortality was 0.83%. In Rotterdam, the observed PC incidence in the intervention arm (10.4%) was higher than expected (4.4%). The incidence in the control arm was 4.6%. The observed overall mortality was lower than expected: 13.6% in the intervention arm and 14.0% in the control arm versus an expected mortality of 16.1%. The observed PC-specific mortality was lower than expected (0.65%) in both the intervention (0.27%) and control arms (0.41%).
  
  
  CONCLUSIONS
  Our results suggest that an efficacy trial with informed consent prior to randomization may have introduced a 'healthy screenee bias'. Therefore, an effectiveness trial with consent after randomization may more accurately estimate the PC-specific mortality reduction if population-based screening is introduced.
authors.affiliation: Department of Urology, Erasmus MC, University Medical Center, Room NH-227, PO Box 2040, 3000 CA Rotterdam, The Netherlands. y.zhu@erasmusmc.nl
authors.forename: Xiaoye
authors.initials: X
authors.lastname: Zhu
authors.forename: Pim J
authors.initials: PJ
authors.lastname: van Leeuwen
authors.forename: Erik
authors.initials: E
authors.lastname: Holmberg
authors.forename: Meelan
authors.initials: M
authors.lastname: Bul
authors.forename: Sigrid
authors.initials: S
authors.lastname: Carlsson
authors.forename: Fritz H
authors.initials: FH
authors.lastname: Schröder
authors.forename: Monique J
authors.initials: MJ
authors.lastname: Roobol
authors.forename: Jonas
authors.initials: J
authors.lastname: Hugosson
mesh_terms: D000368:Aged; D000465:Algorithms; D002986:Clinical Trials as Topic; D055088:Early Detection of Cancer / Q000379:methods*; D005060:Europe; D005189:False Positive Reactions; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D008297:Male; D008403:Mass Screening / Q000379:methods*; D008875:Middle Aged; D017063:Outcome Assessment, Health Care; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000401:mortality; D011788:Quality of Life; D012042:Registries; D012107:Research Design; D013997:Time Factors