title: A Monte Carlo analysis of breast screening randomized trials.
abstract: OBJECTIVE
  To analyze breast screening randomized trials with a Monte Carlo simulation tool.
  
  
  METHODS
  A simulation tool previously developed to simulate breast screening programmes was adapted for that purpose. The history of women participating in the trials was simulated, including a model for survival after local treatment of invasive cancers. Distributions of time gained due to screening detection against symptomatic detection and the overall screening sensitivity were used as inputs. Several randomized controlled trials were simulated. Except for the age range of women involved, all simulations used the same population characteristics and this permitted to analyze their external validity. The relative risks obtained were compared to those quoted for the trials, whose internal validity was addressed by further investigating the reasons of the disagreements observed.
  
  
  RESULTS
  The Monte Carlo simulations produce results that are in good agreement with most of the randomized trials analyzed, thus indicating their methodological quality and external validity. A reduction of the breast cancer mortality around 20% appears to be a reasonable value according to the results of the trials that are methodologically correct. Discrepancies observed with Canada I and II trials may be attributed to a low mammography quality and some methodological problems. Kopparberg trial appears to show a low methodological quality.
  
  
  CONCLUSIONS
  Monte Carlo simulations are a powerful tool to investigate breast screening controlled randomized trials, helping to establish those whose results are reliable enough to be extrapolated to other populations and to design the trial strategies and, eventually, adapting them during their development.
authors.affiliation: Servicio de Física y Protección Radiológica, Hospital Universitario Reina Sofía, E-14004 Córdoba, Spain.
authors.forename: Luis I
authors.initials: LI
authors.lastname: Zamora
authors.affiliation: Servicio de Radiofísica y Protección Radiológica, Hospital Universitario San Cecilio, E-18012 Granada, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Forastero
authors.affiliation: Servicio de Radiofísica y Protección Radiológica, Hospital Universitario San Cecilio, E-18012 Granada, Spain.
authors.forename: Damián
authors.initials: D
authors.lastname: Guirado
authors.affiliation: Departamento de Física Atómica, Molecular y Nuclear, Universidad de Granada, E-18071 Granada, Spain. Electronic address: lallena@ugr.es.
authors.forename: Antonio M
authors.initials: AM
authors.lastname: Lallena
mesh_terms: D000328:Adult; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000473:pathology; D005260:Female; D006801:Humans; D008327:Mammography; D008403:Mass Screening; D008875:Middle Aged; D009010:Monte Carlo Method; D009361:Neoplasm Invasiveness; D016032:Randomized Controlled Trials as Topic; D016019:Survival Analysis
keywords: Breast cancer; Internal and external validities; Monte Carlo; Screening trials; Simulation