title: The Swedish Two-County Trial of mammographic screening: cluster randomisation and end point evaluation.
abstract: BACKGROUND
  The Swedish Two-County Trial has been criticised on the grounds of the cluster randomisation and alleged bias in classification of cause of death.
  
  
  METHODS
  In the Two-County Trial, 77 080 women were randomised to regular invitation to screening (active study population, ASP) and 55 985 to no invitation (passive study population, PSP), in 45 geographical clusters. After approximately 7 years, the PSP was invited to screening and the trial closed. We analysed data using hierarchical statistical models to take account of cluster randomisation, and performed a conservative analysis assuming a systematic difference between ASP and PSP in baseline breast cancer mortality in one of the counties. We also analysed deaths from causes other than breast cancer and from all causes among breast cancer cases diagnosed in the ASP and PSP.
  
  
  RESULTS
  Taking account of the cluster randomisation there was a significant 30% reduction in breast cancer mortality in the ASP. Conservatively, assuming a systematic difference between ASP and PSP clusters in baseline breast cancer mortality, there was a significant 27% reduction in mortality in the ASP. Ignoring classification of cause of death, there was a significant 13% reduction in all-cause mortality in breast cancer cases in the ASP.
  
  
  CONCLUSIONS
  Breast cancer mortality is a valid end point and mammographic screening does indeed reduce mortality from breast cancer. The criticisms of the Swedish Two-County Trial are unfounded.
authors.affiliation: Queen Mary University of London, London, UK. stephen.duffy@cancer.org.uk
authors.forename: S W
authors.initials: SW
authors.lastname: Duffy
authors.forename: L
authors.initials: L
authors.lastname: Tabar
authors.forename: B
authors.initials: B
authors.lastname: Vitak
authors.forename: M F
authors.initials: MF
authors.lastname: Yen
authors.forename: J
authors.initials: J
authors.lastname: Warwick
authors.forename: R A
authors.initials: RA
authors.lastname: Smith
authors.forename: H H
authors.initials: HH
authors.lastname: Chen
mesh_terms: D000328:Adult; D000368:Aged; D001294:Attitude to Health; D001943:Breast Neoplasms / Q000401:mortality* / Q000517:prevention & control*; D016000:Cluster Analysis; D005260:Female; D006801:Humans; D008327:Mammography / Q000379:methods*; D008403:Mass Screening / Q000379:methods*; D008875:Middle Aged; D010358:Patient Participation; D015995:Prevalence; D012016:Reference Values; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D016019:Survival Analysis; D013548:Sweden / Q000453:epidemiology