The Swedish Two-County Trial of mammographic screening: cluster randomisation and end point evaluation.

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. PATIENTS AND 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.

[1]  D. Haggstrom,et al.  All-cause mortality in randomized trials of cancer screening. , 2002, Journal of the National Cancer Institute.

[2]  S. Duffy,et al.  Interpretation of the breast screening trials: a commentary on the recent paper by Gøtzsche and Olsen. , 2001, Breast.

[3]  S. Wall,et al.  Breast cancer screening with mammography: overview of Swedish randomised trials , 1993, The Lancet.

[4]  L. Tabár,et al.  Efficacy of breast cancer screening by age. New results swedish two‐county trial , 1995, Cancer.

[5]  Ingvar Andersson,et al.  Long-term effects of mammography screening: updated overview of the Swedish randomised trials , 2002, The Lancet.

[6]  Peter C Gøtzsche,et al.  Is screening for breast cancer with mammography justifiable? , 2000, The Lancet.

[7]  L. Tabár,et al.  The Mammographic Screening Trials: Commentary on the Recent Work by Olsen and Gøtzsche , 2002, CA: a cancer journal for clinicians.

[8]  L. Tabár,et al.  The Swedish Two-County Trial twenty years later. Updated mortality results and new insights from long-term follow-up. , 2000, Radiologic clinics of North America.

[9]  L. Tabár,et al.  Update of the Swedish two-county program of mammographic screening for breast cancer. , 1992, Radiologic clinics of North America.

[10]  L. Tabár,et al.  All-cause mortality among breast cancer patients in a screening trial: support for breast cancer mortality as an end point , 2002, Journal of medical screening.

[11]  L. Tabár,et al.  The Swedish two county trial of mammographic screening for breast cancer: recent results and calculation of benefit. , 1989, Journal of epidemiology and community health.

[12]  L. Tabár,et al.  REDUCTION IN MORTALITY FROM BREAST CANCER AFTER MASS SCREENING WITH MAMMOGRAPHY Randomised Trial from the Breast Cancer Screening Working Group of the Swedish National Board of Health and Welfare , 1985, The Lancet.

[13]  L. Tabár,et al.  Some random-effects models for the analysis of matched-cluster randomised trials: application to the Swedish two-county trial of breast-cancer screening. , 2000, Journal of epidemiology and biostatistics.

[14]  Peter C Gøtzsche,et al.  Cochrane review on screening for breast cancer with mammography , 2001, The Lancet.

[15]  Ingvar Andersson,et al.  The Swedish Randomised Mammography Screening Trials: Analysis of Their Effect on the Breast Cancer Related Excess Mortality , 1996, Journal of medical screening.